Impairment in a wide range of cognitive abilities has been consistently reported in individuals with schizophrenia. Both neurocognitive and social cognitive deficits are thought to underlie severe functional disabilities associated with schizophrenia. Despite the key role in schizophrenia outcome, cognition is still poorly assessed in both research and clinical settings.

In this guidance paper, we provide a systematic review of the scientific literature and elaborate several recommendations for the assessment of cognitive functions in schizophrenia both in research settings and in real-world clinical practice.

Expert consensus and systematic reviews provided guidance for the optimal assessment of cognitive functions in schizophrenia. Based on the reviewed evidence, we recommend a comprehensive and systematic assessment of neurocognitive and social cognitive domains in schizophrenia, in all phases of the disorder, as well as in subjects at risk to develop psychosis. This European Psychiatric Association guidance recommends not only the use of observer reports but also self-reports and interview-based cognitive assessment tools. The guidance also provides a systematic review of the state of the art of assessment in the first episode of psychosis patients and in individuals at risk for psychosis.

The comprehensive review of the evidence and the recommendations might contribute to advance the field, allowing a better cognitive assessment, and avoiding overlaps with other psychopathological dimensions. The dissemination of this guidance paper may promote the development of shared guidelines concerning the assessment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to obtain recovery.

Although cognitive impairment is a core symptom of schizophrenia related to poorer outcomes in different functional domains, it still remains a major therapeutic challenge. To date, no comprehensive treatment guidelines for cognitive impairment in schizophrenia are implemented.

The aim of the present guidance paper is to provide a comprehensive meta-review of the current available evidence-based treatments for cognitive impairment in schizophrenia. The guidance is structured into three sections: pharmacological treatment, psychosocial interventions, and somatic treatments.

Based on the reviewed evidence, this European Psychiatric Association guidance recommends an appropriate pharmacological management as a fundamental starting point in the treatment of cognitive impairment in schizophrenia. In particular, second-generation antipsychotics are recommended for their favorable cognitive profile compared to first-generation antipsychotics, although no clear superiority of a single second-generation antipsychotic has currently been found. Anticholinergic and benzodiazepine burdens should be kept to a minimum, considering the negative impact on cognitive functioning. Among psychosocial interventions, cognitive remediation and physical exercise are recommended for the treatment of cognitive impairment in schizophrenia. Noninvasive brain stimulation techniques could be taken into account as add-on therapy.

Overall, there is definitive progress in the field, but further research is needed to develop specific treatments for cognitive impairment in schizophrenia. The dissemination of this guidance paper may promote the development of shared guidelines concerning the treatment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to achieve recovery in this population.

Subthreshold/attenuated syndromes are established precursors of full-threshold mood and psychotic disorders. Less is known about the individual symptoms that may precede the development of subthreshold syndromes and associated social/functional outcomes among emerging adults.

We modeled two dynamic Bayesian networks (DBN) to investigate associations among self-rated phenomenology and personal/lifestyle factors (role impairment, low social support, and alcohol and substance use) across the 19Up and 25Up waves of the Brisbane Longitudinal Twin Study. We examined whether symptoms and personal/lifestyle factors at 19Up were associated with (a) themselves or different items at 25Up, and (b) onset of a depression-like, hypo-manic-like, or psychotic-like subthreshold syndrome (STS) at 25Up.

The first DBN identified 11 items that when endorsed at 19Up were more likely to be reendorsed at 25Up (e.g., hypersomnia, impaired concentration, impaired sleep quality) and seven items that when endorsed at 19Up were associated with different items being endorsed at 25Up (e.g., earlier fatigue and later role impairment; earlier anergia and later somatic pain). In the second DBN, no arcs met our a priori threshold for inclusion. In an exploratory model with no threshold, >20 items at 19Up were associated with progression to an STS at 25Up (with lower statistical confidence); the top five arcs were: feeling threatened by others and a later psychotic-like STS; increased activity and a later hypo-manic-like STS; and anergia, impaired sleep quality, and/or hypersomnia and a later depression-like STS.

These probabilistic models identify symptoms and personal/lifestyle factors that might prove useful targets for indicated preventative strategies.

