Blunted neurobiological reactivity and attentional bias to threat underlie stress-related disorders in women survivors of intimate partner violence.

BACKGROUND: Intimate partner violence (IPV) alters women's neurobiological stress response systems. We propose that individual differences early in the attentional processing of threats are associated with these neurobiological mechanisms and contribute to mental illness in this population. METHODS: We assessed attentional bias in relation to threat (AB) in women survivors of IPV (n = 69) and controls (n = 36), and examined overall cortisol secretion using hair cortisol (HC), and stress responsiveness measuring salivary cortisol and α-amylase (sAA) before (T0), and after (T1, T2) an acute psychosocial stress task (Trier Social Stress Test). We used repeated-measures ANCOVAs to explore the associations between Group (IPV, control) and AB with acute stress response, and regression models to examine the associations with mental health symptoms. RESULTS: There were no between-group differences in HC levels. An interaction between Group and AB was found regarding cortisol reactivity (p < 0.05). IPV women with threat avoidance AB showed a blunted cortisol response compared to controls and to IPV participants with threat vigilance AB. The association between sAA reactivity and the interaction between Group, AB, and time approached significance (p = 0.07), with a trend to lower sAA levels particularly in IPV women with threat avoidance AB. Group and cortisol reactivity were associated with symptoms of depression, generalized anxiety, and post-traumatic stress disorder (8-20% explained variance). CONCLUSIONS: Threat avoidance AB is associated with blunted acute cortisol response among women exposed to chronic stress (IPV). Experiencing IPV and acute cortisol response appear to be clearly implicated in long-term mental health problems.

Mental health and COVID-19 in a general population cohort in Spain (COVICAT study).

PURPOSE: Mental health conditions may affect outcome of COVID-19 disease, while exposure to stressors during the pandemic may impact mental health. The purpose of this study was to examine these factors in relation to ocurrence of depression and anxiety after the first outbreak in Spain. METHODS: We contacted 9515 participants from a population-based cohort study in Catalonia between May and October 2020. We drew blood samples to establish infection to the virus. Pre-pandemic mental health conditions were confirmed through Electronic Health Registries. We used the Hospital Anxiety and Depression Scale to assess severe depression and anxiety post-pandemic. Exposure to proximal, financial and wider environment stressors during the lockdown were collected. We calculated Relative Risks (RR), adjusting for individual- and contextual covariates. RESULTS: Pre-pandemic mental health disorders were not associated with SARS-CoV-2 infection , but were associated with severity of COVID-19 disease. People with pre-existing mental health disorders showed higher prevalence of severe depression (25.4%) and anxiety (37.8%) than those without prior mental disorders (4.9% and 10.1%). Living alone was a strong predictor of severe depression among mental health patients (RR = 1.6, 95% CI 1.2-2.2). Among those without prior mental health disorders, post-lockdown depression and anxiety were associated with household interpersonal conflicts (RR = 2.6, 95% CI 2.1-3.1; RR = 2.1, 95% CI 1.9-2.4) and financial instability (RR = 2.2, 95% CI 1.8-2.9; 1.9, 95% CI 1.6-2.2). CONCLUSIONS: The COVID-19 pandemic and the lockdown were associated with increased post-lockdown depression and anxiety. Patients with pre-existing mental health conditions are a vulnerable group for severe COVID-19 disease.

Ventromedial prefrontal cortex activity and pathological worry in generalised anxiety disorder.

BACKGROUND: Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.AimsTo study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals. METHOD: In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging. RESULTS: Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety-threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC. CONCLUSIONS: Poor vmPFC safety-threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.Declaration of interestNone.

Cortical thickness correlates of psychotic experiences: examining the effect of season of birth using a genetically informative design.

Season of birth has been shown to influence risk for several neuropsychiatric diseases. Furthermore, it has been suggested that season of birth modifies a number of brain morphological traits. Since cortical thickness alterations have been reported across some levels of the psychosis-spectrum, this study was aimed at i) assessing the scarcely explored relationship between cortical thickness and severity of subclinical psychotic experiences (PEs) in healthy subjects, and ii) evaluating the potential impact of season of birth in the preceding thickness-PEs relationship. As both PEs and brain cortical features are heritable, the current work used monozygotic twins to separately evaluate familial and unique environmental factors. High-resolution structural MRI scans of 48 twins (24 monozygotic pairs) were analyzed to estimate cortical thickness using FreeSurfer. They were then examined in relation to PEs, accounting for the effects of birth season; putative differential relationships between PEs and cortical thickness depending on season of birth were also tested. Current results support previous findings indicative of cortical thickening in healthy individuals with high psychometrically assessed psychosis scores, probably in line with theories of compensatory aspects of brain features in non-clinical populations. Additionally, they suggest distinct patterns of cortical thickness-PEs relationships depending on birth seasonality. Familial factors underlying the presence of PEs may drive these effects.

The BDNF-Val66Met polymorphism modulates parental rearing effects on adult psychiatric symptoms: a community twin-based study.

PURPOSE: To test whether firstly, different parental rearing components were associated with different dimensions of psychiatric symptoms in adulthood, secondly BDNF-Val66Met polymorphism moderated this association and thirdly, this association was due to genetic confounding. METHOD: Perceived parental rearing according to Parental Bonding Instrument (PBI), psychiatric symptoms evaluated with the Brief Symptom Inventory (BSI) and the BDNF-Val66Met polymorphism were analyzed in a sample of 232 adult twins from the general population. RESULTS: In the whole sample, paternal care was negatively associated with depression. Maternal overprotection was positively associated with paranoid ideation, obsession-compulsion and somatization. Gene-environment interaction effects were detected between the BDNF-Val66Met polymorphism and maternal care on phobic anxiety, paternal care on hostility, maternal overprotection on somatization and paternal overprotection also in somatization. In the subsample of MZ twins, intrapair differences in maternal care were associated with anxiety, paranoid ideation and somatization. CONCLUSIONS: Met carriers were, in general, more sensitive to the effects of parental rearing compared to Val/Val carriers in relation to anxiety and somatization. Contra-intuitively, our findings suggest that high rates of maternal care might be of risk for Met carriers regarding anxiety. Results from analyses controlling for genetic confounding were in line with this finding.

Childhood adversity and psychosis: examining whether the association is due to genetic confounding using a monozygotic twin differences approach.

PURPOSE: To test whether the association between childhood adversity and positive and negative psychotic experiences is due to genetic confounding. METHOD: Childhood adversity and psychotic experiences were assessed in an ongoing sample of 226 twins from the general population. A monozygotic (MZ) twin differences approach was used to assess possible genetic confounding. RESULTS: In the whole sample, childhood adversity was significantly associated with positive (ß=45; SE=0.16; P=0.008) and negative psychotic experiences (ß=0.77; SE=0.18; P<0.01). Within-pair MZ twin differences in exposure to childhood adversity were significantly associated with differences in positive (ß=71; SE=0.29; P=0.016) and negative psychotic experiences (ß=98; SE=0.38; P=0.014) in a subsample of 85 MZ twin pairs. CONCLUSIONS: Individuals exposed to childhood adversity are more likely to report psychotic experiences. Furthermore, our findings indicate that this association is not due to genetic confounding.

Neurodevelopmental liability to schizophrenia: the complex mediating role of age at onset and premorbid adjustment.

Large individual variation in the clinical presentation of schizophrenia-spectrum disorders raises key questions regarding their aetiological underpinnings. In this respect, age at onset of the disorder is a particularly interesting marker of liability, as it has been reported to be associated with other signs of developmental compromise, such as male gender, increased presence of familial history of psychosis and poor premorbid adjustment, as well as a more severe clinical outcome in terms of cognition and symptomatology. The association between these variables has encouraged a neurodevelopmental perspective of the aetiological mechanisms involved in the pathophysiology of schizophrenia. However, the complex relationships within neurobiological liability markers, and between these markers and clinical outcome, remain to be understood. In the present study, we used a path-analytic approach to explore: i) the fit of the model to observed data; and both ii) direct and iii) indirect associations between the variables. In a sample of 106 patients with schizophrenia-spectrum disorders, we found a good fit of the model to the observed data, providing further evidence that supports a neurodevelopmental pathway to the disease in a subgroup of patients. However, the most parsimonious model showed complex relationships, where age at onset and premorbid functioning acted as mediators between gender, familial history of psychosis and clinical outcome. These findings refine earlier explanations of the neurobiological basis of schizophrenia, with potential applications in genetic studies based on more homogeneous forms of the disease. We further discuss the putative implications of our results in clinical practice and prevention policies.