Risk Of Non-affective Psychosis Research Articles

The prevalence of non-affective psychosis in refugee populations: A systematic review.

As we face the largest refugee crisis since World War Two, research is increasingly examining the impact of forced displacement. The risk of non-affective psychosis in refugees is evidenced to be significantly greater than non-refugees, and the role of pre-, peri- and post-migratory trauma and dissociation is increasingly implicated. To determine the prevalence of non-affective psychosis in refugee populations. PRISMA guidelines were followed. Three key databases (PubMed, PsychINFO and Web of Science), Google scholar and study references were searched. The full-text of 62 studies were screened and 23 studies were eligible for inclusion. A narrative synthesis was undertaken and the Quality Assessment Tool for Quantitative Studies was used to assess methodological quality. (PROSPERO registration CRD42019152170). The results were widely heterogeneous. The combined weighted average prevalence of non-affective psychosis in refugee populations was 0.9%. Psychosis prevalence for individual psychotic symptoms was 28.4%; 0.5% for schizophrenia; 1.0% for psychosis; 0.6% for mixed psychotic disorders and 2.9% for psychotic episodes. Variations in examined populations, diagnostic and prevalence classifications, and study designs and methodologies likely contributed to heterogeneity across the data. The findings highlight a greater need to provide more specialist mental health services and trauma-focused interventions, as well as transculturally sensitive assessment and treatment to address refugee vulnerability to psychosis. Future research should examine psychosis prevalence longitudinally and in refugees-only, address methodological bias and further examine the role of trauma and dissociation in refugee psychosis prevalence.

Doxycycline exposure during adolescence and future risk of non-affective psychosis and bipolar disorder: a total population cohort study

Doxycycline has been hypothesized to prevent development of severe mental illness (SMI) through the suppression of microglia, especially if administered during the intense synaptic pruning period of adolescence. However, results from register studies on potential benefits differ considerably. The aim of the present study was to determine whether doxycycline exposure during adolescence is associated with reduced SMI risk, and to investigate if a direct and specific causality is plausible. This is a Swedish national population register-based cohort study of all individuals born from 1993 to 1997, followed from the age of 13 until end of study at the end of 2016. The primary exposure was cumulative doxycycline prescription ≥3000 mg and outcomes were first diagnosis of non-affective psychosis (F20–F29) and first diagnosis of bipolar disorder (F30–F31). Causal effects were explored through Cox regressions with relevant covariates and secondary analyses of multilevel exposure and comparison to other antibiotics. We found no association between doxycycline exposure and risk of subsequent non-affective psychosis (adjusted hazard ratio (HR) 1.15, 95% CI 0.73–1.81, p = 0.541) and an increased risk of subsequent bipolar disorder (adjusted HR 1.95, 95% CI 1.49–2.55, p < 0.001). We do not believe the association between doxycycline and bipolar disorder is causal as similar associations were observed for other common antibiotics.

A Multilevel Mediational Model of the Association of Neighborhood Deprivation With Risk for Nonaffective Psychosis

A Multilevel Mediational Model of the Association of Neighborhood Deprivation With Risk for Nonaffective Psychosis

Association of neighbourhood migrant density and risk of non-affective psychosis: a national, longitudinal cohort study

