School success in childhood and subsequent prodromal symptoms and psychoses in the Northern Finland Birth Cohort 1986.

BACKGROUND: Low IQ is a risk factor for psychosis, but the effect of high IQ is more controversial. The aim was to explore the association of childhood school success with prodromal symptoms in adolescence and psychoses in adulthood. METHODS: In the general population-based Northern Finland Birth Cohort 1986 (n = 8 229), we studied the relationship between teacher-assessed learning deficits, special talents and general school success at age 8 years and both prodromal symptoms (PROD-screen) at age 15-16 years and the occurrence of psychoses by age 30 years. RESULTS: More prodromal symptoms were experienced by those talented in oral presentation [boys: adjusted odds ratio (OR) 1.49; 95% confidence interval 1.14-1.96; girls: 1.23; 1.00-1.52] or drawing (boys: 1.44; 1.10-1.87). Conversely, being talented in athletics decreased the probability of psychotic-like symptoms (boys: OR 0.72; 0.58-0.90). School success below average predicted less prodromal symptoms with boys (OR 0.68; 0.48-0.97), whereas above-average success predicted more prodromal symptoms with girls (OR 1.22; 1.03-1.44). The occurrence of psychoses was not affected. Learning deficits did not associate with prodromal symptoms or psychoses. CONCLUSIONS: Learning deficits in childhood did not increase the risk of prodromal symptoms in adolescence or later psychosis in this large birth cohort. Learning deficits are not always associated with increased risk of psychosis, which might be due to, e.g. special support given in schools. The higher prevalence of prodromal symptoms in talented children may reflect a different kind of relationship of school success with prodromal symptoms compared to full psychoses.

Vitamin D status and correlates of low vitamin D in schizophrenia, other psychoses and non-psychotic depression - The Northern Finland Birth Cohort 1966 study.

There is limited knowledge available on the association of vitamin D with psychiatric disorders in young adults. We aimed to investigate vitamin D levels and associating factors in schizophrenia, other psychoses and non-psychotic depression. We studied 4,987 participants from the Northern Finland Birth Cohort 1966 (31 years) with available serum 25-hydroxyvitamin D [25(OH)D] measurements. The final sample was divided into four groups: schizophrenia (n = 40), other psychoses (n = 24), non-psychotic depression (n = 264) and control (n = 4659). To account for the influence of environmental and technical covariates, we generated a vitamin D score variable with correction for season, sex, batch effect and latitude. We further examined how vitamin D levels correlate with anthropometric, lifestyle, socioeconomic and psychiatric measures. Neither serum 25(OH)D concentration nor vitamin D score differed between schizophrenia, other psychoses, non-psychotic depression and control group. The prevalence of vitamin D deficiency was 3.2%, insufficiency 25.5%, and sufficiency 71.3%. Low vitamin D score correlated with regular smoking in the group with schizophrenia. No difference was observed in other psychiatric conditions. We did not find any difference in vitamin D status between schizophrenia, psychoses, non-psychotic depression and control groups, but future studies are warranted to elucidate the role of vitamin D in psychiatric conditions.

Association between family history of mental disorders and outcome in psychotic disorders.

We investigated the association of family history of mental disorders, especially psychosis, with occupational and clinical outcome in psychotic disorders in a longitudinal population-based cohort. The Northern Finland Birth Cohort 1986 (n = 9432) was used to gather the data. In total 189 individuals with psychosis were identified by age of 28. The outcome was assessed by using register information regarding occupational activity, disability pension and hospital treatments due to psychiatric cause. Parental psychosis and any psychiatric disorder were used as predictors of outcome. The results showed that presence of any parental psychiatric disorder was associated with higher number of days spent at hospital and higher number of hospitalizations in psychotic disorders, but was not associated with occupational outcome or disability pension. The presence of parental psychosis was not associated with outcome. These findings suggest that the presence of any psychiatric disorder among parents may increase the risk of poorer outcome in psychoses in terms of need of hospitalisations. Based on this study the presence of parental psychosis is not associated with outcome, but the result should be interpreted with caution due to the small sample size and conflict with the results of earlier studies.

Smokin' hot: adolescent smoking and the risk of psychosis.

