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.

To characterize the association between the protracted biopsychosocial coronavirus disease 2019 (COVID-19) pandemic exposures and incident suicide attempt rates.

Data were from a nationally representative cohort based on electronic health records from January 2013 to February 2021 (N = 852 233), with an interrupted time series study design. For the primary analysis, the effect of COVID-19 pandemic on incident suicide attempts warranting in-patient hospital treatment was quantified by fitting a Poisson regression and modeling the relative risk (RR) and the corresponding 95% confidence intervals (CIs). Scenarios were forecast to predict attempted suicide rates at 10 months after social mitigation strategies. Fourteen sensitivity analyses were performed to test the robustness of the results.

Despite the increasing trend in the unexposed interval, the interval exposed to the COVID-19 pandemic was statistically significant (p < 0.001) associated with a reduced RR of incident attempted suicide (RR = 0.63, 95% CI 0.52–0.78). Consistent with the primary analysis, sensitivity analysis of sociodemographic groups and methodological factors were statistically significant (p < 0.05). No effect modification was identified for COVID-19 lockdown intervals or COVID-19 illness status. All three forecast scenarios at 10 months projected a suicide attempt rate increase from 12.49 (7.42–21.01) to 21.38 (12.71–35.99).

The interval exposed to the protracted mass social trauma of the COVID-19 pandemic was associated with a lower suicide attempt rate compared to the unexposed interval. However, this trend is likely to reverse 10 months after lifting social mitigation policies, underscoring the need for enhanced implementation of public health policy for suicide prevention.

Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes.

204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up.

Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present.

Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

Although potential links between oxytocin (OT), vasopressin (AVP), and social cognition are well-grounded theoretically, most studies have included all male samples, and few have demonstrated consistent effects of either neuropeptide on mentalizing (i.e. understanding the mental states of others). To understand the potential of either neuropeptide as a pharmacological treatment for individuals with impairments in social cognition, it is important to demonstrate the beneficial effects of OT and AVP on mentalizing in healthy individuals.

In the present randomized, double-blind, placebo-controlled study (n = 186) of healthy individuals, we examined the effects of OT and AVP administration on behavioral responses and neural activity in response to a mentalizing task.

Relative to placebo, neither drug showed an effect on task reaction time or accuracy, nor on whole-brain neural activation or functional connectivity observed within brain networks associated with mentalizing. Exploratory analyses included several variables previously shown to moderate OT's effects on social processes (e.g., self-reported empathy, alexithymia) but resulted in no significant interaction effects.

Results add to a growing literature demonstrating that intranasal administration of OT and AVP may have a more limited effect on social cognition, at both the behavioral and neural level, than initially assumed. Randomized controlled trial registrations: ClinicalTrials.gov; NCT02393443; NCT02393456; NCT02394054.

Neuropsychopharmacologic effects of long-term opioid therapy (LTOT) in the context of chronic pain may result in subjective anhedonia coupled with decreased attention to natural rewards. Yet, there are no known efficacious treatments for anhedonia and reward deficits associated with chronic opioid use. Mindfulness-Oriented Recovery Enhancement (MORE), a novel behavioral intervention combining training in mindfulness with savoring of natural rewards, may hold promise for treating anhedonia in LTOT.

Veterans receiving LTOT (N = 63) for chronic pain were randomized to 8 weeks of MORE or a supportive group (SG) psychotherapy control. Before and after the 8-week treatment groups, we assessed the effects of MORE on the late positive potential (LPP) of the electroencephalogram and skin conductance level (SCL) during viewing and up-regulating responses (i.e. savoring) to natural reward cues. We then examined whether these neurophysiological effects were associated with reductions in subjective anhedonia by 4-month follow-up.

Patients treated with MORE demonstrated significantly increased LPP and SCL to natural reward cues and greater decreases in subjective anhedonia relative to those in the SG. The effect of MORE on reducing anhedonia was statistically mediated by increases in LPP response during savoring.