SummaryBackgroundElevated risk of psychotic disorders in migrant groups is a public mental health priority. We investigated whether living in areas of high own-region migrant density was associated with reduced risk of psychotic disorders among migrants and their children, and whether generation status, probable visible minority status, or region-of-origin affected this relationship.MethodsWe used the Swedish registers to identify migrants and their children born between Jan 1, 1982, and Dec 31, 1996, and living in Sweden on or after their 15th birthday. We tracked all included participants from age 15 years or date of migration until emigration, death, or study end (Dec 31, 2016). The outcome was an ICD-10 diagnosis of non-affective psychosis (F20–29). We calculated own-region and generation-specific own-region density within the 9208 small areas for market statistics neighbourhoods in Sweden, and estimated the relationship between density and diagnosis of non-affective psychotic disorders using multilevel Cox proportional hazards models, adjusting for individual confounders (generation status, age, sex, calendar year, lone dwelling, and time since migration [migrants only]), family confounders (family income, family unemployment, and social welfare), and neighbourhood confounders (deprivation index, population density, and proportion of lone dwellings), and using the Akaike information criterion (AIC) to compare model fit.FindingsOf 468 223 individuals included in the final cohort, 4582 (1·0%) had non-affective psychotic disorder. Lower own-region migrant density was associated with increased risk of psychotic disorders among migrants (hazard ratio [HR] 1·05, 95% CI 1·02–1·07 per 5% decrease) and children of migrants (1·03, 1·01–1·06), after adjustment. These effects were stronger for probable visible minority migrants (1·07, 1·04–1·11), including migrants from Asia (1·42, 1·15–1·76) and sub-Saharan Africa (1·28, 1·15–1·44), but not migrants from probable non-visible minority backgrounds (0·99, 0·94–1·04). Among migrants, adding generation status to the measure of own-region density provided a better fit to the data than overall own-region migrant density (AIC 36 103 vs 36 106, respectively), with a 5% decrease in generation-specific migrant density corresponding to a HR of 1·07 (1·04–1·11).InterpretationMigrant density was associated with non-affective psychosis risk in migrants and their children. Stronger protective effects of migrant density were found for probable visible minority migrants and migrants from Asia and sub-Saharan Africa. For migrants, this risk intersected with generation status. Together, these results suggest that this health inequality is socially constructed.FundingWellcome Trust, Royal Society, Mental Health Research UK, University College London, National Institute for Health Research, Swedish Research Council, and FORTE.

Family networks during migration and risk of non-affective psychosis: A population-based cohort study

ObjectiveThe determinants of increased psychosis risk among immigrants remain unclear. Given ethnic density may be protective, we investigated whether the presence of immediate family, or “family networks”, at time of immigration was associated with risk of non-affective psychosis. MethodsWe followed a cohort of migrants (n = 838,717) to Sweden, born 1968–1997, from their 14th birthday, or earliest immigration thereafter, until diagnosis of non-affective psychosis (ICD-9/ICD-10), emigration, death, or 2011. Using record linkage, we measured family network as the presence of adult first-degree relatives immigrating with the cohort participant or already residing in Sweden. We used Cox proportional hazards regression to examine whether risk varied between those migrating with family, migrating to join family, or migrating alone. ResultsMigrating with immediate family was associated with increased psychosis risk amongst males compared to males who did not migrate with family (adjusted Hazard Ratio [aHR]: 1.16, 95% CI: 1.00–1.34). Migrating with family did not increase risk among females (aHR: 0.91, 95% CI: 0.78–1.07); similar observations were observed for males who immigrated to join family (aHR: 1.35, 95% CI: 1.21–1.51). In contrast, females who migrated alone were at increased risk compared to females who did not migrate alone (aHR: 1.31, 95% CI: 1.11–1.54). ConclusionFamily networks at the time of immigration were associated with differential patterns of non-affective psychotic disorders for males and females. These results suggest sex-specific differences in the perceived role of family networks during the migration process.

Body mass index trajectories in childhood and adolescence - Risk for non-affective psychosis

BackgroundUnderweight in early adulthood increases risk for schizophrenia, but the effect of early childhood underweight on psychosis risk is not well known. MethodsWe studied whether underweight or overweight in childhood and adolescence increases risk for non-affective psychosis or other psychiatric disorders in a population-based cohort study ‘Cardiovascular Risk in Young Finns’. Body mass index (BMI) trajectories were recorded in the years 1980, 1983 and 1986 (in 3–18 years of age), before the first hospitalization due to a psychiatric disorder. BMI was categorized as underweight, normal weight or overweight, using the BMI classification for children and adolescents. We formed DSM-IV based diagnostic groups of non-affective psychosis (n = 69, including a schizophrenia subgroup, n = 41) and affective disorders (i.e. mood and anxiety disorders, n = 112) based on the Care Register for Health Care. Groups were compared with subjects with no psychiatric diagnoses (n = 3310). Sex, age, low birthweight and mother's mental disorders were included in the analyses. ResultsUnderweight, but not overweight, independently predicted later development of non-affective psychosis. The risk of psychosis was over two-fold (relative risk (RR) [95% CI] 2.31 [1.2–4.4]) and of schizophrenia nearly 2.5-fold (RR 2.44 [1.03–5.8]) after underweight in childhood/adolescence. Underweight or overweight in childhood and adolescence was not associated with mood or anxiety disorders. ConclusionsThese results support the hypothesis of non-affective psychosis as a neurodevelopmental disorder with somatic manifestations throughout childhood and adolescence.

