Prenatal tobacco use and the risk of mood disorders in offspring: a systematic review and meta-analysis

Purpose

It is plausible that offspring born to mothers using tobacco during pregnancy may have increased risk of mood disorders (depression and bipolar disorders); however, mixed results have been reported. We conducted a systematic review and meta-analysis to investigate the magnitude and consistency of associations reported between prenatal tobacco use and mood disorders in offspring.

Methods

We systematically searched EMBASE, SCOPUS, PubMed and Psych-INFO for studies on mood disorders and prenatal tobacco use. Methodological quality of studies was assessed with the revised Newcastle–Ottawa Scale. We estimated pooled relative risk (RR) with inverse variance weighted random-effects meta-analysis. We performed leave-one-out analyses, and stratified analyses by a subgroup (depression and bipolar disorder). Potential publication bias was assessed by inspection of the funnel plot and Egger’s test for regression asymmetry. This study protocol was prospectively registered in PROSPERO (CRD42017060037).

Results

Eight cohort and two case–control studies were included in the final meta-analysis. We found an increased pooled relative risk of mood disorders in offspring exposed to maternal prenatal tobacco use RRs 1.43 (95% CI 1.27–1.60) compared to no prenatal tobacco use. Similarly, the pooled relative risks of bipolar and depressive disorders in offspring were 1.44, (95% CI 1.15–1.80) and 1.44, (95% CI 1.21–1.71), respectively. Moreover, the pooled estimated risk of mood disorders was not significantly attenuated in the studies that reported sibling comparison results [RR = 1.21 (95% CI 1.04–1.41)].

Conclusion

Taken together, there was strong evidence for a small (RR < 2) association between prenatal tobacco use and mood disorders in offspring.

     

Risk of affective disorders following prenatal exposure to severe life events: a Danish population-based cohort study

Objective

To examine the effect of prenatal exposure to severe life events on risk of affective disorders in the offspring.

Methods

In a cohort of 1.1 million Danish births from May 1978 until December 1997, mothers were considered exposed if one (or more) of their close relatives died or was diagnosed with serious illness up to 6 months before conception or during pregnancy. Offspring were followed up from their 10th birthday until their death, migration, onset of affective disorder or 31 December 2007; hospital admissions were identified by linkage to the Central Psychiatric Register. Log-linear Poisson regression was used for data analysis.

Results

The risk of affective disorders was increased in male offspring whose mothers were exposed to severe life events during the second trimester (adjusted RR 1.55 [95% CI 1.05-2.28]). There was an increased risk of male offspring affective disorders in relation to maternal exposure to death of a relative in the second trimester (adjusted RR 1.74 [95% CI 1.06-2.84]) or serious illness in a relative before pregnancy (adjusted RR 1.44 [95% CI 1.02-2.05]). There was no evidence for an association between prenatal exposure to severe life events and risk of female offspring affective disorders.

Conclusions

Our population-based study suggests that prenatal maternal exposure to severe life events may increase the risk of affective disorders in male offspring. These findings are consistent with studies of populations exposed to famine and earthquake disasters which indicate that prenatal environment may influence the neurodevelopment of the unborn child.     

Risk of Mental Illness in Offspring of Parents With Schizophrenia,Bipolar Disorder,and Major Depressive Disorder: A Meta-Analysis of Family High-Risk Studies

Objective: Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) are at an increased risk of developing mental illness. We aimed to quantify the risk of mental disorders in offspring and determine whether increased risk extends beyond the disorder present in the parent. Method: Meta-analyses of absolute and relative rates of mental disorders in offspring of parents with schizophrenia, bipolar disorder, or depression in family high-risk studies published by December 2012. Results: We included 33 studies with 3863 offspring of parents with SMI and 3158 control offspring. Offspring of parents with SMI had a 32% probability of developing SMI (95% CI: 24%–42%) by adulthood (age >20). This risk was more than twice that of control offspring (risk ratio [RR] 2.52; 95% CI 2.08–3.06, P < .001). High-risk offspring had a significantly increased rate of the disorder present in the parent (RR = 3.59; 95% CI: 2.57–5.02, P < .001) and of other types of SMI (RR = 1.92; 95% CI: 1.48–2.49, P < .001). The risk of mood disorders was significantly increased among offspring of parents with schizophrenia (RR = 1.62; 95% CI: 1.02–2.58; P = .042). The risk of schizophrenia was significantly increased in offspring of parents with bipolar disorder (RR = 6.42; 95% CI: 2.20–18.78, P < .001) but not among offspring of parents with depression (RR = 1.71; 95% CI: 0.19–15.16, P = .631). Conclusions: Offspring of parents with SMI are at increased risk for a range of psychiatric disorders and one third of them may develop a SMI by early adulthood.Key words: schizophrenia, bipolar disorder, depression, offspring, meta-analysis     

