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Case report article, early-onset schizophrenia with predominantly negative symptoms: a case study of a drug-naive female patient treated with cariprazine.
- Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary
Schizophrenia is a chronic and severe mental disorder characterized by positive, negative, and cognitive symptoms. Negative symptoms are usually present from the prodromal phase; early diagnosis and management of negative symptoms is a major health concern since an insidious onset dominated by negative symptoms is associated with a worse outcome. Antipsychotic medications, which are effective for treating positive symptoms, are generally ineffective for treating negative or cognitive symptoms. We present a 23-year-old woman showing severe symptoms at her first visit to our department. The patient’s parents reported that their daughter had experienced several years of psychosocial decline and putative psychiatric symptoms, but no medical attention had been previously sought; as such, the diagnosis of schizophrenia with predominantly negative symptoms was very much delayed. Early onset of schizophrenia, longer duration of untreated psychosis, and severe negative symptoms, which have limited treatment options, suggested a poor prognosis. We initiated monotherapy with cariprazine, a novel antipsychotic that has recently been proven efficacious in treating schizophrenia with predominantly negative symptoms. This report describes a 52-week cariprazine treatment regimen and follows the patient’s impressive clinical improvement confirmed by PANSS and CGI scores, and psychological tests.
Schizophrenia is a severe, chronic, and heterogeneous mental disorder that often has debilitating long-term outcomes. Its lifetime prevalence rate is estimated to be approximately 1% worldwide in the adult population ( Lehman et al., 2010 ). Onset generally occurs in late adolescence or early adulthood, with an average age of 18 years for men and 25 years for women. 1 The term early-onset schizophrenia (EOS) is used to refer to patients who are diagnosed with the disorder before this age. EOS is a severe, frequently disabling, and chronic condition with a prevalence approaching 0.5% in those younger than 18 years ( Hafner and Van der Heiden, 1997 ).
Schizophrenia is accompanied by a distortion of personality that affects fundamental mental and social functions, making everyday life extremely difficult for patients. Clinical symptoms are often classified in three main domains: positive symptoms, such as hallucinations, delusions, suspiciousness/persecution; negative symptoms, such as emotional withdrawal, blunted affect, and passive social withdrawal; and cognitive symptoms, such as impaired perception, learning, thinking, and memorizing. EOS may be accompanied by greater symptom severity, premorbid developmental impairment, ‘soft’ neurological signs (eg, clumsiness, motor incoordination), and a higher rate of substance abuse ( Hsiao and McClellan, 2008 ; Clemmensen et al., 2012 ; Immonen et al., 2017 ). Accordingly, diagnosis of EOS is often difficult and frequently delayed since onset is more commonly insidious than acute, which makes it difficult to differentiate EOS from underlying cognitive deficits, premorbid functional impairment, or other abnormalities ( Russell, 1994 ; Bartlet, 2014 ). Given this common delay in recognition of the disorder, the duration of untreated psychosis is often very long, further contributing to a poor outcome ( Penttila et al., 2014 ).
Although various hypotheses have been developed, the etiopathogenesis of schizophrenia and EOS is not fully understood ( McGuffin, 2004 ; Klosterkotter et al., 2011 ). 2 Among the rising and falling neurochemical theories, the dopamine hypothesis has remained a primary hypothesis guiding the treatment of schizophrenia. There are four dopaminergic pathways in the human brain: the mesolimbic, the mesocortical, the tuberoinfundibular, and the nigrostriatal. Positive symptoms of schizophrenia are associated with the hyperdopaminergic state of D 2 receptors in the mesolimbic area, while negative and cognitive symptoms are believed to be related to the hypodopaminergic dysregulation of the prefrontal cortex ( Stahl, 2003 ).
Negative symptoms of schizophrenia, which affect up to 60% of patients with schizophrenia ( Rabinowitz et al., 2013 ), form a complex clinical constellation of symptoms that challenge both diagnosis and treatment. By definition, negative symptoms mean the absence of normal functions. Negative symptoms are classified by their etiology as primary negative symptoms, which are core features of the disease itself, and secondary negative symptoms, which are consequences of positive symptoms, antipsychotic treatment, depression or extrapyramidal side effects. Five constructs have been accepted by general consensus as key aspects of negative symptoms: blunted affect, alogia, anhedonia, asociality, and avolition ( Marder and Galderisi, 2017 ). Patients with predominant negative symptoms lose their motivation, cannot function at school or work, and their interpersonal relationships severely decay. Due to impaired daily functioning and social amotivation, they may need constant care.
Although early intervention is associated with improvement in negative symptoms ( Boonstra et al., 2012 ), this may be challenging since negative symptoms develop slowly and may be difficult to detect or differentiate from other clinical features ( Kirkpatrick et al., 2001 ; Galderisi et al., 2018 ). Moreover, a more insidious onset predicts poorer outcome and more severe negative symptoms ( Kao and Liu, 2010 ; Immonen et al., 2017 ; Murru and Carpiniello, 2018 ). Diagnosis of patients with predominantly negative symptoms (lacking manifest psychotic signs) is often delayed, resulting in a longer duration of untreated psychosis. The length of untreated psychosis is closely related to poorer functional outcome ( Perkins et al., 2005 ).
Negative symptoms have traditionally had minimal response to antipsychotic treatment. First-generation antipsychotics are effective in treating positive symptoms, but negative symptom improvement is only evident when symptoms are secondary to positive symptoms. It was initially hoped that second-generation antipsychotics would target both positive and negative symptoms, but efficacy data have been disappointing. This was a large meta-analysis where only four second-generation drugs (amisulpride, risperidone, olanzapine, and clozapine) resulted to be more efficacious than first-generation antipsychotics in the overall change of symptoms, including positive and negative symptoms. The other examined second-generation antipsychotics were only as efficacious as first-generation antipsychotic agents ( Leucht et al., 2009 ). These studies were mainly conducted in patients with general symptoms of schizophrenia, therefore a secondary effect on negative symptoms could not be ruled out. Therefore negative symptom improvement cannot be considered a core component of atypicality ( Veerman et al., 2017 ). Previous studies have demonstrated that no drug had a beneficial effect on negative symptoms when compared to another drug ( Arango et al., 2013 ; Millan et al., 2014 ; Fusar-Poli et al., 2015 ), meaning that head to head comparisons of different agents among each other did not result in superiority of one drug to another. The latest comparison ( Krause et al., 2018 ) evaluated all studies that have been performed in the negative symptom population so far, and has found that amisulpride claimed superiority only to placebo, olanzapine was superior to haloperidol, but only in a small trial (n = 35), and cariprazine outperformed risperidone in a large well-controlled trial.
Hence cariprazine emerged as an agent of particular interest in regard to negative symptoms. Cariprazine is a dopamine D 3 /D 2 receptor partial agonist and serotonin 5-HT 1A receptor partial agonist. It has been hypothesized that cariprazine is the only antipsychotic that can block D 3 receptors in the living brain, thereby exhibiting functions that are related to D 3 blockade (e.g., improvement of negative symptoms) ( Stahl, 2016 ). In that large clinical trial including 460 patients with predominant negative symptoms and stable positive symptoms of schizophrenia, cariprazine was significantly more effective than risperidone in improving negative symptoms and patient functioning ( Nemeth et al., 2017 ).
Case Description
The 23-year-old female patient visited the Institute of Rare Diseases at our university with her parents. They had suspected for a long time that something was wrong with their daughter, but this was the first time they had asked for medical help. The patient was quiet and restrained since she did not speak much, her parents told us her story instead. Initially, the patient had done very well in a bilingual secondary school and was socially active with friends and peers. At the age of 15 years, her academic performance started to deteriorate, with her first problems associated with difficulty learning languages and memorizing. Her school grades dropped, and her personality started to gradually change. She became increasingly irritated, and was verbally and physically hostile toward her classmates, resorting to hitting and kicking at times. She was required to repeat a school year and subsequently dropped out of school at the age of 18 because she was unable to complete her studies. During these years, her social activity greatly diminished. She lived at home with her parents, did not go out with friends, or participate in relationships. Most of the time she was silent and unsociable, but occasionally she had fits of laughter without reason. Once the patient told her mother that she could hear the thoughts of others and was probably hearing voices as well. Slowly, her impulse-control problems faded; however, restlessness of the legs was quite often present.
Our patient’s medical history was generally unremarkable. She lacked neurological or psychiatric signs. She had a tonsillectomy and adenotomy at age 7 years. Epilepsy was identified in the patient’s family history (father’s uncle). On physical examination, there were no signs of internal or neurological disease; body mass index was 21.5 (normal weight).
During the first psychiatric interview and examination, we found that our patient was alert and vigilant, but had trouble relating due to decreased integrity of consciousness. Her attention could be aroused or partially directed, and she had difficulty keeping a target idea. Autopsychic and allopsychic orientations were preserved. Longer thinking latencies and slowed movement responses were observed, sometimes with even cataleptic impressions. Cognitive functions, such as thinking, memory, and concept formation, were severely impaired, and we were unable to carry out some of our neurocognitive tests -such as the Addenbrooke’s Cognitive Examination ( Hsieh et al., 2013 ), the Toulouse-Pieron attention test (Kanizsa G1951), Bells test ( Gauthier et al., 1989 ) and the Trail Making Test- because of the patient’s denial of symptoms and refusal to cooperate.
She often looked aside and laughed frequently, suggesting the presence of perceptual disturbances, but she denied her symptoms when asked. In contrast to the periodic inappropriate laughing, apathy and anhedonia were markedly present. During the examination, the patient could not recall anything she would do or even think of with pleasure. According to the heteroanamnesis, she lost her interest in activities she used to like, did not go out with friends anymore, and showed no signs of joy or intimacy towards her family members either.
Along with the affective hyporesponsiveness, amotivation and a general psychomotor slowing were observed. Hypobulia, void perspectives, and lack of motivation were explored. Parental statements indicated that the patient’s social activity had continued to diminish, and her appearance and personal physical hygiene had deteriorated. When we initiated a conversation, the patient was negativistic and agitated. Her critical thinking ability was reduced, which led to inappropriate behavior (she, e.g., unexpectedly stood up and left the room while the examination was still ongoing). Considering her status, she was admitted to the clinic after her first visit.
After several differential diagnostic tests were performed (e.g., routine diagnostic laboratory parameters, immune serological analyses, electroencephalogram, magnetic resonance imaging, genetic testing), all the possible common and rare disorders, such as Huntington’s disease, Niemann Pick C disease, mitochondrial disorders, and autoimmune diseases, were ruled out.
At first contact, to differentiate the symptoms and severity of putative schizophrenia, we mapped the positive, negative, and general symptoms, as well as a clinical impression, using the Positive and Negative Syndrome Scale (PANSS), the Scale for Assessment of Negative Symptoms, and the Clinical Global Impressions-Severity (CGI-S) ( Groth-Marnat, 2009 ).
The patient had a very high PANSS total score, which corresponded to being considered “severely ill” or “among the most severely ill’ on the CGI-S ( Leucht et al., 2005 ). The PANSS score was derived dominantly from the negative items of the scale. Overall, her negative symptoms fulfilled criteria for predominantly negative symptoms, meaning that positive symptomatology was reduced, while negative symptoms were more explicit and dominated the clinical picture ( Riedel et al., 2005 ; Olie et al., 2006 ; Mucci et al., 2017 ). Baseline rating scale sores are presented in Table 1 .
Table 1 Summary of symptom scale scores at the time of admission to the hospital.
The diagnosis of EOS with predominantly negative symptoms was given and treatment with the antipsychotic agent cariprazine was initiated. The patient was hospitalized for 2 weeks following her arrival at the clinic. Cariprazine was started at the dose of 1.5 mg/day and titrated up to 4.5 mg/day over a 2-week period: the patient received 1.5 mg/day for the first 3 days, 3 mg/day from day 4 to day 12, and eventually 4.5 mg/day from day 13 onward. During these 2 weeks, which were spent in hospital, the patient’s explicit negative symptoms such as poverty of speech, psychomotor retardation, poor eye contact, and affective nonresponsiveness improved; however, delusions and hallucinatory perceptions did not fade significantly.
Two weeks after discharge, we saw the patient for her first outpatient visit. Significant clinical improvement was observed. The patient calmly cooperated during the examination, with no signs of agitation. She was oriented to time, place, and self, attention could be drawn and directed, and she was able to keep a target idea and change the subject. Although according to the family, perceptual disturbances were still present, laughing with no reason and looking aside were much less frequent, and restlessness of the legs had stopped; these symptoms were not observed during the examination. Psychomotoric negativism had improved greatly, the patient was more communicative, and she paid more attention to the activities of family members. The pace of speech was close to normal: the thinking latencies and slowed movement responses as observed at admission were not seen anymore. The patient had adequate reaction time to questions asked and could focus in the interview. Mild obstipation and somnolence in the evening were her main complaints. Apart from some tick-like eye closures, there was no pathological finding during physical and neurological examination. At this point, cariprazine was reduced to 3 mg per day.
At her second outpatient visit, which occurred 8 weeks after treatment initiation, further improvement was observed. According to her mother, the patient was more active and open at home. Neurological examination found that the alternating movements of her fingers were slightly slowed. Cariprazine 3 mg/day was continued with concomitant anticholinergic medication.
