Social anxiety disorder (SAD) is common, first-line treatments are often only partially effective, and reliable predictors of treatment response are lacking. Here, we assessed resting state functional connectivity (rsFC) at pre-treatment and during early treatment as a potential predictor of response to a novel attention bias modification procedure, gaze-contingent music reward therapy (GC-MRT).

Thirty-two adults with SAD were treated with GC-MRT. rsFC was assessed with multi-voxel pattern analysis of fMRI at pre-treatment and after 2–3 weeks. For comparison, 20 healthy control (HC) participants without treatment were assessed twice for rsFC over the same time period. All SAD participants underwent clinical evaluation at pre-treatment, early-treatment (week 2–3), and post-treatment.

SAD and depressive symptoms improved significantly from pre-treatment to post-treatment. After 2–3 weeks of treatment, decreased connectivity between the executive control network (ECN) and salience network (SN), and increased connectivity within the ECN predicted improvement in SAD and depressive symptoms at week 8. Increased connectivity between the ECN and default mode network (DMN) predicted greater improvement in SAD but not depressive symptoms at week 8. Connectivity within the DMN decreased significantly after 2–3 weeks of treatment in the SAD group, while no changes were found in HC over the same time interval.

We identified early changes in rsFC during a course of GC-MRT for SAD that predicted symptom change. Connectivity changes within the ECN, ECN-DMN, and ECN-SN may be related to mechanisms underlying the clinical effects of GC-MRT and warrant further study in controlled trials.

Predicting future states of psychopathology such as depressive episodes has been a hallmark initiative in mental health research. Dynamical systems theory has proposed that rises in certain ‘early warning signals’ (EWSs) in time-series data (e.g. auto-correlation, temporal variance, network connectivity) may precede impending changes in disorder severity. The current study investigates whether rises in these EWSs over time are associated with future changes in disorder severity among a group of patients with major depressive disorder (MDD).

Thirty-one patients with MDD completed the study, which consisted of daily smartphone-delivered surveys over 8 weeks. Daily positive and negative affect were collected for the time-series analyses. A rolling window approach was used to determine whether rises in auto-correlation of total affect, temporal standard deviation of total affect, and overall network connectivity in individual affect items were predictive of increases in depression symptoms.

Results suggested that rises in auto-correlation were significantly associated with worsening in depression symptoms (r = 0.41, p = 0.02). Results indicated that neither rises in temporal standard deviation (r = −0.23, p = 0.23) nor in network connectivity (r = −0.12, p = 0.59) were associated with changes in depression symptoms.

This study more rigorously examines whether rises in EWSs were associated with future depression symptoms in a larger group of patients with MDD. Results indicated that rises in auto-correlation were the only EWS that was associated with worsening future changes in depression.

Previous research has highlighted the importance of understanding which psychosocial factors distinguish between those with suicide thoughts compared to those who attempt suicide. This study aims to investigate these distinguishing factors further within an ideation-to-action framework and to explore sex differences in suicide risk.

Participants (n = 7546, aged 16+) were from the cross-sectional Adult Psychiatric Morbidity Survey (APMS; 2014) of England. Face-to-face and self-completion questionnaires assessed lifetime suicidal ideation, lifetime suicide attempts, demographic characteristics, life experiences, social support, health and mental illness. Multinomial logistic regression examined factors differentiating between those with suicidal ideation only and suicide attempt histories (with or without suicidal ideation) in men and women.

Overall men were less likely to report suicidal thoughts and attempts, compared to females. More factors differentiated between suicidal thoughts and attempts in women compared to in men; these included hospital admission for mental illness, below degree level qualifications, being single and childhood adversity. In men, factors which significantly differentiated between suicidal thoughts and attempts included self-report of professional diagnosis of mental illness and childhood adversity. Higher levels of social support were associated with being in the suicidal thoughts group v. in the attempts group in men.

This study identified some key differences between men and women in factors associated with suicide attempts compared to suicidal thoughts. The findings support the use of the ideation-to-action framework to investigate sex differences in suicidal behaviour. Future research should examine the extent to which these factors are associated with suicide risk over time.

Copy number variants (CNVs) have been associated with the risk of schizophrenia, autism and intellectual disability. However, little is known about their spectrum of psychopathology in adulthood.

