One of the main interests of the MGSS is the understanding of molecular and cellular changes taking place in the brains of individuals that become depressed and commit suicide. Biological studies at the MGSS are translational in nature, that is, they investigate, in humans, concepts and findings from basic neuroscience research. These studies are divided in the following 3 main areas:

Molecular genetics, genomics and epigenetics

These studies are concerned primarily with the effect of gene structure, gene function and gene regulation on depression and suicide. They try to identify gene and/or gene systems that function at different levels in the brains of individuals who died by suicide as compared to control individuals. Subsequently, these studies try to understand the mechanisms accounting for these differences. Over the last years, the MGSS has carried a large number of such studies. We have also been conducting studies to understand how the environment interacts with the genome, resulting in altered gene function. This line of investigation is particularly promising as it is common to observe important environmental stressors, such as a history of early childhood adversity, among individuals who died by suicide.

The following are studies that illustrate this approach:

Cellular neuroanatomy

It is currently hypothesized that depression may arise from the inability of brain circuitries to adapt to variations in cerebral activity. To test this hypothesis, we are conducting several projects aimed at investigating the fine neuroanatomical manifestations of such altered plasticity in postmortem brains from depressed suicide subjects. These studies are focused on limbic brain regions, namely the hippocampus, amygdala and anterior cingulate cortex, which are well known for their implication in emotional processing.



Fig. 1: Pyramidal neuron in the deep layers of the anterior cingulate cortex. Fig. 2: Astrocytes expressing glial cell line-derived neurotrophic factor (GDNF) in the amygdala.

Consult the following studies:

Lipid metabolism

Over the last decades, researchers have been puzzled by the consistent evidence suggesting that low cholesterol levels may be associated with suicidal and related behaviors. While this association remains controversial, there is growing data suggesting that cholesterol and other lipids play an important role in brain plasticity and may modulate behavior as a response to dietary needs. Our group has been interested in the investigation of these interesting relationships.

The following are studies that illustrate this line of investigation: