Poor mental health has consistently been associated with substance use (smoking, alcohol drinking, cannabis use, and consumption of caffeinated drinks). To properly inform public health policy it is crucial to understand the mechanisms underlying these associations, and most importantly, whether or not they are causal.

In this pre-registered systematic review, we assessed the evidence for causal relationships between mental health and substance use from Mendelian randomization (MR) studies, following PRISMA. We rated the quality of included studies using a scoring system that incorporates important indices of quality, such as the quality of phenotype measurement, instrument strength, and use of sensitivity methods.

Sixty-three studies were included for qualitative synthesis. The final quality rating was ‘−’ for 16 studies, ‘– +’ for 37 studies, and ‘+’for 10 studies. There was robust evidence that higher educational attainment decreases smoking and that there is a bi-directional, increasing relationship between smoking and (symptoms of) mental disorders. Another robust finding was that higher educational attainment increases alcohol use frequency, but decreases binge-drinking and alcohol use problems, and that mental disorders causally lead to more alcohol drinking without evidence for the reverse.

The current MR literature increases our understanding of the relationship between mental health and substance use. Bi-directional causal relationships are indicated, especially for smoking, providing further incentive to strengthen public health efforts to decrease substance use. Future MR studies should make use of large(r) samples in combination with detailed phenotypes, a wide range of sensitivity methods, and triangulate with other research methods.

Motor abnormalities (MAs) are the primary manifestations of schizophrenia. However, the extent to which MAs are related to alterations of subcortical structures remains understudied.

We aimed to investigate the associations of MAs and basal ganglia abnormalities in first-episode psychosis (FEP) and healthy controls. Magnetic resonance imaging was performed on 48 right-handed FEP and 23 age-, gender-, handedness-, and educational attainment-matched controls, to obtain basal ganglia shape analysis, diffusion tensor imaging techniques (fractional anisotropy and mean diffusivity), and relaxometry (R2*) to estimate iron load. A comprehensive motor battery was applied including the assessment of parkinsonism, catatonic signs, and neurological soft signs (NSS). A fully automated model-based segmentation algorithm on 1.5T MRI anatomical images and accurate corregistration of diffusion and T2* volumes and R2* was used.

FEP patients showed significant local atrophic changes in left globus pallidus nucleus regarding controls. Hypertrophic changes in left-side caudate were associated with higher scores in sensory integration, and in right accumbens with tremor subscale. FEP patients showed lower fractional anisotropy measures than controls but no significant differences regarding mean diffusivity and iron load of basal ganglia. However, iron load in left basal ganglia and right accumbens correlated significantly with higher extrapyramidal and motor coordination signs in FEP patients.

Taken together, iron load in left basal ganglia may have a role in the emergence of extrapyramidal signs and NSS of FEP patients and in consequence in the pathophysiology of psychosis.

Depressive episodes experienced in unipolar (UD) and bipolar (BD) disorders are characterized by anhedonia and have been associated with abnormalities in reward processes related to reward valuation and error prediction. It remains however unclear whether these deficits are associated with familial vulnerability to mood disorders.

In a functional magnetic resonance imaging study, we evaluated differences in the expected value (EV) and reward prediction error (RPE) signals in ventral striatum (VS) and prefrontal cortex between three groups of monozygotic twins: affected twins in remission for either UD or BD (n = 53), their high-risk unaffected co-twins (n = 34), and low-risk twins with no family history of mood disorders (n = 25).

Compared to low-risk twins, affected twins showed lower EV signal bilaterally in the frontal poles and lower RPE signal bilaterally in the VS, left frontal pole and superior frontal gyrus. The high-risk group did not show a significant change in the EV or RPE signals in frontostriatal regions, yet both reward signals were consistently lower compared with low-risk twins in all regions where the affected twins showed significant reductions.

Our findings strengthen the notion that reduced valuation of expected rewards and reduced error-dependent reward learning may underpin core symptom of depression such as loss of interest in rewarding activities. The trend reduction in reward-related signals in unaffected co-twins warrants further investigation of this effect in larger samples and prospective follow-up to confirm possible association with increased familial vulnerability to mood disorders.