Association between mood stabilizers and hypothyroidism in patients with bipolar disorders: a nested,matched case‐control study

Gau C‐S, Chang C‐J, Tsai F‐J, Chao P‐F, Gau SS‐F. Association between mood stabilizers and hypothyroidism in patients with bipolar disorders: a nested, matched case‐control study.
Bipolar Disord 2010: 12: 253–263. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: This study investigated whether lithium, carbamazepine, and valproate increased the risk for hypothyroidism using Taiwan’s National Health Insurance Dataset. Methods: The sample included 557 bipolar disorder patients with incident hypothyroidism first diagnosed between 1998 and 2004, and 2,228 sex‐, age‐, and index date‐matched bipolar disorder patients without hypothyroidism from 1996–2004. We compared the use of lithium, carbamazepine, and valproate before the onset of hypothyroidism between the two groups using a conditional logistical regression model. Results: Compared with patients who had never used any of the three mood stabilizers, patients were more likely to have hypothyroidism if they only used carbamazepine [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.07–2.65]; or comedication of lithium and valproate (OR = 2.40; 95% CI: 1.70–3.40), lithium and carbamazepine (OR = 1.52; 95% CI: 1.10–2.08), and three mood stabilizers (OR = 2.34; 95% CI: 1.68–3.25). There was a dose‐response relationship between the number of mood stabilizers and risk for hypothyroidism (OR = 1.34, 95% CI: 1.21–1.49) and a significant interaction between lithium and valproate on the risk for hypothyroidism (p = 0.020). Conclusions: Our findings indicate that lithium, carbamazepine, and valproate may increase the risk for hypothyroidism, particularly if combined, and suggest regular monitoring of thyroid function and monotherapy of mood stabilizers for treating patients with bipolar disorders.     

Maternal prepregnant body mass and risk of schizophrenia in adult offspring

This study examined the relation between maternal prepregnant body mass index (BMI) and development of schizophrenia and schizophrenia spectrum disorders in adult offspring from the Prenatal Determinants of Schizophrenia Study. The study drew on a previously studied cohort of births occurring between 1959 and 1967 to women enrolled in a prepaid health plan. Computerized treatment registries were used to identify possible cases of schizophrenia and spectrum disorders in adult offspring belonging to the health plan from 1981 to 1997. Diagnostic interviews and medical record reviews resulted in diagnosis of 63 cases of schizophrenia and spectrum disorders; these cases and 6,570 unrelated and unaffected cohort members whose mothers also had prepregnancy measures of BMI comprised the sample for analyses. High (> or = 30.0), compared with average (20.0-26.9), maternal prepregnant BMI (kg/m2) was significantly associated with schizophrenia and spectrum disorders in the adult offspring (relative risk [RR] = 2.9; 95% confidence interval [CI] 1.3-6.6), independently of maternal age, parity, race, education, or cigarette smoking during pregnancy. Low (< or = 19.9) maternal BMI was not associated with schizophrenia and spectrum disorders (RR = 1.2; 95% CI 0.64-2.2). Future studies of this cohort will examine factors that may help explain the relationship of high maternal prepregnant BMI with schizophrenia, including nutritional and metabolic factors, toxic exposures, and obstetrical complications.     

Maternal smoking during pregnancy and offspring psychiatric disorder: a longitudinal birth cohort study

Background

There is evidence that prenatal stress and smoking during pregnancy both independently increase the risk of offspring psychopathology. Here we examine whether increased levels of self-reported stress is associated with increased smoking in a population of pregnant women, and whether prenatal smoking is associated with offspring psychiatric diagnoses independent of prenatal stress exposure.

Method

Using a longitudinal birth cohort, we used ordered logistic regressions to examine associations between maternal stress and smoking during pregnancy. We then used logistic regression analyses to examine associations between prenatal smoking and later offspring psychiatric disorders.

