Early-onset Psychotic Disorders Research Articles

The association between plasma thyroxine levels and neurocognitive impairment in early-onset schizophrenia and other psychosis spectrum disorders

Background/aimLimited studies have delved into the association between thyroid hormones and neurocognition in schizophrenia. We aimed to evaluate the relationship between thyroid hormone levels and neurocognitive functions in patients with schizophrenia and other psychosis spectrum disorders (SSD). MethodA total of 135 patients with early-onset SSD were included in the study. The participants underwent a cognitive assessment. Blood samples were collected to measure serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). Subgroup analyses were conducted based on the severity of the psychosis. FindingsThe results revealed a significant association between fT4 levels and various cognitive domains, including processing speed, verbal fluency, working memory, verbal learning, verbal memory, and visual memory. However, serum TSH and fT3 levels exhibited no significant association with neurocognitive impairment in adjusted linear regression models. Specifically, the correlation between fT4 levels and global cognition was more pronounced in patients with higher scores. ConclusionsSerum fT4 levels were associated with the performance across various cognitive domains in cases of early-onset psychotic disorders. This correlation was accentuated among patients with higher illness severity. Future studies could focus on the effects of specific pathways that can affect the course and progression of psychosis.

Can diffusion tensor imaging have a diagnostic utility to differentiate early-onset forms of bipolar disorder and schizophrenia: A neuroimaging study with explainable machine learning algorithms

Background/aimAccurate diagnosis of early-onset psychotic disorders is crucial to improve clinical outcomes. This study aimed to differentiate patients with early-onset schizophrenia (EOS) from early-onset bipolar disorder (EBD) with machine learning (ML) algorithms using white matter tracts (WMT). MethodDiffusion tensor imaging was obtained from adolescents with either EOS (n = 43) or EBD (n = 32). Global probabilistic tractography using an automated tract-based TRACULA software was performed to analyze the fractional anisotropy (FA) of forty-two WMT. The nested cross-validation was performed in feature selection and model construction. EXtreme Gradient Boosting (XGBoost) was applied to select the features that can give the best performance in the ML model. The interpretability of the model was explored with the SHApley Additive exPlanations (SHAP). FindingsThe XGBoost algorithm identified nine out of the 42 major WMTs with significant predictive power. Among ML models, Support Vector Machine-Linear showed the best performance. Higher SHAP values of left acoustic radiation, bilateral anterior thalamic radiation, and the corpus callosum were associated with a higher likelihood of EOS. ConclusionsOur findings suggested that ML models based on the FA values of major WMT reconstructed by global probabilistic tractography can unveil hidden microstructural aberrations to distinguish EOS from EBD.

Memory deficits in children and adolescents with psychotic disorders: A systematic review and meta-analysis

IntroductionCognitive symptoms in psychosis represent a major unmet clinical need (Acuna-Vargas et al. Cog in Psych 2019; 21(3), 223–224). Deficit in memory has been largely described in first episode early onset psychosis (Mayoral et al. Eur Psych 2008; 23(5), 375-383) and has been associated to a worse functionality (Øie et al. Neuropsychology 2011; 25(1), 25–35). However, results from existing studies are quite mixed on memory deficits of early psychosis patients, particularly in terms of memory contents and storage resources.ObjectivesThe aims of this study were 1) to examine the nature and extent of cognitive impairment in early-onset psychosis and 2) to analyze which type of memory (verbal and visual) is more affected in the disorder.MethodsThe present systematic review and meta-analysis was conducted according to the PRISMA criteria (Moher et al. Systematic Reviews 2015; 4(1), 1 - 9). A systematic search of CINAHL, PsycInfo, PubMed, Redalyc, SCOPUS and Web of Science (published from 2000 to 2020) identified case-control studies of early onset psychotic disorder (under 18 years old). Those studies focused on both verbal and visual memory performance.ResultsTwenty articles were included in the review. A deficit in memory in child and adolescent psychotic disorders was obtained displaying a large effect size in memory tasks (g = -0.83). Also, a medium effect size was found in visual memory tasks (g = - 0.61) and a large effect size was found in verbal memory tasks (g = -1.00).ConclusionsIt was observed a strong memory deficit on early psychotic disorders already present at the onset of the illness. This deficit was stronger when verbal memory tasks were used compared to the effect found with visual memory tasks. Based on previous literature (García-Nieto et al. Jou Cli Child & Ado Psych 2011; 40(2), 266-280; Lepage et al. Eur Psych 2008; 23(5):368- 74; Hui et al. Psych Med 2016; 46(11):2435-44), these results contribute to describe and characterize the cognitive symptoms in the first-episode psychosis in a youth population.Disclosure of InterestNone Declared

Identifying clinical and psychological correlates of persistent negative symptoms in early-onset psychotic disorders.

Persistent negative symptoms (PNS) contribute to impairment in psychosis. The characteristics of PNS seen in youth remained under-investigated. We aimed to demonstrate clinical, treatment-related, and psychosocial characteristics of PNS in early-onset schizophrenia-spectrum disorders (EOSD). 132 patients with EOSD were assessed with Positive and Negative Symptom Scale, Brief Negative Symptom Scale, Calgary Depression Scale for Schizophrenia, and Simpson-Angus Scale. Parenting skills and resilience were evaluated using Parental Attitude Research Instrument and Child and Youth Resilience Measure-12. Longer duration of untreated psychosis (DUP) and prodromal phase were found in primary and secondary PNS groups, compared to the non-PNS group. The primary PNS group was characterized by earlier age-onset, lower smoking rates, and more common clozapine use. Resilience and egalitarian/democratic parenting were negatively correlated with symptoms related to motivation/pleasure and blunted expression. More blunted expression-related symptoms and longer DUP in the first episode significantly predicted primary/secondary PNS at follow-up. Using the data from total negative symptom scores and DUP, Receiver Operating Characteristic analyses significantly differentiated primary/secondary PNS groups from the non-PNS counterparts. PNS associated with blunted expression and low motivation/pleasure in the first episode could persist into clinical follow-up. Effective pharmacological treatment and psychosocial interventions are needed in youth.

When to Use Amisulpride in Adolescents: A Retrospective Chart Examination of Inpatients.

Despite increasing interest in amisulpride, current knowledge about its use in the pediatric population is scarce. This chart review aimed to investigate the use of amisulpride in a naturalistic adolescent population. Electronic medical records of a tertiary care adolescent inpatient unit were screened between January 2015 and April 2021. Sociodemographic data and all clinical information were collected via data collection forms, and targeted symptoms were obtained from patients' files. Patients with early-onset psychotic disorders (n = 58), bipolar I disorder (n = 29), major depressive disorder (n = 14), and other psychiatric diagnoses (n = 9) were included. Treatment response was defined as a Clinical Global Impression-Improvement of at least much improvement after treatment. Median titration rate of amisulpride was 400 mg/wk, and the maximum administered daily dose ranged between 100 and 1200 mg/d. The maximum daily dose and number of previous antipsychotics were higher in the early-onset psychotic disorder group. Persistent positive symptoms and resistance to previous treatments were leading causes for amisulpride treatment. Other indications were also impulsive/disruptive behaviors, antipsychotic adverse effects, depressive symptoms, somatic complaints, and abnormalities in liver function tests. Finally, patients with lower daily treatment doses and more previous antipsychotic trials are less likely to benefit from the treatment. Persistent psychotic/mood symptoms, impulsive/disruptive behaviors, and abnormalities in liver function tests were reasons for the amisulpride treatment in adolescents. Randomized placebo-controlled trials are needed to evaluate the efficacy and safety of the treatment in adolescents.

