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Background: We studied the cumulative incidence of physical illnesses, and the effect of early environmental factors (EEFs) on somatic comorbidity in schizophrenia, in nonschizophrenic psychosis and among nonpsychotic controls from birth up to the age of 50 years., Methods: The sample included 10,933 members of the Northern Finland Birth Cohort 1966, of whom, 227 had schizophrenia and 205 had nonschizophrenic psychosis. Diagnoses concerning physical illnesses were based on nationwide registers followed up to the end of 2016 and classified into 13 illness categories. Maternal education and age, family type at birth and paternal socioeconomic status were studied as EEFs of somatic illnesses., Results: When adjusted by gender and education, individuals and especially women with nonschizophrenic psychosis had higher risk of morbidity in almost all somatic illness categories compared to controls, and in some categories, compared to individuals with schizophrenia. The statistically significant adjusted hazard ratios varied from 1.27 to 2.42 in nonschizophrenic psychosis. Regarding EEFs, single-parent family as the family type at birth was a risk factor for a higher somatic score among men with schizophrenia and women with nonschizophrenic psychosis. Maternal age over 35 years was associated with lower somatic score among women with nonschizophrenic psychosis., Conclusions: Persons with nonschizophrenic psychoses have higher incidence of somatic diseases compared to people with schizophrenia and nonpsychotic controls, and this should be noted in clinical work. EEFs have mostly weak association with somatic comorbidity in our study.

Aim: To find factors that are associated with not having psychotic illness in a prospective general population sample, with a special interest in individuals with parental psychosis., Methods: Data from the Northern Finland Birth Cohort 1966 (n = 10 458) and several registers were used to detect individuals with and without parental psychosis. Altogether, 594 persons had parent(s) with psychosis and 48 of them also had psychosis subsequently. Variables related to pregnancy and birth, family and childhood, health and habits in adolescence, school performance and physical activity were studied to identify determinants of unaffected status among individuals with and without parental psychosis., Results: In the parental psychosis group, the unaffected persons had more likely a mother who was non-depressed during pregnancy, and who worked outside the home or studied than among those who developed psychosis., Conclusions: Protective factors for psychosis were surprisingly few in this sample. These factors were related to the mother's non-depressed mood and the mother's work outside the home or studies. This could relate to better health and functioning of a mother. This work highlights the need for more research on protective factors for psychosis in order to identify methods for prevention of psychosis., (© 2016 John Wiley & Sons Australia, Ltd.)

