Maternal depression is negatively associated with cognitive development across childhood and adolescence, with mixed evidence on whether this association differs in boys and girls. Herein, we performed a systematic review and meta-analysis of sex-specific estimates of the association between maternal depression and offspring cognitive outcomes.

Seven databases (PubMed, EMBASE, PsycINFO, ERIC, CINAHL, Scopus, ProQuest) were searched for studies examining the longitudinal association between maternal depression and offspring (up to 18 years) cognitive outcomes. Studies were screened and included based on predetermined criteria by two independent reviewers (Cohen's κ = 0.76). We used random-effects models to conduct a meta-analysis and used meta-regression for subgroup analyses. The PROSPERO record for the study is CRD42020161001.

Twelve studies met inclusion criteria. Maternal depression was associated with poorer cognitive outcomes in boys [Hedges’ g = –0.36 (95% CI −0.60 to −0.11)], but not in girls [−0.17 (–0.41 to 0.07)]. The association in boys varied as a function of the measure of depression used (b = –0.70, p = 0.005): when maternal depression was assessed via a diagnostic interview, boys [−0.84 (–1.23 to −0.44)] had poorer cognitive outcomes than when a rating scale was used [−0.16 (–0.36 to 0.04)].

This review and meta-analysis indicates that maternal depression is only significantly associated with cognitive outcomes in boys. Understanding the role of sex differences in the underlying mechanisms of this association can inform the development of targeted interventions to mitigate the negative effects of maternal depression on offspring cognitive outcomes.

Late-life depression (LLD) is associated with poor social functioning. However, previous research uses bias-prone self-report scales to measure social functioning and a more objective measure is lacking. We tested a novel wearable device to measure speech that participants encounter as an indicator of social interaction.

Twenty nine participants with LLD and 29 age-matched controls wore a wrist-worn device continuously for seven days, which recorded their acoustic environment. Acoustic data were automatically analysed using deep learning models that had been developed and validated on an independent speech dataset. Total speech activity and the proportion of speech produced by the device wearer were both detected whilst maintaining participants' privacy. Participants underwent a neuropsychological test battery and clinical and self-report scales to measure severity of depression, general and social functioning.

Compared to controls, participants with LLD showed poorer self-reported social and general functioning. Total speech activity was much lower for participants with LLD than controls, with no overlap between groups. The proportion of speech produced by the participants was smaller for LLD than controls. In LLD, both speech measures correlated with attention and psychomotor speed performance but not with depression severity or self-reported social functioning.

Using this device, LLD was associated with lower levels of speech than controls and speech activity was related to psychomotor retardation. We have demonstrated that speech activity measured by wearable technology differentiated LLD from controls with high precision and, in this study, provided an objective measure of an aspect of real-world social functioning in LLD.

Although accurate differentiation between bipolar disorder (BD) and unipolar major depressive disorder (MDD) has important prognostic and therapeutic implications, the distinction is often challenging based on clinical grounds alone. In this study, we tested whether psychiatric polygenic risk scores (PRSs) improve clinically based classification models of BD v. MDD diagnosis.

Our sample included 843 BD and 930 MDD subjects similarly genotyped and phenotyped using the same standardized interview. We performed multivariate modeling and receiver operating characteristic analysis, testing the incremental effect of PRSs on a baseline model with clinical symptoms and features known to associate with BD compared with MDD status.

We found a strong association between a BD diagnosis and PRSs drawn from BD (R2 = 3.5%, p = 4.94 × 10−12) and schizophrenia (R2 = 3.2%, p = 5.71 × 10−11) genome-wide association meta-analyses. Individuals with top decile BD PRS had a significantly increased risk for BD v. MDD compared with those in the lowest decile (odds ratio 3.39, confidence interval 2.19–5.25). PRSs discriminated BD v. MDD to a degree comparable with many individual symptoms and clinical features previously shown to associate with BD. When compared with the full composite model with all symptoms and clinical features PRSs provided modestly improved discriminatory ability (ΔC = 0.011, p = 6.48 × 10−4).

Our study demonstrates that psychiatric PRSs provide modest independent discrimination between BD and MDD cases, suggesting that PRSs could ultimately have utility in subjects at the extremes of the distribution and/or subjects for whom clinical symptoms are poorly measured or yet to manifest.

Clozapine is mainly used in patients with treatment-resistant schizophrenia and may lead to potentially severe haematologic adverse events, such as agranulocytosis. Whether clozapine might be associated with haematologic malignancies is unknown. We aimed to assess the association between haematologic malignancies and clozapine using Vigibase®, the WHO pharmacovigilance database.