BDNF Val66Met polymorphism is associated with negative symptoms in early-onset schizophrenia spectrum and other psychotic disorders

Background and ObjectivesTo investigate the clinical characteristics of adolescents with early-onset full psychotic disorders either with Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) or DRD2/ANKK1 Taq1A (rs1800497) polymorphisms. Method101 cases with early-onset schizophrenia (EOS) or other psychotic spectrum disorders (SSD) and 150 healthy controls were included in the current study. Using the Positive and Negative Symptom Scale (PANSS), patient subgroups were compared for their psychotic symptoms, age-onset, duration of untreated illness, and family history of psychiatric disorders. The real-time polymerase chain reaction (RT-PCR) was implemented for genotyping procedures. ResultsStudy groups and patient subgroups were similar regarding their sociodemographic characteristics (16.4 ± 2.6 years, 62.2% male for all participants). Results did not reveal any difference between patients and healthy controls for DRD2/ANKK1 Taq1A and BDNF Val66Met genotypes. Patients with A1A2 (Gly/Lys) allele reported higher rates of substance use compared to A2A2 (Glu/Glu) counterparts. Other clinical variables were found similar. EOS/SSD group with Val66Met heterozygote allele revealed lower levels of negative symptoms than Val/Val homozygotes. Conversely, the age onset of full psychotic disorder, total positive symptom score, and total general psychopathology score of PANSS were found comparable between Val/Met and Val/Val groups. In the logistic regression model, Glu/Lys genotypes remained significant for the presence of substance use. ConclusionThe interaction between substance use and the DRD2 gene should be investigated for the development of early-onset psychotic disorders. BDNF Val66Met polymorphism also could be a disease-modifying factor for the presence of negative symptoms.

Correlation between duration of untreated psychosis and working memory in early-onset psychotic disorders

Psychotic disorders are morbid mental disorders that impair working memory. Theory suggests that longer duration of untreated psychosis (DUP) results in worse working memory. However, results from previous studies are contradictory, with no study having been conducted in children. This study aims at finding out the association between duration of untreated psychosis and working memory in children. This is a cross-sectional study with 45 subjects. DUP was collected from medical records whereas working memory was measured using digit span backward raw score. Average digit span backward scores of subjects was 3.7 ± 1.18. Analysis using Spearman test showed no significant association (p = 0.128) between DUP and working memory. In conclusion, there is no association between DUP and working memory in children, therefore we recommend that psychiatrists pay attention to working memory impairment in all pediatric patients with psychotic disorders, regardless of their DUP.

Effect of non-pharmacological interventions on source memory processes in the early course of psychosis: A systematic review.

This systematic review aimed to identify non-pharmacological interventions for early psychosis which have impacted source memory processes. Studies were selected from nine databases when they included: (a) a non-pharmacological intervention involving a sample of patients with early-onset psychotic disorder or subclinical psychotic symptoms; and (b) effects on source memory processes, measured directly or inferred through an episodic memory task. Thirteen studies were identified, including two cognitive remediation programs and one repetitive transcranial magnetic stimulation treatment that reported beneficial effects on source memory. Relevant intervention strategies for source memory impairments were identified. This review points up a need to further develop interventions targeting theoretically defined source memory concepts and assess their effects with specific and valid tasks. Recommendations regarding underlying mechanisms which could have a beneficial impact on source memory may provide guidance for the future development of early psychosis interventions.

Negative and disorganized symptoms mediate the relationship between verbal learning and global functioning in adolescents with early-onset psychosis

Neurocognitive deficits are associated with impaired global functioning and psychotic symptoms. However, whether symptoms can mediate the relationship between neurocognition and global functioning in adolescent psychosis is unclear. Here, we investigated if symptoms assessed with the Positive And Negative Syndrome Scale (PANSS), mediated the relationship between neurocognitive performance and global functioning in adolescents with non-affective early-onset psychotic disorders (EOP). Sixty-one adolescent EOP patients (age 12–18 years) from 2 Norwegian clinical cohorts were included. Linear regression models were applied to investigate associations between neurocognitive domains from the MATRICS Consensus Cognitive Battery (MCCB) and global functioning. PANSS symptoms were analyzed using the Wallwork/Fortgang five-factor model. Using the INDIRECT macro for SPSS, mediation effects were tested using bootstrapping with 95% bias corrected confidence intervals. Verbal learning was positively associated with global functioning (P < 0.001) and negatively associated with the disorganized symptom factor (P = 0.002), controlling for age, sex and cohort. Testing of indirect effects, controlling for age, sex and cohort, showed that the Negative (point estimate = 1.56, 95% CI 0.22, 3.47) and Disorganized (point estimate = 1.24, 95% CI 0.05, 3.69) symptom factors significantly mediated the relationship between verbal learning and global functioning. We found that verbal learning, negative and disorganized symptoms influenced global functioning in adolescents with EOP, while reality-distorted positive symptoms did not. These results suggest that assessing these domains in EOP is helpful for planning treatment and rehabilitation programs focusing on functional outcome.

Neuropersonaltrainer-mh: A new computerized platform for the cognitive remediation in schizophrenia and bipolar disorders

Schizophrenia and mood disorders -including unipolar depression and bipolar disorder-, are severe mental diseases with a highly heterogeneous symptomatology, among which cognitive dysfunction has progressively emerged as a key cornerstone. Patients suffering from these illnesses show significant deficits in different neurocognitive and social cognition domains. These deficits are evident during acute episodes, and in a high percentage of patients persist in periods of recovery, playing a decisive role on functional and clinical outcome. Nowadays, different pharmacological therapies have been tested, obtaining non-conclusive results. In this context, non-pharmacological strategies, such as neurocognitive remediation, have emerged as promising therapeutic intervention. Neurocognitive remediation comprises a program to rehabilitate cognitively impaired subjects, aiming either to restore their cognitive functioning or to compensate them in specific cognitive domains. One evolving approach, beginning to receive attention for its initial promising results, is computerized cognitive training. This technique employs tasks or games that exercise a particular brain function which target specific neural networks in order to improve cognitive functioning through neuroplasticity in a given neural circuit. In this scenario, we report our recent results with neuropersonaltrainer®-MH; a module for neurocognitive remediation consisting in a computerized telerehabilitation platform that enables cognitive remediation programs to be carried out in an intensive and personalized manner. Our group has applied NPTMH® in a pilot study treating patients with early onset psychotic disorder with positive and promising results, involving an improvement in functionality, neurocognition, and social cognition performance. Furthermore, new trials in bipolar disorder and major depressive disorder have been recently started.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Relationship between brain structural abnormalities and early onset psychotic disorder–case presentation

IntroductionContemporary structural models of several psychiatric disorders propose abnormalities in the structure and function of distinct neural networks. Clinical observations of affective and cognitive changes arising from cerebellar lesions and stimulation permit the hypothesis that the cerebellum may not be irrelevant in some neuropsychiatric states. There is evidence that patients with schizophrenia have altered corticocerebellar connectivity.ObjectivesTo evidence a case with early onset psychosis accompanied with brain structural abnormalities.MethodCase description.ResultsThe patient is 15 years old girl with an acute psychotic episode. For more than two months she had demonstrated odd behavior, getting around all the time purposelessly, abandoned school etc. She presented with disorders of perceptions, disorganized speech, insomnia and fluctuations in her mood and behavior. In her brain, MRI was found vermian atrophy, and CT was found hypocampal glyosis and dilatation of temporal corn.ConclusionsAlthough the structural mapping studies have been equivocal, the weight of evidence supports extending the study of cerebellar activity in schizophrenia. For example, the finding that unaffected first-degree relatives of probands with schizophrenia have reduced cerebellar volumes, along with the observation of reduced cerebellar volumes in neurolepticnaïve patients with schizophrenia, suggests that cerebellar atrophy may be a hereditary trait rather than a psychotropic associated epiphenomenon.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study.

