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.

Impaired brain metabolism may be central to schizophrenia pathophysiology, but the magnitude and consistency of metabolic dysfunction is unknown.

We searched MEDLINE, PsychINFO and EMBASE between 01/01/1980 and 13/05/2021 for studies comparing regional brain glucose metabolism using 18FDG-PET, in schizophrenia/first-episode psychosis v. controls. Effect sizes (Hedges g) were pooled using a random-effects model. Primary measures were regional absolute and relative CMRGlu in frontal, temporal, parietal and occipital lobes, basal ganglia and thalamus.

Thirty-six studies (1335 subjects) were included. Frontal absolute glucose metabolism (Hedge's g = −0.74 ± 0.54, p = 0.01; I2 = 67%) and metabolism relative to whole brain (g = −0.44 ± 0.34, p = 0.01; I2 = 55%) were lower in schizophrenia v. controls with moderate heterogeneity. Absolute frontal metabolism was lower in chronic (g = −1.18 ± 0.73) v. first-episode patients (g = −0.09 ± 0.88) and controls. Medicated patients showed frontal hypometabolism relative to controls (−1.04 ± 0.26) while metabolism in drug-free patients did not differ significantly from controls. There were no differences in parietal, temporal or occipital lobe or thalamic metabolism in schizophrenia v. controls. Excluding outliers, absolute basal ganglia metabolism was lower in schizophrenia v. controls (−0.25 ± 0.24, p = 0.049; I2 = 5%). Studies identified reporting voxel-based morphometry measures of absolute 18FDG uptake (eight studies) were also analysed using signed differential mapping analysis, finding lower 18FDG uptake in the left anterior cingulate gyrus (Z = −4.143; p = 0.007) and the left inferior orbital frontal gyrus (Z = −4.239; p = 0.02) in schizophrenia.

We report evidence for hypometabolism with large effect sizes in the frontal cortex in schizophrenia without consistent evidence for alterations in other brain regions. Our findings support the hypothesis of hypofrontality in schizophrenia.

Adolescence is a key developmental period for the emergence of psychiatric disorders. However, there is still no consensus on the core mechanisms of dysfunction in youth. Neurobiological sensitivity to unpredictable threat has been associated with several psychiatric disorders in adults. The present study examined adolescent defensive motivation (startle reflex) and attention (event-related potentials) in anticipation of unpredictable threat in relation to both adolescent and maternal (i.e. familial risk) internalizing and externalizing spectra.

The sample included 395 15-year-old adolescents and their biological mothers. Adolescent startle potentiation and probe P300 suppression (indicating increased attention to threat) were measured in anticipation of predictable and unpredictable threat. Adolescent and maternal lifetime history of psychiatric disorders were assessed via semi-structured diagnostic interviews, and confirmatory factor analysis was used to model internalizing and externalizing spectra.

The adolescent internalizing spectrum was positively associated with adolescent startle potentiation and probe P300 suppression to unpredictable threat. Conversely, the adolescent externalizing spectrum was negatively associated with adolescent P300 suppression to unpredictable threat. The maternal internalizing spectrum was positively associated with adolescent startle potentiation to unpredictable threat and P300 suppression to both predictable and unpredictable threat. The maternal externalizing spectrum was negatively associated with adolescent startle potentiation to unpredictable threat and P300 suppression to both predictable and unpredictable threat. Adolescent and maternal internalizing and externalizing spectra were independently related to adolescent startle potentiation and P300 suppression.

Adolescent neurobiological sensitivity to unpredictable threat is associated with both personal history and familial risk for the internalizing and externalizing spectra.

Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19.

This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis.

In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9–59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1–11.4), an affective disorder (OR 4.1; CI 1.6–10.9), and severe respiratory symptoms (OR 4.6; CI 2.2–9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1–0.9) predicted a lower risk of a confusional state.

COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders.

Contemporary views of emotion dysregulation in post-traumatic stress disorder (PTSD) highlight reduced ability to flexibly select regulatory strategies according to differing situational demands. However, empirical evidence of reduced regulatory selection flexibility in PTSD is lacking. Multiple studies show that healthy individuals demonstrate regulatory selection flexibility manifested in selecting attentional disengagement regulatory strategies (e.g. distraction) in high-intensity emotional contexts and selecting engagement meaning change strategies (e.g. reappraisal) in low-intensity contexts. Accordingly, we hypothesized that PTSD populations will show reduced regulatory selection flexibility manifested in diminished increase in distraction (over reappraisal) preference as intensity increases from low to high intensity.