Family history of psychiatric disorders has been associated with impaired outcome in schizophrenia, but very few studies have investigated its long-term social and occupational outcome. We investigated the association of family history of psychiatric disorders, especially psychosis, with long-term social, occupational, clinical and global outcome in schizophrenia. The study sample comprises of the Northern Finland Birth Cohort 1966. Cohort members with psychosis were detected by Finnish national registers. Altogether 69 individuals with schizophrenia spectrum diagnosis participated, mean age 43, after on average 17 years since onset of illness. The information regarding family history of psychiatric disorders were gathered from registers and interviews. A Strauss-Carpenter Outcome Scale, PANSS and SOFAS were conducted to assess the outcome. Results showed that the family history of any psychiatric disorder was associated with more severe positive and emotional symptoms in PANSS. The family history of psychosis was not associated with outcomes. These findings suggest that family history of psychiatric disorders has a small association with outcome in schizophrenia. Despite family history of psychosis being a strong risk factor for schizophrenia, after years of illness it does not seem to affect outcome., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: We examined mortality in schizophrenia spectrum disorder (SSD) and non-schizophrenic psychosis (NSSD) compared to individuals without psychosis, and whether perinatal factors predict mortality., Methods: Within Northern Finland Birth Cohort 1966 (n=10 933; 203 with SSD, 178 with NSSD), mortality was followed until end of 2011 by national register. Wantedness of pregnancy, mother's antenatal depression, smoking and age, parity, paternal socio-economic status (SES) and family type at birth were examined as predictors of mortality., Results: Mortality was higher in SSD (hazard ratio (HR) 3.60; 95% confidence interval (CI) 2.38-5.45) and NSSD (4.05; 2.65-6.17) compared to persons without psychoses after adjustment for gender. HR for natural death was 2.01 (0.82-4.91) in SSD and 4.63 (2.43-8.80) in NSSD after adjustment for gender. Corresponding figures for unnatural deaths were 4.71 (2.94-7.54) and 2.94 (1.56-5.55), respectively. Among non-psychotic persons, mother's depression, smoking and low SES predicted mortality after adjustment for gender and parental psychoses (and SES), whereas among psychosis those whose father was a farmer had lower risk of mortality compared to those with high SES., Conclusions: Individuals with SSD had a higher risk of unnatural death and individuals with NSSD of natural and unnatural deaths. Perinatal factors seem to be more important predictors of mortality in individuals without psychoses than with psychoses. According to population-based long follow-up data, it is important to pay attention to somatic morbidity behind natural causes of death in psychoses and to prevent suicides in order to prevent excess mortality., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: In this register-based study the rates and durations of psychiatric hospitalizations were compared between patients with very-late-onset schizophrenia-like psychosis (VLOSLP, n = 918) and elderly patients with illness onset before 60 years (n = 6142). The proportion of patients ending up in long-term care (LTC) or long-lasting psychiatric hospital care (LLP) was also studied., Methods: A sample of patients with schizophrenia aged 65 or over was collected from the Finnish Hospital Discharge Register. Psychiatric hospitalizations were calculated per year, and logistic regression was used to compare onset groups and factors associated with ending up in LTC/LLP., Results: Between 1999 and 2003, 27% of patients with VLOSLP and 23% of patients with earlier onset had at least one psychiatric hospitalization (p = 0.020). When the rates of patients' stays in psychiatric hospital per year were compared, the only difference was that in the first year 14% (141/918) and 11% (679/6142) had at least one day in psychiatric hospital (p < 0.001) respectively. In logistic regression onset group of schizophrenia was not associated with LTC/LLP, except weakly the VLOSLP group in women (p = 0.042, OR 1.23). Patients having any cardiovascular disease (p < 0.001, OR 0.63) or a respiratory disease (p = 0.008, OR 0.73) were less likely to end up in LTC/LLP., Conclusion: The patients with VLOSLP needed more psychiatric hospital care than those with earlier illness onset. Ending up in LTC/LLP was equally common in both onset groups, but some physical diseases, such as cardiovascular and respiratory, diminished the likelihood of this., (Copyright © 2015 John Wiley & Sons, Ltd.)

The information on the use of psychiatric medications in general population-based samples is limited. Our aim was to analyse the use of psychiatric medications and factors associated with antipsychotic use in psychoses in a general population sample. Fifty-five persons with schizophrenia, 21 with bipolar psychosis or psychotic depression and 20 with other psychoses from the Northern Finland Birth Cohort 1966 were examined at about 43 years of age. The frequency of use and dosage of psychiatric medication and the factors associated with the use of antipsychotics were analysed. Antipsychotics were used by 85% of schizophrenia, 65% of bipolar psychosis or psychotic depression and 62% of other psychoses cases; antidepressants were used by 22%, 60% and 33%; and benzodiazepines by 42%, 35% and 10%, respectively. In all the diagnostic groups, higher symptom scores and a higher number of hospital days were associated with the use of antipsychotics. In schizophrenia and other psychoses, poorer social and occupational functioning, and in other psychoses, female gender and lower education were also associated with the use of antipsychotics. Our results may partly indicate that, especially in schizophrenia, the effectiveness of antipsychotics is not as good as expected., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: In this register-based study of schizophrenia patients aged 65 years or above, mortality and causes of death diagnosed at age of 60+ (very-late-onset schizophrenia-like psychosis, VLOSLP) were studied in comparison with sex- and age-matched general Finnish population. Standardized Mortality Ratios (SMRs) of VLOSLP patients were also compared with those of earlier onset (below 60 years) schizophrenia patients, and hazard of death was calculated between these patient groups., Methods: The data was obtained from Finnish nationwide registers and consisted of 918 VLOSLP patients and 6142 earlier onset patients who were at least 65 years on 1 January 1999. The register-based follow-up for mortality covered 10 years between 1999 and 2008., Results: Overall SMR was 5.02 (4.61-5.46) in the group of VLOSLP patients and 2.93 (2.83-3.03) in the group of earlier onset patients. In men, SMRs were 8.31 (7.14-9.62; n = 179) and 2.91 (2.75-3.07, n = 1316) and in women 4.21 (3.78-4.66; n = 364) and 2.94 (2.82-3.07, n = 2055). In the VLOSLP group, SMRs were higher in most causes-of-death categories such as accidents, respiratory diseases, dementias, neoplasms and circulatory diseases. However, in direct comparison adjusted for several variables, the difference between these groups was minimal (Hazard Ratio, HR, 1.16 95%CI 1.05-1.27, p = 0.003)., Conclusion: Patients with VLOSLP, especially men, are at even higher risk of death than schizophrenia patients with earlier onset. Physical comorbidities and accidents in the VLOSLP group mostly explained this result. Targeted clinical interventions with effective collaboration between psychiatry and primary and specialist-level somatic care are crucial to reduce their excess mortality, (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Duration of untreated psychosis (DUP) is one of the few potentially modifiable predictors of outcomes of schizophrenia. Long DUP as a predictor of poor short-term outcome has been addressed in previous meta-analyses, but the long-term effects of DUP remain unclear., Aims: To analyse the associations between DUP and long-term outcomes of schizophrenia., Method: A systematic literature search was performed using seven electronic databases and manual searches. Random effects weighted meta-analysis with correlation coefficients was used to pool the results., Results: We identified 3493 unique publications, from which 33 samples met our predefined selection criteria. Long DUP correlated statistically significantly with poor general symptomatic outcome, more severe positive and negative symptoms, lesser likelihood of remission and poor social functioning and global outcome (correlations 0.13-0.18). Long DUP was not associated with employment, quality of life or hospital treatment., Conclusions: The small but mostly consistent correlation between long DUP and poor outcome indicates that early intervention in psychosis may have at least subtle positive effects on the long-term course of illness., (Royal College of Psychiatrists.)

