Current investigations in our laboratory are aimed at understanding the molecular and cellular pathology affecting brain circuits involved in psychiatric disorders, and in particular in emotion dysregulation. The involvement of the amygdala in these disorders has been a long-standing point of focus in our work. Over the past 20 years, we have shown the specific involvement of distinct amygdala nuclei and subregions in the pathophysiology of schizophrenia and bipolar disorder. One of our most recent studies demonstrates that the expression of somatostatin, a peptide known to be involved in the regulation of anxiety, varies in the healthy human amygdala according to circadian rhythms and that this pattern is altered in people with bipolar disorder. A long-standing interest in our laboratory is the role of the interactions between neurons, glia and extracellular matrix in the pathology of psychiatric disorders. Our group was the first to provide evidence for the involvement of extracellular matrix in the pathophysiology of major psychoses. In a series of studies, we showed that several distinct types of perineuronal nets (PNNs), and glial cells synthesizing key PNN components, are robustly altered in multiple brain regions in bipolar disorder and schizophrenia. We also showed that a novel extracellular matrix structure, i.e. CS-6 clusters, is also significantly impacted in the amygdala of donors with bipolar disorder and schizophrenia. Recent studies showed dramatic decreases of PNNs in the thalamic reticular nucleus in schizophrenia and bipolar disorder. Together, these studies have brought extracellular matrix abnormalities in major psychoses to the forefront of the field of psychiatry. These abnormalities may contribute to neural circuit anomalies during development and synaptic destabilization during adulthood, particularly affecting glutamatergic synapses on inhibitory interneurons.