At the third outpatient visit, which occurred 16 weeks after the first contact, the patient’s overall symptoms, including cognitive functions, such as memory and abstract thinking, as well as functions in activities of daily living, had improved remarkably. She had started to participate in the family’s daily life, even taking responsibility for some household duties; further, she went to the hairdresser for the first time in years, a step forward from her previous state of self-neglect. She was probably still having auditory hallucinations, which she considered natural, and some extrapyramidal symptom (EPS)-like ruminating movements, like to-and-fro swinging of her trunk, were observed. She did not look aside any more and tics were no longer present. Compared with previous visits overall, she was very relaxed, retained eye contact, cooperated, and communicated adequately during the interview. She started to develop insight into her condition, and she told us that her “thoughts were not healthy.” At the last two visits, the synkinesis of the arms was reduced.
After 16 weeks of treatment, the patient’s PANSS Negative Subscale Score and PANSS factor score for negative symptoms (PANSS-FSNS) score were reduced by 44.44% and 41.31%, respectively. Recent studies have demonstrated that linking the percentage improvement of PANSS with CGI-S and -Improvement (CGI-I) scores shows that a 25–50% reduction of PANSS scores corresponds to clinically meaningful change ( Correll et al., 2011 ; Fusar-Poli et al., 2015 ). In acutely ill patients with predominantly positive symptoms who are more likely to respond well to treatment, the 50% cutoff would be a more clinically meaningful criterion; however, since even slight improvement might represent a clinically significant effect in a patient with atypical schizophrenia, the use of 25% cutoff is justified ( Correll et al., 2011 ; Fusar-Poli et al., 2015 ).
In this regard, the 44.44% (change from baseline: −20) and 41.31% (change from baseline: −19) improvement demonstrated on PANSS Negative Symptom subscale and PANSS-FSNS, respectively, are considered a clearly clinically relevant change. Beyond the impaired synkinesis and alternating movement of the arms and fingers, there were no other treatment-related physical dysfunctions. Change from baseline on the PANSS and CGI scales are shown over the course of treatment in Table 2 .
Table 2 Summary of symptom scale scores at weeks 16, 32, and 52.
Since our patient’s symptoms demonstrated strong improvement and tolerability was favorable, cariprazine therapy was continued. Improvement in both negative and positive symptoms was maintained over the course of treatment. At her later visits (32 and 52 weeks), PANSS total score was reduced to a level that was close to the minimum, and the decrease in negative symptom scores was considerable (PANSS-NSS=66.67% and PANS-FSNS=70.00% at both time points). The patient’s progress was also reflected in clinical and functional measurements, with the CGI-S score reduced to 2 (borderline mentally ill) and a CGI-I score of 1 (very much improved) indicating notable improvement.
Cariprazine has demonstrated broad spectrum efficacy in the treatment of positive and negative symptoms of schizophrenia. In a field where no treatment is available for difficult-to-treat negative symptoms, this case is unique and may have important implications for schizophrenia treatment. Despite experiencing approximately 8 years of untreated symptoms and functional impairment associated with predominantly negative symptom EOS, our 23-year-old female patient showed considerable symptomatic and functional improvement after several weeks of treatment with cariprazine. Given that the duration of untreated negative symptoms is associated with worse functional outcomes ( Boonstra et al., 2012 ), the remarkable improvement seen in this case shows how valuable cariprazine could be for patients with similar symptom presentations. Although it is not possible to generalize the observations and findings of this single case, it has the novelty of detecting a potential effect of cariprazine in a drug-naïve patient with marked negative symptoms of early-onset schizophrenia. To our knowledge, no cariprazine-related data has been published in this type of patients. A single case study is obviously far from being predictive for the efficacy of a drug, however, the results seen with this case are promising. With a dose recommended for patients with negative symptoms, our patient’s clinical condition, including positive, negative, and cognitive symptoms, as well as social functioning have improved notably, with the effect maintained for over 12 months. Generally, cariprazine has been well tolerated, with mild EPS observed after 8 weeks, but no metabolic, cardiac, or other side effects.
This case report suggests that the management of patients with EOS and prominent negative symptoms is achievable in everyday practice with cariprazine. More real-world clinical experience is needed to support this finding.
Data Availability Statement
All datasets generated for this study are included in the article/supplementary material.
Ethics Statement
Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.
Author Contributions
All authors listed have made substantial, direct, and intellectual contribution to the work and approved it for publication.
This work was supported from Research and Technology Innovation Fund by the Hungarian National Brain Research Program (KTIA_NAP_ 2017-1.2.1-NKP-2017-00002). Editorial support for this case report was supported by funding from Gedeon Richter. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.
Acknowledgments
We are thankful to the patient and her family for giving us the opportunity to share her story in the form of a publication. Also, we acknowledge editorial assistance was provided by Carol Brown, MS, ELS, of Prescott Medical Communications Group, Chicago, Illinois, USA, a contractor of Gedeon Richter plc.
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Keywords: cariprazine, schizophrenia, negative symptoms, early-onset schizophrenia, second-generation antipsychotic
Citation: Molnar MJ, Jimoh IJ, Zeke H, Palásti Á and Fedor M (2020) Early-Onset Schizophrenia With Predominantly Negative Symptoms: A Case Study of a Drug-Naive Female Patient Treated With Cariprazine. Front. Pharmacol. 11:477. doi: 10.3389/fphar.2020.00477
Received: 24 October 2019; Accepted: 26 March 2020; Published: 23 April 2020.
Reviewed by:
Copyright © 2020 Molnar, Jimoh, Zeke, Palásti and Fedor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Maria Judit Molnar, [email protected]
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Early-onset schizophrenia
Affiliation.
- 1 Department of Child and Adolescent Psychiatry, Philipps University, Marburg, Germany. [email protected]
- PMID: 22797279
- DOI: 10.1159/000338548
The available study findings on the course and outcome of schizophrenia beginning in childhood or adolescence can be summarized as follows. (1) Schizophrenic psychoses that arise before the age of 13 have a very poor prognosis. The disease usually continues to progress in adolescence and adulthood. It can be diagnosed with the same criteria that are used for adults. (2) Patients whose disease is of acute onset, with productive schizophrenic manifestations such as hallucinations and delusions (positive manifestations), have a better prognosis than those whose disease begins insidiously and takes an unfavorable course, with depressive states and continually worsening impairment of cognitive function. (3) The patient's premorbid personality plays a major role. Patients who were described as socially active, intelligent, and integrated children and adolescents before they became ill have a better prognosis than those who were intellectually impaired, timid, introverted and uncommunicative before they became ill. (4) The prognosis seems to be better for patients who have no family history of schizophrenia, those whose families cooperate well, and those whose condition improves rapidly during inpatient treatment. (5) The few available studies on the course and outcome of schizophrenia beginning in childhood and early adolescence confirm that they are much worse than in adult-onset schizophrenia. (6) A 42-year longitudinal study of patients with childhood-onset schizophrenia revealed their suicide rate to be higher than that of patients with adult-onset schizophrenia. No further longitudinal studies are available to confirm this finding.
Copyright © 2012 S. Karger AG, Basel.
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Very early-onset psychosis/schizophrenia: Case studies of spectrum of presentation and management issues : Journal of Family Medicine and Primary Care
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Very early-onset psychosis/schizophrenia
Case studies of spectrum of presentation and management issues.
Aneja, Jitender 1, ; Singhai, Kartik 1 ; Paul, Karandeep 1
1 Department of Psychiatry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
Address for correspondence: Dr. Jitender Aneja, Department of Psychiatry, All India Institute of Medical Sciences, Jodhpur - 342 005, Rajasthan, India. E-mail: [email protected]
Schizophrenia occurs very uncommonly in children younger than 13 years. The disease is preceded by premorbid difficulties, familial vulnerability, and a prodromal phase. The occurrence of positive psychotic symptoms such as delusions and hallucinations depends on the level of cognitive development of child. Furthermore, at times it is very difficult to differentiate the psychopathology and sustain a diagnosis of schizophrenia in view of similarities with disorders such as autism, mood disorders, and obsessive compulsive disorders. Here, we present three case studies with varying presentation of childhood-onset psychosis/schizophrenia and associated management issues.
Introduction
Schizophrenia is a chronic severe mental illness with heterogeneous clinical profile and debilitating course. Research shows that clinical features, severity of illness, prognosis, and treatment of schizophrenia vary depending on the age of onset of illness.[ 1 2 ] Hence, age-specific research in schizophrenia has been emphasized. Although consistency has been noted in differentiating early-onset psychosis (onset <18 years of age) and adult-onset psychosis (onset >18 years), considerable variation is observed with regard to the age of childhood-onset schizophrenia or very early-onset psychosis/schizophrenia (VEOP/VEOS).[ 2 3 ] Most commonly, psychosis occurring at <13 years of age has been considered to be of very early onset and that between 13 and 17 years to be of adolescent onset.[ 4 ] Furthermore, VEOS has been considered to be rare and shown to have differing clinical features (including positive and negative symptoms, cognitive decline, and neuroimaging findings), course, and outcome when compared with that of early-onset or adult-onset schizophrenia.[ 3 ] Progress in acknowledgement of psychotic disorders in children in the recent times has led primary care physicians and paediatricians to increasingly serve as the principal identifiers of psychiatrically ill youth. In recent years, there has been substantial research in early intervention efforts (e.g., with psychotherapy or antipsychotic medicines) focused on the early stages of schizophrenia and on young people with prodromal symptoms.[ 5 ] Here, we report a series of cases with very early onset of psychosis/schizophrenia who had varying clinical features and associated management issues.
Case Reports
A 14-year-old boy, educated up to class 6, belonging to a family of middle socioeconomic status and residing in an urban area was brought with complaints of academic decline since 3 years and hearing voices for the past 2 years. The child was born out of a nonconsanguineous marriage, an unplanned, uneventful, but wanted pregnancy. The child attained developmental milestones as per age. From his early childhood, he was exposed to aggressive behavior of his father, who often attempted to discipline him and in this pursuit at times was abusive and aggressive toward him. Marital problems and domestic violence since marriage lead to divorce of parents when the child attained age of 10 years.
The following year, the child and the mother moved to maternal grandparents’ home and his school was also changed. Within a year of this, a decline in his academic performance with handwriting deterioration, and irritable and sad behaviour was noted. Complaints from school were often received by the mother where the child was found engaged in fist fights and undesirable behavior. He also preferred solitary activities and resented to eat with the rest of the family. In addition, a decline in performance of daily routine activities was seen. No history suggestive of depressive cognitions at that time was forthcoming. A private psychiatrist was consulted who treated him with sodium valproate up to 400 mg/day for nearly 2 months which led to a decline in his irritability and aggression. But the diagnosis was deferred and the medications were gradually tapered and stopped. Over the next 1 year, he also started hearing voices that fulfilled dimensions of commanding type of auditory hallucinations. He suspected that family members including his mother collude with the unknown persons, whose voices he heard and believed it was done to tease him. He eventually dropped out of school and was often found awake till late night, seen muttering to self, shouting at persons who were not around with further deterioration in his socialization and self-care. Another psychiatrist was consulted and he was now diagnosed with schizophrenia and treated inpatient for 2 weeks with risperidone 3 mg, olanzapine 2.5 mg, and oxcarbazepine 300 mg/day with some improvement in his symptoms. Significant weight gain with the medication lead to poor compliance which further led to relapse within 3 months of discharge. Frequent aggressive episodes over the next 1 year resulted in multiple hospital admissions. He was brought to us with acute exacerbation of symptoms and was receiving divalproex sodium 1500 mg/day, aripiprazole 30 mg/day, trifluperazine 15 mg/day, olanzapine 20 mg/day, and lorazepam injection as and when required. He was admitted for diagnostic clarification and rationalization of his medications. He had remarkable physical features of elongated face with large ears. Non-cooperation for mental state examination, and aggressive and violent behavior were noted. He was observed to be muttering and laughing to self. His mood was irritable, speech was laconic, and he lacked insight into his illness. We entertained a diagnosis of very early-onset schizophrenia and explored for the possibilities of organic psychosis, autoimmune encephalitis, and Fragile X syndrome. The physical investigations done are shown in Table 1 . Further special investigations in the form of rubella antibodies (serum IgG = 64.12 U/mL, IgM = 2.44 U/mL) and polymerase chain reaction for Fragile X syndrome (repeat size = 24) were normal. His intelligence quotient measured a year ago was 90, but he did not cooperate for the same during present admission. Initially, we reduced the medication and only kept him on aripiprazole 30 mg/day and added lurasidone 40 mg twice a day and discharged him with residual negative symptoms only. However, his hallucinations and aggression reappeared within 2 weeks of discharge and was readmitted. This time eight sessions of bilateral modified electroconvulsive therapy were administered and he was put on aripiprazole 30 mg/day, chlorpromazine 600 mg/day, sodium divalproex 1000 mg/day, and trihexyphenidyl 4 mg/day. The family was psychoeducated about the illness, and mother's expressed emotions and overinvolvement was addressed by supportive psychotherapy. Moreover, an activity schedule for the child was made, and occupational therapy was instituted. Dietary modifications in view of weight gain were also suggested. In the past 6 months, no episodes of violence came to our notice, though irritability on not meeting his demands is persistent. However, poor socialization, lack of motivation, apathy, weight gain subsequent to psychotropic medications, and aversion to start school are still unresolved. Influence of his multiple medications on bone marrow function is an impending issue of concern.