Snus use and risk of schizophrenia and non-affective psychosis

BackgroundRecent studies suggest a possible causal role for smoking in schizophrenia and psychosis. Most studies have focused on cigarette smoking, the most common form of tobacco use, but other forms of tobacco exist, including smokeless products such as Swedish snuff (or “snus”). MethodsWe explored whether snus use is associated with schizophrenia and non-affective psychotic illness in a large Swedish registry data set. The majority of participants were aged 18 or 19 at the time of assessment. ResultsWe observed a positive association between snus use and odds of schizophrenia in all analyses, but the magnitude of the association was small and the confidence interval wide, consistent with no association (fully adjusted HR 1.03, 95% 0.70–1.54). A similar pattern was observed for non-affective psychosis, but the magnitude of the association was somewhat greater and the confidence intervals narrower, so that these analyses provided stronger statistical evidence for this association (fully adjusted HR 1.22, 95% CI, 1.00–1.48). ConclusionsOur results therefore provide modest evidence for an association between snus use and risk for non-affective psychosis. This is consistent with emerging evidence from a range of studies and methodologies that tobacco use may be a risk factor for psychotic illness. However, our results provide some evidence against the hypothesis that it is the burnt products of cigarette smoke that are psychotogenic.

Smoking and schizophrenia in population cohorts of Swedish women and men: a prospective co-relative control study.

The purpose of this study was to clarify the causes of the smoking-schizophrenia association. Using Cox proportional hazard and co-relative control models, the authors predicted future risk for a diagnosis of schizophrenia or nonaffective psychosis from the smoking status of 1,413,849 women and 233,879 men from, respectively, the Swedish birth and conscript registries. Smoking was assessed in women at a mean age of 27 and in men at a mean age of 18. The mean age at end of follow-up was 46 for women and 26 for men. Hazard ratios for first-onset schizophrenia were elevated both for light smoking (2.21 [95% CI=1.90-2.56] for women and 2.15 [95% CI=1.25-3.44] for men) and heavy smoking (3.45 [95% CI=2.95-4.03] for women and 3.80 [95% CI=1.19-6.60] for men). These associations did not decline when schizophrenia onsets 3-5 years after smoking assessment were censored. When age, socioeconomic status, and drug abuse were controlled for, hazard ratios declined only modestly in both samples. Women who smoked into late pregnancy had a much higher risk for schizophrenia than those who quit early. Hazard ratios predicting nonaffective psychosis in the general population, in cousins, in half siblings, and in full siblings discordant for heavy smoking were, respectively, 2.67, 2.71, 2.54, and 2.18. A model utilizing all relative pairs predicted a hazard ratio of 1.69 (95% CI=1.17-2.44) for nonaffective psychosis in the heavy-smoking member of discordant monozygotic twin pairs. Smoking prospectively predicts risk for schizophrenia. This association does not arise from smoking onset during a schizophrenic prodrome and demonstrates a clear dose-response relationship. While little of this association is explained by epidemiological confounders, a portion arises from common familial/genetic risk factors. However, in full siblings and especially monozygotic twins discordant for smoking, risk for nonaffective psychosis is appreciably higher in the smoking member. These results can help in evaluating the plausibility of various etiological hypotheses for the smoking-schizophrenia association.

Neonatal levels of acute phase proteins and later risk of non-affective psychosis.