OBJECTIVE: Daily smoking has been associated with a greater risk of psychosis. However, we are still lacking studies to adjust for baseline psychotic experiences and other substance use. We examined associations between daily smoking and psychosis risk in a 15-year follow-up while accounting for these covariates in a prospective sample (N = 6081) from the Northern Finland Birth Cohort 1986. METHODS: Self-report questionnaires on psychotic experiences (PROD-screen), tobacco smoking and other substance use were completed when the cohort members were 15-16 years old. Tobacco smoking was categorized into three groups (non-smokers, 1-9 cigarettes and ≥10 cigarettes/day). Psychosis diagnoses were obtained from national registers until the age of 30 years. RESULTS: Subjects in heaviest smoking category were at increased risk of subsequent psychosis (unadjusted HR = 3.15; 95% CI 1.94-5.13). When adjusted for baseline psychotic experiences the association persisted (HR = 2.87; 1.76-4.68) and remained significant even after adjustments for multiple known risk factors such as cannabis use, frequent alcohol use, other illicit substance use, parental substance abuse, and psychosis. Furthermore, number of smoked cigarettes increased psychosis risk in a dose-response manner (adjusted OR = 1.05; 1.01-1.08). CONCLUSION: Heavy tobacco smoking in adolescence was associated with a greater risk for psychosis even after adjustment for confounders.

Epidemiology of psychotic depression - systematic review and meta-analysis.

Large amount of data have been published on non-psychotic depression (NPD), schizophrenia (SZ), and bipolar disorder, while psychotic depression (PD) as an own entity has received much smaller attention. We performed a systematic review and meta-analyses on epidemiology, especially incidence and prevalence, risk factors, and outcomes of PD. A systematic search to identify potentially relevant studies was conducted using four electronic databases and a manual search. The search identified 1764 unique potentially relevant articles, the final study included 99 articles. We found that the lifetime prevalence of PD varies between 0.35% and 1%, with higher rates in older age. Onset age of PD was earlier than that of NPD in younger samples, but later in older samples. There were no differences in gender distribution in PD v. NPD, but higher proportion of females was found in PD than in SZ or in psychotic bipolar disorder (PBD). Risk factors have rarely been studied, the main finding being that family history of psychosis and bipolar disorder increases the risk of PD. Outcomes of PD were mostly worse when compared with NPD, but better compared with SZ and schizoaffective disorder. The outcome compared with PBD was relatively similar, and somewhat varied depending on the measure of the outcome. Based on this review, the amount of research on PD is far from that of NPD, SZ, and bipolar disorder. Based on our findings, PD seems distinguishable from related disorders and needs more scientific attention.

Lifetime use of psychiatric medications and cognition at 43years of age in schizophrenia in the Northern Finland Birth Cohort 1966.

BACKGROUND: Higher lifetime antipsychotic exposure has been associated with poorer cognition in schizophrenia. The cognitive effects of adjunctive psychiatric medications and lifetime trends of antipsychotic use remain largely unclear. We aimed to study how lifetime and current benzodiazepine and antidepressant medications, lifetime trends of antipsychotic use and antipsychotic polypharmacy are associated with cognitive performance in midlife schizophrenia. METHODS: Sixty participants with DSM-IV schizophrenia from the Northern Finland Birth Cohort 1966 were examined at 43years of age with an extensive cognitive test battery. Cumulative lifetime and current use of psychiatric medications were collected from medical records and interviews. The associations between medication and principal component analysis-based cognitive composite score were analysed using linear regression. RESULTS: Lifetime cumulative DDD years of benzodiazepine and antidepressant medications were not significantly associated with global cognition. Being without antipsychotic medication (for minimum 11months) before the cognitive examination was associated with better cognitive performance (P=0.007) and higher lifetime cumulative DDD years of antipsychotics with poorer cognition (P=0.020), when adjusted for gender, onset age and lifetime hospital treatment days. Other lifetime trends of antipsychotic use, such as a long antipsychotic-free period earlier in the treatment history, and antipsychotic polypharmacy, were not significantly associated with cognition. CONCLUSIONS: Based on these naturalistic data, low exposure to adjunctive benzodiazepine and antidepressant medications does not seem to affect cognition nor explain the possible negative effects of high dose long-term antipsychotic medication on cognition in schizophrenia.

A comparison of the cumulative incidence and early risk factors for psychotic disorder in young adults in the Northern Finland Birth Cohorts 1966 and 1986.