Results

A dose–response relationship was found between maternally reported stress and smoking during pregnancy. Pregnant women reporting severe stress were more likely to smoke compared to both the moderate stress and no stress groups, and those reporting moderate stress were significantly more likely to smoke compared to the no stress group. Smoking more than 5 cigarettes daily during pregnancy increased the risk of offspring personality disorder (OR 3.08, 95% CI 1.60–5.94) as well as developing any Axis 1 psychiatric disorder, inclusive of mood, anxiety and psychotic disorders (OR 1.45, 95% CI 1.04–2.04). After adjusting for parental psychiatric history and maternal self-reported stress during pregnancy, associations between smoking more than 5 cigarettes daily when pregnancy and offspring personality (OR 2.58 95% CI 1.32–5.06) disorder remained.

Conclusion

Exposure to cigarette smoking during gestation could impact a child’s mental health. Smoking during pregnancy is a prime target for preventative interventions as unlike most other environmental risk factors, it is very amenable to change.

     

Maternal Use of Antiepileptic Drugs and the Risk of Major Congenital Malformations: A Joint European Prospective Study of Human Teratogenesis Associated with Maternal Epilepsy

Summary: Purpose: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and poly-therapy. Methods: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy and for 158 children of unexposed control pregnancies. Results: Overall, when comparing a subgroup of 192 children exposed to AED with 158 children of matched nonepileptic controls, there was an increased risk of major congenital malformations (MCA) in children exposed to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI): 1.2–4.7]. A significant increase in risk was found for children exposed to valproate (VPA) (RR 4.9; 95% CI: 1.6–15.0) or carbamazepine (CBZ) (RR 4.9; 95% CI: 1.3–18.0) in monotherapy. When comparing different AED regimens during all 1,221 pregnancies, risks of MCA were significantly increased for the combination of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4–67.3) and the combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1–57.6). Offspring of mothers using > 1,000 mg VPNday were at a significantly increased risk of MCA, especially neural tube defects, compared to offspring exposed ≥600 mg VPNday (RR 6.8; 95% CI: 1.4–32.7). No difference in risk of MCA was found between the offspring exposed to 601–1,000 mg/day and ≥600 mg/day. Conclusions: This reanalysis shows that VPA is consistently associated with an increased risk of MCA in babies born to mothers with epilepsy. Significant associations were also observed with CBZ. Larger prospective population-based studies are needed to evaluate the risks of many other less frequently prescribed treatment regimens, including newly marketed AEDs.     

Adverse pregnancy outcomes in mothers with affective psychosis

OBJECTIVES: Affective psychosis has its peak incidence during the childbearing years, but little is known about the effects of the illness on pregnancy. We investigated risks of preterm delivery (PTD), low birthweight (LBW), births of infants small for their gestational age (SGA), stillbirth and infant death in births to mothers with affective psychosis using a nested case-control design within a cohort of 1,558,071 singleton births in Sweden during 1983-1997. METHODS: Using prospectively collected data from population registers, we compared the pregnancy outcomes of 5,618 births to women with affective psychosis with the outcomes of 46,246 births to unaffected mothers. RESULTS: Mothers with affective psychosis had elevated risk for giving birth to preterm, small or growth-retarded babies. The risk for stillbirth and infant death during the first year of life was not significantly higher. The risks were greatest in mothers receiving hospital treatment for affective disorder during pregnancy: (i) preterm delivery: odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.71-4.17; (ii) SGA: OR = 2.36; 95% CI = 1.34-4.16; (iii) low birthweight: OR = 2.22; 95% CI = 1.31-3.76; and (iv) stillbirth: OR = 2.19; 95% CI = 0.55-8.76. After adjustment for covariates, particularly smoking, the risks were attenuated but remained significant. CONCLUSIONS: Clinicians should be aware of the increased risk of adverse pregnancy outcomes in women with affective psychosis, some of which may be preventable.     

Parental Infections Before,During, and After Pregnancy as Risk Factors for Mental Disorders in Childhood and Adolescence: A Nationwide Danish Study

Background

Previous studies have shown associations between maternal infections during pregnancy and increased risks of schizophrenia and autism spectrum disorder in the offspring. However, large-scale studies investigating an association between parental infections both during and outside the pregnancy period and the risk of any mental disorder in the child are lacking.