Study 1 compared student participants with high (N = 22) post-traumatic symptoms (PTS, meeting the clinical cutoff for PTSD) and participants with low (N = 22) post-traumatic symptoms. Study 2 compared PTSD diagnosed women (N = 31) due to childhood sexual abuse and matched non-clinical women (N = 31). In both studies, participants completed a well-established regulatory selection flexibility performance-based paradigm that involves selecting between distraction and reappraisal to regulate negative emotional words of low and high intensity.

Beyond demonstrating adequate psychometric properties, Study 1 confirmed that relative to the low PTS group, the high PTS group presented reduced regulatory selection flexibility (p = 0.01, $\eta _{\rm p}^2$ = 0.14). Study 2 critically extended findings of Study 1, in showing similar reduced regulatory selection flexibility in a diagnosed PTSD population, relative to a non-clinical population (p = 0.002, $\eta _{\rm p}^2$ = 0.114).

Two studies provide converging evidence for reduced emotion regulatory selection flexibility in two PTSD populations.

Nonsuicidal self-injury (NSSI) is a risk factor for suicide, yet how changes in NSSI engagement relate to suicide ideation, planning, and attempts remains largely unknown. The current study aims to fill this gap by examining how changes in NSSI frequency over time related to concurrent changes in suicide thoughts and behaviors.

Data came from a sample of 403 self-injuring young adults who completed assessments of NSSI and suicide thoughts and behaviors at baseline, 6, and 12 months. Bivariate latent growth modeling, adjusting for covariates of lifetime NSSI frequency and treatment status, was used to examine the extent to which changes in NSSI frequency related to suicide ideation and suicide planning.

The frequency of NSSI declined across the study period. The slopes of NSSI and suicide ideation were significantly correlated, suggesting individuals with sharper declines in NSSI across time also showed sharper declines in suicide ideation. The intercepts between NSSI and suicide planning were significantly correlated, suggesting those with high NSSI frequency at baseline tended to report higher suicide planning across time. After covariate adjustment, the intercept of suicide planning marginally (p = 0.08) correlated with the slope of NSSI, tentatively suggesting that those who had less reductions in NSSI tended to have higher frequencies of suicide planning.

These results provide new evidence that changes in NSSI are related to subsequent changes in suicide thoughts and behaviors. Monitoring suicide risk among those with NSSI is important and treatment aiming to reduce NSSI may also reduce suicide risk.

Examining neurobiological mechanisms that may transmit the effects of childhood maltreatment on mental health in youth is crucial for understanding vulnerability to psychopathology. This study investigated associations between childhood maltreatment, adolescent structural brain development, and mental health trajectories into young-adulthood.

Structural magnetic resonance imaging data was acquired from 144 youth at three time points (age 12, 16, and 18 years). Childhood maltreatment was reported to occur prior to the first scan. Linear mixed models were utilized to examine the association between total childhood maltreatment, neglect, abuse and (i) amygdala and hippocampal volume development, and (ii) maturational coupling between amygdala/hippocampus volume and the thickness of prefrontal regions. We also examined whether brain development mediated the association between maltreatment and depressive and anxiety symptoms trajectories from age 12 to 28.

Total maltreatment, and neglect, were associated with positive maturational coupling between the amygdala and caudal anterior cingulate cortex (cACC), whereby at higher and lower levels of amygdala growth, maltreatment was associated with lower and higher PFC thinning, respectively. Neglect was also associated with maturational coupling of the hippocampus with prefrontal regions. While positive amygdala-cACC maturational coupling was associated with greater increases in anxiety symptoms, it did not significantly mediate the association between maltreatment and anxiety symptom trajectories.

We found maltreatment to be associated with altered patterns of coupling between subcortical and prefrontal regions during adolescence, suggesting that maltreatment is associated with the development of socio-emotional neural circuitry. The implications of these findings for mental health require further investigation.

The Mini International Neuropsychiatric Interview 7.0.2 (MINI-7) is a widely used tool and known to have sound psychometric properties; but very little is known about its use in low and middle-income countries (LMICs). This study aimed to examine the psychometric properties of the MINI-7 psychosis items in a sample of 8609 participants across four countries in Sub-Saharan Africa.