Mounting evidence suggests that immune disturbances in early life may be implicated in the etiology of non-affective psychoses. Our aim was to assess the levels of neonatal acute phase proteins (APPs), central to innate immune function as well as central nervous system development, in neonatal dried blood spots and their association with later risk of non-affective psychoses. This case-control study included 196 individuals with a verified register-based diagnosis of non-affective psychosis and 502 controls matched on age, sex and hospital of birth. Concentrations of nine different APPs were measured in eluates from dried blood spots using a bead-based multiplex assay. Odds ratios (OR) for non-affective psychoses were calculated for log2-transformed (continuous) as well as tertiles of APP concentrations. In continuous analysis, higher concentrations of two APPs, tissue plasminogen activator (tPA; OR: 0.90, 95% confidence interval (CI): 0.85–0.96) and serum amyloid P (SAP; OR: 0.88, 95% CI: 0.78–0.99) were protective in terms of risk of non-affective psychosis. These relationships were not affected by the addition of covariates relevant to maternal health, pregnancy and delivery to the model. Tertile analysis confirmed a protective relationship for higher levels of tPA and SAP, as well as for procalcitonin (highest tertile OR: 0.54, 95% CI:0.32–0.91). Our results suggest that persons who develop non-affective psychoses have lower levels of certain APPs at the time of birth. These differences may render individuals more susceptible to infectious diseases or cause deficiencies in pathways critical for neurodevelopment.

Age at Migration and Risk of Schizophrenia Among Immigrants in Denmark: A 25-Year Incidence Study

Back to table of contents Previous article Next article Communications and UpdatesFull AccessAge at Migration and Risk of Schizophrenia Among Immigrants in Denmark: A 25-Year Incidence StudyCarsten Bøcker Pedersen, Dr.Med.Sc., and Elizabeth Cantor-Graae, Ph.D.Carsten Bøcker PedersenAarhus, DenmarkSearch for more papers by this author, Dr.Med.Sc., and Elizabeth Cantor-GraaeLund, SwedenSearch for more papers by this author, Ph.D.Published Online:1 Oct 2012https://doi.org/10.1176/appi.ajp.2012.12050614AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: In the December 2011 issue, Veling et al. (1) report on a study from the Netherlands that the risk of psychotic disorders in immigrants decreased with age at the time of immigration. The authors suggest that early life is an important risk period for the development of psychosis in immigrants. We sought to replicate their findings using data from the Danish nationwide population-based registers.Data on persons who were born between 1971 and 1995 and who resided in Denmark by the age of 15 were followed for the development of schizophrenia (ICD-10:F20, ICD-8:295) from age 15 until December 31, 2010, using survival analysis techniques. Immigrants were identified as persons born abroad; developmental level of country of origin was categorized as “developing” or “developed” (2). Age at migration was identified as age at the time of first permanent residence in Denmark.During the study period, 809 immigrants from developing countries, 248 immigrants from developed countries, and 8,767 Danes developed schizophrenia. After adjusting for age, sex, and calendar year, immigrants from developing countries had a 2.34-fold greater risk for schizophrenia (95% confidence interval [CI]=2.17–2.51); immigrants from developed countries had a 1.90-fold greater risk (95% CI=1.67–2.15).The incidence rate ratio of schizophrenia, by country of origin as well as by age at the time of immigration to Denmark, compared with Danish-born individuals, is depicted graphically in Figure 1. For example, individuals from developed countries who immigrated to Denmark before their second birthday had a 1.66-fold significantly greater risk of schizophrenia (95% CI=1.30–2.07), and individuals from developing countries who immigrated to Denmark before their second birthday had a 2.16-fold significantly greater risk of schizophrenia (95% CI=1.88–2.48). When including age at migration as a trend in the model, the incidence rate ratio of schizophrenia increased by 1.02 (95% CI=1.00–1.05) for every 1-year increase in the age at migration from developed countries and increased by 1.01 (95% CI=1.00–1.03) for every 1-year increase in the age at migration from developing countries.FIGURE 1. Adjusted Relative Risks Associated With Immigrants’ Origin and Age at Immigration to Denmarkaa The solid line represents immigrants to Denmark from developing countries, and the punctuated line represents immigrants from developed countries. Estimates of relative risks were adjusted for age, sex, and calendar year.Although the majority of immigrants in our sample originated from developing countries, subdividing the developmental status of country of origin yielded no differences in the impact of age at immigration. Thus, the differences observed between the two studies are not due to any differential impact of age at migration in relation to degree of “Westernization” of the country of origin, a factor that Veling et al. (1) suggest may be important. We found no evidence that risk of schizophrenia decreases with age at the time of immigration to Denmark. Our Danish study investigated the potential effect of age at immigration before the 15th birthday, while the Veling et al. Dutch study investigated the potential effect up until approximately age 30. However, because the greatest impact in the Dutch study was observed in individuals migrating early in life, this cannot explain the differences in the observed results.Aarhus, DenmarkLund, SwedenThe authors report no financial relationships with commercial interests.Funded by the Stanley Medical Research Institute, Bethesda, Md. The funders had no involvement in any aspect of the study.The authors thank Fuller Torrey for helpful comments.References1 Veling W, Hoek HW, Selten JP, Susser E: Age at migration and future risk of psychotic disorders among immigrants in the Netherlands: a 7-year incidence study. Am J Psychiatry 2011; 168:1278–1285Link, Google Scholar2 United Nations Conference on Trade and Development: UNCTAD Handbook of Statistics, 2002. Geneva, United Nations, 2002Google Scholar FiguresReferencesCited byDetailsCited byEffects of country of origin and wave of immigration on prevalence of schizophrenia among first and second-generation immigrants: A 30-year retrospective studySchizophrenia Research, Vol. 243Early childhood adversity and non-affective psychosis: a study of refugees and international adoptees in Sweden2 September 2021 | Psychological MedicineMigration and Psychosis18 September 2021Age at migration and the risk of psychotic disorders: a systematic review and meta‐analysis20 January 2020 | Acta Psychiatrica Scandinavica, Vol. 141, No. 5Association of neighbourhood migrant density and risk of non-affective psychosis: a national, longitudinal cohort studyThe Lancet Psychiatry, Vol. 7, No. 4Cognitive functions associated with developing prefrontal cortex during adolescence and developmental neuropsychiatric disordersNeurobiology of Disease, Vol. 131The association of psychosocial risk factors for mental health with a brain marker altered by inflammation: A translocator protein (TSPO) PET imaging studyBrain, Behavior, and Immunity, Vol. 80Psychological Medicine, Vol. 49, No. 4Psychological Medicine, Vol. 49, No. 14Epidemiology and Psychiatric Sciences, Vol. 28, No. 2Recent Advances in the Genetics of Schizophrenia30 May 2018 | Complex Psychiatry, Vol. 4, No. 1Schizophrenia Bulletin, Vol. 43, No. 6Schizophrenia Bulletin, Vol. 41, No. 2Schizophrenia Bulletin, Vol. 39, No. 6 Volume 169Issue 10 October 2012Pages 1117-1118 Metrics PDF download History Accepted 1 July 2012 Published online 1 October 2012 Published in print 1 October 2012

