Although alterations in medial temporal lobe structures have been previously associated with use of cannabis, one of the most widely used illicit drugs, whether such alterations are a cause or effect of cannabis use has been unclear.

In this cross-sectional observational study involving 404 twins/siblings, we have compared cortical thickness and surface area between groups of gender-matched sibling-pairs (concordant cannabis unexposed, concordant exposed and discordant for cannabis exposure) using permutation tests after controlling for potential confounds. Bi-variate polygenic model was used to assess the genetic and environmental contributions underlying cortical morphological phenotypes and frequency of cannabis use.

Cortical thickness of the right entorhinal cortex was significantly lower in the concordant exposed siblings compared to both discordant unexposed and discordant exposed groups [false discovery rate (FDR)-corrected, q < 0.05]. The association between the right entorhinal cortex thickness and frequency of cannabis use is due to the contribution of significant shared additive genetic (ρg = −0.19 ± 0.08; p = 0.02) factors but not unique environment (ρe = 0.05 ± 0.09; p = 0.53). Significantly lower surface area of the right entorhinal cortex in discordant exposed group compared with the discordant unexposed group furnishes preliminary evidence in support of causal effect of cannabis use (FDR-corrected, q < 0.05). However, bi-variate polygenic model-based analysis did not show any significant effect.

Shared genetic liability may underlie the association between cannabis exposure and thinner right entorhinal cortex. Prospective longitudinal studies are necessary to definitively disentangle the cause–effect relationships of cannabis use.

Studies evaluating depression's role in lung cancer risk revealed contradictory findings, partly because of the small number of cases, short follow-up periods, and failure to account for key covariates including smoking exposure. We investigated the association of depressive symptoms with lung cancer risk in a large prospective cohort over 24 years while considering the role of smoking.

Women from the Nurses' Health Study completed measures of depressive symptoms, sociodemographics, and other factors including smoking in 1992 (N = 42 913). Depressive symptoms were also queried in 1996 and 2000, whereas regular antidepressant use and physician-diagnosed depression were collected starting in 1996. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of lung cancer risk until 2016.

We identified 1009 cases of lung cancer. Women with the highest v. lowest level of depressive symptoms had an increased lung cancer risk (HRsociodemographics-adjusted = 1.62, 95% CI 1.34–1.95; HRfully-adjusted = 1.25, 95% CI 1.04–1.51). In a test of mediation, lifetime pack-years of smoking accounted for 38% of the overall association between depressive symptoms and disease risk. When stratifying by smoking status, the elevated risk was evident among former smokers but not current or never smokers; however, the interaction term suggested no meaningful differences across groups (p = 0.29). Results were similar or stronger when considering time-updated depression status (using depressive symptoms, physician diagnosis, and regular antidepressant use) and chronicity of depressive symptoms.

These findings suggest that greater depressive symptoms may contribute to lung cancer incidence, directly and indirectly via smoking habits, which accounted for over a third of the association.

There is evidence that measures of alcohol consumption, dependence and abuse are valid indicators of qualitatively different subtypes of alcohol involvement yet also fall along a continuum. The present study attempts to resolve the extent to which variations in alcohol involvement reflect a difference in kind versus a difference in degree.

Data were taken from the 2001–2002 National Epidemiologic Survey of Alcohol and Related Conditions. The sample (51% male; 72% white/non-Hispanic) included respondents reporting past 12-month drinking at both waves (wave 1: n = 33644; wave 2: n = 25186). We compared factor mixture models (FMMs), a hybrid of common factor analysis (FA) and latent class analysis (LCA), against FA and LCA models using past 12-month alcohol use disorder (AUD) criteria and five indicators of alcohol consumption reflecting frequency and heaviness of drinking.

Model comparison revealed that the best-fitting model at wave 1 was a one-factor four-class FMM, with classes primarily varying across dependence and consumption indices. The model was replicated using wave 2 data, and validated against AUD and dependence diagnoses. Class stability from waves 1 to 2 was moderate, with greatest agreement for the infrequent drinking class. Within-class associations in the underlying latent factor also revealed modest agreement over time.