Mood changes during pregnancy and the postpartum period: development of a biopsychosocial model

OBJECTIVE: Women are vulnerable to mood changes during pregnancy and the postpartum period. We set out to empirically test the hypothesis that biological and psychosocial variables interact to result in this vulnerability. METHOD: Using structural equation modeling techniques, we developed an integrative model of perinatal mood changes from clinical, psychosocial, hormone and mood data collected from 150 women in late pregnancy and at 6-weeks postpartum. RESULTS: In the prenatal model, biological variables had no direct effect on depressive symptoms. However, they did act indirectly through their significant effects on psychosocial stressors and symptoms of anxiety. The same model did not fit the postpartum data, suggesting that different causal variables may be implicated in postpartum mood. CONCLUSION: This model demonstrates the importance of considering both biological and psychosocial variables in complex health conditions such as perinatal mood disorders.     

Chernobyl exposure as stressor during pregnancy and behaviour in adolescent offspring

Objective: Research in animals has shown that exposure to stressors during pregnancy is associated with offspring behavioural disorders. We aimed to study the effect of in utero exposure to the Chernobyl disaster in 1986, and maternal anxiety presumably associated with that exposure, on behaviour disorder observed at age 14. Method: Exposed (n = 232) and non‐exposed Finnish twins (n = 572) were compared. A semi‐structured interview was used to assess lifetime symptoms of depression, generalized anxiety disorder, attention deficit hyperactivity disorder, conduct disorder and oppositional defiant disorder symptoms. Results: Adolescents who were exposed from the second trimester in pregnancy onwards, had a 2.32‐fold risk (95% CI: 1.13–4.72) of having lifetime depression symptoms, an increased risk of fulfilling DSM‐III‐R criteria of a major depressive disorder (OR = 2.48, 95% CI: 1.06–5.7), and a 2.01‐fold risk (95% CI: 1.14–3.52) of having attention deficit hyperactivity disorder symptoms. Conclusion: Perturbations in fetal brain development during the second trimester may be associated with the increased prevalence of depressive and attention deficit hyperactivity disorder symptoms.     

Maternal household crowding during pregnancy and the offspring's risk of schizophrenia

BACKGROUND: Animal models of schizophrenia suggest a link between maternal crowding during pregnancy and increased risk of the offspring to develop physiological, developmental, and behavioral abnormalities that are comparable to those observed in schizophrenia. We tested the hypothesis that a similar link is present in humans. METHOD: We investigated whether prenatal exposure to household crowding was associated with the risk of schizophrenia in a sub-cohort of the Jerusalem Perinatal Study (JPS) consisting 11,015 individuals born between 1964 and 1976. During these years mothers participated in face to face interviews in early pregnancy. The prenatal and birth data, including the number of rooms and individuals living in the mothers' household, was cross-linked with the Israel Psychiatric Registry by ministry personnel. RESULTS: 104 schizophrenia cases were identified in the cohort. Offspring who, while in utero, their mother resided in a household with five or more individuals had RR of 1.47 (95% CI: 0.99-2.16, p=0.05) to develop schizophrenia, compared to those whose mother resided with four or fewer individuals. However, when adjusted for paternal age, the RR was reduced to 1.18 (95% CI: 0.76-1.84, p=0.46). The number of rooms in the household and the household crowding during pregnancy did not significantly impact the offspring's risk to develop schizophrenia. CONCLUSION: The link between maternal household crowding during pregnancy and the offspring's risk of schizophrenia was explained primarily by the impact of paternal age. The authors discuss the results in view of findings from animal and human studies.     

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

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

Increased incidence of affective disorders, anxiety disorders, and non-natural mortality in women after breast cancer diagnosis: a nation-wide cohort study in Denmark

OBJECTIVE: To investigate whether breast cancer patients have increased incidence of psychiatric admission with affective disorders, anxiety disorders, or non-natural mortality compared with the general female population. METHOD: Register-linkage between nation-wide registries: The Danish Psychiatric Central Register, The Danish Cancer Registry, and The Danish National Register of Causes of Death. A total of 61 709 women registered with primary invasive breast cancer between 1970 and 1993 were included and 356 023 person-years were accrued. RESULTS: The standardized incidence ratio of first-ever psychiatric admission with affective disorder was 1.49 (95% CI: 1.35-1.63) and with anxiety disorder 1.25 (95% CI: 1.06-1.46). The standardized non-natural mortality ratio during the first year after breast cancer diagnosis was 1.54 (95% CI: 1.27-1.87). All analyses were adjusted for age, calendar period, and place of residence. CONCLUSION: Breast cancer patients have significantly increased incidence of psychiatric admission with affective disorders, anxiety disorders, and non-natural mortality.     

Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

OBJECTIVE: Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug treatment during pregnancy. RESULTS: In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment in the third trimester (odds ratio=2.55 [95% CI=1.21-5.37]), and maternal schizophrenia (odds ratio=11.12 [95% CI=4.60-29.91]). Prenatal exposure to both hypertension and diuretic treatment in the third trimester conferred a 4.01-fold (95% CI=1.41-11.40) elevated risk. CONCLUSIONS: Children of mothers with hypertension in pregnancy plus diuretic treatment in the third trimester were at significantly increased risk of developing schizophrenia. In pregnancies complicated by hypertension, diuretics may interfere with aspects of fetal neurodevelopment and thus increase the vulnerability of offspring to the development of schizophrenia later in life.     

Development of mental disorders one year after exposure to psychosocial stressors; a cohort study in primary care patients with a physical complaint

ABSTRACT: BACKGROUND: Mental disorders, common in primary care, are often associated with physical complaints. While exposure to psychosocial stressors and development or presence of principal mental disorders (i.e. depression, anxiety and somatoform disorders defined as multisomatoforme disorders) is commonly correlated, temporal association remains unproven. The study explores the onset of such disorders after exposure to psychosocial stressors in a cohort of primary care patients with at least one physical symptom. METHOD: The cohort study SODA (SOmatization, Depression and Anxiety) was conducted by 21 private-practice GPs and three fellow physicians in a Swiss academic primary care centre. GPs included patients via randomized daily identifiers. Depression, anxiety or somatoform disorders were identified by the full Patient Health Questionnaire (PHQ), a validated procedure to identify mental disorders based on DSM-IV criteria. The PHQ was also used to investigate exposure to psychosocial stressors (before the index consultation and during follow up) and the onset of principal mental disorders after one year of follow up. RESULTS: From November 2004 to July 2005, 1020 patients were screened for inclusion. 627 were eligible and 482 completed the PHQ one year later and were included in the analysis (77%). At one year, prevalence of principal mental disorders was 30/153 (19.6% CI95% 13.6; 26.8) for those initially exposed to a major psychosocial stressor and 26/329 (7.9% CI95% 5.2; 11.4) for those not. Stronger association exists between psychosocial stressors and depression (RR = 2.4) or anxiety (RR = 3.5) than multisomatoforme disorders (RR = 1.8). Patients who are "bothered a lot" (subjective distress) by a stressor are therefore 2.5 times (CI95% 1.5; 4.0) more likely to experience a mental disorder at one year. A history of psychiatric comorbidities or psychological treatment was not a confounding factor for developing a principal mental disorder after exposure to psychosocial stressors. CONCLUSION: This primary care study shows that patients with physical complaints exposed to psychosocial stressors had a higher risk for developing mental disorders one year later. This temporal association opens the field for further research in preventive care for mental diseases in primary care patients.     

Maternal serum docosahexaenoic acid and schizophrenia spectrum disorders in adult offspring

It is believed that during mid-to-late gestation, docosahexaenoic acid (DHA), an n-3 fatty acid, plays an important role in fetal and infant brain development, including neurocognitive and neuromotor functions. Deficits in several such functions have been associated with schizophrenia. Though sufficient levels of DHA appear to be important in neurodevelopment, elevated maternal DHA levels have also been associated with abnormal reproductive outcomes in both animal models and humans. Our objective was to assess whether a disturbance in maternal DHA levels, measured prospectively during pregnancy, was associated with risk of schizophrenia and other schizophrenia spectrum disorders (SSD) in adult offspring. In order to test the hypothesis that abnormal levels of DHA are associated with SSD, a case-control study nested within a large, population-based birth cohort, born from 1959 through 1967 and followed up for SSD from 1981 through 1997, was utilized. Maternal levels of both DHA and arachidonic acid (AA), an n-6 fatty acid, were analyzed in archived maternal sera from 57 cases of SSD and 95 matched controls. There was a greater than twofold increased risk of SSD among subjects exposed to maternal serum DHA in the highest tertile (OR=2.38, 95% CI=1.19, 4.76, p=0.01); no such relationship was found between AA and SSD. These findings suggest that elevated maternal DHA is associated with increased risk for the development of SSD in offspring.     