We performed a disproportionality analysis to compute reporting odds-ratio adjusted for age, sex and concurrent reporting of antineoplastic/immunomodulating agents (aROR) for clozapine and structurally related drugs (loxapine, olanzapine and quetiapine) compared with other antipsychotic drugs. Cases were malignant lymphoma and leukaemia reports. Non-cases were all other reports including at least one antipsychotic report.

Of the 140 226 clozapine-associated reports, 493 were malignant lymphoma cases, and 275 were leukaemia cases. Clozapine was significantly associated with malignant lymphoma (aROR 9.14, 95% CI 7.75–10.77) and leukaemia (aROR 3.54, 95% CI 2.97–4.22). Patients suffering from those haematologic malignancies were significantly younger in the clozapine treatment group than patients treated with other medicines (p < 0.001). The median time to onset (available for 212 cases) was 5.1 years (IQR 2.2–9.9) for malignant lymphoma and 2.5 years (IQR 0.6–7.4) for leukaemia. The aROR by quartile of dose of clozapine in patients with haematologic malignancies suggested a dose-dependent association.

Clozapine was significantly associated with a pharmacovigilance signal of haematologic malignancies. The risk-benefit balance of clozapine should be carefully assessed in patients with risk factors of haematologic malignancies. Clozapine should be used at the lowest effective posology.

Goal-directed control guides optimal decision-making and it is an important cognitive faculty that protects against developing habits. Previous studies have found some evidence of goal-directed deficits when healthy individuals are stressed, and in psychiatric conditions characterised by compulsive behaviours and anxiety. Here, we tested if goal-directed control is affected by state anxiety, which might explain the former results.

We carried out a causal test of this hypothesis in two experiments (between-subject N = 88; within-subject N = 50) that used the inhalation of hypercapnic gas (7.5% CO2) to induce an acute state of anxiety in healthy volunteers. In a third experiment (N = 1413), we used a correlational design to test if real-life anxiety-provoking events (panic attacks, stressful events) are associated with impaired goal-directed control.

In the former two causal experiments, we induced a profoundly anxious state, both physiologically and psychologically, but this did not affect goal-directed performance. In the third, correlational, study, we found no evidence for an association between goal-directed control, panic attacks or stressful life eventsover and above variance accounted for by trait differences in compulsivity.

In sum, three complementary experiments found no evidence that anxiety impairs goal-directed control in human subjects.

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

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

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

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

Depression is a prevalent and impairing condition. Behavioral activation (BA) is a parsimonious, cost-effective, and easily disseminated psychological intervention for depression. The current meta-analysis expands on the existing literature supporting the efficacy of BA for depression by examining the effects of BA on additional relevant outcomes for patients with depression, namely the reduction in anxiety symptoms and increase in activation.

Randomized controlled trials of BA for depression compared to active and inactive control were identified via a systematic review. Effect sizes using Hedges's g were calculated for each outcome compared to both active and inactive control using random effects models. Subgroup analyses were used to examine the inclusion of a discussion of values as a moderator of depression symptom outcome in BA.

Twenty-eight studies were included. Meta-analyses of symptom change between groups from baseline-to-post intervention indicated that BA outperformed inactive control conditions for improvements in depression (g = 0.83), anxiety (g = 0.37), and activation (g = 0.64). The difference between BA and active control conditions was not significant for improvements in depression (g = 0.15), anxiety (g = 0.03), and activation (g = 0.04). There was no evidence for a discussion of values augmenting BA efficacy. Study quality was generally low, and there was evidence of publication bias.

In addition to improving depression, BA shows efficacy for reducing symptoms of anxiety and increasing activation. BA may not offer better outcomes relative to other active interventions. There is room for improvement in the quality of research in this area.

Aberrant salience may contribute to the development of schizophrenia symptoms via alterations in reward processing and motivation. However, tests of this hypothesis have yielded inconsistent results. These inconsistencies may reflect problems with the validity and specificity of measures of aberrant salience in schizophrenia. Therefore, we investigated relationships among measures of aberrant salience, reward, and motivation in schizophrenia and anxiety.

Individuals with schizophrenia (n = 30), anxiety (n = 33) or unaffected by mental disorder (n = 30) completed measures of aberrant salience [Aberrant Salience Inventory (ASI), Salience Attribution Test (SAT)], motivation (Effort Expenditure for Reward Task), and reinforcer sensitivity (Stimulus Chase Task).

