Behavioural inhibition system sensitivity is no longer associated with psychotic-like experiences after controlling for depression and anxiety symptoms.

AIM: Elevated behavioural inhibition system sensitivity has been reported among schizophrenia patients. Yet, no study has investigated the relationship between behavioural inhibition system sensitivity and the occurrence of psychotic-like experiences (subthreshold psychotic symptoms considered to be less severe or impairing), despite evidence that behavioural inhibition system sensitivity is related to other forms of psychopathology known to co-occur with psychotic-like experiences, such as depression and anxiety. Thus, the aim of this study was to assess the relationship between behavioural inhibition system levels and psychotic-like experiences while controlling for depression and anxiety symptoms. We hypothesized that behavioural inhibition system sensitivity would be positively associated with the number of reported psychotic-like experiences, and that this association would be nonsignificant after accounting for depression and anxiety symptoms. METHODS: Psychotic-like experiences, behavioural inhibition system sensitivity, depression symptoms, and anxiety symptoms were measured in 1162 young adults. Bivariate correlations were calculated and linear regressions performed to measure the relationship between variables of interest. RESULTS: Psychotic-like experiences, behavioural inhibition system sensitivity, and symptoms of depression, and anxiety were all significantly and positively correlated with one another. Behavioural inhibition system sensitivity was no longer related to the number of psychotic-like experiences reported after controlling for anxiety symptoms, with and without controlling for depression symptoms. DISCUSSION: These findings suggest that the hypersensitivity to threat observed among individuals reporting higher levels of psychotic-like experiences is likely related to co-occurring depression and anxiety symptoms. Thus, behavioural inhibition system sensitivity may be more reflective of a transdiagnostic phenotype of general psychopathology than specifically related to psychosis.

Factor Structure, Convergent, and Divergent Validity of the Prodromal Questionnaire-Negative Symptom Subscale.

Negative symptoms such as anhedonia are associated with psychosis risk and poorer outcomes. The Prodromal Questionnaire (PQ) is a self-report questionnaire used to screen for psychosis spectrum symptoms. However, the convergent and divergent validity and underlying factor structure of the PQ-negative symptom subscale (PQ-N) have yet to be examined. Undergraduates (N = 1,556) completed the PQ, Temporal Experience of Pleasure Scale, and measures assessing anxiety, depression, and motivation. An exploratory factor analysis conducted on the PQ-N yielded a two-factor solution, reflecting subdimensions of social expression and dissociative-depressive experiences, contrary to previous research examining the factor structure of negative symptoms. Associations between the PQ-N, its two factors, and measures of negative symptoms and other psychopathology were examined. Results indicated that the PQ-N and its factors were more strongly correlated with measures of depression and anxiety than with measures of negative symptoms relating to motivation and pleasure, suggesting poor convergent and divergent validity.

Maternal cortisol during pregnancy and offspring schizophrenia: Influence of fetal sex and timing of exposure.

INTRODUCTION: Maternal stress during pregnancy has been repeatedly linked to increased risk for schizophrenia; however, no study has examined maternal cortisol during pregnancy and risk for the disorder. Study aims were to determine whether prenatal cortisol was associated with risk for schizophrenia and risk for an intermediate phenotype-decreased fetal growth-previously linked to prenatal cortisol and schizophrenia. Timing of exposure and fetal sex also were examined given previous findings. METHODS: Participants were 64 cases diagnosed with schizophrenia spectrum disorders (SSD) and 117 controls from a prospective birth cohort study. Maternal cortisol was determined from stored sera from each trimester and psychiatric diagnoses were assessed from offspring using semi-structured interviews and medical records review. RESULTS: Maternal cortisol during pregnancy was not associated with risk for offspring schizophrenia. There was a significant interaction between 3rd trimester cortisol and case status on fetal growth. Specifically, cases exposed to higher 3rd trimester maternal cortisol had significantly decreased fetal growth compared to controls. In addition, these findings were restricted to male offspring. CONCLUSIONS: Our results indicate that higher prenatal cortisol is associated with an intermediate phenotype linked to schizophrenia, fetal growth, but only among male offspring who developed schizophrenia. Findings were consistent with evidence that schizophrenia genes may disrupt placental functioning specifically for male fetuses, as well as findings that males are more vulnerable to maternal cortisol during pregnancy. Finally, results suggest that examining fetal sex and intermediate phenotypes may be important in understanding the mechanisms involved in prenatal contributors to schizophrenia.