We investigated the psychiatric phenotypes of adult CNV carriers and compared probands, who were ascertained through clinical genetics services, with carriers who were not. One hundred twenty-four adult participants (age 18–76), each bearing one of 15 rare CNVs, were recruited through a variety of sources including clinical genetics services, charities for carriers of genetic variants, and online advertising. A battery of psychiatric assessments was used to determine psychopathology.

The frequencies of psychopathology were consistently higher for the CNV group compared to general population rates. We found particularly high rates of neurodevelopmental disorders (NDDs) (48%), mood disorders (42%), anxiety disorders (47%) and personality disorders (73%) as well as high rates of psychiatric multimorbidity (median number of diagnoses: 2 in non-probands, 3 in probands). NDDs [odds ratio (OR) = 4.67, 95% confidence interval (CI) 1.32–16.51; p = 0.017) and psychotic disorders (OR = 6.8, 95% CI 1.3–36.3; p = 0.025) occurred significantly more frequently in probands (N = 45; NDD: 39[87%]; psychosis: 8[18%]) than non-probands (N = 79; NDD: 20 [25%]; psychosis: 3[4%]). Participants also had somatic diagnoses pertaining to all organ systems, particularly conotruncal cardiac malformations (in individuals with 22q11.2 deletion syndrome specifically), musculoskeletal, immunological, and endocrine diseases.

Adult CNV carriers had a markedly increased rate of anxiety and personality disorders not previously reported and high rates of psychiatric multimorbidity. Our findings support in-depth psychiatric and medical assessments of carriers of CNVs and the establishment of multidisciplinary clinical services.

First-episode psychosis (FEP) is associated with metabolic alterations. However, it is not known if there is heterogeneity in these alterations beyond what might be expected due to normal individual differences, indicative of subgroups of patients at greater vulnerability to metabolic dysregulation.

We employed meta-analysis of variance, indexed using the coefficient of variation ratio (CVR), to compare variability of the following metabolic parameters in antipsychotic naïve FEP and controls: fasting glucose, glucose post-oral glucose tolerance test (OGTT), fasting insulin, insulin resistance, haemoglobin A1c (HbA1c), total-cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides. Standardised mean difference in metabolic parameters between groups was also calculated; meta-regression analyses examined physiological/demographic/psychopathological moderators of metabolic change.

Twenty-eight studies were analysed (1716 patients, 1893 controls). Variability of fasting glucose [CVR = 1.32; 95% confidence interval (CI) 1.12–1.55; p = 0.001], glucose post-OGTT (CVR = 1.43; 95% CI 1.10–1.87; p = 0.008), fasting insulin (CVR = 1.31; 95% CI 1.09–1.58; p = 0.01), insulin resistance (CVR = 1.34; 95% CI 1.12–1.60; p = 0.001), HbA1c (CVR = 1.18; 95% CI 1.06–1.27; p < 0.0001), total-cholesterol (CVR = 1.15; 95% CI 1.01–1.31; p = 0.03), LDL-cholesterol (CVR = 1.28; 95% CI 1.09–1.50; p = 0.002), and HDL-cholesterol (CVR = 1.15; 95% CI 1.00–1.31; p < 0.05), but not triglycerides, was greater in patients than controls. Mean glucose, glucose post-OGTT, fasting insulin, insulin resistance, and triglycerides were greater in patients; mean total-cholesterol and HDL-cholesterol were reduced in patients. Increased symptom severity and female sex were associated with worse metabolic outcomes.

Patients with FEP present with greater variability in metabolic parameters relative to controls, consistent with a subgroup of patients with more severe metabolic changes compared to others. Understanding determinants of metabolic variability could help identify patients at-risk of developing metabolic syndrome. Female sex and severe psychopathology are associated with poorer metabolic outcomes, with implications for metabolic monitoring in clinical practice.

Patients with functional neurological disorders (FND) often present with multiple motor, sensory, psychological and cognitive symptoms. In order to explore the relationship between these common symptoms, we performed a detailed clinical assessment of motor, non-motor symptoms, health-related quality of life (HRQoL) and disability in a large cohort of patients with motor FND. To understand the clinical heterogeneity, cluster analysis was used to search for subgroups within the cohort.

One hundred fifty-two patients with a clinically established diagnosis of motor FND were assessed for motor symptom severity using the Simplified Functional Movement Disorder Rating Scale (S-FMDRS), the number of different motor phenotypes (i.e. tremor, dystonia, gait disorder, myoclonus, and weakness), gait severity and postural instability. All patients then evaluated each motor symptom type severity on a Likert scale and completed questionnaires for depression, anxiety, pain, fatigue, cognitive complaints and HRQoL.