We examined the latent factor structure and the item difficulty of the MINI-7 psychosis items in the full sample and across four countries.

Multiple group confirmatory factor analyses (CFAs) revealed an adequate fitting unidimensional model for the full sample; however, single group CFAs at the country level revealed that the underlying latent structure of psychosis was not invariant. Specifically, although the unidimensional structure was an adequate model fit for Ethiopia, Kenya, and South Africa, it was a poor fit for Uganda. Instead, a 2-factor latent structure of the MINI-7 psychosis items provided the optimal fit for Uganda. Examination of item difficulties revealed that MINI-7 item K7, measuring visual hallucinations, had the lowest difficulty across the four countries. In contrast, the items with the highest difficulty were different across the four countries, suggesting that MINI-7 items that are the most predictive of being high on the latent factor of psychosis are different for each country.

The present study is the first to provide evidence that the factor structure and item functioning of the MINI-7 psychosis vary across different settings and populations in Africa.

Racing thoughts have been found in several states of bipolar disorder (BD), but also in healthy populations with subclinical mood alterations. The evaluation of racing thoughts relies on subjective reports, and objective measures are sparse. The current study aims at finding an objective neuropsychological equivalent of racing thoughts in a mixed group of BD patients and healthy controls by using a bistable perception paradigm.

Eighty-three included participants formed three groups based on participants' levels of racing thoughts reported via the Racing and Crowded Thoughts Questionnaire. Participants reported reversals in their perception during viewing of the bistable Necker cube either spontaneously, while asked to focus on one interpretation of the cube, or while asked to accelerate perceptual reversals. The dynamics of perceptual alternations were studied both at a conscious level (with manual temporal windows reflecting perceptual reversals) and at a more automatic level (with ocular temporal windows derived from ocular fixations).

The rate of windows was less modulated by attentional conditions in participants with racing thoughts, and most clearly so for ocular windows. The rate of ocular windows was especially high when participants with racing thoughts were asked to focus on one interpretation of the Necker cube and when they received these instructions for the first time.

Our results indicate that in subjects with racing thoughts automatic perceptual processes escape cognitive control mechanisms. Racing thoughts may involve not only conscious thought mechanisms but also more automatic processes.

Intellectual disability (ID) is associated with violent and sexual offending and victimization, but the importance of neuropsychiatric comorbidity and severity of disability remains unclear.

In a register-based cohort study of people born in Sweden 1980–1991 (n = 1 232 564), we investigated associations of mild and moderate/severe ID with any, violent and sexual crimes, and with assault victimization, stratified by comorbid autism and attention deficit hyperactivity disorder (ADHD). We defined ID by attendance at a special school or registered diagnosis and obtained data on criminal convictions and injuries or deaths due to assaults from nationwide registers until end of 2013.

Compared to people without ID, autism or ADHD, men and women with mild or moderate/severe ID and comorbid ADHD had elevated risks of violent crimes [range of hazard ratios (HRs) 4.4–10.4] and assault victimization (HRs 2.0–7.7). Women with mild ID without comorbidities or with comorbid autism also had elevated risks of violent crimes and victimization (HRs 1.8–4.6) compared to women without ID, autism or ADHD. The relative risks of sexual offending and victimization were elevated in men and women with ID without comorbidities (HRs 2.6–12.7). The highest risks for sexual offending in men (HRs 9.4–11.0) and for sexual assault victimization in women (HRs 11.0–17.1) related to ID and comorbid ADHD.

The elevated risk of violent offending and assault victimization in people with ID is largely explained by comorbid ADHD, whereas ID is independently associated with sexual crimes and victimization, even though absolute risks are low.

Major depressive disorder (MDD) is a highly prevalent psychiatric condition, yet many patients do not receive adequate treatment. Novel and highly scalable interventions such as internet-based cognitive-behavioral-therapy (iCBT) may help to address this treatment gap. Anhedonia, a hallmark symptom of MDD that refers to diminished interest and ability to experience pleasure, has been associated with reduced reactivity in a neural reward circuit that includes medial prefrontal and striatal brain regions. Whether iCBT can reduce anhedonia severity in MDD patients, and whether these therapeutic effects are accompanied by enhanced reward circuit reactivity has yet to be examined.

