Bipolar disorder (BD) has been associated with altered brain structural and functional connectivity. However, little is known regarding alterations of the structural brain connectome in BD. The present study aimed to use diffusion-tensor imaging (DTI) and graph theory approaches to investigate the rich club organization and white matter structural connectome in BD.

Forty-two patients with unmedicated BD depression and 59 age-, sex- and handedness-matched healthy control participants underwent DTI. The whole-brain structural connectome was constructed by a deterministic fiber tracking approach. Graph theory analysis was used to examine the group-specific global and nodal topological properties, and rich club organizations, and then nonparametric permutation tests were used for group comparisons of network parameters.

Compared with healthy control participants, the patients with BD showed abnormal global properties, including increased characteristic path length, and decreased global efficiency and local efficiency. Locally, the patients with BD showed abnormal nodal parameters (nodal strength, nodal efficiency, and nodal betweenness) predominantly in the parietal, orbitofrontal, occipital, and cerebellar regions. Moreover, the patients with BD showed decreased rich club and feeder connectivity density.

Our results may reflect the disrupted white matter topological organization in the whole-brain, and abnormal regional connectivity supporting cognitive and affective functioning in depressed BD, which, in part, be due to impaired rich club connectivity.

Inflammation and immune activation have been implicated in the pathogenesis of severe mental disorders and cardiovascular disease (CVD). Despite high level of comorbidity, many studies of the immune system in severe mental disorders have not systematically taken cardiometabolic risk factors into account.

We investigated if inflammatory markers were increased in schizophrenia (SCZ) and affective (AFF) disorders independently of comorbid CVD risk factors. Cardiometabolic risk factors (blood lipids, body mass index and glucose) and CVD-related inflammatory markers CXCL16, soluble interleukin-2 receptor (sIL-2R), soluble CD14 (sCD14), macrophage inhibitory factor and activated leukocyte cell adhesion molecule (ALCAM) were measured in n = 992 patients (SCZ, AFF), and n = 647 healthy controls. We analyzed the inflammatory markers before and after controlling for comorbid cardiometabolic risk factors, and tested for association with psychotropic medication and symptom levels.

CXCL16 (p = 0.03) and sIL-2R (p = 7.8 × 10−5) were higher, while sCD14 (p = 0.05) were lower in patients compared to controls after controlling for confounders, with significant differences in SCZ for CXCL16 (p = 0.04) and sIL-2R (p = 1.1 × 10−5). After adjustment for cardiometabolic risk factors higher levels of sIL-2R (p = 0.001) and lower sCD14 (p = 0.002) remained, also in SCZ (sIL-2R, p = 3.0 × 10−4 and sCD14, p = 0.01). The adjustment revealed lower ALCAM levels (p = 0.03) in patients. We found no significant associations with psychotropic medication or symptom levels.

The results indicate that inflammation, in particular enhanced T cell activation and impaired monocyte activation, are associated with severe mental disorders independent of comorbid cardiometabolic risk factors. This suggests a role of novel pathophysiological mechanisms in severe mental disorders, particularly SCZ.

Trauma due to deliberate harm by others is known to increase the likelihood of developing Post-Traumatic Stress Disorder (PTSD). This is the first study investigating basic and dynamic trust in ‘interpersonal’ PTSD.

Thirty-two participants with PTSD and 22 healthy controls played a novel multi-round version of a monetary investment protocol, the so-called ‘Trust Game’, a task from the behavioural economics literature, which is considered to involve trust and reciprocity. We used two ‘Trust Games’ including cooperative and unfair partners.

Findings showed an effect for lower basic investment in PTSD compared to healthy controls, that trended towards significance (p = 0.09). All participants showed behavioural flexibility and modified their trust based on behavioural cues from their cooperative and unfair game partners. However, participants with PTSD made significantly lower investments towards the cooperative partner than controls. Investments towards the unfair partner did not differ between groups. Higher trauma scores were associated with lower levels of trust-related investments towards the cooperative but not the unfair game partner.

The association between reduced trust towards cooperative others in individuals who experienced interpersonal trauma could indicate acquired insensitivity to social rewards or inflexible negative beliefs about others as a sequel of the traumatic experience, which increases in a dose response relationship with the severity of the trauma. A specific focus on cooperation and trusting behaviour could provide a treatment target for future cognitive and pharmacological interventions.

Although cognitive-behavioural therapy (CBT) is a well-established treatment for adult depression, its efficacy and efficiency may be enhanced by better understanding its mechanism(s) of action. According to the theoretical model of CBT, symptom improvement occurs via reductions in maladaptive cognition. However, previous research has not established clear evidence for this cognitive mediation model.