AIMS: Few studies have compared time trends for the incidence of psychosis. To date, the results have been inconsistent, showing a decline, an increase or no significant change. As far as we know, no studies explored changes in prevalence of early risk factors. The aim of this study was to investigate differences in early risk factors and cumulative incidences of psychosis by type of psychosis in two comparable birth cohorts. METHODS: The Northern Finland Birth cohorts (NFBCs) 1966 (N = 12 058) and 1986 (N = 9432) are prospective general population-based cohorts with the children followed since mother's mid-pregnancy. The data for psychoses, i.e. schizophrenia (narrow, spectrum), bipolar disorder with psychotic features, major depressive episode with psychotic features, brief psychosis and other psychoses (ICD 8-10) were collected from nationwide registers including both inpatients and outpatients. The data on early risk factors including sex and place of birth of the offspring, parental age and psychosis, maternal education at birth were prospectively collected from the population registers. The follow-up reached until the age of 27 years. RESULTS: An increase in the cumulative incidence of all psychoses was seen (1.01% in NFBC 1966 v. 1.90% in NFBC 1986; p < 0.001), which was due to an increase in diagnosed affective and other psychoses. Earlier onset of cases and relatively more psychoses in women were observed in the NFBC 1986. Changes in prevalence of potential early risk factors were identified, but only parental psychosis was a significant predictor in both cohorts (hazard ratios ≥3.0; 95% CI 1.86-4.88). The difference in psychosis incidence was not dependent on changes in prevalence of studied early risk factors. CONCLUSIONS: Surprisingly, increase in the cumulative incidence of psychosis and also changes in the types of psychoses were found between two birth cohorts 20 years apart. The observed differences could be due to real changes in incidence or they can be attributable to changes in diagnostic practices, or to early psychosis detection and treatment.

Long-term antipsychotic use and its association with outcomes in schizophrenia - the Northern Finland Birth Cohort 1966.

BACKGROUND: Due to the paucity of previous studies, we wanted to elucidate the pharmacoepidemiology of antipsychotics in schizophrenia in a general population sample, and the association between long-term antipsychotic use and outcomes. METHODS: The sample included 53 schizophrenia subjects from the Northern Finland Birth Cohort 1966 with at least ten years of follow-up (mean 18.6 years since illness onset). Data on lifetime medication and outcomes (remission, Clinical Global Impression [CGI], Social and Occupational Functioning Assessment Scale [SOFAS]) were collected from medical records, interviews, and national registers. RESULTS: During the first two years 22 (42%), between two to five years 17 (32%), and between five to ten years 14 (26%) subjects had used antipsychotics less than half of the time. Drug-free periods became rarer during the follow-up. The mean lifetime daily dose of antipsychotics was 319mg in chlorpromazine equivalents. A high lifetime average and cumulative dose and antipsychotic polypharmacy were associated with a poorer outcome in all measures, whereas having no drug-free periods was associated with a better SOFAS score and a low proportion of time on antipsychotics with a better CGI score. CONCLUSIONS: In our population-based sample, the use of antipsychotics increased during the first five years of illness and was relatively stable after that. Our results suggest that both low dose and proportion of use, and having no drug-free periods, are associated with better outcomes, which concords with current treatment recommendations and algorithms. High long-term doses and polypharmacy may relate to poor outcomes.

Brain structural changes in women and men during midlife.

Brain development during childhood and adolescence differs between boys and girls. Structural changes continue during adulthood and old age, particularly in terms of brain volume reductions that accelerate beyond age 35 years. We investigated whether brain structural change in mid-life differs between men and women. 43 men and 28 women from the Northern Finland 1966 Birth Cohort underwent MRI brain scans at age 33-35 (SD=0.67) and then again at age 42-44 (SD=0.41). We examined sex differences in total percentage brain volume change (PBVC) and regional brain change with FSL SIENA software. Women showed significant PBVC reduction compared with men between the ages of 33-35 and 42-44 years (Mean=-3.21% in men, Mean=-4.03% in women, F (1, 68)=6.37, p<0.05). In regional analyses, women exhibited greater brain reduction than men in widespread areas. After controlling for total percent brain volume change, men show greater relative regional brain reduction than women in bilateral precentral gyri, bilateral paracingulate gyri, and bilateral supplementary motor cortices. The results indicate sex differences in brain changes in mid-life. Women have more total brain reduction, and more reduction on the outer brain surface than men, whereas men exhibit more brain reduction on the mid-line surface than women after co-varying for total brain volume loss. These changes could contribute to sex differences in midlife behaviour and health.

