Where does Resilience against Depression Reside in the Brain?

Resilience is in psychiatry the positive capacity of people to cope with stress and catastrophe. In this post it’s used as having an adaptive system that uses exposure to stress to provide resistance to future negative events.

Stress can lead to depression accompanied by atrophy and loss of neurons in the adult hippocampus in experimental studies. The effect of stress or whether you can become depressed due to stress seem to depend on individual characteristics. One characteristic is gene expression. Is it in your genes?

Caspi et al showed that the 5-HTT genotype (serotonin transporter gene) moderates the depressogenic influence of stressful life events. It moderated the effect of life events that occurred not just in adulthood but also of stressful experiences that occurred in earlier developmental periods. Consistent with the Gene x Environment hypothesis, the longitudinal prediction from childhood maltreatment to adult depression was significantly moderated by 5-HTTLPR. Childhood maltreatment predicted adult depression only among individuals carrying an s allele but not among l/l homozygotes. Unfortunately depression is a broad concept which makes it difficult to find the most responsible genes for this disease.

Moreover, environmental factors like stress can also improve the brain’s ability to adapt, this is what we call resilience.

Diffusion tensor imaging is a brand new imaging method that calculates the random movement of water inside the human brain. Diffusion tensor MRI can provide information about connections among brain regions. In recent research they compared the brains of unaffected healthy relatives of patients with depressive disorder with the brains of healthy subjects without any familial risk for psychiatric diseases..

The researchers were surprised by finding a better white matter integrity in the unaffected healthy relatives compared to the healthy controls in certain brain areas linked to depressive disorder. In depression these white matter integrity is far worse compared to healthy controls. When looking at childhood stress in relation to these findings with diffusion tensor imaging they were even more surprised. In healthy controls the white matter integrity was worse with childhood stress compared to those healthy subjects without childhood stress. At the same time those unaffected relatives with childhood stress had a better white matter integrity in certain brain areas compared to those unaffected relatives without childhood stress.

Larger tracts or tracts with higher white matter integrity in unaffected healthy relatives with childhood stress compared to healthy controls with childhood stress resides in the right inferior fronto-occipital fascicilus. Now where the hack is that? Here it is in a child’s brain.

In the words of the authors this could be the place were resilience for depression might resides in the brain:

These findings might indicate that unaffected healthy relatives who did not become depressed, while more likely to carry a high genetic risk, may have some neurobiological characteristics that are associated with increased resilience. The stronger fibre connections seem to be associated with resilience and might render subjects more stable against environmental stressors suggestively through epigenetic mechanisms

The unaffected relatives suffering childhood stress could manage more early life adversity due to stronger fibre connections. This might be mediated by epigenetic processes, mediating the social environment during childhood on gene expression which persist into adulthood and may be even to be passed on to next generations.

Thomas Frodl,, Angela Carballedo1,, Andrew J. Fagan,, Danusia Lisiecka1,, Yolande Ferguson,, Ian Daly,, James F. Meaney,, & Dermot Kelleher (2010). Microstructural Correlates of Resilience against Major Depressive Disorder: Epigenetic Mechanisms? Nature Precedings