Background: Long duration of untreated psychosis (DUP) may relate to poor outcome in schizophrenia. However, the associations between DUP and outcomes, particularly in later course of illness, remain unclear. Our aim was to explore the associations between DUP and short- and long-term outcomes in schizophrenia., Methods: Data was collected for subjects with schizophrenia (n=89) in the population-based Northern Finland 1966 Birth Cohort. DUP was obtained from medical records, and its associations with short- (under 2years) and long-term clinical and social outcomes were assessed extending to 20years after the onset of the illness., Results: Longer DUP predicted longer length of first hospitalisation and increased the risk of rehospitalisation during the first two years. Longer DUP associated with decreased probability of disability pension, smaller amount of time spent in hospital, and higher proportion of time at work during the first 10years of the follow-up., Conclusions: Regarding early outcome, long DUP may be a modest marker and proxy measure of a more severe clinical phenotype. The divergent results of earlier studies and the association between long DUP and better long-term outcome in our study, indicate that the length of DUP does not necessarily predict poor outcome in long-term follow-up. This may also be due to methodical difficulties, e.g. insufficient power and residual confounding linked to long follow-up studies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The California Verbal Learning Test and structural brain imaging were administered to 57 subjects with schizophrenia spectrum disorders and 94 controls in a general population sample. Cases had lower semantic cluster scores. Poorer verbal memory strategies were associated with longer duration of illness and heavier use of antipsychotic medication. After controlling for duration of illness, sex, and total gray matter, poorer verbal memory was associated with lower gray matter volume in the cingulate cortex, juxtapositional lobule, right superior temporal gyrus, and precuneus. After controlling for use of antipsychotic medication, there was an association between higher serial clustering and smaller anterior cingulate gyrus and larger intracalcarine cortex.

We study the predictive power and associations of several psychopathology and temperament scales with respect to schizophrenia and other psychotic disorders. Measures of psychopathology (Physical and Social Anhedonia Scales, Perceptual Aberration Scale, Hypomanic Personality Scale, Bipolar II Scale, and Schizoidia Scale) and the Temperament and Character Inventory were included in the 31-year follow-up of the prospective Northern Finland 1966 birth cohort (N = 4926). The Perceptual Aberration Scale was the best scale for concurrent validity in psychoses, and also the best psychopathology scale in terms of discriminant validity. Participants scoring high in hypomanic personality were at the highest risk for developing psychosis during the 11-year follow-up. Harm avoidance was a dominant temperament dimension in individuals with psychosis compared with participants without psychiatric diagnoses. These scales are useful as vulnerability markers in studying psychoses.

