Maternal inflammation in early pregnancy has been identified epidemiologically as a prenatal pathogenic factor for the offspring's later mental illness. Early newborn manifestations of the effects of maternal inflammation on human fetal brain development are largely unknown.

Maternal infection, depression, obesity, and other factors associated with inflammation were assessed at 16 weeks gestation, along with maternal C-reactive protein (CRP), cytokines, and serum choline. Cerebral inhibition was assessed by inhibitory P50 sensory gating at 1 month of age, and infant behavior was assessed by maternal ratings at 3 months of age.

Maternal CRP diminished the development of cerebral inhibition in newborn males but paradoxically increased inhibition in females. Similar sex-dependent effects were seen in mothers' assessment of their infant's self-regulatory behaviors at 3 months of age. Higher maternal choline levels partly mitigated the effect of CRP in male offspring.

The male fetal-placental unit appears to be more sensitive to maternal inflammation than females. Effects are particularly marked on cerebral inhibition. Deficits in cerebral inhibition 1 month after birth, similar to those observed in several mental illnesses, including schizophrenia, indicate fetal developmental pathways that may lead to later mental illness. Deficits in early infant behavior follow. Early intervention before birth, including prenatal vitamins, folate, and choline supplements, may help prevent fetal development of pathophysiological deficits that can have life-long consequences for mental health.

Reducing stigma is a perennial target of mental health advocates, but effectively addressing stigma relies on the ability to correctly understand and accurately measure culture-specific and location-specific components of stigma and discrimination.

We developed two culture-sensitive measures that assess the core components of stigma. The 40-item Interpersonal Distance Scale (IDS) asks respondents about their willingness to establish four different types of relationships with individuals with 10 target conditions, including five mental health-related conditions and five comparison conditions. The 40-item Occupational Restrictiveness Scale (ORS) asks respondents how suitable it is for individuals with the 10 conditions to assume four different types of occupations. The scales – which take 15 min to complete – were administered as part of a 2013 survey in Ningxia Province, China to a representative sample of 2425 adult community members.

IDS and ORS differentiated the level of stigma between the 10 conditions. Of the total, 81% of respondents were unwilling to have interpersonal relationships with individuals with mental health-related conditions and 91% considered them unsuitable for various occupations. Substantial differences in attitudes about the five mental health-related conditions suggest that there is no community consensus about what constitutes a ‘mental illness’.

Selection of comparison conditions, types of social relationships, and types of occupations considered by the IDS and ORS make it possible to develop culture-sensitive and cohort-specific measures of interpersonal distance and occupational restrictiveness that can be used to compare the level and type of stigma associated with different conditions and to monitor changes in stigma over time.

Childhood abuse and neglect often occurs within families and can have a large influence on mental well-being across the lifespan. However, the sibling concordance of emotional abuse and neglect (i.e. together referred to as emotional maltreatment; EM), physical abuse (PA) and sexual abuse (SA) and the long-term impact on the context of siblings' maltreatment experiences are unclear. To examine the influence of EM, PA and SA on adult depressive symptoms within the family framework we differentiate between (a) the family-wide (mean level of all siblings) effects and (b) the individual deviation from the mean family level of maltreatment.

The sample (N = 636) consists of 256 families, including at least one lifetime depressed or anxious individual and their siblings. Multilevel modeling was used to examine the family-wide and relative individual effects of childhood maltreatment (CM).

(a) Siblings showed most similarity in their reports of EM followed by PA. SA was mostly reported by one person within a family. In line with these observations, the mean family levels of EM and PA, but not SA, were associated with more depressive symptoms. In addition, (b) depression levels were more elevated in individuals reporting more EM than the family mean.

Particularly in the case of more visible forms of CM, siblings' experiences of EM and PA are associated with the elevated levels of adult depressive symptoms. Findings implicate that in addition to individual maltreatment experiences, the context of siblings' experiences is another crucial risk factor for an individuals' adult depressive symptomatology.

Accurate perception of visual contours is essential for seeing and differentiating objects in the environment. Both the ability to detect visual contours and the influence of perceptual context created by surrounding stimuli are diminished in people with schizophrenia (SCZ). The central aim of the present study was to better understand the biological underpinnings of impaired contour integration and weakened effects of perceptual context. Additionally, we sought to determine whether visual perceptual abnormalities reflect genetic factors in SCZ and are present in other severe mental disorders.

We examined behavioral data and event-related potentials (ERPs) collected during the perception of simple linear contours embedded in similar background stimuli in 27 patients with SCZ, 23 patients with bipolar disorder (BP), 23 first-degree relatives of SCZ, and 37 controls.