As uncertainty remains about whether clinical response influences cognitive function after electroconvulsive therapy (ECT) for depression, we examined the effect of remission status on cognitive function in depressed patients 4 months after a course of ECT.

A secondary analysis was undertaken on participants completing a randomised controlled trial of ketamine augmentation of ECT for depression who were categorised by remission status (MADRS ⩽10 v. >10) 4 months after ECT. Cognition was assessed with self-rated memory and neuropsychological tests of anterograde verbal and visual memory, autobiographical memory, verbal fluency and working memory. Patients were assessed through the study, healthy controls on a single occasion, and compared using analysis of variance.

At 4-month follow-up, remitted patients (N = 18) had a mean MADRS depression score of 3.8 (95% CI 2.2–5.4) compared with 27.2 (23.0–31.5) in non-remitted patients (N = 19), with no significant baseline differences between the two groups. Patients were impaired on all cognitive measures at baseline. There was no deterioration, with some measures improving, 4-months after ECT, at which time remitted patients had significantly improved self-rated memory, anterograde verbal memory and category verbal fluency compared with those remaining depressed. Self-rated memory correlated with category fluency and autobiographical memory at follow-up.

We found no evidence of persistent impairment of cognition after ECT. Achieving remission improved subjective memory and verbal memory recall, but other aspects of cognitive function were not influenced by remission status. Self-rated memory may be useful to monitor the effects of ECT on longer-term memory.

Hierarchical structural models of psychopathology rarely extend to obsessive-compulsive spectrum disorders. The current study sought to examine the higher-order structure of the obsessive-compulsive and related disorders (OCRDs) in DSM-5: obsessive-compulsive disorder (OCD), hoarding disorder (HD), body dysmorphic disorder (BDD), trichotillomania (hair-pulling disorder; HPD) and excoriation (skin-picking) disorder (SPD).

Adult patients in a partial hospital program (N = 532) completed a dimensional measure of the five OCRDs. We used confirmatory factor analysis to identify the optimal model of the comorbidity structure. We then examined the associations between the transdiagnostic factors and internalizing and externalizing symptoms (i.e. depression, generalized anxiety, neuroticism, and drug/alcohol cravings).

The best fitting model included two correlated higher-order factors: an obsessions-compulsions (OC) factor (OCD, BDD, and HD), and a body-focused repetitive behavior (BFRB) factor (HPD and SPD). The OC factor, not the BFRB factor, had unique associations with internalizing symptoms (standardized effects = 0.42–0.66) and the BFRB factor, not the OC factor, had small marginally significant unique association with drug/alcohol cravings (standardized effect = 0.22, p = 0.088).

The results mirror findings from twin research and indicate that OCD, BDD, and HD share liability that is significantly associated with internalizing symptoms, but this liability may be relatively less important for BFRBs. Further research is needed to better examine the associations between BFRBs and addictive disorders.

There is substantial variability in involuntary psychiatric admission rates across countries and sub-regions within countries that are not fully explained by patient-level factors. We sought to examine whether in a government-funded health care system, physician payments for filling forms related to an involuntary psychiatric hospitalization were associated with the likelihood of an involuntary admission.

This is a population-based, cross-sectional study in Ontario, Canada of all adult psychiatric inpatients in Ontario (2009–2015, n = 122 851). We examined the association between the proportion of standardized forms for involuntary admissions that were financially compensated and the odds of a patient being involuntarily admitted. We controlled for socio-demographic characteristics, clinical severity, past-health care system utilization and system resource factors.

Involuntary admission rates increased from the lowest (Q1, 70.8%) to the highest (Q5, 81.4%) emergency department (ED) quintiles of payment, with the odds of involuntary admission in Q5 being nearly significantly higher than the odds of involuntary admission in Q1 after adjustment (aOR 1.73, 95% CI 0.99–3.01). With payment proportion measured as a continuous variable, the odds of involuntary admission increased by 1.14 (95% CI 1.03–1.27) for each 10% absolute increase in the proportion of financially compensated forms at that ED.

We found that involuntary admission was more likely to occur at EDs with increasing likelihood of financial compensation for invoking involuntary status. This highlights the need to better understand how physician compensation relates to the ethical balance between the right to safety and autonomy for some of the world's most vulnerable patients.

