Verbal learning and memory deficits are frequent among patients with schizophrenia and correlate with reduced magnetic resonance imaging (MRI) volumes of the hippocampus in these patients. A crucial question is the extent to which interrelated structural-functional deficits of the hippocampus reflect a vulnerability to schizophrenia, as opposed to the disorder per se.

We combined brain structural measures and the Rey Auditory Verbal Learning Test (RAVLT) to assess hippocampal structure and function in 36 never-medicated individuals suspected to be in early (EPS) or late prodromal states (LPS) of schizophrenia relative to 30 healthy controls.

Group comparisons revealed bilaterally reduced MRI hippocampal volumes in both EPS and LPS subjects. In LPS subjects but not in EPS subjects, these reductions were correlated with poorer performance in RAVLT delayed recall.

Our findings suggest progressive and interrelated structural-functional pathology of the hippocampus, as prodromal symptoms and behaviours accumulate, and the level of risk for psychosis increases. Given the inverse correlation of learning and memory deficits with social and vocational functioning in established schizophrenia, our findings substantiate the rationale for developing preventive treatment strategies that maintain cognitive capacities in the at-risk mental state.

Within Beck's cognitive model of depression, little is known about the mechanism(s) by which activated self-schemas result in the production of negative thoughts. Recent research has demonstrated that inhibitory dysfunction is present in depression, and this deficit is likely valence-specific. However, whether valence-specific inhibitory deficits are associated with increased negative cognition and whether such deficits are specific to depression per se remains unexamined. The authors posit the theory that inhibitory dysfunction may influence the degree to which activated self-schemas result in the production of depressive cognition.

Individuals with major depressive disorder (MDD, n=43) versus healthy (n=36) and non-depressed anxious (n=32) controls were assessed on the Prose Distraction Task (PDT), a measure of cognitive inhibition, and the Stop-Signal Task (SST), a measure of motor response inhibition. These two tasks were modified in order to present emotionally valenced semantic stimuli (i.e. negative, neutral, positive).

Participants with MDD demonstrated performance impairments on the PDT, which were most pronounced for negatively valenced adjectives, relative to both control groups. Moreover, these impairments correlated with self-report measures of negative thinking and rumination. Conversely, the performance of the MDD participants did not differ from either control group on the SST.

Implications of these findings for understanding the mechanisms underlying the development and maintenance of depressive cognition are discussed.

Interpersonal communication problems are common among persons with schizophrenia and may be linked, in part, to deficits in theory of mind (ToM), the ability to accurately perceive the attitudes, beliefs and intentions of others. Particular difficulties might be expected in the processing of counterfactual information such as sarcasm or lies.

The present study included 50 schizophrenia or schizo-affective out-patients and 44 demographically comparable healthy adults who were administered Part III of The Awareness of Social Inference Test (TASIT; a measure assessing comprehension of sarcasm versus lies) as well as measures of positive and negative symptoms and community functioning.

TASIT data were analyzed using a 2 (group: patients versus healthy adults)×2 (condition: sarcasm versus lie) repeated-measures ANOVA. The results show significant effects for group, condition, and the group×condition interaction. Compared to controls, patients performed significantly worse on sarcasm but not lie scenes. Within-group contrasts showed that patients performed significantly worse on sarcasm versus lie scenes; controls performed comparably on both. In patients, performance on TASIT showed a significant correlation with positive, but not negative, symptoms. The group and interaction effects remained significant when rerun with a subset of patients with low-level positive symptoms. The findings for a relationship between TASIT performance and community functioning were essentially negative.

The findings replicate a prior demonstration of difficulty in the comprehension of sarcasm using a different test, but are not consistent with previous studies showing global ToM deficits in schizophrenia.

Recent genetic studies found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be over-represented in patients with psychosis, including schizophrenia, bipolar disorder and major depressive disorder. In these disorders, attention deficits are among the main cognitive symptoms and have been related to altered neural activity in cerebral attention networks. The particular effect of CACNA1C on neural function, such as attention networks, remains to be elucidated.

The current event-related functional magnetic resonance imaging (fMRI) study investigated the effect of the CACNA1C gene on brain activity in 80 subjects while performing a scanner-adapted version of the Attention Network Test (ANT). Three domains of attention were probed simultaneously: alerting, orienting and executive control of attention.

Risk allele carriers showed impaired performance in alerting and orienting in addition to reduced neural activity in the right inferior parietal lobule [Brodmann area (BA) 40] during orienting and in the medial frontal gyrus (BA 8) during executive control of attention. These areas belong to networks that have been related to impaired orienting and executive control mechanisms in neuropsychiatric disorders.

Our results suggest that CACNA1C plays a role in the development of specific attention deficits in psychiatric disorders by modulation of neural attention networks.

Studies in borderline personality disorder (BPD) have consistently revealed abnormalities in fronto-limbic brain regions during emotional, somatosensory and cognitive challenges. Here we investigated changes in resting-state functional connectivity (RSFC) of three fronto-limbic core regions of specific importance to BPD.