Significant correlations were found among the self-reported and all objective motor symptoms severity measures. All self-reported measures including HRQoL correlated strongly with each other. S-FMDRS weakly correlated with HRQoL. Hierarchical cluster analysis supplemented with gap statistics revealed a homogenous patient sample which could not be separated into subgroups.

We interpret the lack of evidence of clusters along with a high degree of correlation between all self-reported and objective measures of motor or non-motor symptoms and HRQoL within current neurobiological models as evidence to support a unified pathophysiology of ‘functional’ symptoms. Our results support the unification of functional and somatic syndromes in classification schemes and for future mechanistic and therapeutic research.

Awareness of adult separation anxiety (ASA) is growing, but there is a dearth of knowledge about how separation anxiety aggregates in families. We examined the intergenerational associations of separation anxiety and other forms of internalizing problems in an American community sample of 515 predominantly white children and their parents.

Children's separation anxiety (CSA), depression, and other anxiety disorders were modeled as latent factors using diagnoses from interviews and symptom scores from questionnaires completed by mothers, fathers, and children when children were 9 years old and again 3 years later. Parents' separation anxiety was assessed via a questionnaire and parents' other anxiety, depressive, and substance use disorders were assessed with a diagnostic interview when children were nine. Relationships between parents' and children's psychopathology were modeled using s.e.m.

Mothers' and fathers' ASA were related to all three psychopathology factors in offspring, over and above other parental disorders, in concurrent and prospective analyses. CSA was also related to maternal depression concurrently and prospectively and to maternal anxiety prospectively. Of all paternal psychopathology variables, only ASA was significantly related to children's psychopathology in either model.

Results indicate that parental separation anxiety is an important, but non-specific, risk factor for children's psychopathology. The pathway by which this risk is transmitted may be genetic or environmental, and the observed statistical associations likely also encompass child-to-parent effects.

Schizophrenia endophenotypes may help elucidate functional effects of genetic risk variants in multiply affected consanguineous families that segregate recessive risk alleles of large effect size. We studied the association between a schizophrenia risk locus involving a 6.1Mb homozygous region on chromosome 13q22–31 in a consanguineous multiplex family and cognitive functioning, haemodynamic response and white matter integrity using neuroimaging.

We performed CANTAB neuropsychological testing on four affected family members (all homozygous for the risk locus), ten unaffected family members (seven homozygous and three heterozygous) and ten healthy volunteers, and tested neuronal responses on fMRI during an n-back working memory task, and white matter integrity on diffusion tensor imaging (DTI) on four affected and six unaffected family members (four homozygous and two heterozygous) and three healthy volunteers. For cognitive comparisons we used a linear mixed model (Kruskal–Wallis) test, followed by posthoc Dunn's pairwise tests with a Bonferroni adjustment. For fMRI analysis, we counted voxels exceeding the p < 0.05 corrected threshold. DTI analysis was observational.

Family members with schizophrenia and unaffected family members homozygous for the risk haplotype showed attention (p < 0.01) and working memory deficits (p < 0.01) compared with healthy controls; a neural activation laterality bias towards the right prefrontal cortex (voxels reaching p < 0.05, corrected) and observed lower fractional anisotropy in the anterior cingulate cortex and left dorsolateral prefrontal cortex.

In this family, homozygosity at the 13q risk locus was associated with impaired cognition, white matter integrity, and altered laterality of neural activation.

While previous studies have suggested that higher levels of cognitive performance may be related to greater wellbeing and resilience, little is known about the associations between neural circuits engaged by cognitive tasks and wellbeing and resilience, and whether genetics or environment contribute to these associations.

The current study consisted of 253 monozygotic and dizygotic adult twins, including a subsample of 187 early-life trauma-exposed twins, with functional Magnetic Resonance Imaging data from the TWIN-E study. Wellbeing was measured using the COMPAS-W Wellbeing Scale while resilience was defined as a higher level of positive adaptation (higher levels of wellbeing) in the presence of trauma exposure. We probed both sustained attention and working memory processes using a Continuous Performance Task in the scanner.

We found significant negative associations between resilience and activation in the bilateral anterior insula engaged during sustained attention. Multivariate twin modelling showed that the association between resilience and the left and right insula activation was mostly driven by common genetic factors, accounting for 71% and 87% of the total phenotypic correlation between these variables, respectively. There were no significant associations between wellbeing/resilience and neural activity engaged during working memory updating.