Affective neuroscience and scar theories propose that increased excessive worry, the hallmark symptom of generalized anxiety disorder (GAD), predicts future declines in executive functioning (EF). However, the preponderance of cross-sectional designs used to examine between-person chronic worry–EF relationships has blocked progress on understanding their potentially causal within-person associations. Accordingly, this study used bivariate dual latent change score (LCS) models to test whether within-person increased GAD severity might relate to future reduced EF.

Community-dwelling adults (N = 2581, 46 years on average, s.d. = 11.40, 54.71% female) were assessed for GAD symptom severity (Composite International Diagnostic Interview-Short Form) across three waves, spaced about 9 years apart. Three aspects of EF [inhibition, set-shifting, and mixing costs (MCs; a measure related to common EF)], were assessed with stop-and-go switch tasks. Participants responded to 20 normal and 20 reverse single-task block trials and 32 mixed-task switch block trials. EF tests were administered at time 2 (T2) and time 3 (T3), but not at time 1 (T1).

After controlling for T1 depression, LCS models revealed that within-person increased T1 − T2 GAD severity substantially predicted future reduced T2 − T3 inhibition and set-shifting (both indexed by accuracy and latency), and MC (indexed by latency) with moderate-to-large effect sizes (|d| = 0.51–0.96).

Results largely support scar theories by offering preliminary within-person, naturalistic evidence that heightened excessive worry can negatively predict future distinct aspects of cognitive flexibility. Effectively targeting pathological worry might prevent difficulties arising from executive dysfunction.

Major depressive disorder (MDD) is a prevalent mental disorder characterized by impairments in affect, behaviour and cognition. Previous studies have indicated that the anterior cingulate cortex (ACC) may play an essential role in the pathophysiology of depression. In this study, we systematically identified changes in functional connectivity (FC) for ACC subdivisions that manifest in MDD and further investigated the relationship between these changes and the clinical symptoms of depression.

Sub-regional ACC FC was estimated in 41 first-episode medication-naïve MDD patients compared to 43 healthy controls. The relationships between depressive symptom severity and aberrant FC of ACC subdivisions were investigated. In addition, we conducted a meta-analysis to generate the distributions of MDD-related abnormal regions from previously reported results and compared them to FC deficits revealed in this study.

In MDD patients, the subgenual and perigenual ACC demonstrated decreased FC with the posterior regions of the default network (DN), including the posterior inferior parietal lobule and posterior cingulate cortex. FC of these regions was negatively associated with the Automatic Thoughts Questionnaire scores and largely overlapped with previously reported abnormal regions. In addition, reduced FC between the caudal ACC and precuneus was negatively correlated with the Hamilton Anxiety Scale scores. We also found increased FC between the rostral ACC and dorsal medial prefrontal cortex.

Our findings confirmed that functional interaction changes in different ACC sub-regions are specific and associated with distinct symptoms of depression. Our findings provide new insights into the role of ACC sub-regions and DN in the pathophysiology of MDD.

Contemporary models of psychosis implicate the importance of affective dysregulation and cognitive factors (e.g. biases and schemas) in the development and maintenance of psychotic symptoms, but studies testing proposed mechanisms remain limited. This study, uniquely using a prospective design, investigated whether the jumping to conclusions (JTC) reasoning bias contributes to psychosis progression and persistence.

Data were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The Composite International Diagnostic Interview and an add-on instrument were used to assess affective dysregulation (i.e. depression, anxiety and mania) and psychotic experiences (PEs), respectively. The beads task was used to assess JTC bias. Time series analyses were conducted using data from T1 and T2 (N = 8666), excluding individuals who reported high psychosis levels at T0.

Although the prospective design resulted in low statistical power, the findings suggest that, compared to those without symptoms, individuals with lifetime affective dysregulation were more likely to progress from low/moderate psychosis levels (state of ‘aberrant salience’, one or two PEs) at T1 to high psychosis levels (‘frank psychosis’, three or more PEs or psychosis-related help-seeking behaviour) at T2 if the JTC bias was present [adj. relative risk ratio (RRR): 3.8, 95% confidence interval (CI) 0.8–18.6, p = 0.101]. Similarly, the JTC bias contributed to the persistence of high psychosis levels (adj. RRR: 12.7, 95% CI 0.7–239.6, p = 0.091).