The present study investigated the cognitive mediation model of CBT in the context of a randomized controlled trial of CBT v. antidepressant medication (ADM) for adult depression. Participants with major depressive disorder were randomized to receive 16 weeks of CBT (n = 54) or ADM (n = 50). Depression symptoms and three candidate cognitive mediators (dysfunctional attitudes, cognitive distortions and negative automatic thoughts) were assessed at week 0 (pre-treatment), week 4, week 8 and week 16 (post-treatment). Longitudinal associations between cognition and depression symptoms, and mediation of treatment outcome, were evaluated in structural equation models.

Both CBT and ADM produced significant reductions in maladaptive cognition and depression symptoms. Cognitive content and depression symptoms were moderately correlated within measurement waves, but cross-lagged associations between the variables and indirect (i.e. mediated) treatment effects were non-significant.

The results provide support for concurrent relationships between cognitive and symptom change, but not the longitudinal relationships hypothesized by the cognitive mediation model. Results may be indicative of an incongruence between the timing of measurement and the dynamics of cognitive and symptom change.

Psychopathy is a personality disorder associated with severe emotional and interpersonal consequences and persistent antisocial behavior. Neurobiological models of psychopathy emphasize impairments in emotional processing, attention, and integration of information across large-scale neural networks in the brain. One of the largest integrative hubs in the brain is the corpus callosum (CC) – a large white matter structure that connects the two cerebral hemispheres.

The current study examines CC volume, measured via Freesurfer parcellation, in a large sample (n = 495) of incarcerated men who were assessed for psychopathic traits using the Hare Psychopathy Checklist-Revised (PCL-R).

Psychopathy was associated with reduced volume across all five sub-regions of the CC. These relationships were primarily driven by the affective/interpersonal elements of psychopathy (PCL-R Factor 1), as no significant associations were found between the CC and the lifestyle/antisocial traits of psychopathy. The observed effects were not attributable to differences in substance use severity, age, IQ, or total brain volume.

These findings align with suggestions that core psychopathic traits may be fostered by reduced integrative capacity across large-scale networks in the brain.

Cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, but risk factors associated with cognitive deficits in euthymic BD are still poorly understood. We aimed to validate classification criteria for the identification of clinically significant cognitive impairment, based on psychometric properties, to estimate the prevalence of neuropsychological deficits in euthymic BD, and identify risk factors for cognitive deficits using a multivariate approach.

We investigated neuropsychological performance in 476 euthymic patients with BD recruited via the French network of BD expert centres. We used a battery of tests, assessing five domains of cognition. Five criteria for the identification of neuropsychological impairment were tested based on their convergent and concurrent validity. Uni- and multivariate logistic regressions between cognitive impairment and several clinical and demographic variables were performed to identify risk factors for neuropsychological impairment in BD.

One cut-off had satisfactory psychometric properties and yielded a prevalence of 12.4% for cognitive deficits in euthymic BD. Antipsychotics use were associated with the presence of a cognitive deficit.

This is the first study to validate a criterion for clinically significant cognitive impairment in BD. We report a lower prevalence of cognitive impairment than previous studies, which may have overestimated its prevalence. Patients with euthymic BD and cognitive impairment may benefit from cognitive remediation.

Identifying factors that influence the functional outcome is an important goal in schizophrenia research. The 22q11.2 deletion syndrome (22q11DS) is a unique genetic model with high risk (20–25%) for schizophrenia. This study aimed to identify potentially targetable domains of neurocognitive functioning associated with functional outcome in adults with 22q11DS.

We used comprehensive neurocognitive test data available for 99 adults with 22q11DS (n = 43 with schizophrenia) and principal component analysis to derive four domains of neurocognition (Verbal Memory, Visual and Logical Memory, Motor Performance, and Executive Performance). We then investigated the association of these neurocognitive domains with adaptive functioning using Vineland Adaptive Behavior Scales data and a linear regression model that accounted for the effects of schizophrenia status and overall intellectual level.

The regression model explained 46.8% of the variance in functional outcome (p < 0.0001). Executive Performance was significantly associated with functional outcome (p = 0.048). Age and schizophrenia were also significant factors. The effects of Executive Performance on functioning did not significantly differ between those with and without psychotic illness.

The findings provide the impetus for further studies to examine the potential of directed (early) interventions targeting Executive Performance to improve long-term adaptive functional outcome in individuals with, or at high risk for, schizophrenia. Moreover, the neurocognitive test profiles may benefit caregivers and clinicians by providing insight into the relative strengths and weaknesses of individuals with 22q11DS, with and without psychotic illness.