There is evidence that alcohol involvement can be considered both categorical and continuous, with responses reduced to four patterns that quantitatively vary along a single dimension. Nosologists may consider hybrid approaches involving groups that vary in pattern of consumption and dependence symptomatology as well as variation of severity within group.

Emerging research suggests that maternal immune activation (MIA) may be associated with an increased risk of adverse neurodevelopmental and mental health outcomes in offspring. Using data from the Raine Study, we investigated whether MIA during pregnancy was associated with increased behavioral and emotional problems in offspring longitudinally across development.

Mothers (Generation 1; N = 1905) were classified into the following categories: AAAE (Asthma/Allergy/Atopy/Eczema; N = 1267); infection (during pregnancy; N = 1082); no AAAE or infection (N = 301). The Child Behavior Checklist (CBCL) was administered for offspring at ages 5, 8, 10, 14, and 17. Generalized estimating equations were used to investigate the effect of maternal immune status on CBCL scores.

AAAE conditions were associated with significant increases in CBCL Total (β 2.49; CI 1.98–3.00), Externalizing (β 1.54; CI 1.05–2.03), and Internalizing (β 2.28; CI 1.80–2.76) scores. Infection conditions were also associated with increased Total (β 1.27; CI 0.77–1.78), Externalizing (β 1.18; CI 0.70–1.66), and Internalizing (β 0.76; CI 0.28–1.24) scores. Exposure to more than one AAAE and/or infection condition was associated with a greater elevation in CBCL scores than single exposures in males and females. Females showed greater increases on the Internalizing scale from MIA, while males showed similar increases on both Internalizing and Externalizing scales.

MIA was associated with increased behavioral and emotional problems in offspring throughout childhood and adolescence. This highlights the need to understand the relationship between MIA, fetal development, and long-term outcomes, with the potential to advance early identification and intervention strategies.

While comorbidity of clinical high-risk for psychosis (CHR-P) status and social anxiety is well-established, it remains unclear how social anxiety and positive symptoms covary over time in this population. The present study aimed to determine whether there are more than one covariant trajectory of social anxiety and positive symptoms in the North American Prodrome Longitudinal Study cohort (NAPLS 2) and, if so, to test whether the different trajectory subgroups differ in terms of genetic and environmental risk factors for psychotic disorders and general functional outcome.

In total, 764 CHR individuals were evaluated at baseline for social anxiety and psychosis risk symptom severity and followed up every 6 months for 2 years. Application of group-based multi-trajectory modeling discerned three subgroups based on the covariant trajectories of social anxiety and positive symptoms over 2 years.

One of the subgroups showed sustained social anxiety over time despite moderate recovery in positive symptoms, while the other two showed recovery of social anxiety below clinically significant thresholds, along with modest to moderate recovery in positive symptom severity. The trajectory group with sustained social anxiety had poorer long-term global functional outcomes than the other trajectory groups. In addition, compared with the other two trajectory groups, membership in the group with sustained social anxiety was predicted by higher levels of polygenic risk for schizophrenia and environmental stress exposures.

Together, these analyses indicate differential relevance of sustained v. remitting social anxiety symptoms in the CHR-P population, which in turn may carry implications for differential intervention strategies.

Homelessness is a major public health problem among U.S. military veterans. However, contemporary, population-based data on the prevalence, correlates, and mental health burden of homelessness among veterans are lacking.

Data were analyzed from the 2019–2020 National Health and Resilience in Veterans Study, a nationally representative survey of veterans (n = 4069). Analyses examined the prevalence and correlates of homelessness, as well as the independent associations between homelessness and current probable psychiatric conditions, suicidality, and functioning.