Within-person growth in life satisfaction (LS) can protect against declines in cognitive functioning, and, conversely, over time. However, most studies have been cross-sectional, thereby precluding causal inferences. Thus, we used bivariate dual latent change score modeling to test within-person change-to-future change relations between LS and cognition.

Community adults completed in-person tests of verbal working memory (WM), processing speed, spatial cognition, and an LS self-report. Five waves of assessment occurred across 23 years.

Reduction in LS predicted future decreases in spatial cognition, processing speed, and verbal WM (|d| = 0.150–0.354). Additionally, depletion in processing speed and verbal WM predicted a future decrease in LS (d = 0.142–0.269). However, change in spatial cognition did not predict change in LS (|d| = 0.085).

LS and verbal WM and processing speed predicted one another across long durations. Evidence-based therapies can be augmented to target LS and cognition.

The salutary effect of window views on greenery for inpatients in hospitals on length of stay and recovery rate has been repeatedly shown, however, not for psychiatric inpatients. The study assessed the association between a window view on green trees or man-made objects and brightness of the room on length of stay in a sample of psychiatric inpatients from one clinic.

Data records of 244 psychiatric inpatients (mean age in years 41.8; SD = 11.8; 59.8% female, length of stay varying between 7 and 100 days) that were admitted between May 2013 and October 2018 with affective disorders were examined. Window view was assessed with images taken from each room and classified into showing man-made objects or green trees. The percentage of green within each image was also calculated as greenness of the view. Brightness was assessed with a luxmeter.

Although no effect was found for the dichotomous measures (man-made objects vs. green trees), a suppression effect emerged for percentage of green and brightness. The results indicate that both greenness of the window view as well as brightness significantly reduce length of stay in psychiatric inpatients with affective disorders.

The suppression effect likely results from the characteristics of the windows; the greenest rooms also being the darkest. Due to the infrastructure of the ward, greenness and brightness came at the expense of each other. The results generally support the importance of a view into greenery and natural sunlight for recovery.

One of the challenges in human neuroscience is to uncover associations between brain organization and psychopathology in order to better understand the biological underpinnings of mental disorders. Here, we aimed to characterize the neural correlates of psychopathology dimensions obtained using two conceptually different data-driven approaches.

Dimensions of psychopathology that were either maximally dissociable or correlated were respectively extracted by independent component analysis (ICA) and exploratory factor analysis (EFA) applied to the Childhood Behavior Checklist items from 9- to 10-year-olds (n = 9983; 47.8% female, 50.8% white) participating in the Adolescent Brain Cognitive Development study. The patterns of brain morphometry, white matter integrity and resting-state connectivity associated with each dimension were identified using kernel-based regularized least squares and compared between dimensions using Spearman’s correlation coefficient.

ICA identified three psychopathology dimensions, representing opposition–disinhibition, cognitive dyscontrol, and negative affect, with distinct brain correlates. Opposition–disinhibition was negatively associated with cortical surface area, cognitive dyscontrol was negatively associated with anatomical and functional dysconnectivity while negative affect did not show discernable associations with any neuroimaging measure. EFA identified three dimensions representing broad externalizing, neurodevelopmental, and broad Internalizing problems with partially overlapping brain correlates. All EFA-derived dimensions were negatively associated with cortical surface area, whereas measures of functional and structural connectivity were associated only with the neurodevelopmental dimension.

This study highlights the importance of cortical surface area and global connectivity for psychopathology in preadolescents and provides evidence for dissociable psychopathology dimensions with distinct brain correlates.

When facing a traumatic event, some people may experience positive changes, defined as posttraumatic growth (PTG).

Understanding the possible positive consequences of the pandemic on the individual level is crucial for the development of supportive psychosocial interventions. The present paper aims to: 1) evaluate the levels of PTG in the general population; 2) to identify predictors of each dimension of post-traumatic growth.

The majority of the sample (67%, N = 13,889) did not report any significant improvement in any domain of PTG. Participants reported the highest levels of growth in the dimension of “appreciation of life” (2.3 ± 1.4), while the lowest level was found in the “spiritual change” (1.2 ± 1.2). Female participants reported a slightly higher level of PTG in areas of personal strength (p < .002) and appreciation for life (p < .007) compared to male participants, while no significant association was found with age. At the multivariate regression models, weighted for the propensity score, only the initial week of lockdown (between 9-15 April) had a negative impact on the dimension of “relating to others” (B = −.107, 95% CI = −.181 to −.032, p < .005), while over time no other effects were found. The duration of exposure to lockdown measures did not influence the other dimensions of PTG.

