Nucleus accumbens seems to play key role in relationship between stress and depression

Individuals with stronger depressive symptoms and those who experienced stressful life events tend to show alterations in volume of the nucleus acumbens, according to new research. Additional changes in the volume and functional connectivity of specific brain regions were also observed. The study was published in Psychological Medicine.

Depression is a mood disorder characterized by persistent feelings of sadness, hopelessness, and a lack of interest or pleasure in previously enjoyed activities. Symptoms can also include changes in appetite, sleep disturbances, fatigue, and difficulty concentrating. Depression can lead to significant impairments in an individual’s personal, social, and professional life. It is currently a leading cause of disability worldwide with over 10% of people experiencing at least one depressive episode in their lifetime.

Stress is a well-established risk factor for the development of depression. Stressful life events can trigger changes in brain chemistry and neurobiology, particularly in areas involved in mood regulation, such as the hippocampus and amygdala. Chronic exposure to stress hormones like cortisol can disrupt these brain processes and increase vulnerability to depression. Additionally, this relationship might be running in both directions – individuals with a diminished ability to cope with stress tend to be more susceptible to depression.

Study author Yizhou Ma and colleagues noted that previous studies have identified changes in the volume and function of certain brain regions associated with both stressful life events and depressive symptoms. These changes include reduced hippocampal volume, diminished thickness or volume in the paralimbic cortex, compromised white matter integrity in the corpus callosum, and altered connectivity within frontostriatal, orbitofrontal, and limbic neuron networks.

To further investigate these associations, they analyzed data from the UK Biobank, focusing on brain volume and functional connectivity related to stressful life events and depressive symptoms.

The UK Biobank is a large-scale biomedical database and research resource, containing in-depth genetic and health information from half a million UK participants, aimed at improving the prevention, diagnosis, and treatment of a wide range of serious and life-threatening illnesses. Stressful life events are significant occurrences that disrupt an individual’s usual activities and require adjustment, such as the death of a loved one, divorce, job loss, or serious illness.

This analysis included neuroimaging data from 22,195 UK adults, collected between 2014 and 2019, with prior data provided at least once before this period. The average age was 63 years at the time of neuroimaging and 55 at the initial data collection. The average interval between the two data collection points was eight years.

The UK Biobank does not specifically assess stressful life events, but the researchers developed a measure based on responses to screening questions about events such as illness, injury, and bereavement. Depressive symptoms were evaluated using items from the Patient Health Questionnaire-2, with data available from both collection points.

The results indicated that depressive symptoms at the initial data collection were associated with subsequent stressful life events eight years later. Conversely, earlier stressful life events were also linked to depressive symptoms at the later data collection point, suggesting a bidirectional relationship between stress and depression.

Functional magnetic resonance imaging (fMRI) showed that individuals experiencing numerous stressful events tended to have smaller nucleus accumbens volumes and reduced fractional anisotropy in the forceps major region—a measure that reflects white matter tract integrity. White matter tracts are bundles of myelinated nerve fibers in the brain that connect different brain regions. Reduced fractional anisotropy indicates diminished structural coherence and function in these brain regions.

Depressive symptoms were significantly associated with extensive white matter hyperintensities (increased brightness on images, indicative of worse condition), thinner cortex, lower subcortical volume, and white matter microstructural deficits, mainly in corticostriatal-limbic structures of the brain.

The only change observed in both depressive symptoms and stressful life events was a reduced volume of the nucleus accumbens. The study authors tested statistical models that suggested depressive symptoms and stressful life events might mediate each other’s effects on this brain region, with results supporting the possibility of partial mediation.

“The nucleus accumbens may play a key role in the reciprocity between stress and depressive symptoms,” the study authors concluded.

The study sheds light on the neural correlates of depression and stress. However, it should be noted that analyses presented in this paper that include neuroimaging data do not allow any definite cause-and-effect conclusions to be derived from the results.

The paper, “Reciprocal relationships between stress and depressive symptoms: the essential role of the nucleus accumbens,” was authored by Yizhou Ma, Peter Kochunov, Mark D. Kvarta, Tara LeGates, Bhim M. Adhikari, Joshua Chiappelli, Andrew van der Vaart, Eric L. Goldwaser, Heather Bruce, Kathryn S. Hatch, Si Gao, Shuo Chen, Ann Summerfelt, Thomas E. Nichols, and L. Elliot Hong.