Background: Duration of untreated psychosis (DUP) has been linked with poor prognosis and changes in the brain structure in schizophrenia at least at the beginning of the disease, but it is still unknown whether DUP relates to brain morphometry in the longer term. Our aim was to analyze the relation between DUP and the brain structure in schizophrenia in the general population, after several years of illness., Methods: Brains of subjects with psychosis from the Northern Finland 1966 Birth Cohort (NFBC 1966) were scanned with MRI during 1999-2001 after an 11-year follow-up. DUP was assessed from medical records and regressed against global and local tissue density measurements. The brain morphometric and the DUP information were available for 46 subjects with DSM-III-R schizophrenia., Results: The DUP did not correlate with volumes of the total gray or white matter or the cerebrospinal fluid. The length of DUP associated positively with reduced densities of the right limbic area and the right hippocampus., Conclusions: Long DUP was slightly associated with reductions of gray matter densities in the limbic area and especially the hippocampus after several years follow-up, supporting the hypothesis that, compared to short DUP, long DUP might be a marker of different disease trajectories including subtle morphometric changes., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: Maternal depression is relatively common during pregnancy. The authors examined whether maternal antenatal depressed mood increased the risk of schizophrenia and other psychoses among offspring with and without a familial history of psychosis., Method: In the Northern Finland 1966 birth cohort, mothers of 12,058 children were asked at mid-gestation at the antenatal clinic if they felt depressed. The offspring were followed for over 30 years, and subsequent schizophrenia and other psychoses were detected using the Finnish Hospital Discharge Register, which was also used for identifying psychosis in the parents. Familial risk for psychosis was considered as a genetic risk factor and mothers' depressed mood as an environmental or genetic risk factor., Results: The risk for schizophrenia was higher in the offspring with both maternal depressed mood during pregnancy and parental psychosis (OR=9.4, 95% CI=4.2-20.9 adjusted for sex and perinatal complications) than in those with a depressed mother but without parental psychosis (OR=1.0, 95% CI=0.6-1.8) or those without maternal depression and with a psychotic parent (OR=2.6, 95% CI=1.2-5.4). The reference group was birth cohort members without maternal antenatal depression and without parental psychosis., Conclusions: Maternal depressed mood during pregnancy per se is unlikely to increase the risk for schizophrenia in the offspring but may affect subjects with a family history for psychosis. This finding could be an example of a gene-environment or possibly a gene-gene interaction in the development of schizophrenia. Mothers' antenatal depression may act as additive factor for subjects vulnerable to schizophrenia.

We studied occupational status of persons with schizophrenic psychoses by age 34 in a longitudinal population-based cohort and predicted which demographic and illness-related factors could support the patients to maintain their occupational capacity. Subjects of the Northern Finland 1966 Birth Cohort with the diagnosis of DSM-III-R schizophrenic psychoses (n=113) by the year 1997 were followed until the end of year 2000. Various illness and socio-demographic factors at the time of onset of illness were used as predictors. At the end of the follow-up time 50 (44%) of patients were not pensioned and 22 (20%) were also working at least half of the time during year 2000. After adjusting for gender, being unemployed at onset, educational level and proportion of time spent in psychiatric hospitals, those who were married or cohabiting at the time of onset of illness were less often on pension than those who were single (OR 6.51; 95% CI 1.83-23.12). Thus, nearly half of the patients with schizophrenic psychoses were not pensioned after an average 10 years follow-up. Based on our findings, those who were single at time of their onset of illness probably need most support to retain their contacts to work life.

We report patterns of hospitalization in schizophrenic psychoses by age 34 in a longitudinal population-based cohort. We test the predictive ability of various demographic and illness-related variables on patterns of hospitalization, with a special focus on the length of the first psychiatric hospitalization. All living subjects of the Northern Finland 1966 Birth Cohort with DSM-III-R schizophrenia (n=88) and other schizophrenia spectrum cases (n=27) by the year 1997 in the Finnish Hospital Discharge Register were followed for an average of 10.5 years. Measures of psychiatric hospitalization included time to re-hospitalization (as continuous and as re-hospitalization within 2 years) and the number of hospital episodes. Length of the first hospitalization, other illness-related and various socio-demographic predictors were used to predict hospitalization patterns. After adjusting for gender, age at first admission and number of hospital days a short (1-14 days) first hospitalization (reference >30 days; adjusted odds ratio 6.39; 95% CI 2.00-20.41) and familial risk of psychosis (OR 3.36; 1.09-10.39) predicted re-hospitalization within 2 years. A short first hospitalization also predicted frequent psychiatric admissions defined as the first three admissions within 3 years (OR 13.77; 3.92-48.36). A short first hospitalization was linked to increased risk of re-hospitalizations. Although short hospitalization is recommended by several guidelines, there may be a group of patients with schizophrenic psychoses in which too short a hospitalization may lead to inadequate treatment response.