To examine glutathione S-transferase (GST) deletion polymorphisms in development of early-onset severe mental disorders, with the hypothesis that patients with GSTM1-null and GSTT1-null genotypes will develop psychotic disorders at a younger age. We identified GSTM1 and GSTT1 deletion polymorphisms by multiplex polymerase chain reaction (PCR) in 93 patients with early onset severe mental disorders and 278 control individuals. The diagnoses were confirmed by Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and Schedule for Affective Disorders and Schizophrenia-Life-Time Version (K-SADS-PL) interviews. Individuals with the GSTM1-null genotype were at 3.36-fold higher risk of developing early-onset severe mental disorders than carriers of a corresponding active genotype. The risk of those disorders was increased by 6.59-fold in patients with GSTM1-null/GSTT1-active genotype. Patients with the GSTM1-null genotype were at approximately 2-fold increased risk for developing early-onset schizophrenia-spectrum disorder (EOS), early-onset bipolar disorder (EOBD) with psychotic symptoms, or early-onset first-episode psychosis (EOFEP), compared with patients with the GSTM1-active genotype. The GSTM1-null genotype might be associated with higher risk for early onset severe mental disorders.

The presentation of early-onset psychotic disorders

This study aims to describe the clinical course of psychotic disorders, including the premorbid history, symptoms and level of functioning in a group of children and adolescents treated by paediatric mental health services, mainly as inpatients. A sample of 45 children and adolescents with a psychotic disorder (mean age 13.2 years) was assessed using questionnaires, semi-structured interviews, parent interviews and file audit. The symptoms of those with a schizophrenia spectrum disorder (SSD) were compared to those with a mood disorder (MD). This population showed a high level of premorbid impairment, including previous treatment for other psychiatric disorders. As well as hallucinations and delusions, high levels of self-harm, aggression, anxiety and depression were reported. The SSD and MD groups differed mainly in their levels of premorbid functioning. While it is well known that childhood-onset schizophrenia is a severe disorder with a poor outcome, this study found that young people diagnosed with other psychotic disorders also have significant impairment and are likely to require high levels of care to maximize their functional recovery.

Clinical Profile of Child and Adolescent (≤16 years) Psychotic Disorders at a Tertiary Care Centre In India

Background: Over past two decades, there is an increasing recognition that the psychotic disorders can begin in children at a very young age.Only a few prior studies from India have explored the clinical profile of non-affective psychotic disorders at a younger age. Aims:The study aims to describe the clinical profile of child and adolescent (≤16 years) psychotic disorders. Methods:The study was conducted as a three-year descriptive, retrospective review. All the patients aged ≤16 years, with a diagnosis of Schizophrenia and other psychotic disorders as per Diagnostic and Statistical Manual, 4th edition Text Revision (DSM-IV TR) criteria who presented to the weekly child and adolescent psychiatry clinic at All India Institute of Medical Sciences, New Delhi were included. Relevant information was retrieved on a semi-structured datasheet. Results:The clinic prevalence for schizophrenia and other psychotic disorders was found to be 2.47% (40/1618), of which five patient records were either unavailable or inadequate for inclusion. The mean age was 13.97(±1.46) years with an equal representation of males and females. A very early-onset (≤12 years) was present in 48.3% of the sample. Median duration of psychotic illness was 12 months (0.1-48 months) and majority (94.3%) had a continuous course. Family history was positive for psychiatric illness in 22.9%, while an identifiable psychosocial stressor was temporally related in 17.1% of sample. A comorbid psychiatric disorder was present in 14.5%, commonest being subnormal intellectual functioning. Auditory hallucinations appeared to be a common (51.5%) symptom, however these were evident primarily from patient’s behavior rather than self-report in over half of them. Visual hallucinations with ghost or animal theme were present in 17.1% and delusions were manifested by 40% of sample. Disorganized speech and catatonia were less frequent. Nearly 17.1% of sample left school after onset of psychosis and all patients showed some disruption in social, inter-personal and academic functioning. Conclusion: The present study adds to the limited literature on clinical presentation and phenomenology of early-onset psychotic disorders in Indian population.

P.1.e.006 Differential brain changes in males with early-onset psychotic disorders by diagnosis

P.1.e.006 Differential brain changes in males with early-onset psychotic disorders by diagnosis

Marked Neurocognitive Deficits Apparent In Early-Onset Psychotic Disorders

Marked Neurocognitive Deficits Apparent In Early-Onset Psychotic Disorders

Substance Abuse in Early Onset Psychotic Disorders

ABSTRACT Objectives: To examine patterns of substance use in youths with schizophrenia or other early onset psychotic disorders. Methods: Youths with psychotic disorders (onset before age 18 years) were assessed annually over two years using standardized diagnostic and symptom rating measures, including the Structured Clinical Interview for DSM-IV (SCID). Subjects with psychosis solely due to substance use were excluded. Subjects were between the ages of 6 and 17 years at study entry, with a mean age of 14.8 ± 2.2 years. Results: Thirty-nine percent of the 69 subjects met criteria for schizophrenia. Forty-five percent of the subjects met criteria for substance use disorders (i.e., substance abuse or dependence), and another 7% tried illicit substances without meeting criteria for abuse or dependence. Substance use disorders (SUDs) were not significantly associated with the type of psychotic illness, gender, ethnicity, socioeconomic status, severity of positive or negative symptoms at baseline, or other hypothesized risk factors (e.g., disruptive behavior disorders, familial substance abuse, and maltreatment). Subjects with SUDs had a significantly older age of entry into the study (p < .001). Subjects with co-occurring schizophrenia and SUDs used substances prior to the onset of psychosis and had a significantly older age of onset of psychosis (p < .021). Only 26% of youths with SUDs had received specific chemical dependency treatment. Conclusions: Substance abuse is a very significant and under-treated problem in this sample of youths with early onset psychosis. Efforts to identify specific risk factors and effective intervention strategies are needed.

Risperidone in adolescent schizophrenic psychoses: A retrospective study

Objective. The aim of the study was to assess the therapeutic effect and tolerability of risperidone in patients with early-onset schizophrenia and other related psychotic disorders. Methods. Our retrospective study included 47 schizophrenic patients (27 boys, 20 girls) with an average age of 16.5±1.3 years. The patients were evaluated based on their medical records prior to being started on risperidone, and then after 1, 3 and 6 weeks of risperidone administration. Efficacy of treatment was evaluated using the first item on the CGI scale. Survivors analysis was used. Results. After week 6, the average dose of risperidone was 3.8±1.4 mg. Eighty-two percent of the patients were evaluated as responders, 64% as full responders and 18% as partial responders. There were eight patients who dropped out of the study during treatment. The initial inclusion score on the CGI was 5.8±0.7. This score showed a steady decrease at each evaluation point during the treatment. At week 1 the score was 4.5±1.1 (P<0.001), at week 3, 3.4±1.2 (P<0.001), and at week 6 it was 2.6±1.2 (P<0.001). The medication was well tolerated. Less than half of the patients (46%) reported any side effects, according to their medical records. Parkinsonism (19%), sedation (8.5%) and hypersalivation (8.5%) were the most commonly reported side effects. The mean weight of the participants increased from 61.2±10.0 kg to 64.7±10.0 kg between baseline and week 6 (P=0.002). Conclusion. Our experience supports the use of risperidone in the treatment of schizophrenic disorders in adolescence.