MORE enhances motivated attention to natural reward cues among chronic pain patients on LTOT, as evidenced by increased electrocortical and sympathetic nervous system responses. Given neurophysiological evidence of clinical target engagement, MORE may be an efficacious treatment for anhedonia among chronic opioid users, people with chronic pain, and those at risk for opioid use disorder.

Conspiracy beliefs are associated with detrimental health attitudes during the coronavirus disease 2019 (Covid-19) pandemic. Most prior research on these issues was cross-sectional, however, and restricted to attitudes or behavioral intentions. The current research was designed to examine to what extent conspiracy beliefs predict health behavior and well-being over a longer period of time.

In this preregistered multi-wave study on a large Dutch research panel (weighted to provide nationally representative population estimates), we examined if conspiracy beliefs early in the pandemic (April 2020) would predict a range of concrete health and well-being outcomes eight months later (December 2020; N = 5745).

The results revealed that Covid-19 conspiracy beliefs prospectively predicted a decreased likelihood of getting tested for corona; if tested, an increased likelihood of the test coming out positive; and, an increased likelihood of having violated corona regulations, deteriorated economic outcomes (job loss; reduced income), experiences of social rejection, and decreased overall well-being. Most of these effects generalized to a broader susceptibility to conspiracy theories (i.e. conspiracy mentality).

These findings suggest that conspiracy beliefs are associated with a myriad of negative life outcomes in the long run. Conspiracy beliefs predict how well people have coped with the pandemic over a period of eight months, as reflected in their health behavior, and their economic and social well-being.

Apathy, a disabling and poorly understood neuropsychiatric symptom, is characterised by impaired self-initiated behaviour. It has been hypothesised that the opportunity cost of time (OCT) may be a key computational variable linking self-initiated behaviour with motivational status. OCT represents the amount of reward which is foregone per second if no action is taken. Using a novel behavioural task and computational modelling, we investigated the relationship between OCT, self-initiation and apathy. We predicted that higher OCT would engender shorter action latencies, and that individuals with greater sensitivity to OCT would have higher behavioural apathy.

We modulated the OCT in a novel task called the ‘Fisherman Game’, Participants freely chose when to self-initiate actions to either collect rewards, or on occasion, to complete non-rewarding actions. We measured the relationship between action latencies, OCT and apathy for each participant across two independent non-clinical studies, one under laboratory conditions (n = 21) and one online (n = 90). ‘Average-reward’ reinforcement learning was used to model our data. We replicated our findings across both studies.

We show that the latency of self-initiation is driven by changes in the OCT. Furthermore, we demonstrate, for the first time, that participants with higher apathy showed greater sensitivity to changes in OCT in younger adults. Our model shows that apathetic individuals experienced greatest change in subjective OCT during our task as a consequence of being more sensitive to rewards.

Our results suggest that OCT is an important variable for determining free-operant action initiation and understanding apathy.

Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.

PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.

Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.

PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.

The prevalence of serious psychological distress (SPD) was elevated during the COVID-19 pandemic in the USA, but the relationships of SPD during the pandemic with pre-pandemic SPD, pre-pandemic socioeconomic status, and pandemic-related social stressors remain unexamined.

A probability-based sample (N = 1751) of the US population age 20 and over was followed prospectively from February 2019 (T1), with subsequent interviews in May 2020 (T2) and August 2020 (T3). Multinomial logistic regression was used to assess prospective relationships between T1 SPD with experiences of disruption of employment, health care, and childcare at T2. Binary logistic regression was then used to assess relationships of T1 SPD, and socioeconomic status and T2 pandemic-related stressors with T3 SPD.