Maternal inflammation during pregnancy and offspring psychiatric symptoms in childhood: Timing and sex matter.

OBJECTIVE: Maternal infection during pregnancy has been associated with increased risk of offspring psychopathology, including depression. As most infections do not cross the placenta, maternal immune responses to infection have been considered as potentially contributing to this relationship. This study examined whether gestational timing of maternal inflammation during pregnancy is associated with offspring internalizing and/or externalizing symptoms during childhood and, further, whether fetal sex moderated this relationship. METHOD: Participants were 737 pregnant women and their offspring who were continuously followed through late childhood. Archived first and second trimester sera were analyzed for markers of inflammation [interleukin 8 (IL-8), IL-6, IL-1 receptor antagonist (IL-1ra), and soluble tumor necrosis factor receptor-II (sTNF-RII)]. When offspring were aged 9-11, mothers completed a questionnaire assessing psychological symptoms. RESULTS: Multivariate regression analyses indicated that elevated IL-8 in the first trimester was associated with significantly higher levels of externalizing symptoms in offspring. Higher IL-1ra in the second trimester was associated with higher offspring internalizing symptoms. Further, second trimester IL-1ra was associated with increased internalizing symptoms in females only. CONCLUSION: These findings demonstrate that elevated maternal inflammation during pregnancy is associated with the emergence of separate psychological phenotypes and that timing of exposure and fetal sex matter for offspring outcomes. Given that internalizing and externalizing symptoms in childhood increase risk for a variety of mental disorders later in development, these findings potentially have major implications for early intervention and prevention work.

Pre- and Perinatal Risk Factors for Serious Mental Disorders: Ethical Considerations in Prevention and Prediction Efforts.

Repeated findings have linked pre- and perinatal risk factors to a variety of mental disorders. Some studies have found large magnitudes of association, suggesting that fetal development represents an important period for understanding neurodevelopmental sequelae. Nevertheless, it remains unclear how best to translate the existing findings into early identification, prevention, and treatment strategies that would be useful for pregnant populations and/or for their offspring. This article will discuss key ethical considerations surrounding the incorporation of findings from studies of the associations between obstetric complications and risk for mental disorders into prevention and prediction efforts.

Maternal Prenatal Stress and Other Developmental Risk Factors for Adolescent Depression: Spotlight on Sex Differences.

Maternal stress during pregnancy has been linked to premorbid abnormalities associated with depression (e.g., difficult temperament, cognitive deficits) in offspring. However, few studies have looked across developmental periods to examine maternal stress during pregnancy and offspring depression during adolescence and whether these associations differ by sex. The current study used data from 1711 mother-offspring dyads (offspring sex: 49.8% male) in a longitudinal birth cohort study. Maternal narratives collected during pregnancy were qualitatively coded for stress-related themes by independent raters. Latent class analysis (LCA) identified distinct subgroups of offspring based on exposure to maternal prenatal stress and other developmental factors from the prenatal, childhood, and adolescent periods that have been associated with depression and/or maternal prenatal stress. LCA identified subgroups that were compared to determine whether and to what extent they differed on adolescent depressive symptoms. LCA revealed a subgroup of "high-risk" individuals, characterized by maternal factors during pregnancy (higher ambivalence/negativity and lower positivity towards the pregnancy, higher levels of hassles, lower maternal education and higher maternal age at birth, higher pre-pregnancy BMI) and offspring developmental factors (decreased cognitive functioning during childhood and adolescence, lower perceived parental support during adolescence, and higher levels of maternal depression during adolescence). High-risk females exhibited elevated conduct symptoms and higher birth order, while high-risk males exhibited decreased internalizing symptoms and lower birth order. Both high-risk males and females reported elevated depressive symptoms during adolescence relative to their "low-risk" counterparts.

Maternal infection and stress during pregnancy and depressive symptoms in adolescent offspring.