The assessment of the levels of PTG is of great importance for the development of ad hoc supportive psychosocial interventions. From a public health perspective, the identification of protective factors is crucial for developing ad-hoc tailored interventions and for preventing the development of full-blown mental disorders in large scale.

Support vector machines (SVMs) based on brain-wise functional connectivity (FC) have been widely adopted for single-subject prediction of patients with schizophrenia, but most of them had small sample size. This study aimed to evaluate the performance of SVMs based on a large single-site dataset and investigate the effects of demographic homogeneity and training sample size on classification accuracy.

The resting functional Magnetic Resonance Imaging (fMRI) dataset comprised 220 patients with schizophrenia and 220 healthy controls. Brain-wise FCs was calculated for each participant and linear SVMs were developed for automatic classification of patients and controls. First, we evaluated the SVMs based on all participants and homogeneous subsamples of men, women, younger (18–30 years), and older (31–50 years) participants by 10-fold nested cross-validation. Then, we hold out a fixed test set of 40 participants (20 patients and 20 controls) and evaluated the SVMs based on incremental training sample sizes (N = 40, 80, …, 400).

We found that the SVMs based on all participants had accuracy of 85.05%. The SVMs based on male, female, young, and older participants yielded accuracy of 84.66, 81.56, 80.50, and 86.13%, respectively. Although the SVMs based on older subsamples had better performance than those based on all participants, they generalized poorly to younger participants (77.24%). For incremental training sizes, the classification accuracy increased stepwise from 72.6 to 83.3%, with >80% accuracy achieved with sample size >240.

The findings indicate that SVMs based on a large dataset yield high classification accuracy and establish models using a large sample size with heterogeneous properties are recommended for single subject prediction of schizophrenia.

The Positive and Negative Syndrome Scale (PANSS) is widely used in schizophrenia and has been divided into distinct factors (5-factor models) and subfactors. Network analyses are newer in psychiatry and can help to better understand the relationships and interactions between the symptoms of a psychiatric disorder. The aim of this study was threefold: (a) to evaluate connections between schizophrenia symptoms in two populations of patients (patients in the acutely exacerbated phase of schizophrenia and patients with predominant negative symptoms [PNS]), (b) to test whether network analyses support the Mohr 5 factor model of the PANSS and the Kahn 2 factor model of negative symptoms, and finally (c) to identify the most central symptoms in the two populations.

Using pooled baseline data from four cariprazine clinical trials in patients with acute exacerbation of schizophrenia (n = 2193) and the cariprazine–risperidone study in patients with PNS (n = 460), separate network analyses were performed. Network structures were estimated for all 30 items of the PANSS.

While negative symptoms in patients with an acute exacerbation of schizophrenia are correlated with other PANSS symptoms, these negative symptoms are not correlated with other PANSS symptoms in patients with PNS. The Mohr factors were partially reflected in the network analyses. The two most central symptoms (largest node strength) were delusions and uncooperativeness in acute phase patients and hostility and delusions in patients with PNS.

This network analysis suggests that symptoms of schizophrenia are differently structured in acute and PNS patients. While in the former, negative symptoms are mainly secondary, in patients with PNS, they are mainly primary. Further, primary negative symptoms are better conceptualized as distinct negative symptom dimensions of the PANSS.

To examine the mortality risk of current and life-time depressive as well as anxiety disorders, whether this risk is moderated by sex or age, and whether this risk can be explained by lifestyle and/or somatic health status.

A cohort study (Lifelines) including 141,377 participants (18–93 years) which were followed-up regarding mortality for 8.6 years (range 3.0–13.7). Baseline depressive and anxiety disorders according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria were assessed with the Mini International Neuropsychiatric Interview and lifetime diagnoses by self-report. All-cause mortality was retrieved from Statistics Netherlands. Cox-regression was applied to calculate proportional hazard ratios, adjusted for lifestyle (physical activity, alcohol use, smoking, and body mass index) and somatic health status (multimorbidity and frailty) in different models.

