Violent Behavior Is Associated With Emotion Salience Network Dysconnectivity in Schizophrenia.

Background: Despite individuals with schizophrenia being at an elevated risk of violence compared to the general population, limited efforts have been invested in investigating the neurobiological etiology explaining the increase. Among the few studies examining functional disruptions pertaining to violent schizophrenia patients using fMRI, only one study has considered functional connectivity. The current state of knowledge does not allow to infer deficits in functional connectivity specific to distinct cognitive/emotional states that have been associated with the emergence of violence in schizophrenia, such as negative emotion processing. This study sought to identify disrupted connectivity among men with schizophrenia and a history of violence (SCZ+V), compared to men with schizophrenia without a history of violence (SCZ-V) and healthy controls, during negative emotion processing using fMRI. Methods: Twenty SCZ+V, 19 SCZ-V, and 21 healthy men were scanned while viewing negative images. Results: Negative images elicited an increased connectivity between the dorsal anterior cingulate cortex (dACC) and the bilateral rostral prefrontal cortex (rPFC), as well as a decreased functional connectivity between the frontal regions (bilateral rPFC and dACC) and the putamen and hippocampus in SCZ+V men as compared to SCZ-V men and healthy controls. Concurrently, the centrality of the dACC within the network was reduced in SCV+V subjects. Conclusions: These results suggest an inefficient integration of the information by the dACC between frontal and limbic regions in SCZ+V men during negative emotion processing and highlight the importance of the ACC in the neurobiological bases of violent behavior in schizophrenia.

Impaired Coupling between the Dorsomedial Prefrontal Cortex and the Amygdala in Schizophrenia Smokers Viewing Anti-smoking Images.

BACKGROUND: Cigarette smoking is highly prevalent in schizophrenia and is one of the main factors contributing to the significantly decreased life expectancy in this population. Schizophrenia smokers, compared to their counterparts with no comorbid psychiatric disorder, are largely unaware and indifferent to the long-term negative consequences of cigarette smoking. The objective of this study was to determine, for the first time, if these meta-cognitive deficits are associated with neuro-functional alterations in schizophrenia smokers. METHODS: Twenty-four smokers with no psychiatric disorder and 21 smokers with schizophrenia (DSM-IV criteria) were scanned using functional magnetic resonance imaging and exposed to anti-smoking images. Granger causality analyses were used to examine the effective connectivity between brain regions found to be significantly activated. RESULTS: Across groups, potent activations were observed in the left ventro-lateral prefrontal cortex, the left amygdala (AMG), and the dorsomedial prefrontal cortex (dmPFC). Using the dmPFC as a seed region, we found an abnormal negative connectivity from the dmPFC to the AMG in schizophrenia smokers during the viewing of anti-smoking stimuli. This abnormal connectivity was not present during the viewing of aversive stimuli unrelated to tobacco. DISCUSSION: Given the well-established roles of the dmPFC in social cognition and of the AMG in emotional processing, our results suggest that the relative indifference of schizophrenia smokers regarding the negative consequences of tobacco smoking could be explained by a cognitive-affective dissonance.

RNF213 Is Associated with Intracranial Aneurysms in the French-Canadian Population.

Intracranial aneurysms (IAs) are the result of focal weakness in the artery wall and have a complex genetic makeup. To date, genome-wide association and sequencing studies have had limited success in identifying IA risk factors. Distinct populations, such as the French-Canadian (FC) population, have increased IA prevalence. In our study, we used exome sequencing to prioritize risk variants in a discovery cohort of six FC families affected by IA, and the analysis revealed an increased variation burden for ring finger protein 213 (RNF213). We resequenced RNF213 in a larger FC validation cohort, and association tests on further identified variants supported our findings (SKAT-O, p = 0.006). RNF213 belongs to the AAA+ protein family, and two variants (p.Arg2438Cys and p.Ala2826Thr) unique to affected FC individuals were found to have increased ATPase activity, which could lead to increased risk of IA by elevating angiogenic activities. Common SNPs in RNF213 were also extracted from the NeuroX SNP-chip genotype data, comprising 257 FC IA-affected and 1,988 control individuals. We discovered that the non-ancestral allele of rs6565666 was significantly associated with the affected individuals (p = 0.03), and it appeared as though the frequency of the risk allele had changed through genetic drift. Although RNF213 is a risk factor for moyamoya disease in East Asians, we demonstrated that it might also be a risk factor for IA in the FC population. It therefore appears that the function of RNF213 can be differently altered to predispose distinct populations to dissimilar neurovascular conditions, highlighting the importance of a population's background in genetic studies of heterogeneous disease.

Increased ventro-medial prefrontal activations in schizophrenia smokers during cigarette cravings.

BACKGROUND: Highly prevalent in schizophrenia, tobacco smoking substantially increases the risk of cardiac-related death. Compared to the general population, tobacco smoking cessation rates are lower in schizophrenia. Unfortunately, the reasons for these low cessation rates remain poorly understood. Recently, it has been shown that tobacco cravings are increased in schizophrenia smokers compared to smokers with no comorbid psychiatric disorder. In view of these results, we sought to examine - for the first time - the neurophysiologic responses elicited by cigarette cues in schizophrenia smokers. We hypothesized that cigarettes cues would elicit increased activations in brain regions involved in drug cravings in schizophrenia smokers relative to control smokers. METHODS: Smokers with (n=18) and without (n=24) schizophrenia (DSM-IV criteria) were scanned using functional magnetic resonance imaging (fMRI) while viewing appetitive cigarette images. RESULTS: Schizophrenia smokers and smokers with no psychiatric comorbidity did not differ in subjective cravings in response to appetitive smoking cues. However, in schizophrenia smokers relative to control smokers, we found that appetitive cigarette cues triggered increased activations of the bilateral ventro-medial prefrontal cortex, a core region of the brain reward system. Moreover, a negative correlation was observed between cigarette cravings and activations of the right ventro-medial prefrontal cortex in schizophrenia smokers. DISCUSSION: The current results highlight a key role of the brain reward system in cigarette craving in schizophrenia, and suggest that the neurophysiologic mechanisms involved in the regulation of cue-induced cigarette craving are impaired in this population.