Blunted brain responses to neutral faces in healthy first-degree relatives of patients with schizophrenia: an image-based fMRI meta-analysis.

Schizophrenia is characterized by the misattribution of emotional significance to neutral faces, accompanied by overactivations of the limbic system. To understand the disorder's genetic and environmental contributors, investigating healthy first-degree relatives is crucial. However, inconsistent findings exist regarding their ability to recognize neutral faces, with limited research exploring the cerebral correlates of neutral face processing in this population. Thus, we here investigated brain responses to neutral face processing in healthy first-degree relatives through an image-based meta-analysis of functional magnetic resonance imaging studies. We included unthresholded group-level T-maps from 5 studies comprising a total of 120 first-degree relatives and 150 healthy controls. In sensitivity analyses, we ran a combined image- and coordinate-based meta-analysis including 7 studies (157 first-degree relatives, 207 healthy controls) aiming at testing the robustness of the results in a larger sample of studies. Our findings revealed a pattern of decreased brain responses to neutral faces in relatives compared with healthy controls, particularly in limbic areas such as the bilateral amygdala, hippocampus, and insula. The same pattern was observed in sensitivity analyses. These results contrast with the overactivations observed in patients, potentially suggesting that this trait could serve as a protective factor in healthy relatives. However, further research is necessary to test this hypothesis.

Molecular mapping of a core transcriptional signature of microglia-specific genes in schizophrenia.

Besides playing a central role in neuroinflammation, microglia regulate synaptic development and is involved in plasticity. Converging lines of evidence suggest that these different processes play a critical role in schizophrenia. Furthermore, previous studies reported altered transcription of microglia genes in schizophrenia, while microglia itself seems to be involved in the etiopathology of the disease. However, the regional specificity of these brain transcriptional abnormalities remains unclear. Moreover, it is unknown whether brain and peripheral expression of microglia genes are related. Thus, we investigated the expression of a pre-registered list of 10 genes from a core signature of human microglia both at brain and peripheral levels. We included 9 independent Gene Expression Omnibus datasets (764 samples obtained from 266 individuals with schizophrenia and 237 healthy controls) from 8 different brain regions and 3 peripheral tissues. We report evidence of a widespread transcriptional alteration of microglia genes both in brain tissues (we observed a decreased expression in the cerebellum, associative striatum, hippocampus, and parietal cortex of individuals with schizophrenia compared with healthy controls) and whole blood (characterized by a mixed altered expression pattern). Our results suggest that brain underexpression of microglia genes may represent a candidate transcriptional signature for schizophrenia. Moreover, the dual brain-whole blood transcriptional alterations of microglia/macrophage genes identified support the model of schizophrenia as a whole-body disorder and lend weight to the use of blood samples as a potential source of biological peripheral biomarkers.

Suicidal ideations and self-dehumanization in recently detoxified patients with severe alcohol use disorder: an experimental exploration through joint explicit-implicit measures.

BACKGROUND: Metadehumanization (the feeling of being considered as less than human by others) is a pervasive phenomenon in psychiatric states, notably promoting self-dehumanization and suicide antecedents. However, its role in suicidal ideations among patients with addictive disorders remains unexplored. We thus investigated the involvement of metadehumanization/self-dehumanization in suicidal ideations and suicidal thoughts interference in severe alcohol use disorder. METHODS: We measured metadehumanization, suicidal ideations, and desire for social contact through questionnaires among 35 recently detoxified patients with severe alcohol use disorder (26 males). We measured animalistic/mechanistic self-dehumanization using an Implicit Association Task, and suicidal thoughts interference using a Stroop Task with suicide-related words. We performed regression analyses while controlling for depression/anxiety. RESULTS: Animalistic self-dehumanization was positively associated with suicidal thoughts interference and with decreased desire for social interactions, such link being absent for metadehumanization or mechanistic self-dehumanization. CONCLUSIONS: This link between self-dehumanization and suicide-related factors suggests that a reduced sense of belonging to humanity is associated with self-harm antecedents. Results also emphasize the importance of using indirect measures to investigate sensitive variables, such as self-dehumanization and suicidal thoughts.

Are Brain Responses to Emotion a Reliable Endophenotype of Schizophrenia? An Image-Based Functional Magnetic Resonance Imaging Meta-analysis.

BACKGROUND: Impaired emotion processing constitutes a key dimension of schizophrenia and a possible endophenotype of this illness. Empirical studies consistently report poorer emotion recognition performance in patients with schizophrenia as well as in individuals at enhanced risk of schizophrenia. Functional magnetic resonance imaging studies also report consistent patterns of abnormal brain activation in response to emotional stimuli in patients, in particular, decreased amygdala activation. In contrast, brain-level abnormalities in at-risk individuals are more elusive. We address this gap using an image-based meta-analysis of the functional magnetic resonance imaging literature. METHODS: Functional magnetic resonance imaging studies investigating brain responses to negative emotional stimuli and reporting a comparison between at-risk individuals and healthy control subjects were identified. Frequentist and Bayesian voxelwise meta-analyses were performed separately, by implementing a random-effect model with unthresholded group-level T-maps from individual studies as input. RESULTS: In total, 17 studies with a cumulative total of 677 at-risk individuals and 805 healthy control subjects were included. Frequentist analyses did not reveal significant differences between at-risk individuals and healthy control subjects. Similar results were observed with Bayesian analyses, which provided strong evidence for the absence of meaningful brain activation differences across the entire brain. Region of interest analyses specifically focusing on the amygdala confirmed the lack of group differences in this region. CONCLUSIONS: These results suggest that brain activation patterns in response to emotional stimuli are unlikely to constitute a reliable endophenotype of schizophrenia. We suggest that future studies instead focus on impaired functional connectivity as an alternative and promising endophenotype.

Drinking frequency matters: links between consumption pattern and implicit/explicit attitudes towards alcohol.

RATIONALE: Attitudes towards alcohol constitute a central factor to predict future consumption. Previous studies showed that young adults with risky alcohol consumption present positive implicit and explicit attitudes towards alcohol. OBJECTIVES: It appears crucial to disentangle the relationship between specific consumption patterns (e.g., binge drinking or moderate daily drinking) and these alcohol-related attitudes. METHODS: We compared implicit/explicit positive attitudes towards alcohol among 101 university students distributed in 4 groups [control low-drinking participants (CP), daily drinkers (DD), low binge drinkers (LBD), high binge drinkers (HBD)] differing regarding alcohol consumption profile, to explore the impact of consumption characteristics on alcohol-related attitudes. Participants performed a visual version of the Implicit Association Test (evaluating implicit attitudes towards alcohol), followed by self-reported measures of explicit alcohol-related attitudes and expectancies. RESULTS: HBD and DD (but not LBD) presented stronger implicit positive attitudes towards alcohol than CP. All drinkers explicitly considered alcohol consumption as pleasant, but only DD qualified it as something good. CONCLUSION: Beyond and above the quantity consumed and the presence of binge drinking habits, consumption frequency appears as a central factor associated with high implicit/explicit positive attitudes towards alcohol in young drinkers. This underlines the need to consider this factor not only in future studies exploring implicit/explicit attitudes but also in the development of prevention and intervention campaigns in youth.