Schizophrenia participants scored higher than anxiety (d = 0.71) and unaffected (d = 1.54) groups on the ASI and exhibited greater aberrant salience (d = 0.60) and lower adaptive salience (d = 0.98) than anxious participants on the SAT. There was no evidence of a correlation between measures of aberrant salience. Schizophrenia was associated with related deficits in motivated behaviour and maladaptive reward processing. However, these differences in reward processing did not correlate with aberrant salience measures.

The results suggest that key measures of aberrant salience have limited specificity and validity. These problems may account for inconsistent findings reported in the literature.

Over half of individuals with eating disorders experience suicidal ideation at some point in their lives, yet few longitudinal studies have examined predictors of ideation in this at-risk group. Moreover, prospective research has focused on relatively distal or trait-level factors that are informative for distinguishing who is most at risk but not when. Little is known about more proximal or state-level risk factors that fluctuate within an individual, which is critical for determining when a person is most likely to engage in suicidal behaviors.

Women (N = 97) receiving treatment for their eating disorder completed questionnaires weekly to assess suicidal ideation and interpersonal constructs (i.e. perceived burdensomeness, thwarted belongingness) theorized to be proximal predictors of suicidal desire. Longitudinal multilevel models were conducted to examine both within- and between-person predictors of suicidal ideation across 12 weeks of treatment.

Statistically significant within-person effects for burdensomeness (β = 0.06; p < 0.001) indicate that when individuals have greater feelings of burdensomeness compared to their own average, they also experience higher suicidal ideation. We did not find any significant influence of thwarted belongingness or the interaction between burdensomeness and belongingness on suicidal ideation.

This study was the first to examine dynamic associations between interpersonal constructs and suicidal ideation in individuals with eating disorders. Results are only partially consistent with the Interpersonal Theory of Suicide and suggest that short-term changes in burdensomeness may impact suicidal behavior in individuals with eating disorders.

This study integrated an experimental medicine approach and a randomized cross-over clinical trial design following CONSORT recommendations to evaluate a cognitive training (CT) intervention for attention deficit hyperactivity disorder (ADHD). The experimental medicine approach was adopted because of documented pathophysiological heterogeneity within the diagnosis of ADHD. The cross-over design was adopted to provide the intervention for all participants and make maximum use of data.

Children (n = 93, mean age 7.3 +/− 1.1 years) with or sub-threshold for ADHD were randomly assigned to CT exercises over 15 weeks, before or after 15 weeks of treatment-as-usual (TAU). Fifteen dropped out of the CT/TAU group and 12 out of the TAU/CT group, leaving 66 for cross-over analysis. Seven in the CT/TAU group completed CT before dropping out making 73 available for experimental medicine analyses. Attention, response inhibition, and working memory were assessed before and after CT and TAU.

Children were more likely to improve with CT than TAU (27/66 v. 13/66, McNemar p = 0.02). Consistent with the experimental medicine hypotheses, responders improved on all tests of executive function (p = 0.009–0.01) while non-responders improved on none (p = 0.27–0.81). The degree of clinical improvement was predicted by baseline and change scores in focused attention and working memory (p = 0.008). The response rate was higher in inattentive and combined subtypes than hyperactive-impulsive subtype (p = 0.003).

Targeting cognitive dysfunction decreases clinical symptoms in proportion to improvement in cognition. Inattentive and combined subtypes were more likely to respond, consistent with targeted pathology and clinically relevant heterogeneity within ADHD.

Ethnic minority groups in Western countries face an increased risk of psychotic disorders. Causes of this long-standing public health inequality remain poorly understood. We investigated whether social disadvantage, linguistic distance and discrimination contributed to these patterns.

We used case–control data from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, carried out in 16 centres in six countries. We recruited 1130 cases and 1497 population-based controls. Our main outcome measure was first-episode ICD-10 psychotic disorder (F20–F33), and exposures were ethnicity (white majority, black, mixed, Asian, North-African, white minority and other), generational status, social disadvantage, linguistic distance and discrimination. Age, sex, paternal age, cannabis use, childhood trauma and parental history of psychosis were included as a priori confounders. Exposures and confounders were added sequentially to multivariable logistic models, following multiple imputation for missing data.

Participants from any ethnic minority background had crude excess odds of psychosis [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.69–2.43], which remained after adjustment for confounders (OR 1.61, 95% CI 1.31–1.98). This was progressively attenuated following further adjustment for social disadvantage (OR 1.52, 95% CI 1.22–1.89) and linguistic distance (OR 1.22, 95% CI 0.95–1.57), a pattern mirrored in several specific ethnic groups. Linguistic distance and social disadvantage had stronger effects for first- and later-generation groups, respectively.