Interaction between parental psychosis and early motor development and the risk of schizophrenia in a general population birth cohort.

BACKGROUND: Delayed motor development in infancy and family history of psychosis are both associated with increased risk of schizophrenia, but their interaction is largely unstudied. AIM: To investigate the association of the age of achieving motor milestones and parental psychosis and their interaction in respect to risk of schizophrenia. METHODS: We used data from the general population-based prospective Northern Finland Birth Cohort 1966 (n=10,283). Developmental information of the cohort members was gathered during regular visits to Finnish child welfare clinics. Several registers were used to determine the diagnosis of schizophrenia among the cohort members and psychosis among the parents. Altogether 152 (1.5%) individuals had schizophrenia by the age of 46 years, with 23 (15.1%) of them having a parent with psychosis. Cox regression analysis was used in analyses. RESULTS: Parental psychosis was associated (P<0.05) with later achievement of holding the head up, grabbing an object, and walking without support. In the parental psychosis group, the risk for schizophrenia was increased if holding the head up (hazard ratio [HR]: 2.46; degrees of freedom [df]=1; 95% confidence interval [95% CI]: 1.07-5.66) and touching the thumb with the index finger (HR: 1.84; df=1; 95% CI: 1.11-3.06) was later. In the group without parental psychosis, a delay in the following milestones increased the risk of schizophrenia: standing without support and walking without support. Parental psychosis had an interaction with delayed touching thumb with index finger (HR: 1.87; df=1; 95% CI: 1.08-3.25) when risk of schizophrenia was investigated. CONCLUSIONS: Parental psychosis was associated with achieving motor milestones later in infancy, particularly the milestones that appear early in a child's life. Parental psychosis and touching the thumb with the index finger had a significant interaction on risk of schizophrenia. Genetic risk for psychosis may interact with delayed development to raise future risk of schizophrenia, or delayed development may be a marker of other risk processes that interact with genetic liability to cause later schizophrenia.

Use of antiepileptic or benzodiazepine medication and suicidal ideation--The Northern Finland Birth Cohort 1966.

Both antiepileptic drugs (AEDs) and benzodiazepines (BZDs) have previously been associated with an increased risk of suicidality. Our aim was to study the association between the use of conventional AEDs and BZDs and suicidal ideation in a large population-based cohort. Information on the medications used in the Northern Finland Birth Cohort 1966 was collected from the subjects at the age of 31 years, using a postal questionnaire (N=8211). The presence of suicidal ideation and other symptoms of depression and anxiety was assessed via the Hopkins Symptom Checklist - 25 questionnaire. The associations between medications and suicidal ideation were studied in different diagnostic groups and adjusted for symptoms of depression and anxiety. No difference was observed in suicidal ideation between AED users (n=54) and nonusers (n=8157). Subjects using BZDs (n=147) had greater suicidal ideation compared with nonusers (n=8064). Antiepileptic drug and benzodiazepine users more often exhibited other depression and anxiety symptoms. After adjustment for these symptoms, both AED and BZD users had less suicidal ideation compared with nonusers. In conclusion, in this population-based cohort, neither the use of AEDs nor that of BZDs was found to be associated with increased suicidal ideation when the symptoms of depression and anxiety were taken into account.

Brain morphometry of individuals with schizophrenia with and without antipsychotic medication ­ The Northern Finland Birth Cohort 1966 Study.

BACKGROUND: In schizophrenia, brain morphometric changes may be associated with antipsychotic medication. Only limited data is available concerning individuals with schizophrenia without antipsychotic medication. We aimed to study the associations of: use versus no use of antipsychotic medication; length of continuous time without antipsychotic medication; cumulative dose of lifetime antipsychotic medication; and type of antipsychotic medication; with brain morphometry in schizophrenia after an average of 10 years of illness. METHODS: Data of 63 individuals with schizophrenia (mean duration of illness 10.4 years) from the Northern Finland Birth Cohort 1966 were gathered by interview and from hospital and outpatient records. Structural MRI data at age 34 years were acquired and grey matter volume maps with voxel-based morphometry were analyzed using FSL tools. RESULTS: Of the individuals studied, 15 (24%) had taken no antipsychotic medication during the previous year. Individuals with antipsychotic medication had lower total grey matter (TGM) volume compared with non-medicated subjects, although this association was not statistically significant (Cohen's d=-0.51, P=0.078). Time without antipsychotic medication associated with increased TGM (P=0.028). Longer time without antipsychotic medication associated with increased regional volume in right precentral gyrus and right middle frontal gyrus. There were no associations between cumulative dose of lifetime antipsychotic medication or type of antipsychotic medication and brain morphometry. CONCLUSIONS: Unlike some previous investigators, we found no association between cumulative dose of lifetime antipsychotic medication and brain morphological changes in this population-based sample. However, longer continuous time without antipsychotic medication preceding the MRI scan associated with increased gray matter volume.

