Neurobiology of Psychosocial Stress and Depression

dorsolateral prefrontal cortex

Psychosocial stress predisposes to depression, especially chronic stress. Stress together with a functional genetic variant of the serotonin transporter gene and dysregulation of the stress hormone cortisol increase the risk of depression. Stress reactivity might be an important link between a genetic variant of the serotonin transporter gene, stressful life events in early years and depression.

Psychosocial stress such as life-events predisposes susceptible patients not only to depression but also other psychiatric diseases such as anxiety disorders, schizophrenia, bipolar disorder. Chronic stress is an important risk factor in psychiatry.

In animals chronic stress has been shown to disrupt the functions of the prefrontal cortex. This disruption is reversible. These reversible disruptions are also present in humans when subjected to chronic stress. This was tested with an attention test, one of the major functions of the prefrontal cortex, focussing attention to important clues. After one month of reduced stress, the same subjects showed no significant differences from controls not only in the test but also on fMRI. In short chronic stress in humans leads to reversible disruption of functional networks in the prefrontal cortex.

These results highlight the plasticity of prefrontal cortex networks in healthy human subjects and suggest one mechanism by which disrupted plasticity may contribute to cognitive impairments characteristic of stress-related neuropsychiatric conditions in susceptible individuals.

The prefrontal cortex is responsible for the executive functions in humans. Executive function relates to abilities to differentiate among conflicting thoughts, determine good and bad, better and best, same and different, future consequences of current activities, working toward a defined goal, prediction of outcomes, expectation based on actions, and social “control” (the ability to suppress urges that, if not suppressed, could lead to socially-unacceptable outcomes).

How was this study done?

Twenty healthy young adults were tested after 4 weeks of psychosocial stress exposure as they prepared for a major academic examination, and their performance was compared with 20 control subjects matched for age, gender, and occupation. Stress exposure was confirmed and quantified using the 10-item Cohen perceived stress scale (PSS), a well-validated questionnaire that gauges chronic stress on a 40-point scale and has been used successfully in related work. Finally, the same subjects returned after 4 weeks of reduced stress and were reassessed relative to matched controls with equal task experience, thus yielding an assessment of the reversibility of stress effects on PFC function while controlling for unidentified group differences, selection biases, or other confounding variables.

Functional neuroimaging with fMRI scans were used to assess the the functionality and structures of the brain with and without stress. Functional imaging data confirmed that attention shifts engaged a frontoparietal network that included dorsolateral prefrontal cortes (DLPFC)
Chronically stressed subjects returned for a second scanning session 4 weeks after cessation of the stressor. This showed that the changes were reversible.
C. Liston, B. S. McEwen, B. J. Casey (2009). Psychosocial stress reversibly disrupts prefrontal processing and attentional control Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0807041106