Fifty-two MDD patients were randomly assigned to either 10-week iCBT (n = 26) or monitored attention control (MAC, n = 26) programs. All patients completed pre- and post-treatment assessments of anhedonia (Snaith–Hamilton Pleasure Scale; SHAPS) and reward circuit reactivity [monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI)]. Healthy control participants (n = 42) also underwent two fMRI scans while completing the MID task 10 weeks apart.

Both iCBT and MAC groups exhibited a reduction in anhedonia severity post-treatment. Nevertheless, only the iCBT group exhibited enhanced nucleus accumbens (Nacc) and subgenual anterior cingulate cortex (sgACC) activation and functional connectivity from pre- to post-treatment in response to reward feedback. Enhanced Nacc and sgACC activations were associated with reduced anhedonia severity following iCBT treatment, with enhanced Nacc activation also mediating the reduction in anhedonia severity post-treatment.

These findings suggest that increased reward circuit reactivity may contribute to a reduction in anhedonia severity following iCBT treatment for depression.

People with serious mental illness are at great risk of suicide, but little is known about the suicide rates among this population. We aimed to quantify the suicide rates among people with serious mental illness (bipolar disorder, major depression, or schizophrenia).

PubMed and Web of Science were searched to identify studies published from 1 January 1975 to 10 December 2020. We assessed English-language studies for the suicide rates among people with serious mental illness. Random-effects meta-analysis was used. Changes in follow-up time and the suicide rates were presented by a locally weighted scatter-plot smoothing (LOESS) curve. Suicide rate ratio was estimated for assessments of difference in suicide rate by sex.

Of 5014 identified studies, 41 were included in this analysis. The pooled suicide rate was 312.8 per 100 000 person-years (95% CI 230.3–406.8). Europe was reported to have the highest pooled suicide rate of 335.2 per 100 000 person-years (95% CI 261.5–417.6). Major depression had the highest suicide rate of 534.3 per 100 000 person-years (95% CI 30.4–1448.7). There is a downward trend in suicide rate estimates over follow-up time. Excess risk of suicide in males was found [1.90 (95% CI 1.60–2.25)]. The most common suicide method was poisoning [21.9 per 100 000 person-years (95% CI 3.7–50.4)].

The suicide rates among people with serious mental illness were high, highlighting the requirements for increasing psychological assessment and monitoring. Further study should focus on region and age differences in suicide among this population.

Extensive evidence indicates that rates of psychotic disorder are elevated in more urban compared with less urban areas, but this evidence largely originates from Northern Europe. It is unclear whether the same association holds globally. This study examined the association between urban residence and rates of psychotic disorder in catchment areas in India (Kancheepuram, Tamil Nadu), Nigeria (Ibadan, Oyo), and Northern Trinidad.

Comprehensive case detection systems were developed based on extensive pilot work to identify individuals aged 18–64 with previously untreated psychotic disorders residing in each catchment area (May 2018–April/May/July 2020). Area of residence and basic demographic details were collected for eligible cases. We compared rates of psychotic disorder in the more v. less urban administrative areas within each catchment area, based on all cases detected, and repeated these analyses while restricting to recent onset cases (<2 years/<5 years).

We found evidence of higher overall rates of psychosis in more urban areas within the Trinidadian catchment area (IRR: 3.24, 95% CI 2.68–3.91), an inverse association in the Nigerian catchment area (IRR: 0.68, 95% CI 0.51–0.91) and no association in the Indian catchment area (IRR: 1.18, 95% CI 0.93–1.52). When restricting to recent onset cases, we found a modest positive association in the Indian catchment area.

This study suggests that urbanicity is associated with higher rates of psychotic disorder in some but not all contexts outside of Northern Europe. Future studies should test candidate mechanisms that may underlie the associations observed, such as exposure to violence.

Previous studies have reported brain structure abnormalities in conduct disorder (CD), but it is unclear whether these neuroanatomical alterations mediate the effects of familial (genetic and environmental) risk for CD. We investigated brain structure in adolescents with CD and their unaffected relatives (URs) to identify neuroanatomical markers of familial risk for CD.