The findings suggest that greater resilience to trauma is associated with less activation of the anterior insula during a condition requiring sustained attention but not working memory updating. This possibly suggests a pattern of ‘neural efficiency’ (i.e. more efficient and/or attenuated activity) in people who may be more resilient to trauma.

Our goal was to examine the association between moral injury, mental health, and suicide attempts during military service and after separation by gender in post-9/11 veterans.

A nationally representative sample of 14057 veterans completed a cross-sectional survey. To examine associations of exposure to potentially morally injurious events (PMIEs; witnessing, perpetrating, and betrayal) and suicidal self-directed violence, we estimated two series of multivariable logistic regressions stratified by gender, with peri- and post-military suicide attempt as the dependent variables.

PMIE exposure accounted for additional risk of suicide attempt during and after military service after controlling for demographic and military characteristics, current mental health status, and pre-military history of suicidal ideation and attempt. Men who endorsed PMIE exposure by perpetration were 50% more likely to attempt suicide during service and twice as likely to attempt suicide after separating from service. Men who endorsed betrayal were nearly twice as likely to attempt suicide during service; however, this association attenuated to non-significance after separation in the fully adjusted models. In contrast, women who endorsed betrayal were over 50% more likely to attempt suicide during service and after separation; PMIE exposure by perpetration did not significantly predict suicide attempts before or after service among women in the fully adjusted models.

Our findings indicate that suicide assessment and prevention programs should consider the impact of moral injury and attend to gender differences in this risk factor in order to provide the most comprehensive care.

Prevention of violent behaviors (VB) in the early phase of psychosis (EPP) is a real challenge. Impulsivity was shown to be strongly related to VB, and different evolutions of impulsivity were noticed along treatments. One possible variable involved in the relationship between VB and the evolution of impulsivity is cannabis use (CU). The high prevalence of CU in EPP and its relationship with VB led us to investigate: 1/the impact of CU and 2/the impact of early CU on the evolution of impulsivity levels during a 3-year program, in violent and non-violent EPP patients.

178 non-violent and 62 violent patients (VPs) were followed-up over a 3 year period. Age of onset of CU was assessed at program entry and impulsivity was assessed seven times during the program. The evolution of impulsivity level during the program, as a function of the violent and non-violent groups of patients and CU precocity were analyzed with linear mixed-effects models.

Over the treatment period, impulsivity level did not evolve as a function of the interaction between group and CU (coef. = 0.02, p = 0.425). However, when including precocity of CU, impulsivity was shown to increase significantly only in VPs who start consuming before 15 years of age (coef. = 0.06, p = 0.008).

The precocity of CU in VPs seems to be a key variable of the negative evolution of impulsivity during follow-up and should be closely monitored in EPP patients entering care since they have a higher risk of showing VB.

Treatment-resistant schizophrenia (TRS) and non-TRS may be associated with different dopaminergic and glutamatergic regulations. The concept of dysregulated glutamatergic concentrations in specific brain regions remains controversial. Herein, we aimed to assess (i) the distribution of the glutamatergic concentration in the brain, (ii) the association between working memory (WM) differences in TRS and non-TRS patients, and (iii) whether an alteration in the glutamate (Glu) level is associated with WM.

The participants included 38 TRS patients, 35 non-TRS patients, and 19 healthy controls (HCs), all of whom underwent 1.5-Tesla proton magnetic resonance spectroscopy of anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC). The ratios of glutamatergic neurometabolites to N-acetylaspartate + N-acetyl aspartylglutamate (NAAx) were calculated. Cognitive function was assessed using the Wechsler Adult Intelligence Scales, 4th Edition, which included the working memory index (WMI).

The TRS patients had a higher glutamate + glutamine (Glx)/NAAx ratio compared to the non-TRS patients and HCs in the ACC, but this was not significantly different in the MPFC. WM was negatively correlated with Glx/NAAx in the ACC among the non-TRS patients, but not in the TRS patients or HCs.

Our findings were consistent with most studies indicating that the glutamatergic concentration in the ACC plays important roles in the classification of TRS and cognition. Our results may provide potential evidence for predictors and treatment response biomarkers in TRS patients. Further research is needed to probe the value using the relationship between Glu and WM as a potential prognostic predictor of schizophrenia.