SCZ exhibited impaired visual contour detection while BP exhibited intermediate performance. The orientation of neighboring stimuli (i.e. flankers) relative to the contour modulated perception across all groups, but SCZ exhibited weakened suppression by the perceptual context created by flankers. Late visual (occipital P2) and cognitive (centroparietal P3) neural responses showed group differences and flanker orientation effects, unlike earlier ERPs (occipital P1 and N1). Moreover, behavioral effects of flanker context on contour perception were correlated with modulation in P2 & P3 amplitudes.

In addition to replicating and extending findings of abnormal contour integration and visual context modulation in SCZ, we provide novel evidence that the abnormal use of perceptual context is associated with higher-order sensory and cognitive processes.

Cognitive impairment is a core feature of Huntington's disease (HD), however, the onset and rate of cognitive decline is highly variable. Apathy is the most common neuropsychiatric symptom of HD, and is associated with cognitive impairment. The aim of this study was to investigate apathy as a predictor of subsequent cognitive decline over 2 years in premanifest and early HD, using a prospective, longitudinal design.

A total of 118 premanifest HD gene carriers, 111 early HD and 118 healthy control participants from the multi-centre TRACK-HD study were included. Apathy symptoms were assessed at baseline using the apathy severity rating from the Short Problem Behaviours Assessment. A composite of 12 outcome measures from nine cognitive tasks was used to assess cognitive function at baseline and after 24 months.

In the premanifest group, after controlling for age, depression and motor signs, more apathy symptoms predicted faster cognitive decline over 2 years. In contrast, in the early HD group, more motor signs, but not apathy, predicted faster subsequent cognitive decline. In the control group, only older age predicted cognitive decline.

Our findings indicate that in premanifest HD, apathy is a harbinger for cognitive decline. In contrast, after motor onset, in early diagnosed HD, motor symptom severity more strongly predicts the rate of cognitive decline.

Psychotic experiences (PE) are highly prevalent in childhood and are known to be associated with co-morbid mental health disorders and functional difficulties in adolescence. However, little is known about the long-term outcomes of young people who report PE.

As part of the Adolescent Brain Development Study, 211 young people were recruited in childhood (mean age 11.7 years) and underwent detailed clinical interviews, with 25% reporting PE. A 10 year follow-up study was completed and 103 participants returned (mean age 20.9 years). Structured clinical interviews for DSM-5 (SCID-5) and interviewer-rated assessments of functioning were conducted. A detailed neuropsychological battery was also administered. Analyses investigated group differences between those who had ever reported PE and controls in early adulthood.

The PE group was at a significantly higher risk of meeting DSM-5 criteria for a current (OR 4.08, CI 1.16–14.29, p = 0.03) and lifetime psychiatric disorder (OR 3.27, CI 1.43–7.47, p = 0.005). They were also at a significantly higher risk of multi-morbid lifetime psychiatric disorders. Significantly lower scores on current social and global functioning measures were observed for the PE group. Overall, there were no differences in neuropsychological performance between groups apart from significantly lower scores on the Stroop Word task and the Purdue Pegboard task for the PE group.

Our findings suggest that reports of PE are associated with poorer mental health and functional outcomes in early adulthood, with some persisting cognitive and motor deficits. Young people who report such symptoms could be considered a target group for interventions to aid functional outcomes.

This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment.

This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization.

A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects.

After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.

Health anxiety is an under-recognised but a frequent cause of distress. It is particularly common in general hospitals.

We carried out an 8-year follow-up of medical out-patients with health anxiety (hypochondriasis) enrolled in a randomised-controlled trial in five general hospitals in London, Middlesex and Nottinghamshire. Randomisation was to a mean of six sessions of cognitive behaviour therapy adapted for health anxiety (CBT-HA) or to standard care in the clinics. The primary outcome was a change in score on the Short Health Anxiety Inventory, with generalised anxiety and depression as secondary outcomes. Of 444 patients aged 16–75 years seen in cardiology, endocrinology, gastroenterology, neurology and respiratory medicine clinics, 306 (68.9%) were followed-up 8 years after randomisation, including 36 who had died. The study is registered with controlled-trials.com, ISRCTN14565822.

There was a significant difference in the HAI score in favour of CBT-HA over standard care after 8 years [1.83, 95% confidence interval (CI) 0.25–3.40, p = 0.023], between group differences in generalised anxiety were less (0.54, 95% CI −0.29 to 1.36), p = 0.20, ns), but those for depression were greater at 8 years (1.22, 95% CI 0.42–2.01, p < 0.003) in CBT-HA than in standard care, most in standard care satisfying the criteria for clinical depression. Those seen by nurse therapists and in cardiology and gastrointestinal clinics achieved the greatest gains with CBT-HA, with greater improvement in both symptoms and social function.