The mortality rate of depressive and anxiety disorders was conditional upon age but not on sex. Only in people below 60 years, current depressive and anxiety disorders were associated with mortality. Only depressive disorder and panic disorder independently predicted mortality when all mental disorders were included simultaneously in one overall model (hazard ratio [HR] = 2.18 [95% confidence intervals (CI): 1.56–3.05], p < 0.001 and HR = 2.39 [95% CI: 1.15–4.98], p = 0.020). Life-time depressive and anxiety disorders, however, were independent of each other associated with mortality. Associations hardly changed when adjusted for lifestyle characteristics but decreased substantially when adjusted for somatic health status (in particular physical frailty).

In particular, depressive disorder is associated with excess mortality in people below 60 years, independent of their lifestyle. This effect seems partly explained by multimorbidity and frailty, which suggest that chronic disease management of depression-associated somatic morbidity needs to be (further) improved.

The COVID-19 pandemic caused an unprecedented worldwide crisis affecting several sectors, including health, social care, economy and society at large. The World Health Organisation has emphasized that mental health care should be considered as one of the core sectors within the overall COVID-19 health response. By March 2020, recommendations for the organization of mental health services across Europe have been developed by several national and international mental health professional associations.

The European Psychiatric Association (EPA) surveyed a large European sample of psychiatrists, namely the “EPA Ambassadors”, on their clinical experience of the impact of COVID-19 pandemic on the treatment of psychiatric patients during the month of April 2020 in order to: a) identify and report the views and experiences of European psychiatrists; and b) represent and share these results with mental health policy makers at European level. Based on the recommendations issued by national psychiatric associations and on the results of our survey, we identified important organisational aspects of mental health care during the peak of the first wave of the COVID-19.

While most of the recommendations followed the same principles, significant differences between countries emerged in service delivery, mainly relating to referrals to outpatients and for inpatient admission, assessments and treatment for people with mental disorders. Compared to previous months, the mean number of patients treated by psychiatrists in outpatient settings halved in April 2020. In the same period, the number of mentally ill patients tested for, or developing, COVID-19 was low. In most of countries, traditional face-to-face visits were replaced by online remote consultations.

Based on our findings we recommend: 1) to implement professional guidelines into practice and harmonize psychiatric clinical practice across Europe; 2) to monitor the treatment outcomes of patients with COVID-19 and pre-existing mental disorders; 3) to keep psychiatric services active by using all available options (for example telepsychiatry); 4) to increase communication and cooperation between different health care providers.

New recommendations regarding the use of personal protective equipment (PPE) during delivery have changed the maternal birth experience. In this study, we investigated the mental perceived impact of PPE use during delivery on the development of maternal postpartum depression (PPD) and post-traumatic stress symptoms (PTSS).

This was a multicenter, retrospective cohort study concerning women who delivered during the COVID-19 pandemic first lockdown period in Israel. Postpartum women were approached and asked to complete a comprehensive online questionnaire. Impact of PPE was graded on a scale of 1–5, and Impact of PPE ≥4 was considered high. PPD and PTSS were assessed using the EPDS and City BiTS questionnaires.

Of 421 parturients, 36 (9%) reported high Impact of PPE. Parturients with high Impact of PPE had significantly higher PPD and PTSS scores)EPDS 8.4 ± 5.8 vs. 5.7 ± 5.3; City BiTS 9.2 ± 10.3 vs. 5.8 ± 7.8, p < 0.05 for both). Following adjustment for socio-demographic and delivery confounders and fear of COVID-19 (using Fear of COVID19 scale), Impact of PPE remained positively correlated with PPD symptoms (ß = 0.103, 95% confidence intervals [CI] 0.029–1.006, p = 0.038).

When examining the risk factors for developing postpartum PTSS—experiences during labor and PPE were found to be significant variables. As the use of PPE is crucial in this era of COVID-19 pandemic in order to protect both parturients and caregivers, creative measures should be taken in order to overcome the communication gap it poses.

Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.