We found some evidence that the JTC bias may contribute to psychosis progression and persistence in individuals with affective dysregulation. However, well-powered prospective studies are needed to replicate these findings.

Prevalence estimates of autistic traits in individuals with psychotic disorders (PD) vary greatly and it is unclear whether individuals with a familial risk (FR) for psychosis have an increased propensity to display autistic traits. Furthermore, it is unknown whether the presence of comorbid autism traits disproportionally affects the cognitive and behavioral aspects of social functioning in PD.

In total, 504 individuals with PD, 587 unaffected siblings with FR, and 337 typical comparison (TC) individuals (16–50 years) were included. Autistic and psychotic traits were measured with the Autism Spectrum Quotient (AQ) and the Community Assessment of Psychic Experiences (CAPE). Social cognition was assessed with the Picture Sequencing Task (PST) and social behavior with the Social Functioning Scale (SFS).

For PD 6.5% scored above AQ clinical cut-off (⩾32), 1.0% for FR, and 1.2% for TC. After accounting for age, sex, and IQ, the PD group showed significantly more autistic traits and alterations in social behavior and cognition, while FR and TC only displayed marginal differences. Within the PD group autistic traits were a robust predictor of social behavior and there were no interactions with positive psychotic symptoms.

Levels of autistic traits are substantially elevated in PD and have a profoundly negative association with social functioning. In contrast, autistic traits above the clinical cut-off are not elevated in those with FR, and only marginally on a dimensional level. These findings warrant specific clinical guidelines for psychotic patients who present themselves with autistic comorbidity to help address their social needs.

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.

Postpartum psychosis (PP) is a severe postpartum disorder. While working memory and emotional processing-related brain function are consistently impaired in psychoses unrelated to the puerperium, no studies have investigated them in PP.

Twenty-four women at risk of developing PP (11 developed an episode – PE; 13 remained well – NPE) and 20 healthy postpartum women completed two functional magnetic resonance imaging tasks within a year of delivery: working memory (n-back) and emotional face recognition (fearful faces). We compared women at-risk of PP to controls, as well as NPE, PE, and controls to test for potential effects of a PP episode occurrence.

Women at-risk of PP and PE showed hyperactivation of lateral visual areas, precuneus, and posterior cingulate during the n-back task. The at-risk group as a whole, as well as the PE and NPE groups, showed hyperconnectivity of the right dorsolateral prefrontal cortex (DLPFC) with various parieto-occipito-temporo-cerebellar regions compared to controls during several n-back conditions. Increases in connectivity between the right DLPFC and ipsilateral middle temporal gyrus were observed in the PE group compared to NPE during 2-back. During the fearful faces task, at-risk women as a group showed hyperactivation of fronto-cingulo-subcortical regions, and hypoconnectivity between the left amygdala and ipsilateral occipito-parietal regions compared to controls. No significant performance differences were observed.

These results present preliminary evidence of a differential nature of functional brain abnormalities in PP compared to the typically observed reduced connectivity with the DLPFC in psychoses unrelated to puerperium, such as bipolar disorder.

The risk for depression markedly rises during the 5–6 years leading up to the cessation of menstruation, known as the menopause transition. Exposure to extreme estradiol levels may help explain this increase but few studies have examined individual sensitivity to estradiol in predicting perimenopausal depression.

The current study recruited 101 perimenopausal women. During Phase 1, we quantified each woman's sensitivity to changes in estradiol using 12 weekly measures of estrone-3-glucuronide (E1G), a urinary metabolite of estradiol, and concurrent depressive symptoms. The weekly cortisol awakening response was measured to examine the hypothalamic-pituitary-adrenal (HPA) axis in mediating mood sensitivity to estradiol. In Phase 2, depressive symptoms and major depression diagnoses were assessed monthly for 9 months. The relationship between Phase 1 E1G sensitivity and Phase 2 depressive symptoms and major depressive episodes was examined. Several baseline characteristics were examined as potential moderators of this relationship.