At T1, SPD was associated with age, race/ethnicity, and household income. SPD at T1 predicted disruption of employment (OR 4.5, 95% CI 1.4–3.8) and health care (OR 3.2, 95% CI 1.4–7.1) at T2. SPD at T1 (OR 10.2, 95% CI 4.5–23.3), low household income at T1 (OR 2.6, 95% CI 1.1–6.4), disruption of employment at T2 (OR 3.2, 95% CI 1.4–7.6), and disruption of healthcare at T2 (OR 3.3, 95% CI 1.5–7.2) were all significantly associated with elevated risk for SPD at T3.

Elevated risk for SPD during the COVID-19 pandemic is related to multiple psychological and social pathways that are likely to interact over the life course. Policies and interventions that target individuals with pre-existing mental health conditions as well as those experiencing persistent unemployment should be high priorities in the mental health response to the pandemic.

We aimed to identify unmet treatment needs for improving social and occupational functioning in early schizophrenia using a data-driven causal discovery analysis.

Demographic, clinical, and psychosocial measures were obtained for 276 participants from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) trial at baseline and 6-months, along with measures of social and occupational functioning from the Quality of Life Scale. The Greedy Fast Causal Inference algorithm was used to learn a partial ancestral graph modeling causal relationships across baseline variables and 6-month functioning. Effect sizes were estimated using a structural equation model. Results were validated in an independent dataset (N = 187).

In the data-generated model, greater baseline socio-affective capacity was a cause of greater baseline motivation [Effect size (ES) = 0.77], and motivation was a cause of greater baseline social and occupational functioning (ES = 1.5 and 0.96, respectively), which in turn were causes of their own 6-month outcomes. Six-month motivation was also identified as a cause of occupational functioning (ES = 0.92). Cognitive impairment and duration of untreated psychosis were not direct causes of functioning at either timepoint. The graph for the validation dataset was less determinate, but otherwise supported the findings.

In our data-generated model, baseline socio-affective capacity and motivation are the most direct causes of occupational and social functioning 6 months after entering treatment in early schizophrenia. These findings indicate that socio-affective abilities and motivation are specific high-impact treatment needs that must be addressed in order to promote optimal social and occupational recovery.

Cannabis use is a global public health issue associated with increased risks of developing mental health disorders, especially in young people. We aimed to investigate the relationships between cannabis exposure and risks of receiving mental illness diagnoses or treatment as outcomes.

A population based, retrospective, open cohort study using patients recorded in ‘IQVIA medical research data’, a UK primary care database. Read codes were used to confirm patients with recorded exposure to cannabis use who were matched up to two unexposed patients. We examined the risk of developing three categories of mental ill health: depression, anxiety or serious mental illness (SMI).

At study entry, the exposed cohort had an increased likelihood of having experienced mental ill health [odds ratio (OR) 4.13; 95% confidence interval (CI) 3.99–4.27] and mental ill health-related prescription (OR 2.95; 95% CI 2.86–3.05) compared to the unexposed group. During the study period we found that exposure to cannabis was associated with an increased risk of developing any mental disorder [adjusted hazard ratio (aHR) 2.73; 95% CI 2.59–2.88], also noted when examining by subtype of disorder: anxiety (aHR 2.46; 95% CI 2.29–2.64), depression (aHR 2.34; 95% CI 2.20–2.49) and SMI (aHR 6.41; 95% CI 5.42–7.57). These results remained robust in sensitivity analyses.

These findings point to the potential need for a public health approach to the management of people misusing cannabis. However, there is a gross under-recording of cannabis use in GP records, as seen by the prevalence of recorded cannabis exposure substantially lower than self-reported survey records.

A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.

We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders.

There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88).

Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

Cognitive and motor dysfunction are hallmark features of the psychosis continuum, and have been detected during late childhood and adolescence in youth who report psychotic experiences (PE). However, previous investigations have not explored infancy and early childhood development. It remains unclear whether such deficits emerge much earlier in life, and whether they are associated with psychotic, specifically hallucinatory, experiences (HE).