Maternal antibodies to dietary antigens and risk of non-affective psychosis in offspring

Maternal antibodies to dietary antigens and risk of non-affective psychosis in offspring

Maternal Antibodies to Dietary Antigens and Risk for Nonaffective Psychosis in Offspring

The authors analyzed archival dried blood spots obtained from newborns to assess whether levels of immunoglobulin G (IgG) directed at dietary antigens were associated with a later diagnosis of a nonaffective psychotic disorder. The study population consisted of individuals born in Sweden between 1975 and 1985 with verified register-based diagnoses of nonaffective psychoses made between 1987 and 2003 and comparison subjects matched on sex, date of birth, birth hospital, and municipality. A total of 211 case subjects and 553 comparison subjects consented to participate in the study. Data on factors associated with maternal status, pregnancy, and delivery were extracted from the Swedish Medical Birth Register. Levels of IgG directed at gliadin (a component of gluten) and casein (a milk protein) were analyzed in eluates from dried blood spots by enzyme-linked immunosorbent assay. Odds ratios were calculated for levels of IgG directed at gliadin or casein for nonaffective psychosis. Levels of anti-gliadin IgG (but not anti-casein IgG) above the 90th percentile of levels observed among comparison subjects were associated with nonaffective psychosis (odds ratio=1.7, 95% CI=1.1-2.8). This association was not confounded by differences in maternal age, immigrant status, or mode of delivery. Similarly, gestational age at birth, ponderal index, and birth weight were not related to maternal levels of anti-gliadin IgG. High levels of anti-gliadin IgG in the maternal circulation are associated with an elevated risk for the development of a nonaffective psychosis in offspring. Research is needed to identify the mechanisms underlying this association in order to develop preventive strategies.