The within-person correlation between weekly E1G and mood varied greatly from woman to woman, both in strength and direction. Phase 1 E1G mood sensitivity predicted the occurrence of clinically significant depressive symptoms in Phase 2 among certain subsets of women: those without a prior history of depression, reporting a low number of baseline stressful life events, and reporting fewer months since their last menstrual period. HPA axis sensitivity to estradiol fluctuation did not predict Phase 2 outcomes.

Mood sensitivity to estradiol predicts risk for perimenopausal depression, particularly among women who are otherwise at low risk and among those who are early in the transition.

Social anxiety disorder (SAD) is a prevalent mental disorder diagnosed in childhood and adolescence. Theories regarding brain development and SAD suggest a close link between neurodevelopmental dysfunction at the adolescent juncture and SAD, but direct evidence is rare. This study aims to examine brain structural abnormalities in adolescents with SAD.

High-resolution T1-weighted images were obtained from 31 adolescents with SAD (15–17 years) and 42 matching healthy controls (HC). We evaluated symptom severity with the Social Anxiety Scale for Children (SASC) and the Screen for Child Anxiety Related Emotional Disorders (SCARED). We used voxel-based morphometry analysis to detect regional gray matter volume abnormalities and structural co-variance analysis to investigate inter-regional coordination patterns.

We found significantly higher gray matter volume in the orbitofrontal cortex (OFC) and the insula in adolescents with SAD compared to HC. We also observed significant co-variance of the gray matter volume between the OFC and amygdala, and the OFC and insula in HC, but these co-variance relationships diminished in SAD.

These findings provide the first evidence that the brain structural deficits in adolescents with SAD are not only in the core regions of the fronto-limbic system, but also represented by the diminished coordination in the development of these regions. The delayed and unsynchronized development pattern of the fronto-limbic system supports SAD as an adolescent-sensitive developmental mental disorder.

While taxonomy segregates anxiety symptoms into diagnoses, patients typically present with multiple diagnoses; this poses major challenges, particularly for youth, where mixed presentation is particularly common. Anxiety comorbidity could reflect multivariate, cross-domain interactions insufficiently emphasized in current taxonomy. We utilize network analytic approaches that model these interactions by characterizing pediatric anxiety as involving distinct, inter-connected, symptom domains. Quantifying this network structure could inform views of pediatric anxiety that shape clinical practice and research.

Participants were 4964 youths (ages 5–17 years) from seven international sites. Participants completed standard symptom inventory assessing severity along distinct domains that follow pediatric anxiety diagnostic categories. We first applied network analytic tools to quantify the anxiety domain network structure. We then examined whether variation in the network structure related to age (3-year longitudinal assessments) and sex, key moderators of pediatric anxiety expression.

The anxiety network featured a highly inter-connected structure; all domains correlated positively but to varying degrees. Anxiety patients and healthy youth differed in severity but demonstrated a comparable network structure. We noted specific sex differences in the network structure; longitudinal data indicated additional structural changes during childhood. Generalized-anxiety and panic symptoms consistently emerged as central domains.

Pediatric anxiety manifests along multiple, inter-connected symptom domains. By quantifying cross-domain associations and related moderation effects, the current study might shape views on the diagnosis, treatment, and study of pediatric anxiety.

Social media platforms have long been recognised as major disseminators of health misinformation. Many previous studies have found a negative association between health-protective behaviours and belief in the specific form of misinformation popularly known as ‘conspiracy theory’. Concerns have arisen regarding the spread of COVID-19 conspiracy theories on social media.

Three questionnaire surveys of social media use, conspiracy beliefs and health-protective behaviours with regard to COVID-19 among UK residents were carried out online, one using a self-selecting sample (N = 949) and two using stratified random samples from a recruited panel (N = 2250, N = 2254).

All three studies found a negative relationship between COVID-19 conspiracy beliefs and COVID-19 health-protective behaviours, and a positive relationship between COVID-19 conspiracy beliefs and use of social media as a source of information about COVID-19. Studies 2 and 3 also found a negative relationship between COVID-19 health-protective behaviours and use of social media as a source of information, and Study 3 found a positive relationship between health-protective behaviours and use of broadcast media as a source of information.

When used as an information source, unregulated social media may present a health risk that is partly but not wholly reducible to their role as disseminators of health-related conspiracy beliefs.