Self-report of family functioning and risk for psychotic disorders in male adolescents with behavioural disturbances

Objective: Previous studies indicate that a poor family environment might affect vulnerability for the later manifestation of psychotic illness. The current study aims to examine family functioning prior to the onset of psychosis. Method: Subjects were 42 948, 17‐year old males with behavioural disturbances who were asked about the functioning of their family by the Israeli Draft Board. Data on later psychiatric hospitalizations were obtained from a National Psychiatric Hospitalization Registry. Results: Poorer self‐reported family functioning was associated with greater risk for later hospitalization for psychosis [adjusted hazard ratio (HR) = 1.16, 95% CI = 1.05–1.27], with a trend in the same direction for schizophrenia (adjusted HR = 1.1, 95% CI = 0.98–1.24). Conclusion: In male adolescents with behavioural disturbances, perceived poorer family functioning is associated with increased risk for non‐affective psychotic disorders and schizophrenia. These data do not enable us to determine if perceived familial dysfunction increases vulnerability for psychosis, if premorbid behavioural abnormalities disrupt family life, or neither.     

Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents.

OBJECTIVE: Subtle behavioral and intellectual abnormalities are often present in apparently healthy adolescents who later develop schizophrenia. The authors investigated whether these abnormalities can predict vulnerability for schizophrenia before the first psychotic manifestation. METHOD: The study consisted of linking the Israeli Draft Board Registry with the National Psychiatric Hospitalization Case Registry. The draft board tests measure intelligence, social functioning, organizational ability, interest in physical activity, and individual autonomy. Patients (N = 509) were compared to nonpatients, i.e., adolescents not appearing in the National Psychiatric Registry (N = 9,215), matched to patients by age, gender, and school attended at time of testing. RESULTS: Healthy male adolescents who were later hospitalized for schizophrenia had significantly lower test scores on all measures than adolescents not reported to the National Psychiatric Registry. The strongest predictors for schizophrenia were deficits in social functioning, organizational ability, and intellectual functioning. When patients were compared to matched nonpatients, the prediction model had a 75% sensitivity, a 100% specificity, a positive predictive value of 72%, and an overall rate of correct classification of 87.5%. Applied to the Israeli Draft Board Registry, the model yielded a sensitivity of 74.7%, a validated specificity of 99.7%, and a positive predictive value of 42.7%. CONCLUSIONS: This study demonstrated that simple assessment tools can predict predisposition to schizophrenia in healthy male adolescents. The model's predictive ability does not change as a function of the time elapsed between testing and first hospitalization. This suggests that the model identifies apparently healthy individuals who will manifest the disease later who are not prodromal to psychosis. Easily applied tools allowing early identification of schizophrenia or vulnerability to it may enable early intervention.     

Self-reported drug abuse in male adolescents with behavioral disturbances, and follow-up for future schizophrenia.

BACKGROUND:The prevalence of illicit drug abuse in persons with schizophrenia is greater then in the general population and has been attributed to self-medication of the symptoms of the illness; however, limited data indicate that drug abuse is already prevalent before the manifestation of psychosis, consistent with the possibility that drug abuse might be associated with increased risk for schizophrenia. METHODS: The Israeli Draft Board screens the entire, unselected population of 16- to 17-year-old male adolescents for behavioral or personality disturbances. In a cohort of 270,000 male adolescents screened, 50,413 adolescents were suspected of having behavioral or personality disturbances and were questioned about drug use and abuse. These adolescents were followed for hospitalization for schizophrenia using a national, population-based psychiatric hospitalization registry; 268 of 50,413 (.5%) were hospitalized for schizophrenia over the following 5-11 years. RESULTS: The prevalence of self-reported drug abuse in adolescents later hospitalized for schizophrenia was 12.4%, compared with 5.9% prevalence of drug abuse in adolescents not later hospitalized; adjusted RR = 2.016, 95% confidence interval: 1.309-3.104. CONCLUSIONS: In this cohort of male adolescents with behavior disturbances, these results further support the hypothesis that drug abuse may be associated with increased risk for future schizophrenia.     