Functional magnetic resonance imaging data were acquired in 20 unmedicated female BPD patients and 17 healthy controls (HC, matched for age, sex and education) during rest. The amygdala, and the dorsal and ventral anterior cingulate cortex (ACC) were defined as seeds to investigate RSFC patterns of a medial temporal lobe network, the salience network and default mode network. The Dissociation Experience Scale (DES), a measure of trait dissociation, was additionally used as a predictor of RSFC with these seed regions.

Compared with HC, BPD patients showed a trend towards increased RSFC between the amygdala and the insula, orbitofrontal cortex and putamen. Compared with controls, patients furthermore exhibited diminished negative RSFC between the dorsal ACC and posterior cingulate cortex, a core region of the default mode network, and regions of the dorsomedial prefrontal cortex. Last, increased negative RSFC between the ventral ACC and medial occipital regions was observed in BPD patients. DES scores were correlated with amygdala connectivity with the dorsolateral prefrontal cortex and fusiform gyrus.

Our findings suggest alterations in resting-state networks associated with processing of negative emotions, encoding of salient events, and self-referential processing in individuals with BPD compared with HC. These results shed more light on the role of abnormal brain connectivity in BPD.

Endothelial dysfunction (ED), low-grade inflammation (LGI) and oxidative stress (OxS) may be involved in the pathobiology of depression. Previous studies on the association of these processes in depression have yielded contradictory results. We therefore investigated comprehensively, in a population-based cohort study, the association between ED, LGI and OxS on the one hand and depressive symptoms on the other.

We used data from the Hoorn Study and determined biomarkers of ED [flow-mediated dilatation (FMD), von Willebrand factor, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1, soluble thrombomodulin and soluble endothelial selectin], LGI [C-reactive protein, tumour necrosis factor-α, interleukin 6, interleukin 8, serum amyloid A, myeloperoxidase (MPO) and sICAM-1] and OxS (oxidized low density lipoprotein and MPO). Depressive symptoms were quantified by the Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire (n = 493; age 68 years; 49.9% female). Regression analyses were performed with the use of biomarker Z scores. Adjustments were made for age, sex and glucose metabolism status (cohort stratification variables) and prior cardiovascular disease, hypertension, waist-to-hip ratio, cholesterol levels, education level, physical activity, dietary habits, and the use of antihypertensive and/or lipid-lowering medication and/or metformin (potential confounders).

After adjustment for age, sex and glucose metabolism status, one standard deviation increase in the ED Z score was associated with a 1.9 [95% confidence interval (CI) 0.7–3.1] higher CES-D score. Additional adjustments did not materially change this result. LGI and OxS were not associated with the CES-D score.

ED, as quantified by an array of circulating biomarkers and FMD, was independently associated with depressive symptoms. This study supports the hypothesis that ED plays an important role in the pathobiology of depression.

At present there are no objective, biological markers that can be used to reliably identify individuals with post-traumatic stress disorder (PTSD). This study assessed the diagnostic potential of structural magnetic resonance imaging (sMRI) for identifying trauma-exposed individuals with and without PTSD.

sMRI scans were acquired from 50 survivors of the Sichuan earthquake of 2008 who had developed PTSD, 50 survivors who had not developed PTSD and 40 healthy controls who had not been exposed to the earthquake. Support vector machine (SVM), a multivariate pattern recognition technique, was used to develop an algorithm that distinguished between the three groups at an individual level. The accuracy of the algorithm and its statistical significance were estimated using leave-one-out cross-validation and permutation testing.

When survivors with PTSD were compared against healthy controls, both grey and white matter allowed discrimination with an accuracy of 91% (p < 0.001). When survivors without PTSD were compared against healthy controls, the two groups could be discriminated with accuracies of 76% (p < 0.001) and 85% (p < 0.001) based on grey and white matter, respectively. Finally, when survivors with and without PTSD were compared directly, grey matter allowed discrimination with an accuracy of 67% (p < 0.001); in contrast the two groups could not be distinguished based on white matter.

These results reveal patterns of neuroanatomical alterations that could be used to inform the identification of trauma survivors with and without PTSD at the individual level, and provide preliminary support to the development of SVM as a clinically useful diagnostic aid.

Obsessive-compulsive disorder (OCD) has been associated with impairments in stop-signal inhibition, a measure of motor response suppression. The study used a novel paradigm to examine both thought suppression and response inhibition in OCD, where the modulatory effects of stimuli relevant to OCD could also be assessed. Additionally, the study compared inhibitory impairments in OCD patients with and without co-morbid depression, as depression is the major co-morbidity of OCD.

Volitional response suppression and unintentional thought suppression to emotive and neutral stimuli were examined using a novel thought stop-signal task. The thought stop-signal task was administered to non-depressed OCD patients, depressed OCD patients and healthy controls (n=20 per group).

Motor inhibition impairments were evident in OCD patients, while motor response performance did not differ between patients and controls. Switching to a new response but not motor inhibition was affected by stimulus relevance in OCD patients. Additionally, unintentional thought suppression as measured by repetition priming was intact. OCD patients with and without depression did not differ on any task performance measures, though there were significant differences in all self-reported measures.

Results support motor inhibition deficits in OCD that remain stable regardless of stimulus meaning or co-morbid depression. Only switching to a new response was influenced by stimulus meaning. When response inhibition was successful in OCD patients, so was the unintentional suppression of the accompanying thought.