The lifetime prevalence of homelessness was 10.2% (95% confidence interval 9.3–11.2). More than 8-of-10 veterans reported experiencing their first episode of homelessness following military service, with a mean of 10.6 years post-discharge until onset (s.d. = 12.6). Adverse childhood experiences (ACEs), cumulative trauma burden, current household income, younger age, and drug use disorder emerged as the strongest correlates of homelessness (49% of total explained variance). Veterans with a history of homelessness had elevated odds of lifetime suicide attempt, attempting suicide two or more times, and past-year suicide ideation [odd ratios (ORs) 1.3–3.1]. They also had higher rates of current probable posttraumatic stress disorder, major depressive, generalized anxiety, and drug use disorders (ORs 1.7–2.4); and scored lower on measures of mental, physical, cognitive, psychosocial functioning (d = 0.11–0.15).

One in ten U.S. veterans has experienced homelessness, and these veterans represent a subpopulation at substantially heightened risk for poor mental health and suicide. ACEs were the strongest factor associated with homelessness, thus underscoring the importance of targeting early childhood adversities and their mental health consequences in prevention efforts for homelessness in this population.

Smoking is highly prevalent in people diagnosed with schizophrenia, but the reason for this co-morbidity is currently unclear. One possible explanation is that a common abnormality underpins the development of psychosis and independently enhances the incentive motivational properties of drugs and their associated cues. This study aimed to investigate whether incentive salience attribution towards smoking cues, as assessed by attentional bias, is heightened in schizophrenia and associated with delusions and hallucinations.

Twenty-two smokers diagnosed with schizophrenia and 23 control smokers were assessed for smoking-related attentional bias using a modified Stroop task. Craving, nicotine dependence, smoking behaviour and positive and negative symptoms of schizophrenia were also recorded.

Both groups showed similar craving scores and smoking behaviour according to self-report and expired carbon monoxide (CO), although the patient group had higher nicotine dependence scores. Attentional bias, as evidenced by significant interference from smoking-related words on the modified Stroop task, was similar in both groups and correlated with CO levels. Attentional bias was positively related to severity of delusions but not hallucinations or other symptoms in the schizophrenia group.

This study supports the hypothesis that the development of delusions and the incentive motivational aspects of smoking may share a common biological substrate. These findings may offer some explanation for the elevated rates of smoking and other drug use in people with psychotic illness.

We investigated whether source-monitoring deficits (here a discrimination between imagined and performed actions) underlie hallucinations among patients with a history of hallucinations in the course of their alcohol dependence.

We assessed 29 patients with alcohol dependence who had no history of hallucinations during their course of alcoholism and 29 patients with a history of at least one episode of hallucinations of any modality during their course of alcohol dependency. The control group consisted of 24 healthy participants. Participants were assessed with an action memory task. Simple actions were presented to the participants verbally or non-verbally. Some actions were performed physically and others were imagined. In the recognition phase, participants were asked whether the action was presented verbally or non-verbally (action presentation type discrimination) and whether the action was performed or imagined (self-monitoring). A confidence score related to self-monitoring responses was also obtained.

Alcoholics with a history of hallucinations misremembered imagined actions as perceived ones more frequently than patients without hallucinations, but not the reverse. Only patients with a history of hallucinations committed more errors of this type than healthy subjects. There were no group differences regarding discrimination between an action presentation type. Both clinical groups committed errors with a higher degree of confidence than healthy subjects.

Our results tentatively suggest that a specific type of source-monitoring deficit (i.e. confusing imagery with reality) may be involved in the hallucinations in patients with alcohol dependence. The findings are discussed in the light of a transdiagnostic approach to hallucinations.

Unpaid carers who look after another member of their household (home-carers) have poorer mental health than the general population. The first COVID-19 national lockdown led to an increasing reliance on home-carers and we investigate the short- and longer-term impacts of lockdown on their mental health.

Data from 9737 adult participants (aged 16+) from the UK Household Longitudinal Study (Understanding Society) were used to explore changes in 12-item General Health Questionnaire (GHQ-12) score between (a) pre-pandemic (2019) and early lockdowns (April 2020) and (b) early and later (July 2020) lockdowns.