CBT-HA is a highly long-term effective treatment for pathological health anxiety with long-term benefits. Standard care for health anxiety in medical clinics promotes depression. Nurse therapists are effective practitioners.

Social isolation and loneliness have each been associated with cognitive decline, but most previous research is limited to Western populations. This study examined the relationships of social isolation and loneliness on cognitive function among Chinese older adults.

This study used two waves of data (2011 and 2015) from the China Health and Retirement Longitudinal Study (CHARLS) and analyses were restricted to those respondents aged 50 and older. Social isolation, loneliness, and cognitive function were measured at baseline. Follow-up measures on cognitive function were obtained for 7761 participants (mean age = 60.97, s.d. = 7.31; male, 50.8%). Lagged dependent variable models adjusted for confounding factors were used to evaluate the association between baseline isolation, loneliness, and cognitive function at follow-up.

Loneliness was significantly associated with the cognitive decline at follow-up (episodic memory: β = −0.03, p < 0.01; mental status: β = −0.03, p < 0.01) in the partially adjusted models. These associations became insignificant after additional confounding variables (chronic diseases, health behaviors, disabilities, and depressive symptoms) were taken into account (all p > 0.05). By contrast, social isolation was significantly associated with decreases in all cognitive function measures at follow-up (episodic memory: β = −0.05, p < 0.001; mental status: β = −0.03, p < 0.01) even after controlling for loneliness and all confounding variables.

Social isolation is associated with cognitive decline in Chinese older adults, and the relationships are independent of loneliness. These findings expand our knowledge about the links between social relationships and the cognitive function in non-Western populations.

There is a paucity of long-term prospective disaster studies of the psychological sequelae among survivors.

At 1½ and 25 years after the Spitak earthquake, 142 early adolescents from two cities were assessed: Gumri (moderate–severe exposure) and Spitak (very severe exposure). The Gumri group included treated and not-treated subjects, while the Spitak group included not-treated subjects. Instruments included: DSM-III-R PTSD-Reaction Index (PTSD-RI); DSM-5 PTSD-Checklist (PCL); Depression Self-Rating Scale (DSRS); and Center for Epidemiological Studies-Depression Scale (CES-D).

(1) Between 1½ and 25 years, PTSD rates and mean scores decreased significantly in the three groups (over 50%). However, at 25 years 9.1–22.4% met DSM-5 PTSD criteria. (2) At 1½ years, the Spitak group had higher PTSD-RI (p < 0.001) and DSRS scores (p < 0.001) compared to the Gumri-not-treated group. At 25 years, the Spitak group that had experienced fewer post-earthquake adversities (p < 0.03), had a greater decrease in PTSD-RI scores (p < 0.02), and lower CES-D scores (p < 0.01). (3) Before treatment, PTSD-RI and DSRS scores did not differ between the Gumri-treated and not-treated groups. At 25-years, the Gumri-treated group showed a greater decrease in PTSD-RI scores (p < 0.03), and lower mean PTSD-RI (p < 0.02), PCL (p < 0.02), and CES-D (p < 0.01) scores. (4) Predictors of PTSD symptom severity at 25-years included: home destruction, treatment, social support, post-earthquake adversities, and chronic medical illnesses.

Post-disaster PTSD and depressive symptoms can persist for decades. Trauma-focused treatment, alleviation of post-disaster adversities, improving the social ecology, and monitoring for chronic medical illnesses are essential components of recovery programs.

The aim of the current study was to examine the heterogeneity of functional outcomes in first episode psychosis (FEP) patients and related clinical, neurocognitive and sociodemographic factors using a cluster analytic approach.

A large sample of FEP patients (N = 209) was functionally reassessed 10 years after the first contact with an early intervention service. Multiple baseline, 3-year and 10-year follow-up variables were explored.

The cluster analysis emphasized the existence of six independent clusters of functioning: one cluster was normal overall (42.16%), two clusters showed moderate interpersonal (9.63%) or instrumental (12.65%) deficits, two clusters showed more severe interpersonal (12.05%) or interpersonal and instrumental (13.85%) deficits and there was a significantly overall impaired cluster (9.63%). Cluster comparisons showed that several baseline and follow-up factors were differentially involved in functional outcomes.

The current study demonstrated that distinct clusters of functioning in FEP patients can be identified. The fact that a variety of profiles was observed contributes to a better understanding of the nature of the heterogeneity characterizing FEP patients and has clinical implications for developing individualized treatment plans.