Cognitive deficits and levels of IQ in adolescent onset schizophrenia and other psychotic disorders

Cognitive deficits have been found to be prevalent in early onset schizophrenia. Whether these deficits also characterise other early onset psychotic disorders to a similar degree is unclear, as very few comparative studies have been done. The primary purpose of this study was to compare the profile and severity of cognitive impairments in first-episode early onset psychotic patients who received the schizophrenia diagnosis to those diagnosed with other non-organic, non-affective psychotic disorders. The secondary purpose was to examine whether the profile of cognitive deficits, in terms of intelligence, executive functions, memory, attention and processing speed was global or specific. First-episode psychotic adolescents ( N = 39) between the ages 11 and 17 years were included, 18 of whom were diagnosed with schizophrenia, and 21 with other non-organic, non-affective psychoses, using ICD-10 criteria. A healthy control group ( N = 40) was included, matched on gender and age. Cognitive functions were assessed using WISC-III/R, the CANTAB battery, WCST, Trail Making B, fluency tasks, and Buschke's selective reminding task. A similar profile and level of impairment was found on measures of attention, executive functions, reaction time, and memory in the schizophrenic and psychotic adolescent groups. However, analyses of WISC-III factor profiles suggested that early onset schizophrenia patients may have more global IQ deficits than non-organic, non-affective psychoses when examined recently after illness onset. Compared to the deficits of adult schizophrenia described in the literature, the results suggest relatively spared simple reaction times in early onset patients.

Children and adolescents who have schizophrenia.

1. Adriana E. Groisman, MD 2. Martha L. Seminatore, MD 1. Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 1. Practice Parameter for the Assessment and Treatment of Children and Adolescents with Schizophrenia. McClellan J, Werry J, and the Work Group on Quality Issues of the AACAP. J Am Acad Child Adolesc Psychiatry. 2001;40(suppl) :4S -23S 2. Symptom Factors in Early-Onset Psychotic Disorders . McClellan J, McCurry C, Speltz ML, Jones K. J Am Acad Child Adolesc Psychiatry. 2002;41 :791– 798 [OpenUrl][1][CrossRef][2][PubMed][3] 3. Substance Abuse and Emergency Psychiatry . Zealberg JJ, Brady KT. Psychiatr Clin North Am. 1999;22 :808– 817 [OpenUrl][4] 4. Diagnostic and Statistical Manual of Mental Disorders . 4th ed (DSM-IV). Washington, DC: American Psychiatric Association; 1994:273–315 Schizophrenia is a chronic disorder associated with deficits in cognition, affect, and social functioning. The onset of illness can occur rarely as early as 5 years of age, but after the age of 13 years, the incidence increases steadily. Early-onset (before age 18 y) and very early-onset (before age 13 y) schizophrenia are diagnosed by using the same criteria as in adults, and these forms appear to be continuous with the adult form of the disorder. Youths who have schizophrenia are predominantly males, have high rates of premorbid abnormalities and higher ratings on negative and positive symptoms, and often exhibit poor outcome. Schizophrenia is a phasic disorder, with individual variability. The phases are: [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2Bthe%2BAmerican%2BAcademy%2Bof%2BChild%2Band%2BAdolescent%2BPsychiatry%26rft.stitle%253DJ%2BAm%2BAcad%2BChild%2BAdolesc%2BPsychiatry%26rft.aulast%253DMcClellan%26rft.auinit1%253DJ.%26rft.volume%253D41%26rft.issue%253D7%26rft.spage%253D791%26rft.epage%253D798%26rft.atitle%253DSymptom%2Bfactors%2Bin%2Bearly-onset%2Bpsychotic%2Bdisorders.%26rft_id%253Dinfo%253Adoi%252F10.1097%2524583-200207000-00010%26rft_id%253Dinfo%253Apmid%252F12108803%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1097/00004583-200207000-00010&link_type=DOI [3]: /lookup/external-ref?access_num=12108803&link_type=MED&atom=%2Fpedsinreview%2F24%2F10%2F356.atom [4]: {openurl}?query=rft.jtitle%253DPsychiatr%2BClin%2BNorth%2BAm.%26rft.volume%253D22%26rft.spage%253D808%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx