Childhood adversity is associated with epigenetic alterations in the promoters of several genes in hippocampal neurons.

Major depressive disorder (MDD), is a prevalent mood disorder that associates with differential prefrontal brain expression patterns1. Treatment of MDD includes a variety of biopsychosocial approaches, but in medical practice, antidepressant drugs are the most common treatment for depressive episodes, and not surprisingly, they are among the most prescribed medications in North America2,3. While they are clearly effective, particularly for moderate to severe depressive episodes, there is important variability in how individuals respond to antidepressant treatment. Failure to respond has important individual, economic and social consequences for patients and their families4. Several lines of evidence demonstrate that genes are regulated through the activity of microRNAs (miRNAs), which act as fine–tuners and on–off switches in gene expression patterns5–7. Here we report on complementary studies using postmortem human brain samples, cellular assays and samples from clinical trials of depressed patients, and show that miR-1202, a miRNA specific to primates and enriched in the human brain, is differentially expressed in depressed individuals. Additionally, miR-1202 regulates the expression of the Metabotropic Glutamate Receptor 4 (GRM4) gene and predicts antidepressant response at baseline. These results suggest that miR-1202 is associated with the pathophysiology of depression and is a potential target for novel antidepressant treatments.

Increasing evidence suggests that cortical astrocytic function is disrupted in mood disorders and suicide. The fine neuroanatomy of astrocytes, however, remains to be investigated in these psychiatric conditions. In this study, we performed a detailed morphometric analysis of 3D-reconstructed gray and white matter astrocytes in Golgi-impregnated anterior cingulate cortex (ACC) samples from depressed suicides and matched controls. Postmortem ACC samples (BA24) from 10 well-characterized depressed suicides and 10 matched sudden-death controls were obtained from the Quebec Suicide Brain Bank. Golgi-impregnated protoplasmic astrocytes (gray matter, layer VI) and fibrous astrocytes (adjacent white matter) were reconstructed, and their morphometric features were analyzed using the Neurolucida software. For each cell, the soma size as well as the number, length, and branching of processes were determined. The densities of thorny protrusions found along the processes of both astrocytic subtypes were also determined. Protoplasmic astrocytes showed no significant difference between groups for any of the quantified parameters. However, fibrous astrocytes had significantly larger cell bodies, as well as longer, more ramified processes in depressed suicides, with values for these parameters being about twice as high as those measured in controls. These results provide the first evidence of altered cortical astrocytic morphology in mood disorders. The presence of hypertrophic astrocytes in BA24 white matter is consistent with reports suggesting white matter alterations in depression, and provides further support to the neuroinflammatory theory of depression.