Obsessive-compulsive disorder (OCD) is a psychiatric disorder with multiple symptom dimensions (e.g. contamination, symmetry). OCD clusters in families and decades of twin studies clearly demonstrate an important role for genetics in the etiology of the disorder.

In this review, we summarize the genetic epidemiology and molecular genetic studies of OCD and obsessive-compulsive symptoms.

OCD is a heritable, polygenic disorder with contributions from both common and rare variants, including de novo deleterious variations. Multiple studies have provided reliable support for a large additive genetic contribution to liability to OCD, with discrete OCD symptom dimensions having both shared and unique genetic risks. Genome-wide association studies have not produced significant results yet, likely because of small sample sizes, but larger meta-analyses are forthcoming. Both twin and genome-wide studies show that OCD shares genetic risk with its comorbid conditions (e.g. Tourette syndrome and anorexia nervosa).

Despite significant efforts to uncover the genetic basis of OCD, the mechanistic understanding of how genetic and environmental risk factors interact and converge at the molecular level to result in OCD's heterogeneous phenotype is still mostly unknown. Future investigations should increase ancestral genetic diversity, explore age and/or sex differences in genetic risk for OCD and expand the study of pharmacogenetics, gene expression, gene × environment interactions and epigenetic mechanisms for OCD.

Bipolar disorder and borderline personality disorder (BPD) are each significant public health problems. It has been frequently noted that distinguishing BPD from bipolar disorder is challenging. Consequently, reviews and commentaries have focused on differential diagnosis and identifying clinical features to distinguish the two disorders. While there is a burgeoning literature comparing patients with BPD and bipolar disorder, much less research has characterized patients with both disorders. In the current report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we compare psychiatric outpatients with both BPD and bipolar disorder to patients with BPD without bipolar disorder and patients with bipolar disorder without BPD.

Psychiatric outpatients presenting for treatment were evaluated with semi-structured interviews. The focus of the current study is the 517 patients with both BPD and bipolar disorder (n = 59), BPD without bipolar disorder (n = 330), and bipolar disorder without BPD (n = 128).

Compared to patients with bipolar disorder, the patients with bipolar disorder and BPD had more comorbid disorders, psychopathology in their first-degree relatives, childhood trauma, suicidality, hospitalizations, time unemployed, and likelihood of receiving disability payments. The added presence of bipolar disorder in patients with BPD was associated with more posttraumatic stress disorder in the patients as well as their family, more bipolar disorder and substance use disorders in their relatives, more childhood trauma, unemployment, disability, suicide attempts, and hospitalizations.

Patients with both bipolar disorder and BPD have more severe psychosocial morbidity than patients with only one of these disorders.

The rise of social media use in young people has sparked concern about the impact of cyber-victimisation on mental health. Although cyber-victimisation is associated with mental health problems, it is not known whether such associations reflect genetic and environmental confounding.

We used the co-twin control design to test the direct association between cyber-victimisation and multiple domains of mental health in young people. Participants were 7708 twins drawn from the Twins Early Development Study, a UK-based population cohort followed from birth to age 22.

Monozygotic twins exposed to greater levels of cyber-victimisation had more symptoms of internalising, externalising and psychotic disorders than their less victimised co-twins at age 22, even after accounting for face-to-face peer victimisation and prior mental health. However, effect sizes from the most stringent monozygotic co-twin control analyses were decreased by two thirds from associations at the individual level [pooled β across all mental health problems = 0.06 (95% CI 0.03–0.10) v. 0.17 (95% CI 0.15–0.19) in individual-level analyses].

Cyber-victimisation has a small direct association with multiple mental health problems in young people. However, a large part of the association between cyber-victimisation and mental health is due to pre-existing genetic and environmental vulnerabilities and co-occurring face-to-face victimisation. Therefore, preventative interventions should target cyber-victimisation in conjunction with pre-existing mental health vulnerabilities and other forms of victimisation.

The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.

We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.

The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.

The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.

Care-as-usual (CAU) is often used as a control condition in psychotherapy research, but it may vary considerably what that entails, ranging from no treatment, to routine treatment in primary care, general medical care, perinatal care, and specialized mental health care.

We conducted a meta-analysis of trials comparing psychotherapy for depression to CAU, with a focus on the different categories of CAU and countries where the studies were conducted. We used an existing database of randomized trials on psychotherapy for depression that is updated every year.