An 11-year-old boy, educated up to class 3, belonging to a rural family of lower socioeconomic status was brought with complaints of academic decline since 2 years, repetition of acts, irritability since a year, and adoption of abnormal postures since 6 months. He was born out of a nonconsanguineous marriage, uneventful birth, and pregnancy. He was third in birth order and achieved developmental milestones at an appropriate age. Since 2 years, he would not attend to his studies, had poor attention, and difficult memorization. He attributed it to lack of friends at school and asked for school change. There was no history of low mood, depressive cognitions, conduct problems, or bullying and he performed his daily routine like his premorbid self at that time. Since a year, he was observed to repeat certain acts such as pacing in the room from one end to another, continuously for up to 1–2 h, with intermittent stops and often insisted his mother to follow the suit, stand nearby him, or else he would clang on her. He prohibited other family members except his mother near him and would accept his meals only from her. He repeatedly sought assurance of his mother if he had spoken everything right. He also washed his hands repeatedly, up to 10–20 times at one time, and was unable to elaborate reason for the same. His mood during that period was largely irritable with no sadness or fearfulness. He mostly wore the same set of clothes, would be forced to take bath or get nails/hair trimmed, and efforts to these were often met with aggression from the patient. Eventually, he stopped going to school and his family sought faith healing. Within the next 5–6 months, his illness worsened. Fixed gaze, reduced eye blinking, smiling out of context, diminished speech, and refusal to eat food were the reasons for which he was brought to us. His physical examination was unremarkable and his mental state examination using the Kirby's method showed an untidy and ill-kempt child, with infrequent spontaneous acts, and occasional resentment for examination. He had an expressionless face, with occasional smiling to self, negativism, and mutism. No rigidity in any of the limb was observed. He was diagnosed with catatonic schizophrenia and probable obsessive compulsive disorder (vs mannerisms). We performed a battery of physical investigation to rule out organic psychosis [ Table 1 ]. He responded to injection lorazepam with which catatonia melted away. He was also prescribed olanzapine up to 15 mg/day, fluoxetine 20 mg/day, and dietary modification and lactulose for constipation. The family left against medical advice with 50%–60% clinical improvement [rating on Bush Francis Catatonia Rating scale (BFCRS) reduced from 10 to 4]. He relapsed within a month of discharge, initially with predominance of the probable obsessive compulsive symptoms. Fluoxetine was further increased to up to 60 mg/day. But within the next 2 months, the catatonic symptoms reappeared and he was readmitted. He had received olanzapine up to 25 mg/day, which was replaced with risperidone. In view of nonresponse to intravenous lorazepam, we administered him five sessions of modified bilateral Electro-convulsive therapy (ECT) (rating on BFCRS reduced from 8 to 0). The family was psychoeducated about the child's illness and the need for continuous treatment was emphasized. He was discharged with up to 80%–90% improvement. At follow-ups, he started participating at farm work of the family, took care of self, with some repetition of acts such as washing of hands, and denied any associated anxiety symptoms. However, efforts to re-enroll in school had been futile as the child did not agree for it. He has been maintaining at the same level since 6 months of discharge.
A 7-year-old girl, student of second class, belonging to a high socioeconomic status family living in an urban locality was brought with complaints of academic decline, irritability, and abnormal behavior for the past 9 months. The child was born out of a nonconsanguineous marriage, is first in order, and was a wanted child. Maternal health during pregnancy was normal, but the period of labor was prolonged beyond 18 h, so a lower segment caesarean section was performed. There was no history of birth-related complications and the child's birth weight was 2.80 kg. The child attained developmental milestones as per age. The child had a temperament characterized by high activity levels, below average threshold of distractibility, average ability to sustain attention and persist, easy to warm up, adaptation to new situations, and regular bowel and bladder habits. She was enrolled in school at the age of 4 years and progressed well till 9 months back when a decline in her academic interest was observed by her class teacher. Deterioration of her handwriting skills and avoidance of group activities in school were observed. Similarly, at home persistent irritable behavior was seen and her play activities with her siblings reduced. However, her biofunctions were normal during this period.
One month prior to visiting us, she started insisting on wearing the same dress. She wore the same colored or at times the same dress which she would not take off even at bed or bath time. In addition, a change in her mood from largely irritable to cheerful was noted. Her activity levels were increased and it would be difficult to make her sit quietly in class. Her speech output was more than her usual self and she talked incessantly. Her sleep duration also decreased and she started getting up 3–4 h earlier than her usual routine. In view of these symptoms, her family made first contact with us. Her physical examination was normal and mental state examination revealed her to be cheerful, overactive, and difficult to interrupt. She sang and danced during the interview. We diagnosed her with acute mania on the basis of clinical evaluation and assessment on MINI Kid 6.0.[ 6 ] The details of her physical examination are depicted in Table 1 . She was initially treated with olanzapine 5 mg/day which was later on increased to 10 mg/day. However, no response was observed with it in the next 2 weeks, so it was cross tapered with sodium valproate which was built up to 400 mg/day. She improved by nearly 50%, but her mood still remained cheerful/irritable. She did not resume her school and was brought irregularly for the follow-up. Within the next 2 months, she also started muttering to herself and made certain abnormal gestures. She often feared staying alone, or while going to bed insisted the lights to be kept on and ask someone to accompany her in the toilet unlike her previous self. When asked, she reported seeing a lady in white clothes, with no other details. She stopped asking for food on her own and remained lost in her fantasy world. However, her interest in dressing and appreciating herself in mirror persisted. Her mood during this period was mostly labile and often changed from cheerful to sad or irritable. As per the family, the medications were continued as advised. So in view of the emerging picture, the diagnosis was revised to schizo-affective disorder, and in addition to hike in dose of sodium valproate to 500 mg/day, risperidone 2 mg/day was also added. However, even after 8 weeks of treatment with this combination with hike of risperidone to 4 mg/day, there was no relief. The child is still symptomatic, does not go to school, and has significant dysfunction. Psychosocial intervention in the form of psychoeducation, activity scheduling for the child, and occupational therapy has been instituted in addition to the existing treatment regimen, but results are yet to be seen.
The older concept of neurodegenerative etiology of schizophrenia has been superseded by evolving neurodevelopmental nature of this disease. The latter has been attributed to initiation of the underlying pathophysiological processes long before the onset of clinical disease and interaction of the various genetic and environmental factors. The more accommodating theorist propose schizophrenia to be of neurodevelopmental in origin which in turn speeds the process of neurodegeneration.
On clinical front, VEOS is associated with a more insidious onset, prominent negative symptoms, auditory hallucinations, poorly formed delusions which is in part due to less developed cognitive abilities.[ 7 ] The presence of history of speech and language delay as well as motor development deficits have been observed in major studies on childhood-onset schizophrenia, be it the Maudsley early-onset schizophrenia project or the NIMH study.[ 8 9 ] Premorbid deficits in social adjustments and presence of autistic symptoms have also been shown. Moreover, the early onset of psychosis is associated with poor prognosis, worse overall functioning, and multiple hospitalizations.[ 7 ] The duration of untreated psychosis in childhood-onset psychosis has been shown to be smaller in hospital-based studies[ 10 ] and larger in community settings.[ 11 ] In addition, the presence of comorbidities and an organic etiology or history of maternal illness during pregnancy is a common finding in VEOS.[ 10 ] In addition, obsessive compulsive symptoms are frequently observed in first-episode drug-naive schizophrenia patients and have a poorer outcome, more severe impairment of social behavior, and lower functioning.[ 12 ] However, in many instances it is very difficult to differentiate the obsessive compulsive symptoms from the motor symptoms of schizophrenia such as stereotypy and mannerisms and varying degree of insight.[ 13 ]
In the present case series, all the children had an insidious onset of illness, with initial symptom of academic decline, and poorly formed psychotic symptoms/psychotic-like experiences. All the children reported here had dropped out of school, showed a shift in their interests, withdrew from social circle, appeared to be distant, had impaired self-care, and often lacked concern for others along with a range of mood disturbances. All these symptoms fit into the classical description of prodromal symptoms of schizophrenia.[ 14 ] In contrast to available evidence, no history of motor, speech, or language delay was noted in any of the child. Furthermore, no history suggestive of autistic features or problems in social adjustments prior to onset of illness was forthcoming.
However, the diagnosis of schizophrenia could be clearly made in the first case, while the second child had predominant catatonic and probably obsessive compulsive symptoms. It is difficult to ascertain the diagnosis of schizophrenia on the basis of presence of only catatonic symptoms and no delusions and hallucinations or negative symptoms as required by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition or International Classification of Diseases, Tenth Revision. However, it is very difficult to sustain any other diagnosis for the second child. In the third child, the illness has been evolving and the clinical picture changed from predominant mood symptoms to psychotic-like experiences at later stage. Therefore, at present a diagnosis of schizo-affective disorder is entertained. We could not find any possible organic etiology in any of the three cases with the best of our efforts.
With provision of pharmacological and psychosocial treatment in accordance to the available treatment guidelines,[ 15 ] remission was not achieved in two of the three children. Currently, the available evidence also suggests that the prognosis of childhood-onset schizophrenia is mainly poor as it disrupts the social and cognitive development and thus nearly two-third of children do not achieve remission.[ 16 ] On a positive note, we have been able to retain all the children in treatment.
Other issues faced by the families of three children and the treating team are briefly discussed below. In countries like India, where significant expenses are born by patients/family, associated stigma, limited social services, and the anti-psychotic related adverse effects raise the burden of care exponentially. In 2/3 index patients, the family bore the costs of special investigations, which was not possible in the second child and led to financial difficulties for the single mother of the first child. Adding on, the availability of rehabilitation services for children with major mental illnesses is scarce in various parts of our country. Furthermore, we successfully used ECT for management of acute disturbance in two of the three patients prior to the notification of Mental Health Care Act, 2017 that prohibits its use in minors. The case series also put forward a strong case for strengthening and sensitizing primary care physicians and pediatricians in identifying and treating cases of VEOP, since they are more likely to be the first points of contact with patients of the discussed age group. In view of the duration of untreated psychosis being a very eloquent prognostic factor for VEOP and the symptomatology of the same showing significant heterogeneity, armoring primary care physicians and pediatricians with the right skills to identify, treat, or refer patients with VEOP, especially in the prodromal period, might profoundly contribute in decreasing the morbidity and improving prognosis. Citing this lacuna which could be filled and used to our advantage, Stevens et al .[ 17 ] elaborated and discussed various questions which practitioners might find useful.
Childhood-onset schizophrenia is a rare occurrence. The current case series highlights differing clinical presentation of VEOS/VEOP in children and adolescents. Certain other issues pertinent to the management of VEOS/VEOP are also touched upon in this article. With the early recognition of childhood mental health illnesses, we need to build and strengthen ample child and adolescent mental health services in India.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest.
There are no conflicts of interest.
Acknowledgement
The authors thank Dr. Sonam Arora, MD, DNB (Pathology), for providing assistance in laboratory investigations and article writing.
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Childhood onset; psychosis; schizophrenia; very early onset
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Early Signs and Symptoms of Schizophrenia
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Ruth is a journalist with experience covering a wide range of health and medical issues.
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Steven Gans, MD, is board-certified in psychiatry and is an active supervisor, teacher, and mentor at Massachusetts General Hospital.
- Early Warning Signs
In Early Adulthood
- When Symptoms Start
Complications
When to see a healthcare provider, frequently asked questions.
Schizophrenia is a chronic psychiatric disorder that affects how a person thinks, feels, and behaves. Common early signs of schizophrenia vary by age group and include:
- Young children: Delayed development
- Older kids and teens: Depression, isolation, behavioral problems (e.g., stealing) or changes (e.g., bizarre or unusual thoughts or actions), and trouble focusing
- Adults: Restlessness, anxiety, low energy, not taking care of one's self (e.g., personal hygiene), decrease in work performance, suicidal thoughts, and social withdrawal
Schizophrenia usually develops slowly, with early warning signs developing before the first severe episode ( psychosis ). That is when what are known as positive symptoms—those not generally seen in healthy people, such as hallucinations and delusions—are experienced for the first time.
Early diagnosis and treatment of schizophrenia increase the chances of a successful recovery. Knowing the early warning signs can be important in identifying the onset of schizophrenia and getting the care that's needed.
Westend61 / Getty images
Early Warning Signs of Schizophrenia
The period in which early warning signs are experienced is called the prodromal stage . The onset of schizophrenia can last from months to several years, and the first signs differ depending on at what age the disorder develops.
The age at which someone develops schizophrenia is thought to have an impact on the symptoms that person will experience. Even though men and women have roughly similar rates of schizophrenia, they tend to develop the condition at slightly different ages.
In Young Children
People who are diagnosed with schizophrenia in childhood have more developmental issues than those diagnosed later in life.
Very early developmental warning signs include:
- Delayed motor development : Such as not walking until over 18 months old
- Delayed speech and/or language development : Such as not speaking meaningful two- or three- word phrases until over 36 months old
- Impaired social development at an early age : Such as not using gestures to communicate or failing to regulate facial expressions
It is important to note that these issues are not necessarily indicative of schizophrenia and may instead be related to something completely different.