Individuals, Schools, and Neighborhood

Incidence of schizophrenia and other nonaffective psychoses is greater in urban than rural areas, but the reason is unclear. Few studies have examined whether both individual and neighborhood characteristics can explain this association. Furthermore, as has been shown for ethnicity, the effect of individual characteristics may depend on neighborhood context. To examine (1) whether individual, school, or area characteristics are associated with psychosis and can explain the association with urbanicity and (2) whether effects of individual characteristics on risk of psychosis vary according to school context (reflecting both peer group and neighborhood effects). Multilevel longitudinal study of all individuals born in Sweden in 1972 and 1977. Diagnoses were identified through linkage with the Swedish National Patient Register until December 31, 2003. Population-based. A total of 203 829 individuals with data at individual, school, municipality, and county levels. Any nonaffective psychosis, including schizophrenia (881 subjects; 0.43% cumulative incidence). For the study of interactions, the outcome was any psychosis (1944 subjects; 0.95% cumulative incidence). Almost all the variance in risk of nonaffective psychosis was explained by individual-level rather than higher-level variation. An association between urbanicity and nonaffective psychosis was explained by higher-level characteristics, primarily school-level social fragmentation. We observed cross-level interactions between individual- and school-level markers of ethnicity, social fragmentation, and deprivation on risk of developing any psychotic disorder, all with qualitative patterns of interaction. The association between urbanicity and psychosis appears to be a reflection of increased social fragmentation present within cities. The qualitative interactions observed are consistent with a hypothesis that certain characteristics that define individuals as being different from most other people in their local environment may increase risk of psychosis. These findings have potentially important implications for understanding the etiology of psychotic disorders and for informing social policy.

Unemployment, social isolation, achievement-expectation mismatch and psychosis: findings from the AESOP Study.

In this study, we aimed to establish: (1) whether social isolation modifies the effect of unemployment on first episode psychosis and duration of untreated psychosis (DUP); and (2) whether the gap between high employment expectations and perceived poor employment achievement is associated with first-episode psychosis; and (3) whether the relationship of this achievement-expectation gap and first-episode psychosis is strongest in the African-Caribbean population. All patients with a first episode of psychosis presenting to specialist mental health services within tightly defined catchment areas in south-east London and Nottingham over a 2-year period were included in the study. A random sample of healthy participants living within the same catchment areas was also recruited. Data were collected on socio-demographic and clinical characteristics, DUP, social contacts, and perceived levels of employment achievement and expectation. Analysis was conducted on data of 546 participants (224 cases, 322 controls) from the AESOP study. The relationship between unemployment and risk of non-affective psychosis was moderated by social contacts (unemployed/low social contacts, OR 7.52, 95% CI 2.97-19.08; unemployed/medium social contacts, OR 3.27, 95% CI 1.66-6.47; unemployed/high social contacts, OR 1.36, 95% CI 0.47-3.93). Unemployed patients experienced a longer DUP when having reported lower levels of social contacts. Participants whose employment achievement was lower than their expectations were more likely to be cases than those in whom achievement matched or exceeded expectations (adjusted OR 1.84, 95% CI 1.13-3.02). This applied equally to both African-Caribbean and White British participants (the Mantel-Haenszel test for homogeneity of odds ratios, chi (2 )= 0.96, P = 0.33). This study suggests that unemployment, social isolation, employment achievement and expectations are important environmental factors associated with risk of psychosis. More attention needs to be focused on interactions between environmental factors as well as subjective experience of those factors in future research on the aetiology of psychosis.