This study included data from Gen2 participants of The Raine Study (n = 1101), a population-based longitudinal cohort study in Western Australia. Five areas of childhood development comprising: communication; fine motor; gross motor; adaptive (problem-solving); and personal-social skills, were assessed serially at ages 1, 2 and 3 years. Information on HE, depression and anxiety at ages 10, 14 and 17 years was obtained. HE were further subdivided into those with transient or recurrent experiences. Mixed effects logistic regression models and cumulative risk analyses based on multiple domain delays were performed.

Early poorer development in multiple areas was noted from ages 1, 2 and 3 years among youth who reported HE. Early developmental delays significantly increased the risk for later HE. This association was particularly marked in the recurrent HE group, with over 40% having early developmental delays in multiple domains. There was no significant association between early childhood development and later anxiety/depression apart from lower gross motor scores at age 3.

The findings suggest that early pan-developmental deficits are associated with later HE, with the effect strongest for young people who report recurrent HE throughout childhood and adolescence.

Disorders involving compulsivity, fear, and anxiety are linked to beliefs that the world is less predictable. We lack a mechanistic explanation for how such beliefs arise. Here, we test a hypothesis that in people with compulsivity, fear, and anxiety, learning a probabilistic mapping between actions and environmental states is compromised.

In Study 1 (n = 174), we designed a novel online task that isolated state transition learning from other facets of learning and planning. To determine whether this impairment is due to learning that is too fast or too slow, we estimated state transition learning rates by fitting computational models to two independent datasets, which tested learning in environments in which state transitions were either stable (Study 2: n = 1413) or changing (Study 3: n = 192).

Study 1 established that individuals with higher levels of compulsivity are more likely to demonstrate an impairment in state transition learning. Preliminary evidence here linked this impairment to a common factor comprising compulsivity and fear. Studies 2 and 3 showed that compulsivity is associated with learning that is too fast when it should be slow (i.e. when state transition are stable) and too slow when it should be fast (i.e. when state transitions change).

Together, these findings indicate that compulsivity is associated with a dysregulation of state transition learning, wherein the rate of learning is not well adapted to the task environment. Thus, dysregulated state transition learning might provide a key target for therapeutic intervention in compulsivity.

Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia.

A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest.

The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms.

We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.

Impaired self-awareness of cognitive deficits (ISAcog) has rarely been investigated in Parkinson's disease (PD). ISAcog is associated with poorer long-term outcome in other diseases. This study examines ISAcog in PD with and without mild cognitive impairment (PD-MCI), compared to healthy controls, and its clinical-behavioral and neuroimaging correlates.

We examined 63 PD patients and 30 age- and education-matched healthy controls. Cognitive state was examined following the Movement Disorder Society Level II criteria. ISAcog was determined by subtracting z-scores (based on controls' scores) of objective tests and subjective questionnaires. Neural correlates were assessed by structural magnetic resonance imaging (MRI) and 2-[fluorine-18]fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) in 47 patients (43 with MRI) and 11 controls. We analyzed whole-brain glucose metabolism and cortical thickness in regions where FDG-uptake correlated with ISAcog.

PD-MCI patients (N = 23) showed significantly more ISAcog than controls and patients without MCI (N = 40). When all patients who underwent FDG-PET were examined, metabolism in the bilateral superior medial frontal gyrus, anterior and midcingulate cortex negatively correlated with ISAcog (FWE-corrected p < 0.001). In PD-MCI, ISAcog was related to decreased metabolism in the right superior temporal lobe and insula (N = 13; FWE-corrected p = 0.023) as well as the midcingulate cortex (FWE-corrected p = 0.002). Cortical thickness was not associated with ISAcog in these regions. No significant correlations were found between ISAcog and glucose metabolism in controls and patients without MCI.

Similar to Alzheimer's disease, the cingulate cortex seems to be relevant in ISAcog in PD. In PD-MCI patients, ISAcog might result from a disrupted network that regulates awareness of cognition and error processes.