Social Deprivation,Inequality, and the Neighborhood-Level Incidence of Psychotic Syndromes in East London

Although urban birth, upbringing, and living are associated with increased risk of nonaffective psychotic disorders, few studies have used appropriate multilevel techniques accounting for spatial dependency in risk to investigate social, economic, or physical determinants of psychosis incidence. We adopted Bayesian hierarchical modeling to investigate the sociospatial distribution of psychosis risk in East London for DSM-IV nonaffective and affective psychotic disorders, ascertained over a 2-year period in the East London first-episode psychosis study. We included individual and environmental data on 427 subjects experiencing first-episode psychosis to estimate the incidence of disorder across 56 neighborhoods, having standardized for age, sex, ethnicity, and socioeconomic status. A Bayesian model that included spatially structured neighborhood-level random effects identified substantial unexplained variation in nonaffective psychosis risk after controlling for individual-level factors. This variation was independently associated with greater levels of neighborhood income inequality (SD increase in inequality: Bayesian relative risks [RR]: 1.25; 95% CI: 1.04–1.49), absolute deprivation (RR: 1.28; 95% CI: 1.08–1.51) and population density (RR: 1.18; 95% CI: 1.00–1.41). Neighborhood ethnic composition effects were associated with incidence of nonaffective psychosis for people of black Caribbean and black African origin. No variation in the spatial distribution of the affective psychoses was identified, consistent with the possibility of differing etiological origins of affective and nonaffective psychoses. Our data suggest that both absolute and relative measures of neighborhood social composition are associated with the incidence of nonaffective psychosis. We suggest these associations are consistent with a role for social stressors in psychosis risk, particularly when people live in more unequal communities.Key words: psychosis, epidemiology, urban, social environment, inequality, deprivation, Bayesian modeling, schizophrenia     

Ante- and perinatal circumstances and risk of attempted suicides and suicides in offspring: the Northern Finland birth cohort 1966 study

Purpose

To investigate those ante- and perinatal circumstances preceding suicide attempts and suicides, which have so far not been studied intensively.

Methods

Examination of the Northern Finland Birth Cohort 1966 (n?=?10,742), originally based on antenatal questionnaire data and now followed up from mid-pregnancy to age 39, to ascertain psychiatric disorders in the parents and offspring and suicides or attempted suicides in the offspring using nationwide registers.

Results

A total of 121 suicide attempts (57 males) and 69 suicides (56 males) had occurred. Previously unstudied antenatal factors (maternal depressed mood and smoking, unwanted pregnancy) were not related to these after adjustment. Psychiatric disorders in the parents and offspring were the risk factors in both genders. When adjusted for these, the statistically significant risk factors among males were a single-parent family for suicide attempts (OR 3.71, 95% CI 1.62–8.50) and grand multiparity for suicides (OR 2.67, 95% CI 1.15–6.18). When a psychiatric disorder in females was included among possible risk factors for suicide attempts, it alone remained significant (OR 15.55, 8.78–27.53).

Conclusions

A single-parent family was a risk factor for attempted suicides and grand multiparity for suicides in male offspring even after adjusting for other ante- and perinatal circumstances and mental disorders in the parents and offspring. Mothers’ antenatal depressed mood and smoking and unwanted pregnancy did not increase the risk of suicide, which is a novel finding.     

Inflammation: A Proposed Intermediary Between Maternal Stress and Offspring Neuropsychiatric Risk

During pregnancy, programming of the fetal central nervous system establishes vulnerabilities for emergence of neuropsychiatric phenotypes later in life. Psychosocial influences during pregnancy, such as stressful life events and chronic stress, correlate with offspring neuropsychiatric disorders and inflammation, respectively. Stress promotes inflammation, but the role of inflammation as a mediator between maternal psychosocial stress and offspring neuropsychiatric outcomes has not been extensively studied in humans. This review summarizes clinical evidence linking specific types of stress to maternal inflammatory load during pregnancy. We propose that inflammation is a mediator in the relationship between psychosocial stress and offspring neuropsychiatric outcomes, potentially influenced by poor maternal glucocorticoid–immune coordination. We present relevant experimental animal research supporting this hypothesis. We conclude that clinical and preclinical research supports the premise that stress-induced maternal immune activation contributes in part to prenatal programming of risk. Programming of risk is likely due to a combination of vulnerabilities, including multiple or repeated inflammatory events; timing of such events; poor maternal regulation of inflammation; genetic vulnerability; and lifestyle contributors.