Maternal infection during pregnancy has been linked to increased risk of offspring depression. Additionally, maternal stress during pregnancy has been consistently linked with adverse offspring outcomes associated with depression. Relatedly, stress has been associated with increased risk of infection; however no study has investigated stress-infection interactions during pregnancy and risk for offspring depression. Participants were drawn from the Child Health and Development Studies (CHDS), a prospective, longitudinal study that enrolled pregnant women from 1959 to 1966. Maternal health and birth outcome information were collected, as well as open-ended interviews about worrisome events during pregnancy. The present study included participants from a subsample of women whose offspring (n = 1711) completed self-reports of depressive symptoms during adolescence. Results indicated that maternal infection during only the second trimester was associated with higher scores on adolescent offspring depressive symptoms, while controlling for maternal education at birth, adolescent age, and maternal depressive symptoms at adolescence. Maternal experiences of daily stress during pregnancy moderated this association, such that mothers diagnosed with second trimester infection and who experienced daily stress had offspring with significantly higher depression scores than mothers of adolescents diagnosed with an infection alone. Findings have potential implications for prevention and intervention strategies.

Fetal exposure to maternal stress and risk for schizophrenia spectrum disorders among offspring: Differential influences of fetal sex.

Exposure to adverse life events during pregnancy has been linked to increased risk of schizophrenia spectrum disorders (SSD) in offspring. Nevertheless, much of the previous work inferred maternal stress from severe life events rather than directly assessing maternal reports of stress. The present study aimed to examine maternal reports of stress during pregnancy and risk for offspring SSD. Participants were 95 SSD cases and 206 controls who were offspring from a large birth cohort study that followed pregnant women from 1959 to 1966. During pregnancy interviews, women were asked if anything worrisome had occurred recently. Interviews were qualitatively coded for stress-related themes, including reports of daily life stress, by two independent raters. None of the maternal psychosocial stress themes were significantly associated with increased odds of offspring SSD in analyses of the full sample. However, results indicated a significant daily life stress by infant sex interaction. Maternal daily life stress during pregnancy was associated with significantly increased odds of SSD among male offspring. Findings suggest sex-specific fetal sensitivity to maternal reported daily life stress during pregnancy on risk for SSD, with males appearing to be more vulnerable to the influences of maternal stress during pregnancy.

Anxiety mediates the association between cannabis use and attenuated positive psychotic symptoms.

Cannabis use has been associated with a continuum of psychotic experiences. However, it is unclear whether mood and anxiety symptoms account for increases in attenuated positive psychotic symptoms (APPS) among cannabis users. We predicted that depression and anxiety symptoms would mediate the relation between cannabis use and APPS, and between cannabis use and endorsement of eight or more distressing APPS (D-APPS), a potentially more clinically meaningful group. Young adults (n=674) completed the Prodromal Questionnaire (PQ); Drug Use Frequency measure; Center for Epidemiologic Studies Depression Scale; State-Trait Anxiety Inventory, Trait Form, Anxiety Subscale; and Social Phobia Scale. Results indicated that symptoms of trait anxiety, but not symptoms of depression or social anxiety, mediated the relationship between cannabis use and APPS, as well as the relationship between cannabis use and D-APPS. Results indicate that symptoms of trait anxiety may play a role in the relation between cannabis use and APPS. Findings underscore the importance of considering clinical characteristics co-occurring with psychotic symptoms, such as affective symptoms, when examining the association between cannabis use and psychotic symptoms.

Stress sensitivity mediates the relationship between traumatic life events and attenuated positive psychotic symptoms differentially by gender in a college population sample.

The purpose of this study was to investigate whether stress sensitivity mediates the relationship between traumatic life events and total attenuated positive psychotic symptoms, as well as the relationship between traumatic life events and endorsement of 8 or more attenuated positive psychotic symptoms as distressing (a threshold that has been associated with higher risk for psychosis in clinical groups). Participants (n = 671, aged 17-35, 29% male) were college students who were administered the Prodromal Questionnaire, the Perceived Stress Scale and the Life Events Checklist. Bootstrapping results indicated that stress sensitivity significantly mediated the relationships between traumatic life events and the number of attenuated positive psychotic symptoms endorsed and between traumatic life events and those who endorsed 8 or more distressing attenuated positive psychotic symptoms. Stratified gender analyses indicated the findings were specific to females. Results suggest that stress sensitivity may represent a specific vulnerability factor for risk of attenuated psychotic symptoms in those previously exposed to traumatic life events and that this liability appears stronger in females.