GHQ-12 scores among home-carers were higher pre-lockdown and increased more than for non-carers from 2019 to April 2020 with further increases for home-carers compared with non-carers between April and July. Compared with respondents caring for a spouse/partner, those caring for a child under 18 had a particularly marked increase in GHQ-12 score between 2019 and April, as did those caring for someone with a learning disability. Home-carers of children under 18 improved from April to July while those caring for adult children saw a marked worsening of their mental health. Home-carers with greater care burden saw larger increases in GHQ-12 score from 2019 to April and from April to July, and increases through both periods were greater for home-carers who had formal help prior to lockdown but then lost it.

The mental health of home-carers deteriorated more during lockdown than non-carers. Policies that reinstate support for them and their care-recipients will benefit the health of both vulnerable groups.

The amygdala is a subcortical limbic structure consisting of histologically and functionally distinct subregions. New automated structural magnetic resonance imaging (MRI) segmentation tools facilitate the in vivo study of individual amygdala nuclei in clinical populations such as patients with anorexia nervosa (AN) who show symptoms indicative of limbic dysregulation. This study is the first to investigate amygdala nuclei volumes in AN, their relationships with leptin, a key indicator of AN-related neuroendocrine alterations, and further clinical measures.

T1-weighted MRI scans were subsegmented and multi-stage quality controlled using FreeSurfer. Left/right hemispheric amygdala nuclei volumes were cross-sectionally compared between females with AN (n = 168, 12–29 years) and age-matched healthy females (n = 168) applying general linear models. Associations with plasma leptin, body mass index (BMI), illness duration, and psychiatric symptoms were analyzed via robust linear regression.

Globally, most amygdala nuclei volumes in both hemispheres were reduced in AN v. healthy control participants. Importantly, four specific nuclei (accessory basal, cortical, medial nuclei, corticoamygdaloid transition in the rostral-medial amygdala) showed greater volumetric reduction even relative to reductions of whole amygdala and total subcortical gray matter volumes, whereas basal, lateral, and paralaminar nuclei were less reduced. All rostral-medially clustered nuclei were positively associated with leptin in AN independent of BMI. Amygdala nuclei volumes were not associated with illness duration or psychiatric symptom severity in AN.

In AN, amygdala nuclei are altered to different degrees. Severe volume loss in rostral-medially clustered nuclei, collectively involved in olfactory/food-related reward processing, may represent a structural correlate of AN-related symptoms. Hypoleptinemia might be linked to rostral-medial amygdala alterations.

Openness on one's health condition or (stigmatized) identity generally improves mental health. Intersex or differences of sex development (DSD) conditions have long been kept concealed and high levels of (internalizing) mental health problems are reported. This study examines the effects of condition openness on anxiety and depression and the role of mediating concepts in this population.

Cross-sectional data of individuals of 16 years and older with an intersex/DSD condition was collected in 14 specialized European clinics as part of the dsd-LIFE study. Patient-reported measures were taken on openness and shame (Coping with DSD), self-esteem (Rosenberg Self-Esteem Scale), satisfaction with care (CSQ4), anxiety and depression (HADS). Scores were compared per clinical group and data were analyzed via structural equation modeling (SEM) to calculate prediction and mediation models.

Data of 903 individuals were included in this study (Turner syndrome (n = 284), 46, XY DSD (n = 233), CAH (n = 206) and Klinefelter syndrome (n = 180)). Participants were moderately open on their condition. High levels of both anxiety and depression were observed across the sample. In SEM analysis, the tested models predicted 25% of openness, 31% of anxiety and 48% of depression. More condition openness directly predicted lower anxiety and depression symptoms, as well as indirectly through increased self-esteem, self-satisfaction and satisfaction with social support.

Condition openness is associated with lower anxiety and depression in individuals with an intersex/DSD condition. Healthcare may provide the necessary knowledge and skills to employ one's optimal level of self-disclosure in order to improve mental health.

U.S. veterans report high rates of traumatic experiences and mental health symptomology [e.g. posttraumatic stress disorder (PTSD)]. The stress sensitization hypothesis posits experiences of adversity sensitize individuals to stress reactions which can lead to greater psychiatric problems. We extend this hypothesis by exploring how multiple adversities such as early childhood adversity, combat-related trauma, and military sexual trauma related to heterogeneity in stress over time and, subsequently, greater risk for PTSD.