Longitudinal association between epilepsy and schizophrenia:A population-based study

A large number of studies have reported an association between epilepsy and major psychiatric conditions. This study investigated the association between epilepsy and later schizophrenia, utilizing a historical-prospective, population-based design. Of the 861,062 17-year-old male adolescents consecutively screened by the Israeli Draft Board and found free of major mental illness, 0.06% suffered from severe, treatment-refractory epilepsy, 0.25% had treated, controlled epilepsy, and 0.16% had a history of seizures which had abated 5 or more years prior to screening. Hospitalization for schizophrenia was ascertained through the Israeli National Psychiatric Hospitalization Case Registry, with an average follow-up of 9.6 ± 1.0 years (range: 1.0–10.0 years). Risk of hospitalization was calculated using Cox regression analyses, compared to socioeconomic-adjusted risk of hospitalization in the general population of male adolescents. Among adolescents whose epilepsy was nonresponsive to medication, the adjusted risk of hospitalization was significantly increased for schizophrenia (HR = 3.89, 95% CI = 1.75–89.67). Male adolescents with successfully treated epilepsy were not at increased risk for schizophrenia.Male adolescents with severe, treatment-refractory epilepsy are at increased risk of later schizophrenia. Future studies attempting to understand the biology of this association might focus on this subset of patients, and these patients should be monitored for the appearance of psychosis.     

Body mass index and future schizophrenia in Israeli male adolescents

BACKGROUND: Compared with the general population, individuals suffering from schizophrenia are more likely to be overweight, a finding attributed to the effect of antipsychotic medications, poor nutrition, and sedentary lifestyle. As evidence accumulates indicating that some aspects of the illness manifest before the onset of psychosis and establishment of the diagnosis, it has been suggested that increased weight, like other metabolic dysfunctions, might precede active illness. METHOD: Data on height and weight of 203,257 male adolescents assessed by the Israeli Draft Board, and followed for 2-6 years for later hospitalization for schizophrenia using the Israeli National Psychiatric Hospitalization Case Registry, were analyzed. RESULTS: From the entire cohort, 309 (0.15%) were later hospitalized for schizophrenia (ICD-10). After removing adolescents with evidence of illness before or within 1 year of the Draft Board assessment, 204 future schizophrenia patients were available for analysis. Compared with the rest of the cohort, future schizophrenia patients had lower body mass indexes (21.24 +/- 3.3 kg/m2 vs. 21.77 +/- 3.5 kg/m2; F = 4.682, df = 1, p = .03) and weighed slightly but significantly less (64.2 +/- 11.6 kg vs. 66.3 +/- 12.0 kg; F = 6.615, df = 1, p = .01). The mean height of the future patients did not differ significantly from the mean height of the remaining cohort (173.63 +/- 6.7 cm vs. 174.40 +/- 6.9 cm; F = 2.520, df = 1, p = .112). When reanalyzing the data, controlling for physical activity and socioeconomic status, the differences between the groups remained significant. CONCLUSION: Before the onset of illness, future schizophrenia patients are not heavier compared with their peers. This implies that the increased weight of patients with schizophrenia is related to illness effects, including the effects of antipsychotic medication.     

Association between nonpsychotic psychiatric diagnoses in adolescent males and subsequent onset of schizophrenia

BACKGROUND: Nonpsychotic psychiatric symptoms may occasionally herald the later development of schizophrenia. This study followed a population-based cohort of adolescents with nonpsychotic, non-major affective psychiatric disorders to ascertain future hospitalization for schizophrenia. METHODS: Results of the medical and mental health assessments on 124 24416- to 17-year-old males screened by the Israeli draft board were cross-linked with the National Psychiatric Hospitalization case registry, which contains data on all psychiatric hospitalizations in the country, during a 4- to 8-year-long follow-up through age 25 years. In the cohort, 9365 adolescents were assigned a nonpsychotic, non-major affective diagnosis by the draft board. RESULTS: After excluding 167 adolescents who were hospitalized before or up to 1 year after the draft board assessment, 1.03% of the adolescents assigned a nonpsychotic, non-major affective psychiatric diagnosis, compared with only 0.23% of the adolescents without any psychiatric diagnosis, were later hospitalized for schizophrenia. Of the patients with schizophrenia, 26.8%, compared with only 7.4% in the general population, had been assigned a nonpsychotic, non-major affective psychiatric diagnosis in adolescence (overall odds ratio [OR], 4.5; 95% confidence interval [CI], 3.6-5.6), ranging from OR, 21.5 (95% CI, 12.6-36.6) for schizophrenia spectrum personality disorders to OR, 3.6 (95% CI, 2.1-6.2) for neurosis. CONCLUSION: These results reflect the relatively common finding of impaired functioning in patients later hospitalized for schizophrenia and the relatively low power of these disorders in predicting schizophrenia.     

Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study

OBJECTIVE: The prevalence of cigarette smoking among schizophrenia patients is significantly higher than in the general population; this may reflect self-medication of symptoms and/or adverse effects of neuroleptics. The authors examined the prevalence of cigarette smoking in apparently healthy adolescents later hospitalized for schizophrenia. METHOD: Each year, a random sample of male Israeli military recruits, who have been screened and found not to be suffering from major psychopathology, complete a smoking questionnaire. Through the Israeli National Psychiatric Hospitalization Case Registry, 14,248 of these adolescents were followed to determine later psychiatric hospitalization. RESULTS: Of the 14,248 adolescents assessed, 4,052 (28.4%) reported smoking at least one cigarette a day. Over a 4-16-year follow-up, the prevalence of schizophrenia in the entire cohort was 0.3% (N=44). Smokers were at greater risk for later schizophrenia; the adjusted relative risk was 1.94, and the 95% confidence interval (CI) was 1.05-3.58. The number of cigarettes smoked was significantly associated with the risk for schizophrenia. Compared to nonsmokers, adolescents who smoked 1-9 cigarettes/day were 1.38 times (95% CI=0.48-4.00) as likely to be hospitalized later for schizophrenia, and adolescents who smoked 10 cigarettes/day or more were 2.28 times (95% CI=1.19-4.34) as likely; the latter difference was statistically significant. CONCLUSIONS: Taken together with the existing data on abnormalities in nicotinic transmission in patients and their relatives, this higher prevalence of smoking in future schizophrenia patients, before the onset of their illness, might indicate that impaired nicotinic neurotransmission is involved in the pathophysiology of schizophrenia.     

Intellectual functioning in adolescents with indicators of psychosis: evidence for decline in functioning related to number of psychotic features?

Substantial research has demonstrated that adults with schizophrenia display intellectual decline compared to their premorbid levels of functioning. Research of this type, however, is not as common in adolescents with psychotic disorders. Since many first-episode adolescents with psychotic disorders other than schizophrenia may eventually meet criteria for this diagnosis, we examined first admission adolescents with variable psychiatric diagnoses. In this study, current intellectual functioning was compared to estimated premorbid functioning (estimated with word recognition reading), and the difference between these scores was related to the number of indicators of psychosis that was present in each case. Subjects consisted of 513 inpatients, ranging in age from 13 to 17 years, who were admitted to the adolescent service of a private psychiatric hospital. Indicators of psychosis came from clinical diagnoses, self-report measures, and clinical rating scales. Across the entire sample of 513 subjects the greater the number of indicators of psychosis that was present, the greater the estimated premorbid/current intelligence quotient (IQ) discrepancy. Type of IQ test, differences in intellectual premorbid functioning, demographic variables, and type of treatment were all unassociated with risk for IQ discrepancy. Within the limitations of estimation of premorbid intellectual functioning, these data suggest that intellectual decline is present at the time of the first psychiatric admission in psychotic adolescent patients who do not necessarily meet diagnostic criteria for schizophrenia and that this discrepancy is greater in patients with more indicators of psychosis.     

Self-reported mental health difficulties and subsequent risk for schizophrenia in females: a 5-year follow-up cohort study

BACKGROUND: Patients with schizophrenia often report a history of premorbid mild to severe psychological distress. We investigated the association between self-reported mental health difficulties and later psychiatric hospitalization for schizophrenia. METHODS: 13,357 females aged 17, mandatory assessed by the Israeli Draft Board were followed up over 5 years for psychiatric hospitalization by means of the Israeli National Psychiatric Hospitalization Case Registry. Seventeen females, judged healthy at Draft Board assessment, were hospitalized for schizophrenia or schizoaffective disorder over the follow-up period. RESULTS: There was a significant monotonic association between increasing self-reported mental health difficulties (psychological distress and increasing need for psychological counseling) and prevalence of schizophrenia [odds ratios over four levels: 1.56; 95% CI:1.04 to 2.34; chi2 (1) = 4.62, p = 0.03], after controlling for low IQ, immigration, SES, and presence of psychiatric disorders at age 17. Increasing severity of self-reported mental health difficulties was related to earlier age of first hospitalization [r = -0.48, p = 0.05]. CONCLUSIONS: Increased undifferentiated self-reported mental health difficulties are associated with increased risk of later hospitalization for schizophrenia prior to age 23 in females. This may reflect the prodromal phase of the illness.     