Neurocognition as a predictor of outcome in schizophrenia in the Northern Finland Birth Cohort 1966.

The purpose of this study was to study neurocognitive performance as a predictor of outcomes in midlife schizophrenia. There is a lack of studies with unselected samples and a long follow-up. The study is based on the prospective, unselected population-based Northern Finland Birth Cohort 1966. The study includes 43 individuals with schizophrenia and 73 controls, whose neurocognitive performance was assessed twice, at 34 and 43 years. At both time points we used identical neurocognitive tests to assess verbal and visual memory and executive functions. Our main aim was to analyse neurocognitive performance at 34 years as a predictor of clinical, vocational and global outcomes at 43 years. Additionally, the analysis addressed cross-sectional associations between cognitive performance and clinical, vocational and global measures at 43 years. The assessment of outcomes was performed in the schizophrenia group only. In the longitudinal analysis poorer visual memory predicted poorer vocational outcome and poorer long-term verbal memory predicted poorer global outcome. In the cross-sectional analysis poorer visual memory and lower composite score of neurocognition were associated with poorer global outcome. No individual neurocognitive test or the composite score of these predicted remission. These data indicate that neurocognition, especially memory function, is an important determinant of long-term functional outcome in midlife schizophrenia.

Family history of psychosis and social, occupational and global outcome in schizophrenia: a meta-analysis.

OBJECTIVE: We aimed to investigate associations between family history of psychosis and long-term occupational, social and global (i.e. combined occupational, social and clinical) outcome in schizophrenia. METHOD: A systematic search to identify potentially relevant studies was conducted using seven electronic databases and a manual search of literature. Only observational studies with a follow-up period of at least 2 years were included. RESULTS: The search identified 4081 unique potentially relevant articles, of which 14 met our inclusion criteria. The presence of family history of psychosis was associated with poor occupational and global outcome (n=3; r=0.17; P=0.008, n=11; r=0.13; P=0.002, respectively). CONCLUSION: This was the first systematic review on the effects of family history of psychosis on occupational and social outcome in schizophrenia. Based on the review, the presence of family history of psychosis has a relatively small but statistically significant association with long-term occupational and global outcome in patients with schizophrenia.

The onset and offset of psychosis--and what happens in between--a commentary on 'Reappraising the long-term course and outcome of psychotic disorders: the AESOP-10 Study' by Morgan et al. (2014).

As one would expect for a heterogeneous syndrome like schizophrenia, at the individual level the course of symptoms and disability vary widely. Mindful that the definition of recovery/remission varies widely between studies, a recent systematic review and meta-analysis reported that the proportion of those with schizophrenia who recover on both symptom and functional outcome is modest (approximately 14%). A 10-year follow-up of the English multicentre AESOP incidence study provides more 'fine-grained' insights into the time course of symptom fluctuation for schizophrenia and other psychotic disorders. We highlight selected findings from the new study and speculate on the role of different outcome domains for future study (e.g., symptom, occupational/functional, cognition, physical health, patient-nominated outcomes). Because recovery is a multifaceted process, we need to develop a panel of practical and operationalizable criteria for remission and recovery.

Difficulty in making contact with others and social withdrawal as early signs of psychosis in adolescents--the Northern Finland Birth Cohort 1986.