1230 veterans were recruited for an observational, longitudinal study. Veterans responded to questionnaires on PTSD, stress, and traumatic experiences five times over an 18-month study period. We used latent transition analysis to understand how heterogeneity in adverse experiences is related to transition into stress trajectory classes. We also explored how transition patterns related to PTSD symptomology.

Across all models, we found support for stress sensitization. In general, combat trauma in combinations with other types of adverse experiences, namely early childhood adversity and military sexual trauma, imposed a greater probability of transitioning into higher risk stress profiles. We also showed differential effects of early childhood and military-specific adversity on PTSD symptomology.

The present study rigorously integrates both military-specific and early life adversity into analysis on stress sensitivity, and is the first to examine how sensitivity might affect trajectories of stress over time. Our study provides a nuanced, and specific, look at who is risk for sensitization to stress based on previous traumatic experiences as well as what transition patterns are associated with greater PTSD symptomology.

This study sought to determine the social and emotional impact of maternal loss on Aboriginal children and young people using data from the Western Australian Aboriginal Child Health Survey (WAACHS).

Data were from a population-based random sample of 5289 Aboriginal children aged under 18 years. Interview data about the children were gathered from primary carers and from their school teachers. Probabilistic record linkage to death registrations was used to ascertain deaths. Association between maternal death and subsequent psychosocial outcomes was assessed using univariate analyses and logistic regression.

Of the 5289 Aboriginal children, 57 had experienced the death of their birth mother prior to the survey. Multi-variable adjustment accounting for age and gender found that, relative to children who were living with their birth mother, children whose birth mother had died were at higher risk for sniffing glue or other substances [odds ratio (OR) 3.4, 95% confidence interval (CI) 1.3–8.7], using other drugs (OR 2.8, 95% CI 1.2–6.8), talking about suicide (OR 2.6, 95% CI 1.2–5.7) and attempting suicide (OR 7.0, 95% CI 1.6–31.1).

Although the death of a birth mother is relatively rare and the vast majority of Aboriginal children with adverse developmental outcomes live in families and are cared for by their birth mother, the findings here suggest that the loss of a birth mother and the circumstances arising from this impart a level of onward developmental risk for mental health morbidity in Australian Aboriginal children.

Obesity and anxiety are often linked but the direction of effects is not clear.

Using genetic instrumental variable (IV) analyses in 5911 female participants from the Nurses' Health Study (NHS, initiated 1976) and 3697 male participants from the Health Professional Follow-up Study (HPFS, initiated 1986), we aimed to determine whether obesity increases symptoms of phobic anxiety. As instrumental variables we used the fat mass and obesity-associated (FTO) gene, the melanocortin 4 receptor (MC4R) gene and a genetic risk score (GRS) based on 32 single nucleotide polymorphisms (SNPs) that significantly predict body mass index (BMI). ‘Functional’ GRSs corresponding with specific biological pathways that shape BMI (adipogenesis, appetite and cardiopulmonary) were considered. The main outcome was phobic anxiety measured by the Crown Crisp Index (CCI) in 2004 in the NHS and in 2000 in the HPFS.

In observational analysis, a 1-unit higher BMI was associated with higher phobic anxiety symptoms [women: β = 0.05, 95% confidence interval (CI) 0.030–0.068; men: β = 0.04, 95% CI 0.016–0.071). IV analyses showed that BMI was associated with higher phobic anxiety symptoms in the FTO-instrumented analysis (p = 0.005) but not in the GRS-instrumented analysis (p = 0.256). Functional GRSs showed heterogeneous, non-significant effects of BMI on phobic anxiety symptoms.

Our findings do not provide conclusive evidence in favor of the hypothesis that higher BMI leads to higher levels of phobic anxiety, but rather suggest that genes that influence obesity, in particular FTO, may have direct effects on phobic anxiety, and hence that obesity and phobic anxiety may share common genetic determinants.