Structural brain differences have been reported in many studies with schizophrenia, but few have involved a general population birth cohort. We investigated differences in volume, shape and laterality of hippocampus and amygdala in patients with schizophrenia, all psychoses and comparison subjects within a large general birth cohort sample, and explored effects of family history of psychosis, perinatal risk and age-at-onset of illness. All subjects with psychosis from the Northern Finland 1966 birth cohort were invited to a survey including MRI scan of the brain, conducted in 1999-2001. Comparison subjects not known to have psychosis were randomly selected from the same cohort. Volumes of hippocampus and amygdala were measured in 56 subjects with DSM-III-R schizophrenia, 26 patients with other psychoses and 104 comparison subjects. Small hippocampal volume reductions in schizophrenia (2%) and all psychoses (3%) were not significant when adjusted for total brain volume. The shape of hippocampus in schizophrenia did not differ significantly from comparison subjects. Right hippocampus and amygdala were significantly larger than the left in all groups. Mean amygdala volume in schizophrenia or all psychoses did not differ from comparison subjects. Patients with family history of psychosis had larger hippocampus than patients without. Neither perinatal risk nor age-at-onset of illness had any effect on hippocampal or amygdala volumes. Small hippocampal volume reduction in schizophrenia and all psychoses was not disproportionate to reduced whole brain volume in this population-based sample. Perinatal events that have been suggested as of etiological importance in structural pathology of psychosis had no effect.

Childhood precursors of schizophrenia include multiple abnormalities of development. Continuities between early and subsequent deviance are poorly characterised. We studied associations among premorbid developmental deviance using data at ages 1 year (learning to stand, walk, and speak, attainment of bladder and bowel control) and 16 years (success at school). Generalised linear modelling was used to examine differential linear associations and trends across adult psychiatric diagnoses. In babies who, as adults, suffered schizophrenia or any psychosis, those who learned to stand latest were also more likely to perform poorly at school in both motor and theoretical domains at age 16 when compared with earlier learners. The effect was independent of genetic and perinatal factors. We conclude that the early developmental deviation in the first year of life is associated with lower school performance at age 16. Developmental continuity among children who develop psychoses was stronger than among normal controls and those hospitalized for nonpsychotic psychiatric disorder. These findings are in line with the hypothesis that a neural diathesis is present during postnatal brain development before schizophrenia. This supports the longitudinal dimension and life span models of schizophrenia.

Subtle developmental (motor, emotional, cognitive, and behavioral) abnormalities are often present in apparently healthy individuals who later develop psychosis, suggesting that some aspects of causation are established before overt psychosis. These impairments may restrict information processing and social achievements years before manifesting psychosis. The main known risk factors in the development of schizophrenic psychosis are genetic factors, pregnancy and delivery complications, slow neuromotor development, and deviant cognitive and academic performance. However, their effect size and predictive power are small. Developmental precursors are not necessarily specific to schizophrenia, but also common to other psychotic disorders. No powerful risk factor, premorbid sign, or risk indicator has been identified that is useful for prediction of psychoses in the general population.