Using data from 9,421 individuals aged 8–21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with executive function, episodic memory, complex reasoning, social cognition, motor speed, and general cognitive ability. Gene × Age analyses determined whether genetic influences on these factors show developmental variation.

Externalizing was heritable (h2 = 0.46, p = 1 × 10−6), but not anxious-misery (h2 = 0.09, p = 0.183), fear (h2 = 0.04, p = 0.337), psychosis-spectrum (h2 = 0.00, p = 0.494), or general psychopathology (h2 = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρg = −0.412, p = 0.004), verbal reasoning (ρg = −0.485, p = 0.001), spatial reasoning (ρg = −0.426, p = 0.010), motor speed (ρg = 0.659, p = 1x10−4), verbal knowledge (ρg = −0.314, p = 0.002), and general cognitive ability (g)(ρg = −0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γg = −0.146, p = 0.004) and increasing environmental variance (γe = 0.059, p = 0.009) on externalizing.

Cognitive impairment may be a useful endophenotype of externalizing psychopathology and, therefore, help elucidate its pathophysiological underpinnings. Decreasing genetic variance suggests that gene discovery efforts may be more fruitful in children than adolescents or young adults.

Self-harm and suicidality are common presentations in children and adolescents requiring a mental health inpatient admission. Although there are several studies on adolescents, there is relatively limited research into childhood self-harm and suicidality during such admissions.

A retrospective electronic file review was conducted on all children discharged from a national mental health inpatient children’s unit over a 6-year period. Several independent variables were compared between self-harm/suicidal and non-self-harm/non-suicidal children. Separate analyses investigated changes in self-harm/suicidality, functional outcomes, and risk assessment ratings between admission and discharge.

A total of 105 children were included in this study. During admission, 65.7% of them reported self-harm thoughts, 61% engaged in self-harm, 50.5% expressed suicidal thoughts, and 14.3% engaged in suicidal behavior. Thoughts and acts of self-harm were associated with previous self-harm, longer admissions, and Attention Deficit Hyperactivity Disorder. Suicidality overlapped with self-harm and was strongly predicted by previous self-harm. The prevalence of self-harm and suicidal thoughts and acts significantly decreased during admission. Children in the non-self-harm group had marginally better functional outcomes upon discharge compared to those in the self-harm group. Children and parents/caregivers were similarly satisfied with treatment, irrespective of children’s self-harm/suicidality.

Self-harm and suicidality were widespread among children admitted to hospital. Better understanding of the mechanisms and factors related to self-harm and suicidality in this age group could help mitigate associated risks and improve existing safety strategies.

There is growing interest in new factors contributing to the genesis of eating disorders (EDs). Research recently focused on the study of microbiota. Dysbiosis, associated with a specific genetic susceptibility, may contribute to the development of anorexia nervosa (AN), bulimia nervosa, or binge eating disorder, and several putative mechanisms have already been identified. Diet seems to have an impact not only on modification of the gut microbiota, facilitating dysbiosis, but also on its recovery in patients with EDs.

This systematic review based on the PICO strategy searching into PubMed, EMBASE, PsychINFO, and Cochrane Library examined the literature on the role of altered microbiota in the pathogenesis and treatment of EDs.

Sixteen studies were included, mostly regarding AN. Alpha diversity and short-chain fatty acid (SCFA) levels were lower in patients with AN, and affective symptoms and ED psychopathology seem related to changes in gut microbiota. Microbiota-derived proteins stimulated the autoimmune system, altering neuroendocrine control of mood and satiety in EDs. Microbial richness increased in AN after weight regain on fecal microbiota transplantation.

Microbiota homeostasis seems essential for a healthy communication network between gut and brain. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of EDs. A restored microbial balance may be a possible treatment target for EDs. A better and more in-depth characterization of gut microbiota and gut–brain crosstalk is required. Future studies may deepen the therapeutic and preventive role of microbiota in EDs.

People living with serious mental illness (SMI) experience debilitating symptoms that worsen their physical health and quality of life. Regular physical activity (PA) may bring symptomatic improvements and enhance wellbeing. When undertaken in community-based group settings, PA may yield additional benefits such as reduced isolation. Initiating PA can be difficult for people with SMI, so PA engagement is commonly low. Designing acceptable and effective PA programs requires a better understanding of the lived experiences of PA initiation among people with SMI.