AIM: Social withdrawal is among the first signs of the prodromal state of psychosis seen in clinical samples. The aim of this prospective study was to find out whether difficulty in making contact with others and social withdrawal precede first episode psychosis in the young general population. METHODS: The members of the Northern Finland Birth Cohort 1986 (n=6274) completed the PROD-screen questionnaire in 2001-2002. The Finnish Hospital Discharge Register was used to detect both new psychotic and non-psychotic disorders requiring hospitalisation during 2003-2008. RESULTS: Twenty-three subjects developed psychosis and 89 developed a non-psychotic mental disorder requiring hospitalisation during the follow-up. Of those who developed psychosis, 35% had reported difficulty or uncertainty in making contact with others and 30% social withdrawal in adolescence. In hospitalised non-psychotic disorder, the corresponding precentages were 10 and 13% and in the control group without hospital-treated mental disorder 9 and 11%. The differences between psychotic and non-psychotic hospitalised subjects (P<0.01) as well as controls (P<0.001) were statistically significant regarding difficulty or uncertainty in making contact with others. CONCLUSIONS: In this general population-based sample self-reported difficulty or uncertainty in making contact with others in adolescence preceded psychosis specifically compared to hospitalised non-psychotic mental disorders and controls.

Associations between brain morphology and outcome in schizophrenia in a general population sample.

OBJECTIVE: To analyse associations between brain morphology and longitudinal and cross-sectional measures of outcomes in schizophrenia in a general population sample. METHODS: The sample was the Northern Finland 1966 Birth Cohort. In 1999-2001, structural brain MRI and measures of clinical and functional outcomes were analysed for 54 individuals with schizophrenia around the age of 34. Sex, total grey matter, duration of illness and the use of antipsychotic medication were used as covariates. RESULTS: After controlling for multiple covariates, increased density of the left limbic area was associated with less hospitalisations and increased total white matter volume with being in remission. Higher density of left frontal grey matter was associated with not being on a disability pension and higher density of the left frontal lobe and left limbic area were related to better functioning. Higher density of the left limbic area was associated with better longitudinal course of illness. CONCLUSIONS: This study, based on unselected general population data, long follow-up and an extensive database, confirms findings of previous studies, that morphological abnormalities in several brain structures are associated with outcome. The difference in brain morphology in patients with good and poor outcomes may reflect separable aetiologies and developmental trajectories in schizophrenia.

Response initiation in young adults at risk for psychosis in the Northern Finland 1986 Birth Cohort.

INTRODUCTION: This is one of the very few studies to investigate the specific executive function/processing speed component of response initiation in subjects at familial risk (FR) for psychosis, and the first such study in subjects at clinical risk (CR) for psychosis. METHODS: Participants (N = 177) were members of the general population-based Northern Finland 1986 Birth Cohort in the following four groups: FR for psychosis (n = 62), CR for psychosis (n = 21), psychosis (n = 25) and control subjects (n = 69). The response initiation of these groups was compared in three different tests: Semantic fluency, Stockings of Cambridge and Spatial working memory. RESULTS: The two risk groups did not differ significantly from control group, but differed from, and outperformed the psychosis group in semantic fluency response initiation. CONCLUSIONS: Response initiation deficits were not evident in a non-help seeking psychosis high-risk sample.

Interaction between parental psychosis and risk factors during pregnancy and birth for schizophrenia - the Northern Finland 1966 Birth Cohort study.

Our aim was to investigate the association between parental psychosis and potential risk factors for schizophrenia and their interaction. We evaluated whether the factors during pregnancy and birth have a different effect among subjects with and without a history of parental psychosis and whether parental psychosis may even explain their effects on the risk of schizophrenia. The sample comprised 10,526 individuals from the Northern Finland 1966 Birth Cohort. A total of 150 (1.4%) cohort members had schizophrenia by the age of 44 years, of them 18 (12.0%) had a parent with a history of psychosis. In non-psychotic cohort members, this figure was 495 (4.8%). In the parental psychosis group, significant early biological risk factors for schizophrenia included high birth weight (hazard ratio, HR 11.4; 95% confidence interval 3.3-39.7) and length (HR 4.1; 1.3-12.5), high birth weight in relation to gestational age (HR 3.2; 1.1-9.0), and high maternal age (HR 2.6.; 1.0-6.7). High birth weight and length and high maternal education had a significant interaction with parental psychosis. The presence of any biological risk factor increased the risk of schizophrenia significantly only among the parental psychosis group (HR 4.0; 1.5-10.5), whereas the presence of any psychosocial risk factor had no interaction with parental psychosis. Parental psychosis can act as an effect modifier on early risk factors for schizophrenia. Evaluation of the mechanisms behind the risk factors should, therefore, include consideration of the parental history of psychosis.