Social disadvantage and linguistic distance, two potential markers of sociocultural exclusion, were associated with increased odds of psychotic disorder, and adjusting for these led to equivocal risk between several ethnic minority groups and the white majority.

Studies of Internet gaming disorder (IGD) suggest an imbalanced relationship between cognitive control and reward processing in people with IGD. However, it remains unclear how these two systems interact with each other, and whether they could serve as neurobiological markers for IGD.

Fifty IGD subjects and matched individuals with recreational game use (RGU) were selected and compared when they were performing a cue-craving task. Regions of interests [anterior cingulate cortex (ACC), lentiform nucleus] were selected based on the comparison between brain responses to gaming-related cues and neutral cues. Directional connectivities among these brain regions were determined using Bayesian estimation. We additionally examined the posterior cingulate cortex (PCC) in a separate analysis based on data implicating the PCC in craving in addiction.

During fixed-connectivity analyses, IGD subjects showed blunted ACC-to-lentiform and lentiform-to-ACC connectivity relative to RGU subjects, especially in the left hemisphere. When facing gaming cues, IGD subjects trended toward lower left-hemispheric modulatory effects in ACC-to-lentiform connectivity than RGU subjects. Self-reported cue-related craving prior to scanning correlated inversely with left-hemispheric modulatory effects in ACC-to-lentiform connectivity.

The results suggesting that prefrontal-to-lentiform connectivity is impaired in IGD provides a possible neurobiological mechanism for difficulties in controlling gaming-cue-elicited cravings. Reduced connectivity ACC-lentiform connectivity may be a useful neurobiological marker for IGD.

The output of many healthy physiological systems displays fractal fluctuations with self-similar temporal structures. Altered fractal patterns are associated with pathological conditions. There is evidence that patients with bipolar disorder have altered daily behaviors.

To test whether fractal patterns in motor activity are altered in patients with bipolar disorder, we analyzed 2-week actigraphy data collected from 106 patients with bipolar disorder type I in a euthymic state, 73 unaffected siblings of patients, and 76 controls. To examine the link between fractal patterns and symptoms, we analyzed 180-day actigraphy and mood symptom data that were simultaneously collected from 14 patients.

Compared to controls, patients showed excessive regularity in motor activity fluctuations at small time scales (<1.5 h) as quantified by a larger scaling exponent (α1 > 1), indicating a more rigid motor control system. α1 values of siblings were between those of patients and controls. Further examinations revealed that the group differences in α1 were only significant in females. Sex also affected the group differences in fractal patterns at larger time scales (>2 h) as quantified by scaling exponent α2. Specifically, female patients and siblings had a smaller α2 compared to female controls, indicating more random activity fluctuations; while male patients had a larger α2 compared to male controls. Interestingly, a higher weekly depression score was associated with a lower α1 in the subsequent week.

Our results show sex- and scale-dependent alterations in fractal activity regulation in patients with bipolar disorder. The mechanisms underlying the alterations are yet to be determined.

The typical onset of schizophrenia coincides with the maturational peak in cognition; however, for a significant proportion of patients the onset is before age 18 and after age 30 years. While cognitive deficits are considered core features of schizophrenia, few studies have directly examined the impact of age of illness onset on cognition.

The aim of the study was to examine if the effects of age on cognition differ between healthy controls (HCs) and patients with schizophrenia at illness onset. We examined 156 first-episode antipsychotic-naïve patients across a wide age span (12–43 years), and 161 age- and sex-matched HCs. Diagnoses were made according to ICD-10 criteria. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS), and IQ was estimated using subtests from the Wechsler adult- or child-intelligence scales. Multivariate analysis of covariance (MANCOVA) was used to examine linear and quadratic effects of age on cognitive scores and interactions by group, including sex and parental socioeconomic status as covariates.

There was a significant overall effect of age on BACS and IQ (p < 0.001). Significant group-by-age interactions for verbal memory (for age-squared, p = 0.009), and digit sequencing (for age, p = 0.01; age-squared, p < 0.001), indicated differential age-related trajectories between patients and HCs.

Cognitive functions showing protracted maturation into adulthood, such as verbal memory and verbal working memory, may be particularly impaired in both early- and late-schizophrenia onset. Our findings indicate a potential interaction between the timing of neurodevelopmental maturation and a possible premature age effect in late-onset schizophrenia.