This systematic review of qualitative studies used the meta-ethnography approach by Noblit and Hare (1988). Electronic databases were searched from inception to November 2017. Eligible studies used qualitative methodology; involved adults (≥18 years) with schizophrenia, bipolar affective disorder, major depressive disorder, or psychosis; reported community-based group PA; and captured the experience of PA initiation, including key features of social support. Study selection and quality assessment were performed by four reviewers.

Sixteen studies were included in the review. We identified a “journey” that depicted a long sequence of phases involved in initiating PA. The journey demonstrated the thought processes, expectations, barriers, and support needs of people with SMI. In particular, social support from a trusted source played an important role in getting people to the activity, both physically and emotionally.

The journey illustrated that initiation of PA for people with SMI is a long complex transition. This complex process needs to be understood before ongoing participation in PA can be addressed. Registration—The review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) on 22/03/2017 (registration number CRD42017059948).

The Coronavirus disease 2019 (COVID-19) pandemic is an unprecedented traumatic event influencing the healthcare, economic, and social welfare systems worldwide. In order to slow the infection rates, lockdown has been implemented almost everywhere. Italy, one of the countries most severely affected, entered the “lockdown” on March 8, 2020.

The COvid Mental hEalth Trial (COMET) network includes 10 Italian university sites and the National Institute of Health. The whole study has three different phases. The first phase includes an online survey conducted between March and May 2020 in the Italian population. Recruitment took place through email invitation letters, social media, mailing lists of universities, national medical associations, and associations of stakeholders (e.g., associations of users/carers). In order to evaluate the impact of lockdown on depressive, anxiety and stress symptoms, multivariate linear regression models were performed, weighted for the propensity score.

The final sample consisted of 20,720 participants. Among them, 12.4% of respondents (N = 2,555) reported severe or extremely severe levels of depressive symptoms, 17.6% (N = 3,627) of anxiety symptoms and 41.6% (N = 8,619) reported to feel at least moderately stressed by the situation at the DASS-21.

According to the multivariate regression models, the depressive, anxiety and stress symptoms significantly worsened from the week April 9–15 to the week April 30 to May 4 (p < 0.0001). Moreover, female respondents and people with pre-existing mental health problems were at higher risk of developing severe depression and anxiety symptoms (p < 0.0001).

Although physical isolation and lockdown represent essential public health measures for containing the spread of the COVID-19 pandemic, they are a serious threat for mental health and well-being of the general population. As an integral part of COVID-19 response, mental health needs should be addressed.

The 2019 coronavirus disease (COVID-19) pandemic, with its associated restrictions on daily life, is like a perfect storm for poor mental health and wellbeing. The purpose of this study was therefore to examine the impacts of COVID-19 on mental health and wellbeing during the ongoing pandemic in Sweden.

Standardized measures of depression, anxiety, and insomnia as well as measures of risk and vulnerability factors known to be associated with poor mental health outcomes were administered through a national, online, cross-sectional survey (n = 1,212; mean age 36.1 years; 73% women).

Our findings show significant levels of depression, anxiety, and insomnia in Sweden, at rates of 30%, 24.2%, and 38%, respectively. The strongest predictors of these outcomes included poor self-rated overall health and a history of mental health problems. The presence of COVID-19 symptoms and specific health and financial worries related to the pandemic also appeared important.

The impacts of COVID-19 on mental health in Sweden are comparable to impacts shown in previous studies in Italy and China. Importantly, the pandemic seems to impose most on the mental health of those already burdened with the impacts of mental health problems. These results provide a basis for providing more support for vulnerable groups, and for developing psychological interventions suited to the ongoing pandemic and for similar events in the future.

Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear.

The phenotypic data of 12,872–91,009 participants (59.18–63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations.

We observed associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957–0.979, p = 2.29 × 10−6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51 × 10−74) and white matter (B = 0.129, p = 1.67 × 10−74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850–0.933, p = 4.46 × 10−5) and right thalamus (OR = 0.884, 95% CI = 0.841–0.928, p = 2.67 × 10−5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = –0.220, p = 0.020) and right thalamus (B = –0.207, p = 0.014).

Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations.