Reduced cortical thickness and increased gyrification in generalized anxiety disorder: a 3 T MRI study.

BACKGROUND: Although the study of the neuroanatomical correlates of generalized anxiety disorder (GAD) is gaining increasing interest, up to now the cortical anatomy of GAD patients has been poorly investigated and still no data on cortical gyrification are available. The aim of the present study is to quantitatively examine the cortical morphology in patients with GAD compared with healthy controls (HC) using magnetic resonance imaging (MRI). To the best of our knowledge, this is the first study analyzing the gyrification patterns in GAD. METHODS: A total of 31 GAD patients and 31 HC underwent 3 T structural MRI. For each subject, cortical surface area (CSA), cortical thickness (CT), gray matter volume (GMV), and local gyrification index (LGI) were estimated in 19 regions of interest using the Freesurfer software. These parameters were then compared between the two groups using General Linear Model designs. RESULTS: Compared with HC, GAD patients showed: (1) reduced CT in right caudal middle frontal gyrus (p < 0.05, Bonferroni corrected), (2) hyper-gyrification in right fusiform, inferior temporal, superior parietal and supramarginal gyri and in left supramarginal and superior frontal gyri (p < 0.05, Bonferroni corrected). No significant alterations in CSA and GMV were observed. CONCLUSIONS: Our findings support the hypothesis of a neuroanatomical basis for GAD, highlighting a possible key role of the right hemisphere. The alterations of CT and gyrification in GAD suggest a neurodevelopmental origin of the disorder. Further studies on GAD are needed to understand the evolution of the cerebral morphology with age and during the clinical course of the illness.

Cortico-cortical transfer of socially derived information gates emotion recognition.

Emotion recognition and the resulting responses are important for survival and social functioning. However, how socially derived information is processed for reliable emotion recognition is incompletely understood. Here, we reveal an evolutionarily conserved long-range inhibitory/excitatory brain network mediating these socio-cognitive processes. Anatomical tracing in mice revealed the existence of a subpopulation of somatostatin (SOM) GABAergic neurons projecting from the medial prefrontal cortex (mPFC) to the retrosplenial cortex (RSC). Through optogenetic manipulations and Ca2+ imaging fiber photometry in mice and functional imaging in humans, we demonstrate the specific participation of these long-range SOM projections from the mPFC to the RSC, and an excitatory feedback loop from the RSC to the mPFC, in emotion recognition. Notably, we show that mPFC-to-RSC SOM projections are dysfunctional in mouse models relevant to psychiatric vulnerability and can be targeted to rescue emotion recognition deficits in these mice. Our findings demonstrate a cortico-cortical circuit underlying emotion recognition.

Social behavior in 16p11.2 and 22q11.2 copy number variations: Insights from mice and humans.

Genetic 16p11.2 and 22q11.2 deletions and duplications in humans may alter behavioral developmental trajectories increasing the risk of autism and schizophrenia spectrum disorders, and of attention-deficit/hyperactivity disorder. In this review, we will concentrate on 16p11.2 and 22q11.2 deletions' effects on social functioning, beyond diagnostic categorization. We highlight diagnostic and social sub-constructs discrepancies. Notably, we contrast evidence from human studies with social profiling performed in several mouse models mimicking 16p11.2 and 22q11.2 deletion syndromes. Given the complexity of social behavior, there is a need to assess distinct social processes. This will be important to better understand the biology underlying such genetic-dependent dysfunctions, as well as to give perspective on how therapeutic strategies can be improved. Bridges and divergent points between human and mouse studies are highlighted. Overall, we give challenges and future perspectives to sort the genetics of social heterogeneity.

Reciprocal cortico-amygdala connections regulate prosocial and selfish choices in mice.

Decisions that favor one's own interest versus the interest of another individual depend on context and the relationships between individuals. The neurobiology underlying selfish choices or choices that benefit others is not understood. We developed a two-choice social decision-making task in which mice can decide whether to share a reward with their conspecifics. Preference for altruistic choices was modulated by familiarity, sex, social contact, hunger, hierarchical status and emotional state matching. Fiber photometry recordings and chemogenetic manipulations demonstrated that basolateral amygdala (BLA) neurons are involved in the establishment of prosocial decisions. In particular, BLA neurons projecting to the prelimbic (PL) region of the prefrontal cortex mediated the development of a preference for altruistic choices, whereas PL projections to the BLA modulated self-interest motives for decision-making. This provides a neurobiological model of altruistic and selfish choices with relevance to pathologies associated with dysfunctions in social decision-making.

Functional neuroimaging in treatment resistant schizophrenia: A systematic review.

Despite the availability of several drugs, about 30% of patients with schizophrenia still fail to respond properly to a course of appropriate antipsychotic treatment. Functional neuroimaging studies have shown widespread patterns of altered activation and functional connectivity in treatment-resistant schizophrenia (TRS). The aim of the present study was to examine the available functional magnetic resonance imaging studies investigating TRS and to identify common patterns of altered brain function that could predict the lack of response to antipsychotic treatment in this disorder. Alterations of activation and functional connectivity in fronto-temporal, cortico-striatal, default mode network and salience networks, and of their interplay, were associated with TRS. Our findings support the notion that large-scale network alterations present in schizophrenia lie in a continuum within treatment response with the most severe dysfunction in TRS. Few studies with small sample size and without adequate control group limit the generalizability of current literature. Future controlled longitudinal studies are needed to identify neuroimaging biomarkers of pharmacotherapy response to inform individual treatment selection and facilitate early clinical response.