Forty-one adolescents with CD, 24 URs of CD probands, and 38 healthy controls (aged 12–18), underwent structural magnetic resonance imaging. We performed surface-based morphometry analyses, testing for group differences in cortical volume, thickness, surface area, and folding. We also assessed the volume of key subcortical structures.

The CD and UR groups both displayed structural alterations (lower surface area and folding) in left inferior parietal cortex compared with controls. In contrast, CD participants showed lower insula and pars opercularis volume than controls, and lower surface area and folding in these regions than controls and URs. The URs showed greater folding in rostral anterior cingulate and inferior temporal cortex than controls and greater medial orbitofrontal folding than CD participants. The surface area and volume differences were not significant when controlling for attention-deficit/hyperactivity disorder comorbidity. There were no group differences in subcortical volumes.

These findings suggest that alterations in inferior parietal cortical structure partly mediate the effects of familial risk for CD. These structural changes merit investigation as candidate endophenotypes for CD. Neuroanatomical changes in medial orbitofrontal and anterior cingulate cortex differentiated between URs and the other groups, potentially reflecting neural mechanisms of resilience to CD.

Women experience major depression and post-traumatic stress disorder (PTSD) approximately twice as often as men. Estrogen is thought to contribute to sex differences in these disorders, and reduced estrogen is also known to be a key driver of menopause symptoms such as hot flashes. Moreover, estrogen is used to treat menopause symptoms. In order to test for potential shared genetic influences between menopause symptoms and psychiatric disorders, we conducted a genome-wide association study (GWAS) of estrogen medication use (as a proxy for menopause symptoms) in the UK Biobank.

The analysis included 232 993 women aged 39–71 in the UK Biobank. The outcome variable for genetic analyses was estrogen medication use, excluding women using hormonal contraceptives. Trans-ancestry GWAS meta-analyses were conducted along with genetic correlation analyses on the European ancestry GWAS results. Hormone usage was also tested for association with depression and PTSD.

GWAS of estrogen medication use (compared to non-use) identified a locus in the TACR3 gene, which was previously linked to hot flashes in menopause [top rs77322567, odds ratio (OR) = 0.78, p = 7.7 × 10−15]. Genetic correlation analyses revealed shared genetic influences on menopause symptoms and depression (rg = 0.231, s.e. = 0.055, p = 2.8 × 10−5). Non-genetic analyses revealed higher psychiatric symptoms scores among women using estrogen medications.

These results suggest that menopause symptoms have a complex genetic etiology which is partially shared with genetic influences on depression. Moreover, the TACR3 gene identified here has direct clinical relevance; antagonists for the neurokinin 3 receptor (coded for by TACR3) are effective treatments for hot flashes.

Preschool psychiatric symptoms significantly increase the risk for long-term negative outcomes. Transdiagnostic hierarchical approaches that capture general (‘p’) and specific psychopathology dimensions are promising for understanding risk and predicting outcomes, but their predictive utility in young children is not well established. We delineated a hierarchical structure of preschool psychopathology dimensions and tested their ability to predict psychiatric disorders and functional impairment in preadolescence.

Data for 1253 preschool children (mean age = 4.17, s.d. = 0.81) were drawn from three longitudinal studies using a similar methodology (one community sample, two psychopathology-enriched samples) and followed up into preadolescence, yielding a large and diverse sample. Exploratory factor models derived a hierarchical structure of general and specific factors using symptoms from the Preschool Age Psychiatric Assessment interview. Longitudinal analyses examined the prospective associations of preschool p and specific factors with preadolescent psychiatric disorders and functional impairment.

A hierarchical dimensional structure with a p factor at the top and up to six specific factors (distress, fear, separation anxiety, social anxiety, inattention-hyperactivity, oppositionality) emerged at preschool age. The p factor predicted all preadolescent disorders (ΔR2 = 0.04–0.15) and functional impairment (ΔR2 = 0.01–0.07) to a significantly greater extent than preschool psychiatric diagnoses and functioning. Specific dimensions provided additional predictive power for the majority of preadolescent outcomes (disorders: ΔR2 = 0.06–0.15; functional impairment: ΔR2 = 0.05–0.12).

Both general and specific dimensions of preschool psychopathology are useful for predicting clinical and functional outcomes almost a decade later. These findings highlight the value of transdiagnostic dimensions for predicting prognosis and as potential targets for early intervention and prevention.