Psychosis in a pediatric mood and anxiety disorders clinic: phenomenology and correlates

OBJECTIVES: To examine the demographics and phenomenology of psychosis in a sample of children and adolescents referred to a mood and anxiety disorders clinic. METHOD: Patients (N = 2,031) were assessed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode version and classified as definite, probable, or nonpsychotic. Clinical and demographic characteristics of the groups were compared,and symptoms of psychosis were analyzed using factor analysis. RESULTS: Definite psychotic symptoms were seen in approximately 90 (4.5%) patients: 80% of these reported hallucinations (mainly auditory), 22% delusions, and 3.3% thought disorder. Of the patients with definite psychotic symptoms, 24% had bipolar disorder, 41% had major depression, 21% had subsyndromal depression, and 14% had schizophrenia spectrum disorders (schizophrenia and schizoaffective disorders). Factor analysis of the definite psychotic symptoms yielded 4 factors: hallucinations, thought disorder, delusions, and manic thought disorder. Psychotic patients had a higher frequency of comorbid disorders and suicidal ideation than nonpsychotic patients. CONCLUSIONS: Outpatient youngsters with mood disorders frequently present with psychotic symptoms, in particular auditory hallucinations. These patients commonly have comorbid psychiatric disorders and suicidal ideation.     

Untreated psychotic illness in the survivors of violent suicide attempts

Background: Recent studies suggest that violence is more common in the first episode of psychosis than after treatment. Aim: To estimate the proportion of survivors of violent suicide attempts during psychotic illness who had not previously received treatment with antipsychotic medication. Methods: An audit of the medical records of patients admitted to an inner city trauma centre after having survived a jump of more than 3 m or a self‐inflicted gunshot wound or stab wound to a vital body part. Results: There were 88 survivors of violent suicide attempts. Thirty‐seven of those had a psychotic illness, including 33 with a schizophrenia‐spectrum psychosis. Of the 37, 18 (48.6%, 95% confidence interval (CI) 32.3–65.0%) had never received treatment for psychosis. Conclusion: As first episode psychosis is less common than previously treated psychosis, there appears to be a higher risk of violent suicide attempts during the first episode of psychosis than later in the illness.     

Impaired reading comprehension and mathematical abilities in male adolescents with average or above general intellectual abilities are associated with comorbid and future psychopathology

Research indicates that persons with learning disorders often suffer from psychopathology. We assessed current and future psychopathology in male adolescents with discrete impairments in reading comprehension (IRC) or arithmetic abilities (IAA) but with average or above-average general intellectual abilities. Subjects were a population-based cohort of 174,994 male adolescents screened by the Israeli Draft Board with average or above-average intellectual abilities but with low scores (8.6th and 10th lowest percentile respectively) on reading or arithmetic tests. They were compared with adolescents who scored in the 10th percentile and above on these tests (comparison group). Relative to the comparison group, male adolescents with IRC, IAA, or IRC and IAA (0.69%), had poorer scores on most behavioral assessments and higher prevalence of current psychopathology: 4.2% (comparison group), 8.0% (IRC), 7.0% (IAA), and 9.8% (IRC and IAA). Adolescents with IRC were also at increased risk for later hospitalization for schizophrenia (hazard ratios = 1.8, 95% confidence interval: 1.3-2.6). Male adolescents with average and above-average general intellectual abilities but with IRC or IAA are more likely to have current and future psychopathology. Impairments in intellectual functioning and abnormal behaviors leading to mental illnesses may share common neurobiological substrates. The results support screening male adolescents with learning disorders for psychopathology.     

Premorbid intra-individual variability in intellectual performance and risk for schizophrenia: a population-based study

BACKGROUND: Some, but not most, schizophrenia patients have below-average intelligence years before they manifest psychosis. However, it is not clear if those whose intelligence falls within-normal-range nevertheless have cognitive abnormalities. We examined the association between intra-individual variability in intellectual performance and risk for schizophrenia in individuals with normal IQ. METHODS: 555,326 adolescents, mandatory assessed by the Israeli Draft Board were followed up over 8 to 17 years for psychiatric hospitalization by means of the Israeli National Psychiatric Hospitalization Case Registry. Data were available on 4 intelligence sub-tests, and on behavioral and psychosocial variables. Variability was computed from the variance of the four intelligence tests' standardized scores. RESULTS: There was a significant monotonic association between increased intra-individual variability in intellectual performance and risk of schizophrenia in individuals with within-normal-range IQ. Individuals with the highest variability were 3.8 times more likely to have schizophrenia [95%CI: 2.32-6.08; p < 0.0001] compared with individuals with the lowest variability. This association held after controlling for the effects of potential confounders. CONCLUSIONS: Despite within-normal-range premorbid IQ, apparently healthy adolescents who will later on manifest schizophrenia, nevertheless have cognitive abnormalities such as increased variability across intellectual tasks, possibly related to frontal lobe abnormalities.     

Initial diagnosis and treatment in first‐episode psychosis: can an operationalized diagnostic classification system enhance treating clinicians' diagnosis and the treatment chosen?

Aim: Diagnosis during the initial stages of first‐episode psychosis is particularly challenging but crucial in deciding on treatment. This is compounded by important differences in the two major classification systems, International Classification of Diseases, 10th revision (ICD‐10) and Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM‐IV). We aimed to compare the concordance between an operationalized diagnosis using Operational Criteria Checklist (OPCRIT) and treating clinician‐generated diagnosis in first‐episode psychosis diagnosis and its correlation with treatment prescribed. Methods: Operationalized polydiagnostic assessments were conducted on 150 first‐episode psychosis patients using OPCRIT. OPCRIT‐generated ICD‐10, DSM‐IV and treating clinician diagnoses were compared. The association between these diagnoses and choice of treatment was evaluated. Results: General agreement between the three classification systems was moderate to good, with kappa values between 0.460 and 0.674. There was a higher frequency of schizophrenia diagnosis in ICD‐10 (n = 85) comparing to DSM‐IV (n = 45) and similar in clinical diagnosis (n = 76), with moderate to good agreement between classifications (kappa between 0.602 and 0.731). No significant differences were found for ratings of psychotic depressive and manic/bipolar disorders with psychosis, with affective disorders having the higher agreement. Heterogeneous group of ‘other disorders’ achieved a kappa value from 0.250 (DSM‐IV/ICD‐10) to 0.566 (DSM‐IV/clinical diagnosis). Conclusion: Despite the challenges in first‐episode psychosis diagnosis, it is possible to have a good agreement between OPCRIT‐generated (DSM‐IV and ICD‐10) diagnoses and clinician‐based diagnoses, although some differences exist. The choice of psychopharmacological treatment prescribed matches well with these operationalized diagnoses.     

Premorbid functioning in a national population of male twins discordant for psychoses

OBJECTIVE: The goal of the current study was to compare premorbid behavioral and cognitive functioning between co-twins discordant for psychotic disorder and between these pairs of twins and pairs of twins with no psychotic disorders. METHOD: The authors linked data from the Israeli Draft Board Registry, which contains cognitive and behavioral assessments of all 16-17-year-old male Israeli twins, with data from the National Psychiatric Hospitalization Case Registry. Pairs of male twins who were healthy at the time of testing but discordant for psychoses later on were compared with one another and with pairs of healthy male twins. RESULTS: The affected twins performed significantly worse than healthy twins on measures of individual autonomy, social functioning, and physical activity and nonsignificantly worse on measures of abstract reasoning. There were no significant differences in cognitive or behavioral scores between the co-twins who did or did not develop psychotic disorders. CONCLUSIONS: The authors conclude that these findings underscore the familial nature of behavioral and cognitive deficits antecedent to psychoses.     

Increased number of offspring in first degree relatives of psychotic individuals: a partial explanation for the persistence of psychotic illnesses

Objective: As patients with psychotic illness have fewer offspring than controls, the persistence of psychotic illness is puzzling. We hypothesized that unaffected first‐degree relatives of patients have more offspring than controls. Method: Probands were 4904, individuals with non‐affective psychotic disorders identified from a hospitalization registry. Unaffected first degree relatives and matched controls were identified from the Israeli Population Registry. The number of offspring of unaffected parents, biological siblings and controls was ascertained. Results: Unaffected parents of psychotic patients had more offspring/person than controls; 4.5 ± 2.7 vs. 3.4 ± 2.2, P = 0.000. Unaffected parents from familial psychosis families (more than one affected family member) had 1.83 more offspring than controls; unaffected parents from non‐familial psychosis families had 0.97 more offspring than controls (both P < 0.001). Conclusion: These findings might imply that genes which increase susceptibility for schizophrenia may be associated with increased number of offspring, perhaps supplying a partial explanation for the persistence of psychosis.     

Cognitive performance in schizophrenia patients assessed before and following the first psychotic episode

BACKGROUND: The purpose of this historical prospective study was to follow the cognitive impairment in schizophrenia from the premorbid period until shortly after the onset of the first psychotic episode within the same subjects. METHODS: Forty-four first episode schizophrenia patients were enrolled in the study. Their cognitive performance was assessed as part of the Israeli Draft Board aptitude assessments at ages 16-17, when all were found to be in good mental health (first assessment) and again, following the manifestation of the first psychotic episode (second assessment). Forty-four healthy comparisons were also enrolled and tested twice, at the same ages as the patients. Both times, the assessments included four subtests assessing abstract reasoning (Raven Progressive Matrices-R), mental speed and concentration (Otis-R), verbal reasoning (Similarities-R), and mathematical abilities (Arithmetic-R). RESULTS: A within group analysis did not reveal statistically significant changes between the first and the second assessment among the schizophrenia patients on any measure. However, a between group comparison of changes showed that relative to the healthy comparisons, schizophrenia patients deteriorated on the RPM-R (p=0.021) and Otis-R (p<0.001), but not on the Similarities-R and Arithmetic-R. Schizophrenia patients performed worse than comparisons in all four subtests on the first and second assessments (all p<0.01). CONCLUSIONS: The results indicate that most of the cognitive impairment exhibited by first-episode schizophrenia patients precedes the first psychotic episode. A decline between ages 16 and 17 and the onset of psychosis is evident in some but not all cognitive functions.     

Comorbid depressive symptoms in the developmental course of adolescent‐onset psychosis

Aim: Depressive symptoms are common in the early prodromal phase of schizophrenia and other psychotic disorders. The objectives of the present study were to retrospectively examine the severity of depressive symptoms and their relationship to positive symptoms over the developmental course of adolescent‐onset psychosis (AO‐PSY). Methods: The subjects were 62 unmedicated adolescents with DSM‐IV psychosis and 104 normal controls from a Pacific island isolate with an elevated prevalence of schizophrenia. We used a modified K‐SADS‐PL to assess adolescents for a full range of Axis I psychopathology and quantified severity of depressive and positive symptoms over the adolescent’s lifespan. Results: Among AO‐PSY subjects, 84% reported abnormal levels of depressive symptoms with mean onset 1.3 years prior to transition to psychosis. In 60% of the AO‐PSY subjects with depressive symptoms, positive symptoms began first. A continuous linear increase in depressive symptom severity over the developmental course of illness mirrored the steady rise in positive symptom severity as psychosis emerged. Conclusions: We found that it is typically a combination of positive symptoms and depressive symptoms building in parallel that leads from the prodrome to frank psychosis. These results suggest that depressive symptoms represent more of an integral component of disease progression than an independent risk factor that predicts transition to early onset psychosis.     

Findings of proton magnetic resonance spectometry in the dorsolateral prefrontal cortex in adolescents with first episodes of psychosis

Knowledge of the neurobiology of early onset psychosis is limited. We used proton magnetic resonance spectroscopy to investigate the possible existence of dorsolateral prefrontal brain biochemical abnormalities in adolescents with psychosis and to determine possible differential effects related to specific psychotic diagnoses. We measured the ratios of N-acetyl-aspartate (NAA), choline (Cho), and creatine (Cr) to water in two groups of adolescents with a first episode of psychosis (schizophrenia n=8; non-schizophrenia n=15) and in 32 healthy controls matched for age, gender, and years of education. Proton magnetic resonance spectroscopy at 1.5 T was used to study two 6.75-cc voxels placed in the left and right dorsolateral prefrontal region. The schizophrenia patients presented statistically significant reductions in NAA/water levels in the left dorsolateral prefrontal voxel as compared with non-schizophrenia patients and healthy controls. No significant differences were detected between groups for NAA/water in the right dorsolateral prefrontal voxel or for Cho/water and Cr/water levels in any hemisphere. A reduction of the NAA/water level in the left dorsolateral prefrontal region may be selectively present at the onset of psychosis during adolescence in patients who later progress to schizophrenia, but not in those who later progress to other psychotic disorders.