Background: Shortly after phenothiazines were introduced, they were found to elevate serum triglyceride and total cholesterol levels. During the past decade, an increasing body of literature has also documented this effect in atypical antipsychotics. Previous studies of antipsychotic-associated hyperlipidemias are based on clinical samples, mostly from case series. We studied the prevalence of hyperlipidemia in subjects who did and did not take antipsychotic medication in a prospective, general population-based birth cohort., Method: The study sample consisted of 5654 members of the unselected Northern Finland 1966 Birth Cohort who participated in the 1997-1998 clinical examination at 31 years of age. Blood samples were taken after an overnight fast, and serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels were determined. Health habits and other possible correlates for hyperlipidemia were assessed using a questionnaire. The sample was analyzed in 4 categories according to use of antipsychotic medication: (1) atypical, (2) typical, (3) atypical and typical (for the 3 antipsychotic categories, total N = 45), and (4) no antipsychotic medication (N = 5609). Nonparametric tests and multiple logistic regression analysis were used to measure the effect of antipsychotics on serum lipids., Results: High lipid levels were found in persons treated with both atypical and typical medication (mean total cholesterol = 233 mg/dL, mean triglycerides = 163 mg/dL). Mean total cholesterol and triglycerides were also high in subjects who used only typical medication (215 mg/dL and 148 mg/dL, respectively). The prevalence of hypercholesterolemia, high LDL cholesterol, and hypertriglyceridemia was high in persons using antipsychotic medication (31.1%, 20.0%, and 22.2%, respectively) compared with persons not using such medication (12.2%, 10.2%, and 7.0%, respectively). After we adjusted for risk factors for hyperlipidemia (sex, diet, waist circumference, physical exercise, smoking, and alcohol consumption), the results of logistic regression analysis showed that in persons treated with antipsychotic medication the risk of hypercholesterolemia was 2.8 (95% CI = 1.4 to 5.6); of hypertriglyceridemia, 2.3 (95% CI = 1.0 to 5.4); and of high LDL cholesterol, 1.6 (95% CI = 0.7 to 3.5)., Conclusion: Lipid levels in subjects who used both atypical and typical medication and those who used only typical medication were high even in young age. As these persons are at special risk of hyperlipidemia, their lipid levels should be regularly monitored, and a cholesterol-lowering diet, as well as medication, should be considered. The results indicate an elevated risk of hyperlipidemia in persons using antipsychotic medication independent of the other risk factors assessed.

Antipsychotic medication is the mainstay of treatment for functional psychotic illnesses. However, for some patients weight gain and the disturbances in blood-lipid levels and glucose balance associated with their use are significant disadvantages, and pose health risks that may affect prognosis. A substantial body of evidence suggests that weight gain is at least partly related to the blocking effects of antipsychotic medication on serotonin- and histamine-mediated neurotransmission. The disadvantages associated with weight gain can be reduced by an appropriate choice of antipsychotic and avoidance of polypharmacy, by regular monitoring of the patient's weight, and, if necessary, by the patient's participation in a dieting programme.

Objective The association between long-term antipsychotic treatment and changes in brain structure in schizophrenia is unclear. Our aim was to conduct a systematic review and a meta-analysis on long-term antipsychotic effects on brain structures in schizophrenia focusing on studies with at least 2 years of follow-up between MRI scans. Design Studies were systematically collected using 4 databases, and we also contacted authors for unpublished data. We calculated correlations between antipsychotic dose and/or type and brain volumetric changes and used random effect meta-analysis to study correlations by brain area. Results Thirty-one publications from 16 samples fulfilled our inclusion criteria. In meta-analysis, higher antipsychotic exposure associated statistically significantly with parietal lobe decrease (studies, n = 4; r = −.14, p = .013) and with basal ganglia increase ( n = 4; r = .10, p = .044). Most of the reported correlations in the original studies were statistically nonsignificant. There were no clear differences between typical and atypical exposure and brain volume change. The studies were often small and highly heterogeneous in their methods and seldom focused on antipsychotic medication and brain changes as the main subject. Conclusions Antipsychotic medication may associate with brain structure changes. More long-term follow-up studies taking into account illness severity measures are needed to make definitive conclusions. [ABSTRACT FROM AUTHOR]

Abstract: Negative symptoms are a major scientific and therapeutic challenge in schizophrenia. We report the occurrence and predicting factors of negative symptoms at two time points in a population-based birth cohort. The negative symptoms of subjects with Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R) schizophrenia (n =46) were scrutinized at the first hospitalization due to psychosis from hospital records (first-episode psychosis) and with an interview approximately 10 years later (follow-up phase). Developmental and sociodemographic predictors of negative symptoms in first-episode psychosis, follow-up phase and at both measurements were analysed. Forty-one percent of the subjects had negative symptoms at the first episode, 39% in the follow-up phase, and in 24% the symptoms persisted at both measurements. Smoking at the age of 14, definite psychosocial stressor and not being married predicted more negative symptoms whereas good school performance and using less alcohol at age 14 predicted fewer persistent negative symptoms. These findings are new. However, we were not able to identify any major premorbid phenotype or endophenotype predicting negative symptoms which support the view that negative symptoms might mainly be a specific part of the illness. [Copyright &y& Elsevier]