Parental age and risk for schizophrenia: A nested case-control study

Background: Premorbid neurocognitive, neuromotor, and behavioral function tends to be disturbed in schizophrenia. We previously demonstrated that a birth cohort clinically and serologically documented with prenatal rubella evidenced a marked increase in risk of nonaffective psychosis. In our study, we examined whether rubella-exposed subjects destined to develop schizophrenia and other schizophrenia spectrum disorders (SSD), compared with exposed control subjects, had greater impairment in several premorbid functions.Methods: Subjects were interviewed using a direct, comprehensive research assessment and diagnosed by consensus. We compared the degree of IQ decline, as well as premorbid neuromotor and behavioral dysfunction, between rubella-exposed subjects who developed schizophrenia spectrum psychosis (SSP) and exposed control subjects from the cohort. We also compared the gestational timing of rubella infection between the cases and control subjects.Results: This rubella-exposed birth cohort evidenced a markedly increased risk of SSD (20.4% or 11/53). Rubella-exposed SSP cases, compared with rubella-exposed control subjects, demonstrated a decline in IQ from childhood to adolescence, and increased premorbid neuromotor and behavioral abnormalities. Moreover, it appears that early gestational rubella exposure may represent a period of increased vulnerability for SSD.Conclusions: These findings link a known prenatal exposure, a deviant neurodevelopmental trajectory in childhood and adolescence, and SSP in adulthood within the same individuals.

Prenatal rubella, premorbid abnormalities, and adult schizophrenia

Background: Premorbid neurocognitive, neuromotor, and behavioral function tends to be disturbed in schizophrenia. We previously demonstrated that a birth cohort clinically and serologically documented with prenatal rubella evidenced a marked increase in risk of nonaffective psychosis. In our study, we examined whether rubella-exposed subjects destined to develop schizophrenia and other schizophrenia spectrum disorders (SSD), compared with exposed control subjects, had greater impairment in several premorbid functions. Methods: Subjects were interviewed using a direct, comprehensive research assessment and diagnosed by consensus. We compared the degree of IQ decline, as well as premorbid neuromotor and behavioral dysfunction, between rubella-exposed subjects who developed schizophrenia spectrum psychosis (SSP) and exposed control subjects from the cohort. We also compared the gestational timing of rubella infection between the cases and control subjects. Results: This rubella-exposed birth cohort evidenced a markedly increased risk of SSD (20.4% or 11/53). Rubella-exposed SSP cases, compared with rubella-exposed control subjects, demonstrated a decline in IQ from childhood to adolescence, and increased premorbid neuromotor and behavioral abnormalities. Moreover, it appears that early gestational rubella exposure may represent a period of increased vulnerability for SSD. Conclusions: These findings link a known prenatal exposure, a deviant neurodevelopmental trajectory in childhood and adolescence, and SSP in adulthood within the same individuals.

Prenatal exposure to the 1957 influenza pandemic and non-affective psychosis in The Netherlands

Second-trimester exposure to the 1957 A2 influenza pandemic is a controversial risk factor for schizophrenia. Two earlier studies of the Dutch psychiatric registry failed to find an increased risk for exposed subjects, but diagnostic misclassification within the spectrum of non-affective psychoses has not yet been ruled out as an explanation for the negative findings. Using an enlarged data-set we examined not only whether second-trimester exposure to the epidemic is associated with an increased risk of schizophrenia (ICD:295), but also whether it is associated with an increased risk of paranoid states (ICD:297) or other non-organic psychoses (ICD:298). In this retrospective cohort study the risks of the above-mentioned disorders were compared for those exposed and unexposed to A2 influenza during the second trimester of fetal life. The risks for the exposed subjects were not significantly higher than the risks for the unexposed. The power of the study to detect a significant increase in the risk of schizophrenia was sufficient. If the relative risk of a lifetime hospitalization for schizophrenia for second-trimester exposed subjects (born January–April 1958) is assumed to be 1.3, the power of the study would be 0.97 (alpha=0.05; one-tailed testing). If the relative risk for subjects born five months after the peak of the epidemic (mid-February to mid-March 1958) is assumed to be 1.88, as reported for England and Wales, the power of the study would be close to 1.00. This was the largest study of its kind in Europe: 275 subjects were born in the period January–April 1958 and had a lifetime hospitalization for schizophrenia. This study indicates that there is no relation between second-trimester exposure to the 1957 influenza pandemic and risk of non-affective psychosis in the Dutch population. It adds to a growing body of work which does not support an association between maternal influenza and schizophrenia.