A total of 140 studies with 15 419 patients were included. We found no significant differences in effects between categories of CAU (effect sizes ranging from g = 0.43 for CAU in primary care to g = 0.73 for no treatment), but heterogeneity was high in all CAU categories. After stratifying effects across specific countries (within CAU categories) we found that heterogeneity was considerably lower and there were several significant differences between countries. Overall, effects were larger in non-Western countries (g = 0.84 to 1.28) compared to those in Western countries (g = 0.52; p for difference = 0.002). Effects were smaller in studies with risk of bias (p = 0.01).

There are no significant differences between major categories of CAU when compared to psychotherapy conditions in randomized trials. However, effects of psychotherapy differ considerably across CAU conditions in specific countries. CAU therefore is a heterogeneous control condition in psychotherapy research.

Polygenic scores (PGS) are widely used to characterize genetic liability for heritable mental disorders, including attention-deficit/hyperactivity disorder (ADHD). However, little is known about the effects of a low burden of genetic liability for ADHD, including whether this functions as a low risk or protective factor for ADHD and related functional outcomes in later life. The current study examines the association of low ADHD PGS and functional outcomes in adulthood.

Participants were from Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health) (N = 7088; mean age = 29, s.d. = 1.74). ADHD PGS was computed from an existing genome-wide association study, and adult functional outcomes, including cognition, educational attainment, mental health, and physical health were assessed during in-home interviews.

Individuals at the lowest end of the ADHD PGS distribution (i.e. lowest 20th percentile) had the lowest probabilities of ADHD, exhibiting a 17–19% reduction in risk for ADHD relative to the observed 8.3% prevalence rate of ADHD in Add Health. Furthermore, individuals with low ADHD PGS had higher cognitive performance, greater levels of educational attainment, and lower BMI relative to individuals representing the rest of the ADHD PGS distribution, including those who were in the medium and high-PGS groups.

Findings indicate that psychiatric PGS likely capture far more than just the risk and the absence of risk for a psychiatric outcome; where one lies along the PGS distribution may predict diverging functional consequences, for better and for worse.

Major depressive disorder (MDD) is a common mood disorder, with a heritability of around 34%. Molecular genetic studies made significant progress and identified genetic markers associated with the risk of MDD; however, progress is slowed down by substantial heterogeneity as MDD is assessed differently across international cohorts. Here, we used a standardized online approach to measure MDD in multiple cohorts in the Netherlands and evaluated whether this approach can be used in epidemiological and genetic association studies of depression.

Within the Biobank Netherlands Internet Collaboration (BIONIC) project, we collected MDD data in eight cohorts involving 31 936 participants, using the online Lifetime Depression Assessment Self-report (LIDAS), and estimated the prevalence of current and lifetime MDD in 22 623 unrelated individuals. In a large Netherlands Twin Register (NTR) twin-family dataset (n ≈ 18 000), we estimated the heritability of MDD, and the prediction of MDD in a subset (n = 4782) through Polygenic Risk Score (PRS).

Estimates of current and lifetime MDD prevalence were 6.7% and 18.1%, respectively, in line with population estimates based on validated psychiatric interviews. In the NTR heritability estimates were 0.34/0.30 (s.e. = 0.02/0.02) for current/lifetime MDD, respectively, showing that the LIDAS gives similar heritability rates for MDD as reported in the literature. The PRS predicted risk of MDD (OR 1.23, 95% CI 1.15–1.32, R2 = 1.47%).

By assessing MDD status in the Netherlands using the LIDAS instrument, we were able to confirm previously reported MDD prevalence and heritability estimates, which suggests that this instrument can be used in epidemiological and genetic association studies of depression.

Cigarette smoking is strongly associated with major depressive disorder (MDD). However, any genetic etiology of such comorbidity and causal relations is poorly understood, especially at the genome-wide level.

In the present in silico research, we analyzed summary data from the genome-wide association study of the Psychiatric Genetic Consortium for MDD (n = 191 005) and UK Biobank for smoking (n = 337 030) by using various biostatistical methods including Bayesian colocalization analysis, LD score regression, variant effect size correlation analysis, and Mendelian randomization (MR).

By adopting a gene prioritization approach, we identified 43 genes shared by MDD and smoking, which were significantly enriched in membrane potential, gamma-aminobutyric acid receptor activity, and retrograde endocannabinoid signaling pathways, indicating that the comorbid mechanisms are involved in the neurotransmitter system. According to linkage disequilibrium score regression, we found a strong positive correlation between MDD and current smoking (rg = 0.365; p = 7.23 × 10−25) and a negative correlation between MDD and former smoking (rg = −0.298; p = 1.59 × 10−24). MR analysis suggested that genetic liability for depression increased smoking.

These findings inform the concomitant conditions of MDD and smoking and support the use of self-medication with smoking to counteract depression.