In Teenagers
Prior to the onset of schizophrenia, adolescents often develop changes in behavior. This can lead to them struggling in school, one of the most common issues reported in teens diagnosed with schizophrenia.
Early warning signs include:
- Difficulty concentrating and paying attention
- Unexplained functional decline
- Increased introversion
- Suicidal ideation
- Bizarre behaviors
It is hard to diagnose schizophrenia in adolescents because many of the features of the condition are common during normal childhood development. For example, a normal part of childhood is having vivid imaginations and fantasies. However, these can be misunderstood to be hallucinations, a symptom of schizophrenia.
Those developing the disorder at a young age are more likely to go on to experience certain symptoms compared to those who develop it later.
It is also thought that children may be less likely to experience paranoid delusions, which is the belief that others are out to harm you, than people who develop schizophrenia at an older age.
Ellen Lindner / Verywell
Schizophrenia typically develops during early adulthood. Its onset is characterized by changes in behavior and a deterioration in functioning in daily life.
The most common earliest signs are:
- Nervousness and/or restlessness
- Difficulty in thinking clearly or concentrating
- Lack of self-confidence
- Lack of energy and/or slowness
- A worrying drop in grades or job performance
- Social withdrawal and/or or uneasiness around other people
Not everyone will experience these early warning signs at the same time in their lives. According to some studies, these prodromal symptoms can be present for years.
While the exact cause of the disorder is unknown, schizophrenia has a strong genetic component and is highly heritable. Having a family member with schizophrenia increases your risk of developing the disease.
These risk factors will be taken into account regarding a diagnosis if you are thought to be experiencing these early warning signs of schizophrenia.
It is estimated that schizophrenia affects approximately 1% of adults worldwide.
Over the Age of 45
The majority of early warning signs for this age group are the same as for people who develop schizophrenia at early adulthood. However, there are some differences.
A study has reported that men who develop schizophrenia over the age of 35 tend to have fewer negative symptoms during the early warning stage. Specifically, the study found that they were less likely to experience social isolation and difficulties with concentration.
Some scientists think that those who develop schizophrenia later in life will experience less disorganized thinking and negative symptoms.
When Schizophrenia Symptoms Start
Symptoms usually start to develop in early adulthood, between late adolescence and the early 30s. The disorder typically becomes evident slightly earlier in men than in women. Symptoms often emerge between late adolescence and the early 20s in men and between the early 20s and the early 30s in women.
Early Onset Schizophrenia
If the disease is diagnosed prior to the age of 18, it is referred to as early onset schizophrenia (EOS). EOS is rare, with an estimated prevalence of 0.23%. Rarer still, the disease can develop in very young children. This is called childhood-onset schizophrenia (COS), when the disease is diagnosed before the age of 13.
According to the National Institute of Mental Health, approximately one in 40,000 children will have COS. It is thought to be extremely uncommon that COS develops before the age of 10.
Late-Onset Schizophrenia
Although schizophrenia most commonly presents between late adolescence and the early 30s, it is estimated that up to 20% of patients first develop symptoms after the age of 40 years old. Some scientists have identified this as a subtype of schizophrenia called late-onset schizophrenia (LOS).
Women are more likely to be in this group than men. Symptoms typically develop in menopause , between ages 44 and 49 years old. However, even for women, it is still more common for schizophrenia to develop in early adulthood than at this age.
In the early stages of schizophrenia, the disorder can be confused with others, including depression. This is because the majority of the most common early warning signs for schizophrenia are also the most common initial symptoms for moderate to severe depression.
It is not until positive symptoms (such as hallucinations, delusions, and disorganized thoughts and speech) are experienced that schizophrenia can be more easily distinguished from mood disorders such as depression.
People with schizophrenia may experience suicidal thoughts. The risk of suicide for those with schizophrenia is higher for men and for those that develop the disease at a young age.
Depression has been identified as a major risk factor for suicide among those with schizophrenia. Having other disorders that are highly prevalent among those with schizophrenia, such as substance use disorder, also increase the risk of suicide.
Substance abuse, in general, is linked to poor outcomes in terms of recovery. For those affected, a comprehensive plan that includes treatment for the substance use disorder along with the schizophrenia is important.
As schizophrenia usually develops gradually, it can be difficult to pinpoint when changes in behavior start or know whether they are something to worry about. Identifying that you are experiencing a pattern of concerning behaviors can be a sign you should consult with a professional.
Symptoms may intensify in the run-up to an acute episode of psychosis in schizophrenia. The warning signs include:
- New difficulty thinking clearly or concentrating
- Suspiciousness of or uneasiness with others
- Withdrawing socially, spending a lot more time alone than usual
- Unusual, overly intense new ideas, strange feelings, or having no feelings at all
- Decline in self-care or personal hygiene
- Difficulty telling reality from fantasy
- Confused speech or trouble communicating
While these changes might not be concerning by themselves, if you or a loved one are experiencing a number of these symptoms, you should contact a mental health professional. It can be difficult for those with schizophrenia to want to get help, especially if they are experiencing symptoms such as paranoia .
If you or your loved one is thinking of or talking about harming themselves, contact someone who can help right away. You can call the toll-free, 24-hour National Suicide Prevention Lifeline (Lifeline) at 800-237-8255.
If you require immediate emergency care, call 911 for emergency services or go to the nearest hospital emergency room.
A Word From Verywell
Getting help as early as possible increases your chances for a successful recovery. You should speak to your healthcare provider, or your loved one's healthcare provider, if you are concerned about any changes in behavior. The early warning signs highlighted above do not necessarily point to schizophrenia and might instead be related to something else, but they still may warrant medical intervention.
This is especially true for children. Because schizophrenia is very rare for this age group, it is likely that, even if they are experiencing the early warning signs highlighted above, your child doesn't have this disorder.
If you, or a loved one, do receive a diagnosis of schizophrenia, know that there are effective treatments available that can help manage symptoms well.
Paranoid schizophrenia used to be considered a subtype of schizophrenia, but this is no longer the case. While paranoia is a common symptom, not everyone experiences it. The different types of schizophrenia include hebephrenic schizophrenia (disorganized schizophrenia), residual schizophrenia, and catatonic schizophrenia . There is also undifferentiated schizophrenia, which is a collection of multiple symptoms that do not cleanly fit into an existing subtype.
The exact causes of schizophrenia are not known, but there are a few risk factors that can lead to its development. Genetics, brain structure and function, and the surrounding environment (exposure to poverty, stress, viruses, nutritional problems) can influence whether a person will have schizophrenia.
In the U.S, schizophrenia and other closely related psychotic disorders affect between 0.25 percent and 0.64 percent of people. On a worldwide scale, this percentage increases to a range between 0.33 percent to 0.75 percent of people.
In many cases, men and women are affected differently by schizophrenia. Men who have schizophrenia often show more signs of social withdrawal and substance abuse. Women with schizophrenia usually experience more frequent mood disturbance and depression. The frequency and severity of these symptoms can be affected by age and onset of the condition.
Catts SV, O'Toole BI. The treatment of schizophrenia: Can we raise the standard of care? Aust N Z J Psychiatry . 2016;50(12):1128-1138. doi:10.1177/0004867416672725
Coulon N, Godin O, Bulzacka E, et al. Early and very early‐onset schizophrenia compared with adult‐onset schizophrenia: French FACE‐SZ database. Brain Behav . 2020;10(2). doi:10.1002/brb3.1495
Parellada M, Gomez-Vallejo S, Burdeus M, Arango C. Developmental differences between schizophrenia and bipolar disorder . Schizophr Bull . 2017;43(6):1176-1189. doi:10.1093/schbul/sbx126
Bartlett J. Childhood-onset schizophrenia: what do we really know? Health Psychology and Behavioral Medicine . 2014;2(1):735-747. doi:10.1080/21642850.2014.927738
McClellan J, Stock S. Practice parameter for the assessment and treatment of children and adolescents with schizophrenia. Journal of the American Academy of Child & Adolescent Psychiatry . 2013;52(9):976-990. doi:10.1016/j.jaac.2012.02.008
Häfner H. From onset and prodromal stage to a life-long course of schizophrenia and its symptom dimensions: how sex, age, and other risk factors influence incidence and course of illness. Psychiatry Journal. 2019;1-15. doi:10.1155/2019/9804836
Häfner H, Maurer K. Early detection of schizophrenia: current evidence and future perspectives . World Psychiatry . 2006;5(3):130-138.
Hany M, Rehman B, Azhar Y, et al. Schizophrenia . StatPearls.
Skokou M, Katrivanou A, Andriopoulos I, Gourzis P. Active and prodromal phase symptomatology of young-onset and late-onset paranoid schizophrenia. Revista de Psiquiatría y Salud Mental (English Edition) . 2012;5(3):150-159. doi:10.1016/j.rpsmen.2012.03.002
Maglione JE, Thomas SE, Jeste DV. Late-onset schizophrenia: do recent studies support categorizing LOS as a subtype of schizophrenia? Current Opinion in Psychiatry . 2014;27(3):173-178. doi:10.1097/YCO.0000000000000049
National Institute of Mental Health. Schizophrenia .
Petruzzelli MG, Margari L, Bosco A, Craig F, Palumbi R, Margari F. Early onset first episode psychosis: dimensional structure of symptoms, clinical subtypes and related neurodevelopmental markers. Eur Child Adolesc Psychiatry . 2018;27(2):171-179. doi:10.1007/s00787-017-1026-7
Driver DI, Gogtay N, Rapoport JL. Childhood onset schizophrenia and early onset schizophrenia spectrum disorders. Child Adolesc Psychiatr Clin N Am . 2013;22(4):539-555. doi:10.1016/j.chc.2013.04.001
Hor K, Taylor M. Suicide and schizophrenia: a systematic review of rates and risk factors. J Psychopharmacol . 2010;24(4_supplement):81-90. doi:10.1177/1359786810385490
National Institutes of Mental Health. Fact Sheet: Early Warning Signs of Psychosis.
National Institute of Mental Health. Statistics. Schizophrenia .
Li R, Ma X, Wang G, Yang J, Wang C. Why sex differences in schizophrenia? J Transl Neurosci (Beijing). 2016;1(1):37-42. PMID:29152382.
By Ruth Edwards Ruth is a journalist with experience covering a wide range of health and medical issues. As a BBC news producer, she investigated issues such as the growing mental health crisis among young people in the UK.
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- v.7(6); Nov-Dec 2018
Very early-onset psychosis/schizophrenia: Case studies of spectrum of presentation and management issues
Jitender aneja.
1 Department of Psychiatry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
Kartik Singhai
Karandeep paul.
Schizophrenia occurs very uncommonly in children younger than 13 years. The disease is preceded by premorbid difficulties, familial vulnerability, and a prodromal phase. The occurrence of positive psychotic symptoms such as delusions and hallucinations depends on the level of cognitive development of child. Furthermore, at times it is very difficult to differentiate the psychopathology and sustain a diagnosis of schizophrenia in view of similarities with disorders such as autism, mood disorders, and obsessive compulsive disorders. Here, we present three case studies with varying presentation of childhood-onset psychosis/schizophrenia and associated management issues.
Introduction
Schizophrenia is a chronic severe mental illness with heterogeneous clinical profile and debilitating course. Research shows that clinical features, severity of illness, prognosis, and treatment of schizophrenia vary depending on the age of onset of illness.[ 1 , 2 ] Hence, age-specific research in schizophrenia has been emphasized. Although consistency has been noted in differentiating early-onset psychosis (onset <18 years of age) and adult-onset psychosis (onset >18 years), considerable variation is observed with regard to the age of childhood-onset schizophrenia or very early-onset psychosis/schizophrenia (VEOP/VEOS).[ 2 , 3 ] Most commonly, psychosis occurring at <13 years of age has been considered to be of very early onset and that between 13 and 17 years to be of adolescent onset.[ 4 ] Furthermore, VEOS has been considered to be rare and shown to have differing clinical features (including positive and negative symptoms, cognitive decline, and neuroimaging findings), course, and outcome when compared with that of early-onset or adult-onset schizophrenia.[ 3 ] Progress in acknowledgement of psychotic disorders in children in the recent times has led primary care physicians and paediatricians to increasingly serve as the principal identifiers of psychiatrically ill youth. In recent years, there has been substantial research in early intervention efforts (e.g., with psychotherapy or antipsychotic medicines) focused on the early stages of schizophrenia and on young people with prodromal symptoms.[ 5 ] Here, we report a series of cases with very early onset of psychosis/schizophrenia who had varying clinical features and associated management issues.
Case Reports
A 14-year-old boy, educated up to class 6, belonging to a family of middle socioeconomic status and residing in an urban area was brought with complaints of academic decline since 3 years and hearing voices for the past 2 years. The child was born out of a nonconsanguineous marriage, an unplanned, uneventful, but wanted pregnancy. The child attained developmental milestones as per age. From his early childhood, he was exposed to aggressive behavior of his father, who often attempted to discipline him and in this pursuit at times was abusive and aggressive toward him. Marital problems and domestic violence since marriage lead to divorce of parents when the child attained age of 10 years.
The following year, the child and the mother moved to maternal grandparents’ home and his school was also changed. Within a year of this, a decline in his academic performance with handwriting deterioration, and irritable and sad behaviour was noted. Complaints from school were often received by the mother where the child was found engaged in fist fights and undesirable behavior. He also preferred solitary activities and resented to eat with the rest of the family. In addition, a decline in performance of daily routine activities was seen. No history suggestive of depressive cognitions at that time was forthcoming. A private psychiatrist was consulted who treated him with sodium valproate up to 400 mg/day for nearly 2 months which led to a decline in his irritability and aggression. But the diagnosis was deferred and the medications were gradually tapered and stopped. Over the next 1 year, he also started hearing voices that fulfilled dimensions of commanding type of auditory hallucinations. He suspected that family members including his mother collude with the unknown persons, whose voices he heard and believed it was done to tease him. He eventually dropped out of school and was often found awake till late night, seen muttering to self, shouting at persons who were not around with further deterioration in his socialization and self-care. Another psychiatrist was consulted and he was now diagnosed with schizophrenia and treated inpatient for 2 weeks with risperidone 3 mg, olanzapine 2.5 mg, and oxcarbazepine 300 mg/day with some improvement in his symptoms. Significant weight gain with the medication lead to poor compliance which further led to relapse within 3 months of discharge. Frequent aggressive episodes over the next 1 year resulted in multiple hospital admissions. He was brought to us with acute exacerbation of symptoms and was receiving divalproex sodium 1500 mg/day, aripiprazole 30 mg/day, trifluperazine 15 mg/day, olanzapine 20 mg/day, and lorazepam injection as and when required. He was admitted for diagnostic clarification and rationalization of his medications. He had remarkable physical features of elongated face with large ears. Non-cooperation for mental state examination, and aggressive and violent behavior were noted. He was observed to be muttering and laughing to self. His mood was irritable, speech was laconic, and he lacked insight into his illness. We entertained a diagnosis of very early-onset schizophrenia and explored for the possibilities of organic psychosis, autoimmune encephalitis, and Fragile X syndrome. The physical investigations done are shown in Table 1 . Further special investigations in the form of rubella antibodies (serum IgG = 64.12 U/mL, IgM = 2.44 U/mL) and polymerase chain reaction for Fragile X syndrome (repeat size = 24) were normal. His intelligence quotient measured a year ago was 90, but he did not cooperate for the same during present admission. Initially, we reduced the medication and only kept him on aripiprazole 30 mg/day and added lurasidone 40 mg twice a day and discharged him with residual negative symptoms only. However, his hallucinations and aggression reappeared within 2 weeks of discharge and was readmitted. This time eight sessions of bilateral modified electroconvulsive therapy were administered and he was put on aripiprazole 30 mg/day, chlorpromazine 600 mg/day, sodium divalproex 1000 mg/day, and trihexyphenidyl 4 mg/day. The family was psychoeducated about the illness, and mother's expressed emotions and overinvolvement was addressed by supportive psychotherapy. Moreover, an activity schedule for the child was made, and occupational therapy was instituted. Dietary modifications in view of weight gain were also suggested. In the past 6 months, no episodes of violence came to our notice, though irritability on not meeting his demands is persistent. However, poor socialization, lack of motivation, apathy, weight gain subsequent to psychotropic medications, and aversion to start school are still unresolved. Influence of his multiple medications on bone marrow function is an impending issue of concern.
Details of investigations done in the three children
An 11-year-old boy, educated up to class 3, belonging to a rural family of lower socioeconomic status was brought with complaints of academic decline since 2 years, repetition of acts, irritability since a year, and adoption of abnormal postures since 6 months. He was born out of a nonconsanguineous marriage, uneventful birth, and pregnancy. He was third in birth order and achieved developmental milestones at an appropriate age. Since 2 years, he would not attend to his studies, had poor attention, and difficult memorization. He attributed it to lack of friends at school and asked for school change. There was no history of low mood, depressive cognitions, conduct problems, or bullying and he performed his daily routine like his premorbid self at that time. Since a year, he was observed to repeat certain acts such as pacing in the room from one end to another, continuously for up to 1–2 h, with intermittent stops and often insisted his mother to follow the suit, stand nearby him, or else he would clang on her. He prohibited other family members except his mother near him and would accept his meals only from her. He repeatedly sought assurance of his mother if he had spoken everything right. He also washed his hands repeatedly, up to 10–20 times at one time, and was unable to elaborate reason for the same. His mood during that period was largely irritable with no sadness or fearfulness. He mostly wore the same set of clothes, would be forced to take bath or get nails/hair trimmed, and efforts to these were often met with aggression from the patient. Eventually, he stopped going to school and his family sought faith healing. Within the next 5–6 months, his illness worsened. Fixed gaze, reduced eye blinking, smiling out of context, diminished speech, and refusal to eat food were the reasons for which he was brought to us. His physical examination was unremarkable and his mental state examination using the Kirby's method showed an untidy and ill-kempt child, with infrequent spontaneous acts, and occasional resentment for examination. He had an expressionless face, with occasional smiling to self, negativism, and mutism. No rigidity in any of the limb was observed. He was diagnosed with catatonic schizophrenia and probable obsessive compulsive disorder (vs mannerisms). We performed a battery of physical investigation to rule out organic psychosis [ Table 1 ]. He responded to injection lorazepam with which catatonia melted away. He was also prescribed olanzapine up to 15 mg/day, fluoxetine 20 mg/day, and dietary modification and lactulose for constipation. The family left against medical advice with 50%–60% clinical improvement [rating on Bush Francis Catatonia Rating scale (BFCRS) reduced from 10 to 4]. He relapsed within a month of discharge, initially with predominance of the probable obsessive compulsive symptoms. Fluoxetine was further increased to up to 60 mg/day. But within the next 2 months, the catatonic symptoms reappeared and he was readmitted. He had received olanzapine up to 25 mg/day, which was replaced with risperidone. In view of nonresponse to intravenous lorazepam, we administered him five sessions of modified bilateral Electro-convulsive therapy (ECT) (rating on BFCRS reduced from 8 to 0). The family was psychoeducated about the child's illness and the need for continuous treatment was emphasized. He was discharged with up to 80%–90% improvement. At follow-ups, he started participating at farm work of the family, took care of self, with some repetition of acts such as washing of hands, and denied any associated anxiety symptoms. However, efforts to re-enroll in school had been futile as the child did not agree for it. He has been maintaining at the same level since 6 months of discharge.
A 7-year-old girl, student of second class, belonging to a high socioeconomic status family living in an urban locality was brought with complaints of academic decline, irritability, and abnormal behavior for the past 9 months. The child was born out of a nonconsanguineous marriage, is first in order, and was a wanted child. Maternal health during pregnancy was normal, but the period of labor was prolonged beyond 18 h, so a lower segment caesarean section was performed. There was no history of birth-related complications and the child's birth weight was 2.80 kg. The child attained developmental milestones as per age. The child had a temperament characterized by high activity levels, below average threshold of distractibility, average ability to sustain attention and persist, easy to warm up, adaptation to new situations, and regular bowel and bladder habits. She was enrolled in school at the age of 4 years and progressed well till 9 months back when a decline in her academic interest was observed by her class teacher. Deterioration of her handwriting skills and avoidance of group activities in school were observed. Similarly, at home persistent irritable behavior was seen and her play activities with her siblings reduced. However, her biofunctions were normal during this period.
One month prior to visiting us, she started insisting on wearing the same dress. She wore the same colored or at times the same dress which she would not take off even at bed or bath time. In addition, a change in her mood from largely irritable to cheerful was noted. Her activity levels were increased and it would be difficult to make her sit quietly in class. Her speech output was more than her usual self and she talked incessantly. Her sleep duration also decreased and she started getting up 3–4 h earlier than her usual routine. In view of these symptoms, her family made first contact with us. Her physical examination was normal and mental state examination revealed her to be cheerful, overactive, and difficult to interrupt. She sang and danced during the interview. We diagnosed her with acute mania on the basis of clinical evaluation and assessment on MINI Kid 6.0.[ 6 ] The details of her physical examination are depicted in Table 1 . She was initially treated with olanzapine 5 mg/day which was later on increased to 10 mg/day. However, no response was observed with it in the next 2 weeks, so it was cross tapered with sodium valproate which was built up to 400 mg/day. She improved by nearly 50%, but her mood still remained cheerful/irritable. She did not resume her school and was brought irregularly for the follow-up. Within the next 2 months, she also started muttering to herself and made certain abnormal gestures. She often feared staying alone, or while going to bed insisted the lights to be kept on and ask someone to accompany her in the toilet unlike her previous self. When asked, she reported seeing a lady in white clothes, with no other details. She stopped asking for food on her own and remained lost in her fantasy world. However, her interest in dressing and appreciating herself in mirror persisted. Her mood during this period was mostly labile and often changed from cheerful to sad or irritable. As per the family, the medications were continued as advised. So in view of the emerging picture, the diagnosis was revised to schizo-affective disorder, and in addition to hike in dose of sodium valproate to 500 mg/day, risperidone 2 mg/day was also added. However, even after 8 weeks of treatment with this combination with hike of risperidone to 4 mg/day, there was no relief. The child is still symptomatic, does not go to school, and has significant dysfunction. Psychosocial intervention in the form of psychoeducation, activity scheduling for the child, and occupational therapy has been instituted in addition to the existing treatment regimen, but results are yet to be seen.
The older concept of neurodegenerative etiology of schizophrenia has been superseded by evolving neurodevelopmental nature of this disease. The latter has been attributed to initiation of the underlying pathophysiological processes long before the onset of clinical disease and interaction of the various genetic and environmental factors. The more accommodating theorist propose schizophrenia to be of neurodevelopmental in origin which in turn speeds the process of neurodegeneration.
On clinical front, VEOS is associated with a more insidious onset, prominent negative symptoms, auditory hallucinations, poorly formed delusions which is in part due to less developed cognitive abilities.[ 7 ] The presence of history of speech and language delay as well as motor development deficits have been observed in major studies on childhood-onset schizophrenia, be it the Maudsley early-onset schizophrenia project or the NIMH study.[ 8 , 9 ] Premorbid deficits in social adjustments and presence of autistic symptoms have also been shown. Moreover, the early onset of psychosis is associated with poor prognosis, worse overall functioning, and multiple hospitalizations.[ 7 ] The duration of untreated psychosis in childhood-onset psychosis has been shown to be smaller in hospital-based studies[ 10 ] and larger in community settings.[ 11 ] In addition, the presence of comorbidities and an organic etiology or history of maternal illness during pregnancy is a common finding in VEOS.[ 10 ] In addition, obsessive compulsive symptoms are frequently observed in first-episode drug-naive schizophrenia patients and have a poorer outcome, more severe impairment of social behavior, and lower functioning.[ 12 ] However, in many instances it is very difficult to differentiate the obsessive compulsive symptoms from the motor symptoms of schizophrenia such as stereotypy and mannerisms and varying degree of insight.[ 13 ]
In the present case series, all the children had an insidious onset of illness, with initial symptom of academic decline, and poorly formed psychotic symptoms/psychotic-like experiences. All the children reported here had dropped out of school, showed a shift in their interests, withdrew from social circle, appeared to be distant, had impaired self-care, and often lacked concern for others along with a range of mood disturbances. All these symptoms fit into the classical description of prodromal symptoms of schizophrenia.[ 14 ] In contrast to available evidence, no history of motor, speech, or language delay was noted in any of the child. Furthermore, no history suggestive of autistic features or problems in social adjustments prior to onset of illness was forthcoming.
However, the diagnosis of schizophrenia could be clearly made in the first case, while the second child had predominant catatonic and probably obsessive compulsive symptoms. It is difficult to ascertain the diagnosis of schizophrenia on the basis of presence of only catatonic symptoms and no delusions and hallucinations or negative symptoms as required by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition or International Classification of Diseases, Tenth Revision. However, it is very difficult to sustain any other diagnosis for the second child. In the third child, the illness has been evolving and the clinical picture changed from predominant mood symptoms to psychotic-like experiences at later stage. Therefore, at present a diagnosis of schizo-affective disorder is entertained. We could not find any possible organic etiology in any of the three cases with the best of our efforts.
With provision of pharmacological and psychosocial treatment in accordance to the available treatment guidelines,[ 15 ] remission was not achieved in two of the three children. Currently, the available evidence also suggests that the prognosis of childhood-onset schizophrenia is mainly poor as it disrupts the social and cognitive development and thus nearly two-third of children do not achieve remission.[ 16 ] On a positive note, we have been able to retain all the children in treatment.
Other issues faced by the families of three children and the treating team are briefly discussed below. In countries like India, where significant expenses are born by patients/family, associated stigma, limited social services, and the anti-psychotic related adverse effects raise the burden of care exponentially. In 2/3 index patients, the family bore the costs of special investigations, which was not possible in the second child and led to financial difficulties for the single mother of the first child. Adding on, the availability of rehabilitation services for children with major mental illnesses is scarce in various parts of our country. Furthermore, we successfully used ECT for management of acute disturbance in two of the three patients prior to the notification of Mental Health Care Act, 2017 that prohibits its use in minors. The case series also put forward a strong case for strengthening and sensitizing primary care physicians and pediatricians in identifying and treating cases of VEOP, since they are more likely to be the first points of contact with patients of the discussed age group. In view of the duration of untreated psychosis being a very eloquent prognostic factor for VEOP and the symptomatology of the same showing significant heterogeneity, armoring primary care physicians and pediatricians with the right skills to identify, treat, or refer patients with VEOP, especially in the prodromal period, might profoundly contribute in decreasing the morbidity and improving prognosis. Citing this lacuna which could be filled and used to our advantage, Stevens et al .[ 17 ] elaborated and discussed various questions which practitioners might find useful.
Childhood-onset schizophrenia is a rare occurrence. The current case series highlights differing clinical presentation of VEOS/VEOP in children and adolescents. Certain other issues pertinent to the management of VEOS/VEOP are also touched upon in this article. With the early recognition of childhood mental health illnesses, we need to build and strengthen ample child and adolescent mental health services in India.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest.
There are no conflicts of interest.
Acknowledgement
The authors thank Dr. Sonam Arora, MD, DNB (Pathology), for providing assistance in laboratory investigations and article writing.
- Case report
- Open Access
- Published: 08 June 2019
Early onset first-episode psychosis during treatment with thalidomide for refractory ulcerative colitis: a case report
- Maria Giuseppina Petruzzelli 1 ,
- Lucia Margari 1 ,
- Sara Ivagnes 1 ,
- Roberto Palumbi 1 &
- Francesco Margari 2
Journal of Medical Case Reports volume 13 , Article number: 175 ( 2019 ) Cite this article
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Inflammatory bowel disease and schizophrenia spectrum disorders are complex and multifactorial conditions characterized by great variability of age at onset, clinical presentation, and longitudinal course. Several lines of evidence suggested different connections among immunological dysregulation, gastrointestinal inflammation, and psychosis, but to date many controversial issues still exist in this field.
Case presentation
We present the case of a 14-year-old Caucasian boy with refractory ulcerative colitis, admitted to the Child Neuropsychiatry Unit of the Polyclinic Hospital of Bari in the course of his first-episode psychosis. He showed an acute onset of psychotic symptomatology during treatment with thalidomide, an immunomodulatory drug used in the experimental therapy of refractory inflammatory bowel disease. Thalidomide was discontinued and orally administered mesalazine was restarted. In addition, treatment with antipsychotics and mood stabilizers was introduced with gradual improvement of psychotic symptoms. According to Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition criteria, a diagnosis of partial remission of a first episode of schizoaffective disorder was formulated after a 6-month follow-up. Throughout this period, both psychopharmacological and mesalazine-based gastrointestinal treatments were maintained with partial remission of psychiatric and gastrointestinal symptoms.
Conclusions
We propose that refractory ulcerative colitis and psychosis might represent different manifestations of a common pathological pathway. However, it is also conceivable that thalidomide may have played a role in promoting the manifestation of psychotic symptoms in an individual with a specific vulnerability to schizoaffective disorders. Further investigations are needed to improve our knowledge regarding the complexity of brain–gut interactions, thus improving the management of co-existing inflammatory bowel and schizophrenia spectrum disorders.
Peer Review reports
Introduction
Schizophrenia spectrum disorders are considered a heterogeneous group of conditions with a multifactorial etiopathogenesis. Current evidence suggests that the neurodevelopmental model best explains the pathogenesis of schizophrenia, and that the interaction of genetic background and multiple environmental risk factor exposures might cause disease pathogenesis. While early onset (before 13 years) appears to be quite rare, the rate of onset increases during adolescence, with a peak age ranging from 18 to 30 years [ 1 ]. Although neurobiologically and phenomenologically continuous with its adult counterpart, childhood-onset schizophrenia represents a more severe disorder, with more prominent pre-psychotic developmental disorders, brain abnormalities, and genetic risk factors [ 2 ].
In the last decades, multiple lines of evidence support the association between autoimmunity/inflammation and schizophrenia spectrum disorders [ 3 , 4 ]. Overlaps in clinical course, in addition to epidemiological and genetic associations, raised the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches [ 5 ]. In more recent years, the focus of the research regarding the relationship between autoimmune diseases and schizophrenia has been narrowed to gastrointestinal (GI) disorders [ 6 ]. In the context of the intricate interaction between the gut and the brain, the normal ecological balance of gut microorganisms plays an important role. Disorders in the composition and quantity of gut microorganisms, the so-called gut microbiota, have been reported to be associated with various central nervous system diseases [ 7 ] and current evidence suggests that probiotic supplementation could improve mild and moderate depressive symptoms [ 8 ]. On the other hand, a recently published systematic review found that there is a paucity of clinical studies to support the benefits of probiotic supplementation in patients with schizophrenia [ 9 ]. At the turn of the twenty-first century, inflammatory bowel disease (IBD) has become a global disease with accelerating incidence in newly industrialized countries with a prevalence surpassing 0.3% [ 10 ]. Ulcerative colitis (UC) is a form of IBD with diffuse inflammation of the rectal and colonic mucosa, manifesting with abdominal pain, diarrhea, bleeding, and weight loss. The pathogenesis of IBD, which is only partly understood, is thought to arise from dysregulation of the innate and adaptive immune systems, leading to an abnormal inflammatory response to commensal bacteria in genetically susceptible individuals [ 11 ]. The incidence rate of UC may vary from 0.5 to 31.5 per 100,000 people each year, depending on the studied population; the majority of patients with UC are in the age group of 30–40 years at diagnosis, while pediatric IBD, so defined when the age at onset is < 19 years, covers approximately 5–25% of patients [ 12 ]. UC displays a chronic clinical course, characterized by periods of exacerbation and remission, which may occur either spontaneously or in response to treatment [ 12 ]. UC rarely exists in isolation but is rather part of a complex matrix of disorders arising in patients over time [ 13 ]. Psychiatric comorbidity in IBD is well known, but to date the nature of the relationship between these two diseases has not been fully understood and is still a matter of debate. The most common psychiatric disorders in IBD are depression and anxiety, whereas data on other conditions, such as bipolar disorders and psychoses, are limited [ 14 , 15 ].
In the current paper we present the case of an adolescent patient with a severe form of early onset UC, refractory to conventional therapies, manifesting an early onset first-episode psychosis (FEP) during treatment with thalidomide.
In April 2018, a 14-year-old Caucasian boy with acute onset of affective FEP was referred to the Child Neuropsychiatry Unit of the Polyclinic Hospital of Bari. Since the age of 12 he presented with debilitating intestinal symptoms as mucohemorragic diarrhea (discharge frequency, > 10/day), tenesmus, and abdominal pain, resulting in severe disability impairing his general and social well-being. He was diagnosed as having UC on the basis of clinical, laboratory, instrumental, and histologic criteria. In accordance with the “Guidelines for Management of Pediatric Ulcerative Colitis” [ 16 ], he was treated with conventional therapies (mesalazine, prednisone, metronidazole, azathioprine, and biological agents such as infliximab and adalimumab) with no clinical response. Before elective surgery, a medical treatment with thalidomide was started, as an off-label option for patients with primary refractory IBD, and a clinical response was gradually observed. Two months later, he showed an acute onset of irritable mood, decreased need for sleeping, abnormally increased activity, disorganized behavior and speech, and thought alterations including inflated self-esteem and flight of insight-lacking ideas. These symptoms prompted the discontinuation of thalidomide and a mesalazine-based treatment was restarted. After admission at our Child Neuropsychiatry Unit, he was found to have no history of obstetric complications, neurological or psychiatric diseases, or substance abuse and no psychopathological symptoms prior to this acute episode. His parents reported a normal achievement of early childhood neurodevelopmental milestones and a normal intelligence quotient (IQ) was assessed. General and neurological examination, laboratory tests, and a brain magnetic resonance imaging resulted in normal ranges. An electroencephalogram showed slow waves including isolated spikes in the right temporal and parietal regions. After a mild improvement of symptoms, he developed a grossly disorganized behavior, with conceptual disorganization, auditory and visual hallucinations, delusion and suspiciousness, hostility, social and emotional withdrawal, somatic concerns, anxiety, and tension. Psychopathological assessment was performed by the use of Positive and Negative Syndrome Scale (PANSS). His PANSS total score was 115, while PANSS subscale scores were 29 for positive, 26 for negative, and 60 for general psychopathological symptoms. After proper informed consent, a treatment with antipsychotics and mood stabilizers (risperidone 6 mg/day, levosulpiride 72 mg/day, valproic acid 1000 mg/day) was started, leading to progressive improvement of psychopathological symptoms. During this phase his GI symptomatology remained silent, with 2–3 regular bowel movements/day and no blood or mucus emissions.
After a 6-month follow-up, a psychopharmacological maintenance with risperidone (4 mg/day) and valproic acid (1000 mg/day) ensured a partial remission of symptomatology. His PANSS total score was 71, with subscale scores of 11 for positive symptoms, 21 for negative symptoms and 39 for general psychopathological symptoms. On the other hand, only mesalazine efficiently controlled GI symptoms (2–3 regular bowel movements/day and no abdominal pain, diarrhea or rectal bleeding). Therefore, according to Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-5) criteria, a diagnosis of partial remission of a first episode of schizoaffective disorder was formulated.
Several lines of evidence suggest that a proportion of psychotic illnesses have a plausible autoimmune component [ 5 ], although its definition and role for treatment are still a matter of debate. This case report supports the idea that, although the co-existence of a schizoaffective disorder and UC may be an accidental coincidence, their co-occurrence, early onset, and high severity, are in line with growing evidence supporting the relationship between inflammation, autoimmunity, and psychosis [ 17 ]. Thus, we raise the question of whether UC is a risk factor for the schizoaffective disorders and/or whether these two different clinical conditions may be considered two distinct manifestations of a common pathway. The clinical history of our patient indicates that UC preceded the onset of psychosis by approximately 2 years, in absence of additional risk factors for schizophrenia spectrum disorders (psychotic illness in relatives, obstetric complications, abnormalities of early phases of neurodevelopment, gradual impairment in academic or psychosocial functioning). This temporal relationship, suggestive of a risk for immunologically mediated psychotic disorders, also emerges from a large Danish study [ 18 ] showing that several autoimmune diseases, including IBD, were associated with an increased risk of developing bipolar disorder or schizophrenia within 4–5 years from diagnosis. In addition, some previous data supported the hypothesis of an association between central nervous system infections in childhood and increased risk of schizophrenia related to abnormalities in immune mediators such as cytokines and chemokines or raised antibodies, triggered by a postnatal viral infection [ 19 ]. On the other hand, schizophrenia and immune disorders share some genetic factors. A polygenic risk score analysis suggested that a spectrum of genetic factors are shared by schizophrenia and different disorders characterized by immune dysregulation [ 20 ]. In fact, studies on schizophrenia revealed an intricate association of environmentally driven immune activation and genetically encoded immune dysfunctions. The intestinal mucosa is part of an intricate enteric immune system and is endowed with a large variety of immune cells [ 21 ]. As the largest immune organ in the body, the GI tract is a plausible junction to reconcile hypotheses regarding how the autoimmune response and GI-related products can become neuropathogenic. GI inflammation affects endothelial permeability and provides a means by which gut-derived products might penetrate the blood-brain barrier. These faulty barriers may be particularly important if autoantibodies generated in the inflamed gut would cross a compromised blood–brain barrier [ 6 , 22 ]. Despite the growing evidence that increased intestinal permeability with subsequent immune activation has a major role in the pathophysiology of various psychiatric disorders [ 23 ], to date, the “leaky gut” hypothesis needs further demonstrations.
Moreover, considering IBD across the age spectrum, some authors proposed that, especially in younger patients, genetics might play a more significant role as compared to other components, such as the immune system, environmental factors, and composition of the intestinal microbiota [ 24 ]. On the basis of these observations, we hypothesize that the increased genetic vulnerability characterizing IBD may also increase the risk of developing psychotic diseases and that the co-occurrence of UC and schizoaffective disorder may arise from a common pathological pathway deriving from brain–gut interactions.
One last consideration must be made on the relationship between pharmacological treatment of UC and psychotic onset. After a long period of resistance to conventional therapies, a good clinical response was achieved after treatment with thalidomide, an immunomodulatory drug used in the experimental treatment of refractory IBD. At the same time, after approximately 2 months of treatment with thalidomide, our patient developed an acute onset of FEP. The timing of such events might suggest that the psychotic symptoms are adverse events after thalidomide treatment. Of note, two different systematic reviews on the efficacy and safety of thalidomide in the treatment of IBD reported that among the most frequent adverse events are neurological disturbances, such as sedation and peripheral neuropathy, without any report of psychotic symptoms [ 25 , 26 ]. Therefore, on the basis of current data, it is not possible to exclude that thalidomide may have played a role in promoting psychotic manifestations in an individual with a specific vulnerability to schizoaffective disorders.
To the best of our knowledge this is the first case report of an adolescent patient presenting with early onset UC and a schizoaffective disorder. Questions arise from our report regarding whether and how immunological changes correlate with the clinical course of schizophrenia spectrum disorders, potentially modifying the current dogma about disease pathogenesis and leading to novel disease prevention and treatment strategies. Finally, we suggest that particular attention must be placed on the potential effects that immunomodulatory drugs might exert on autoimmunity, inflammation, and psychosis.
Abbreviations
First-episode psychosis
Gastrointestinal
- Inflammatory bowel disease
Positive and Negative Syndrome Scale
Ulcerative colitis
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Maria Giuseppina Petruzzelli, Lucia Margari, Sara Ivagnes & Roberto Palumbi
Psychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Policlinico Piazza, G. Cesare 11, 70124, Bari, Italy
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Petruzzelli, M.G., Margari, L., Ivagnes, S. et al. Early onset first-episode psychosis during treatment with thalidomide for refractory ulcerative colitis: a case report. J Med Case Reports 13 , 175 (2019). https://doi.org/10.1186/s13256-019-2106-8
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- Schizophrenia
Schizophrenia: When Do Symptoms Usually Start?
Schizophrenia usually takes hold after puberty. Most people are diagnosed in their late teens to early 30s.
What Is the Typical Age of Onset for Schizophrenia?
Men and women are equally likely to get this brain disorder, but guys tend to get it slightly earlier. On average, men are diagnosed in their late teens to early 20s. Women tend to get diagnosed in their late 20s to early 30s. People rarely develop schizophrenia before they're 12 or after they're 40.
The Turning Point: Adolescence
An interaction between something in your genes and something in your environment probably causes the disease. Researchers still have a lot to learn about it, but it's likely that many things play a role. Some, like exposure to a virus or malnutrition (according to one theory about causes), might have happened while you were still in your mother's womb. For vulnerable individuals, cannabis use can increase the risk of developing psychotic disorders such as schizophrenia.
No one knows exactly why it usually crops up in late adolescence, but there are many theories.
Your brain changes and develops a lot during puberty. These shifts might trigger the disease in people who are at risk for it.
Some scientists believe it has to do with development in an area of the brain called the frontal cortex. Others think it has to do with too many connections between nerve cells being eliminated as the brain matures.
Hormones also play a major role in puberty. One theory is that women get schizophrenia later than men because they go through puberty earlier and the hormone estrogen might somehow protect them. Know how to recognize the signs of schizophrenia in teens .
Early Warning Signs of Schizophrenia
Schizophrenia can be hard to diagnose for a few reasons. One is that people with the disorder often don't realize they're ill, so they're unlikely to go to a doctor for help. Another issue is that many of the changes leading up to schizophrenia, called the prodrome, can mirror other normal life changes. For example, a teen who's developing the illness might drop their group of friends and take up with new ones. They may also have trouble sleeping or suddenly start coming home with poor grades.
Some research suggests that if a doctor strongly thinks someone is getting the disorder while still in this early phase, low doses of antipsychotic medication might delay it. More studies need to be done to know whether these drugs work for young people at risk for the disease. Cognitive behavioral therapy, family therapy, and social skills training appear to have clearer benefits for them, at least in the short term, when used early on. Learn more about the prodrome phase of schizophrenia .
How Many People Have Schizophrenia?
About 3.5 million people in the United States are diagnosed with schizophrenia. It affects about 1.1% of the world’s population.
Characteristics of Schizophrenia
Schizophrenia is a syndrome. People with schizophrenia have several types of symptoms:
- Hallucinations . You hear voices or see or smell things that others say aren't there. The voices might criticize or threaten you. They might tell you to do things you otherwise wouldn't.
- Delusions . You believe things that aren't true, even when others show you proof or share facts that explain why your beliefs are wrong. Delusions can seem bizarre to others.
- For example, you might think that the TV is sending you special messages or that the radio is broadcasting your thoughts for everyone to hear. You might also feel paranoid and believe that others are trying to harm you.
- Thought disorders. You might have trouble organizing your thoughts, and you might speak in a way that's hard for others to understand. Perhaps you stop talking in the middle of a thought because you feel like it’s been taken out of your head. This is called thought withdrawal. Another type of disordered thinking, called thought blocking, happens when someone has a sudden stopping of their flow of thinking and as a consequence they may become silent until a new thought enters their mind.
- Movement disorders. You might move your body over and over again as if you're upset, or you might stop moving and responding. Doctors call this catatonia.
- Negative symptoms . Maybe you speak in a dull, flat tone, have trouble following through, lack interest in your daily life, and find it hard to keep up relationships . You might appear to be depressed. But while sadness, tearfulness, and other symptoms point to depression , so-called negative symptoms more likely point to a problem with the way the brain works.
Read more about the symptoms of schizophrenia .
Late-Onset Schizophrenia
Schizophrenia can develop later in life. Late-onset schizophrenia is diagnosed after age 45. People who have it are more likely to have symptoms like delusions and hallucinations. They’re less likely to have negative symptoms, disorganized thoughts, impaired learning, or trouble understanding information.
Doctors think genetics may be to blame, just as it is with early-onset schizophrenia. They also think late onset might be a subtype that doesn’t affect the person until the right trigger appears. People with cognitive, vision, or hearing problems, or those who are suspicious, isolated, or reclusive may be more likely to get it.
Early-Onset Schizophrenia
It’s rare for someone younger than 13 to be diagnosed with schizophrenia, but it can happen. In young children, early-onset schizophrenia often causes:
- Talking delays
- Late or unusual crawling
- Late walking
- Unusual movements like arm flapping or rocking
Parents of teens might notice:
- Not spending as much time with friends and family
- Drop in school performance
- Trouble sleeping
- No motivation
- Using drugs or alcohol
- Odd behavior
Teens are less likely to have delusions but more likely to have visual hallucinations. Find out more on early childhood schizophrenia symptoms .
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What Are the Early Signs of Schizophrenia?
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Akeem Marsh, MD, is a board-certified child, adolescent, and adult psychiatrist who has dedicated his career to working with medically underserved communities.
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- When Do Symptoms Appear?
- Early Signs of Schizophrenia
Schizophrenia is a condition that affects a person's thoughts, behaviors, and feelings. It is often first diagnosed in early adulthood. Early signs of schizophrenia may include:
- Developmental delays in childhood
- Struggles during school
- Suspiciousness of other people
- Decreased self-care and poor personal hygiene
- Social isolation and increased introversion
- Disorganized thinking and problems recognizing cause-and-effect
- Inappropriate social behavior
- Slow, uncoordinated movements
- Flat gaze or lack of facial expression
- Significant mood swings
- Delusions and hallucinations
- Difficulty communicating and disorganized speech
- Drug or alcohol use
- Inability to maintain relationships
- Changes in personality or behavior
- Lack of energy and decreased activity
Such symptoms are not always signs of schizophrenia and can sometimes occur with other mental health conditions. Awareness of these symptoms and when they are likely to occur can help loved ones spot the signs of a problem so the individual can get treatment as soon as possible.
When Do Symptoms of Schizophrenia Appear?
Early symptoms of schizophrenia vary depending on the person. Symptoms may develop slowly over months or years with several symptoms building sequentially before the diagnosis is made.
A person experiencing schizophrenia symptoms will likely need to see a psychiatrist for an assessment and diagnosis. However, family members and friends sometimes recognize symptoms in the early stages of the disorder. Early signs of schizophrenia usually manifest between the ages of 15 and 30.
The early signs of schizophrenia are often subtle and may even be mistaken for normal behavior in teenagers, college students, or young adults.
It is not until the symptoms become more pronounced that the disorder is recognized as schizophrenia.
Delayed Development in Childhood
Early signs of schizophrenia may include delays in motor development, speech or language development, and social development.
For example, a child may fail to learn to talk or walk as expected, and they also may not show normal emotional responses .
Struggling in School
A child or teenager may show early signs of schizophrenia by withdrawing from friends and family, avoiding contact with other people, or refusing to go to school.
Students who were once high academic achievers could become chronically truant, eventually dropping out of school altogether.
Later in adolescence, it is common for children with schizophrenia to withdraw socially and start lagging behind their peers in terms of academic and vocational achievement.
Suspiciousness of Others
Early warning signs of schizophrenia may include suspicions about the motives of others. A teen might believe that strangers on the street are "talking" to him through their secret thoughts, for example, or he might think his friends don't like him and want to harm him.
Ideas that people or objects can belong to someone else (called "possession" delusions ) may be early signs of schizophrenia.
People with early signs of schizophrenia might stay up all night, believing they are protecting themselves from dangerous forces such as the FBI or CIA. This unusual behavior is called " delusions of reference ."
People with early signs of schizophrenia may also experience delusions of grandeur , such as the belief that they are a famous rock star or have special powers.
Inappropriate Social Behavior
Inappropriate social behavior may be an early sign of schizophrenia in teens and young adults.
For example, someone with schizophrenia might stand too close to others during a conversation or laugh at a joke that others do not find funny.
Inappropriate sexual behavior, such as making inappropriate sexual comments to strangers, also could indicate the possible onset of schizophrenia.
If you are a survivor of sexual assault, you can contact the RAINN National Sexual Assault Hotline at 1-800-656-4673 to receive confidential support from a trained staff member at a local RAINN affiliate.
For more mental health resources, see our National Helpline Database .
Moving Slowly
Schizophrenia symptoms may present as a movement disorder such as uncoordinated movements or catatonia . A person with catatonia may move very little or remain in strange postures for hours at a time.
Flat or Expressionless Gaze
Some people with early signs of schizophrenia have a "blank" or "flat" expression on their face. Others may have a blank facial expression when speaking, resulting in a sort of verbal and facial "downtime," which is considered another possible early sign of schizophrenia.
Mood Swings
People with schizophrenia may have noticeable mood swings from being elated one moment to being severely depressed the next.
These mood swings also can include other symptoms such as frantic efforts to avoid real or imagined enemies and a general sense of being overwhelmed by life circumstances.
Delusions and Hallucinations
In the early stages of schizophrenia, a person may have delusions or hallucinations that are short-lived or come and go. A teenager might believe, for example, that his classmates at school are talking about him behind his back, or he might hear a voice that no one else can hear.
Commonly reported hallucinations include hearing voices or seeing things that are not there, while delusions usually involve ideas of persecution or paranoia. A young person with schizophrenia might be preoccupied with a particular delusion and talk about it incessantly.
Associative Problems
Associative thinking problems are among the earliest warning signs of schizophrenia. People with associative thinking problems may have difficulty understanding cause-and-effect relationships.
For example, they often don't recognize that their thoughts influence their feelings or behavior.
Disorganized Thinking
Disorganized thinking is another early warning sign of schizophrenia. The person afflicted with the disorder may struggle to comprehend information and solve problems. He or she may also withdraw socially, act inappropriately for the situation, and behave in a bizarre fashion.
Prolonged Social Withdrawal
People who are experiencing severe anxiety or depression may show signs of withdrawal. A person with early warning signs of schizophrenia often loses interest in friends and activities that were once important.
Decline in Personal Hygiene
In the early stages of schizophrenia, a person may stop caring about his or her appearance or personal hygiene.
For example, a teenager with schizophrenia might not bathe for days and wear dirty clothes despite their obvious appearance to others.
Disorganized Speech (Trouble Communicating)
Early warning signs of schizophrenia often include trouble communicating . For example, a person might get confused when talking to people and forget what they wanted to say in the middle of speaking.
When writing essays for school, they may struggle with grammar, spelling, and putting words in the proper sequence.
A person with early warning signs of schizophrenia also may have a monotone voice and speak in a flat tone. Their facial expressions may be limited, and they might avoid eye contact with others. They might also seem confused, with a vacant stare and unable to hold a conversation.
Drugs or Alcohol Abuse
People with schizophrenia may turn to drugs or alcohol to ease their anxiety. They may abuse these substances during the day despite knowing that they are harmful.
According to a 2018 study in Schizophrenia Research , substance abuse often worsens the symptoms of schizophrenia.
Inability to Maintain Relationships
People with early warning signs of schizophrenia often have trouble maintaining relationships. For example, they may constantly fight with friends and family members or lose friends due to their bizarre behavior. Unable to cope with the symptoms of schizophrenia, they often withdraw from society.
Changes in Behavior and Personality
A person with early warning signs of schizophrenia may show changes in their personality and behavior. These changes often occur before the first psychotic episode. For example, a teenager might become more irritable and hostile than usual and lose interest in activities that they once enjoyed. They might be unable to focus on school or work.
Lack of Energy
In the early stage of schizophrenia, a person may suffer from psychomotor retardation, which involves a decrease in physical activity and a lack of energy.
Physical symptoms include an inability to get up in the morning and sleeping excessively during the day. In some cases, people with schizophrenia have problems with appetite and weight loss, leading to malnutrition.
A Word From Verywell
If you're concerned that you or a loved one might be showing early symptoms of schizophrenia, it's important to see a mental health professional right away. If you are having a difficult time managing your symptoms, know that you're not alone and that schizophrenia can be managed with proper treatment and care.
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By Arlin Cuncic Arlin Cuncic, MA, is the author of "Therapy in Focus: What to Expect from CBT for Social Anxiety Disorder" and "7 Weeks to Reduce Anxiety."
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- Childhood schizophrenia
Childhood schizophrenia is an uncommon but severe mental disorder in which children and teenagers interpret reality abnormally. Schizophrenia involves a range of problems with thinking (cognitive), behavior or emotions. It may result in some combination of hallucinations, delusions, and extremely disordered thinking and behavior that impairs your child's ability to function.
Childhood schizophrenia is essentially the same as schizophrenia in adults, but it starts early in life — generally in the teenage years — and has a profound impact on a child's behavior and development. With childhood schizophrenia, the early age of onset presents special challenges for diagnosis, treatment, education, and emotional and social development.
Schizophrenia is a chronic condition that requires lifelong treatment. Identifying and starting treatment for childhood schizophrenia as early as possible may significantly improve your child's long-term outcome.
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Schizophrenia involves a range of problems with thinking, behavior or emotions. Signs and symptoms may vary, but usually involve delusions, hallucinations or disorganized speech, and reflect an impaired ability to function. The effect can be disabling.
In most people with schizophrenia, symptoms generally start in the mid- to late 20s, though it can start later, up to the mid-30s. Schizophrenia is considered early onset when it starts before the age of 18. Onset of schizophrenia in children younger than age 13 is extremely rare.
Symptoms can vary in type and severity over time, with periods of worsening and remission of symptoms. Some symptoms may always be present. Schizophrenia can be difficult to recognize in the early phases.
Early signs and symptoms
Schizophrenia signs and symptoms in children and teenagers are similar to those in adults, but the condition may be more difficult to recognize in this age group.
Early signs and symptoms may include problems with thinking, behavior and emotions.
- Problems with thinking and reasoning
- Bizarre ideas or speech
- Confusing dreams or television for reality
- Withdrawal from friends and family
- Trouble sleeping
- Lack of motivation — for example, showing up as a drop in performance at school
- Not meeting daily expectations, such as bathing or dressing
- Bizarre behavior
- Violent or aggressive behavior or agitation
- Recreational drug or nicotine use
- Irritability or depressed mood
- Lack of emotion, or emotions inappropriate for the situation
- Strange anxieties and fears
- Excessive suspicion of others
Later signs and symptoms
As children with schizophrenia age, more typical signs and symptoms of the disorder begin to appear. Signs and symptoms may include:
- Delusions. These are false beliefs that are not based in reality. For example, you think that you're being harmed or harassed; that certain gestures or comments are directed at you; that you have exceptional ability or fame; that another person is in love with you; or that a major catastrophe is about to occur. Delusions occur in most people with schizophrenia.
- Hallucinations. These usually involve seeing or hearing things that don't exist. Yet for the person with schizophrenia, hallucinations have the full force and impact of a normal experience. Hallucinations can be in any of the senses, but hearing voices is the most common hallucination.
- Disorganized thinking. Disorganized thinking is inferred from disorganized speech. Effective communication can be impaired, and answers to questions may be partially or completely unrelated. Rarely, speech may include putting together meaningless words that can't be understood, sometimes known as word salad.
- Extremely disorganized or abnormal motor behavior. This may show in several ways, from childlike silliness to unpredictable agitation. Behavior is not focused on a goal, which makes it hard to do tasks. Behavior can include resistance to instructions, inappropriate or bizarre posture, a complete lack of response, or useless and excessive movement.
- Negative symptoms. This refers to reduced or lack of ability to function normally. For example, the person may neglect personal hygiene or appear to lack emotion — doesn't make eye contact, doesn't change facial expressions, speaks in a monotone, or doesn't add hand or head movements that normally occur when speaking. Also, the person may avoid people and activities or lack the ability to experience pleasure.
Compared with schizophrenia symptoms in adults, children and teens may be:
- Less likely to have delusions
- More likely to have visual hallucinations
Symptoms may be difficult to interpret
When childhood schizophrenia begins early in life, symptoms may build up gradually. Early signs and symptoms may be so vague that you can't recognize what's wrong. Some early signs can be mistaken for typical development during early teen years, or they could be symptoms of other mental or physical conditions.
As time goes on, signs may become more severe and more noticeable. Eventually, your child may develop the symptoms of psychosis, including hallucinations, delusions and difficulty organizing thoughts. As thoughts become more disorganized, there's often a "break from reality" (psychosis) frequently requiring hospitalization and treatment with medication.
When to see a doctor
It can be difficult to know how to handle vague behavioral changes in your child. You may be afraid of rushing to conclusions that label your child with a mental illness. Your child's teacher or other school staff may alert you to changes in your child's behavior.
Seek medical care as soon as possible if you have concerns about your child's behavior or development.
Suicidal thoughts and behavior
Suicidal thoughts and behavior are common among people with schizophrenia. If you have a child or teen who is in danger of attempting suicide or has made a suicide attempt, make sure someone stays with him or her. Call 911 or your local emergency number immediately. Or if you think you can do so safely, take your child to the nearest hospital emergency room.
It's not known what causes childhood schizophrenia, but it's thought that it develops in the same way as adult schizophrenia does. Researchers believe that a combination of genetics, brain chemistry and environment contributes to development of the disorder. It's not clear why schizophrenia starts so early in life for some and not for others.
Problems with certain naturally occurring brain chemicals, including neurotransmitters called dopamine and glutamate, may contribute to schizophrenia. Neuroimaging studies show differences in the brain structure and central nervous system of people with schizophrenia. While researchers aren't certain about the significance of these changes, they indicate that schizophrenia is a brain disease.
Risk factors
Although the precise cause of schizophrenia isn't known, certain factors seem to increase the risk of developing or triggering schizophrenia, including:
- Having a family history of schizophrenia
- Increased immune system activation, such as from inflammation
- Older age of the father
- Some pregnancy and birth complications, such as malnutrition or exposure to toxins or viruses that may impact brain development
- Taking mind-altering (psychoactive) drugs during teen years
Complications
Left untreated, childhood schizophrenia can result in severe emotional, behavioral and health problems. Complications associated with schizophrenia may occur in childhood or later, such as:
- Suicide, suicide attempts and thoughts of suicide
- Self-injury
- Anxiety disorders, panic disorders and obsessive-compulsive disorder (OCD)
- Abuse of alcohol or other drugs, including nicotine
- Family conflicts
- Inability to live independently, attend school or work
- Social isolation
- Health and medical problems
- Being victimized
- Legal and financial problems, and homelessness
- Aggressive behavior, although uncommon
Early identification and treatment may help get symptoms of childhood schizophrenia under control before serious complications develop. Early treatment is also crucial in helping limit psychotic episodes, which can be extremely frightening to a child and his or her parents. Ongoing treatment can help improve your child's long-term outlook.
- Schizophrenia. In: Diagnostic and Statistical Manual of Mental Disorders DSM-5. 5th ed. American Psychiatric Association; 2013. https://dsm.psychiatryonline.org. Accessed Sept. 5, 2019.
- AskMayoExpert. Schizophrenia (adult). Mayo Clinic; 2018.
- Roberts LW, et al. Schizophrenia spectrum and other psychotic disorders. In: The American Psychiatric Publishing Textbook of Psychiatry. 7th ed. American Psychiatric Publishing; 2019. https://psychiatryonline.org. Accessed Sept. 7, 2019.
- Schizophrenia in children. American Academy of Child and Adolescent Psychiatry. https://www.aacap.org/AACAP/Families_and_Youth/Facts_for_Families/FFF-Guide/Schizophrenia-In-Children-049.aspx. Accessed Sept. 10, 2019.
- How to cope when a loved one has a serious mental illness. American Psychological Association. https://www.apa.org/helpcenter/serious-mental-illness. Accessed Sept. 5, 2019.
- Schizophrenia. National Institute of Mental Health. https://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml. Accessed Sept. 5, 2019.
- Supporting a friend or family member with mental health problems. MentalHealth.gov. https://www.mentalhealth.gov/talk/friends-family-members. Accessed Sept. 5, 2019.
- Schizophrenia in children and adolescents. Merck Manual Professional Version. https://www.merckmanuals.com/professional/pediatrics/mental-disorders-in-children-and-adolescents/schizophrenia-in-children-and-adolescents#. Accessed Sept. 5, 2019.
- McClellan J, et al. Practice parameter for the assessment and treatment of children and adolescents with schizophrenia. Journal of the American Academy of Child and Adolescent Psychiatry. 2013; doi:10.1016/j.jaac.2013.02.008.
- Skehan B, et al. Pharmacotherapy and psychosocial interventions for schizophrenia in children and adolescents. https://www.uptodate.com/contents/search. Accessed Sept. 10, 2019.
- Atypical antipsychotic medications: Use in pediatric patients. Centers for Medicare and Medicaid Services. https://www.cms.gov/Medicare-Medicaid-Coordination/Fraud-Prevention/Medicaid-Integrity-Education/Pharmacy-Education-Materials/atyp-antipsych-education. Accessed Sept. 10, 2019.
- What is schizophrenia? American Psychiatric Association. https://www.psychiatry.org/patients-families/schizophrenia/what-is-schizophrenia. Accessed Sept. 5, 2019.
- Hayes D, et al. Dilemmas in the treatment of early-onset first-episode psychosis. Therapeutic Advances in Psychopharmacology. 2018; doi:10.1177/2045125318765725.
- Huxsahl JE (expert opinion). Mayo Clinic. Dec. 10, 2019.
- Krieger CA (expert opinion). Mayo Clinic. Jan. 3, 2020.
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Very early-onset schizophrenia has a premorbid period characterized by global delay in domains of motor, speech, social, and cognitive development; it is often misdiagnosed as pervasive developmental disorder due to the presence of stereotypy.
Background. Schizophrenia is a severe, chronic, and heterogeneous mental disorder that often has debilitating long-term outcomes. Its lifetime prevalence rate is estimated to be approximately 1% worldwide in the adult population (Lehman et al., 2010).Onset generally occurs in late adolescence or early adulthood, with an average age of 18 years for men and 25 years for women. 1 The term early ...
We describe the case of a 6-year-old boy with new-onset schizophrenia, who showed unusual behavior suggestive of psychotic symptoms as early as infancy. Case "Kyle" is a 6-year-old boy with a history of mild developmental delay who presented with one month of disorganized behavior, hallucinations, and developmental regression.
Early-Onset Schizophrenia With Predominantly Negative Symptoms: A Case Study of a Drug-Naive Female Patient Treated With Cariprazine Front Pharmacol. 2020 Apr 23;11:477. doi: 10.3389/fphar.2020.00477. eCollection 2020. Authors Maria Judit Molnar 1 , Idris János Jimoh 1 , Helga Zeke 1 , Ágnes Palásti 1 , Marianna Fedor 1 Affiliation
Onset generally occurs in late adolescence or early adulthood, with an average age of 18 years for men and 25 years for women. 1 The term early-onset schizophrenia (EOS) is used to refer to patients who are diagnosed with the disorder before this age.
Very Early Onset Schizophrenia: A Case Study 143. the premorbid condition. We gradually decreased risperidone to 1 mg/day. At the end of the one year period of treatment and
The available study findings on the course and outcome of schizophrenia beginning in childhood or adolescence can be summarized as follows. (1) Schizophrenic psychoses that arise before the age of 13 have a very poor prognosis. The disease usually continues to progress in adolescence and adulthood.
The presence of history of speech and language delay as well as motor development deficits have been observed in major studies on childhood-onset schizophrenia, be it the Maudsley early-onset schizophrenia project or the NIMH study. [ 8 9] Premorbid deficits in social adjustments and presence of autistic symptoms have also been shown.
patients with early-onset first psychotic episodes of short duration. We hypothesize that patients with early psychosis will have increased oxidative stress in compar-ison with a healthy control group. Methods Subjects The Child and Adolescent First-Episode Psychosis Study (CAFEPS) was a case-control study that included
While schizophrenia can occur at any age, the average age of onset is in the late teens to early 20s for males, and late 20s to early 30s for females. While possible, it's uncommon for...
Very early onset schizophrenia is when symptoms appear before the age of 13 years. The researchers describe a child who experienced unusual perceptions from the age of 3 months. There are no...
Abstract and Figures Schizophrenia occurs very uncommonly in children younger than 13 years. The disease is preceded by premorbid difficulties, familial vulnerability, and a prodromal phase. The...
Early Onset Schizophrenia . If the disease is diagnosed prior to the age of 18, it is referred to as early onset schizophrenia (EOS). EOS is rare, with an estimated prevalence of 0.23%. Rarer still, the disease can develop in very young children. This is called childhood-onset schizophrenia (COS), when the disease is diagnosed before the age of 13.
National Center for Biotechnology Information
Background Inflammatory bowel disease and schizophrenia spectrum disorders are complex and multifactorial conditions characterized by great variability of age at onset, clinical presentation, and longitudinal course. Several lines of evidence suggested different connections among immunological dysregulation, gastrointestinal inflammation, and psychosis, but to date many controversial issues ...
In young children, early-onset schizophrenia often causes: Talking delays Late or unusual crawling Late walking Unusual movements like arm flapping or rocking Parents of teens might notice:...
Early signs of schizophrenia usually manifest between the ages of 15 and 30 and can be subtle at first. Learn more about the signs, symptoms, and treatments. ... Aneja J, Singhai K, Paul K. Very early-onset psychosis/schizophrenia: Case studies of spectrum of presentation and management issues.
Symptoms. Schizophrenia involves a range of problems with thinking, behavior or emotions. Signs and symptoms may vary, but usually involve delusions, hallucinations or disorganized speech, and reflect an impaired ability to function. The effect can be disabling. In most people with schizophrenia, symptoms generally start in the mid- to late 20s ...
adult studies (Brown et al., 2008). Schizophrenia with onset in youth accounts for approximately 1% of all individuals with schizophrenia (Kumra, 2008). Onset before age 18 is commonly categorized as early-onset schizophrenia (EOS), having either an acute or insidious, i.e., a gradual onset without obvious symptoms. Onset before 13 years of age is
The early stage of schizophrenia usually involves non-specific symptoms that also occur in other mental illnesses, such as depression. ... Very early-onset psychosis/schizophrenia: Case studies of ...