The Neuroanatomy of, and Cognitive Deficits in, Depression: A Brief Overview

Serotonin map of brain could lead to better targeted antidepressants
Serotonin map of brain could lead to better targeted antidepressants
Atrophy of numerous structures within the central nervous system has been observed in persons suffering from depression.

It is well established that major depression (MDD) is a disorder with a neurobiological basis that has a tremendous negative impact upon psychological and social functioning, as well as on overall quality of life. This highly disabling condition affects nearly 15 million American adults in a given year.

One of the principal goals in the study of MDD is to identify the brain areas that are involved in, and contribute to, the pathogenesis of symptoms in individuals who are affected by this extremely common neuropsychiatric disorder. Peter Oaks and colleagues recently published an article on this topic in Clinical Anatomy. In their review, they suggest that, “an improved knowledge of anatomical sites involved in patients with depression will help in future treatment modalities.”

Atrophy of numerous structures within the central nervous system has been observed in persons suffering from depression. For example, neuroscientists have found that the amygdala, hippocampus, prefrontal cortex, striatum, nucleus accumbens, and the cerebellum are some of the many structures of the brain that are smaller in patients diagnosed with depression compared with those of typical, healthy individuals. It is important to mention that this is certainly not an exhaustive list…

Dysfunction across several cognitive domains is often concomitant with depression. The hippocampus is a structure that plays a critical role in learning and memory. Data show that the magnitude of the hippocampal volume loss among persons with MDD can reach as high as 19%. According to the published findings, it does appear that hippocampal shrinkage doesn’t precede depression but is rather a consequence of depression. “The number of days that one has suffered from untreated depression affects hippocampal size directly,” the authors wrote. The histological examination of post-mortem tissue in individuals who suffered from severe depression revealed morphological alterations, including synaptic reorganization in the hippocampal formation.

One of the known neurogenic regions in the adult brain is the subgranular zone of the dentate gyrus in the hippocampus. Based on data from pre-clinical and clinical research, the “neurogenic hypothesis” was established as an effort to elucidate the nature of neuropsychiatric illnesses such as MDD. Exposure to antidepressant medications, interestingly, promotes adulthood hippocampal neurogenesis, and the generation of new neurons from stem cells was shown to be required for some of the behavioral effects of antidepressants. It is worth noting that, in addition to antidepressant medications, environmental enrichment, aerobic physical exercise, and cognitive stimulation also promote neurogenesis.

In line with the observed structural modifications, researchers also report functional alterations of neural circuits among individuals with depression. Compared with non-depressed controls, patients with MDD present with aberrant neural activity in the hippocampus, striatum, prefrontal cortex, anterior cingulate cortex, and the thalamus, among many other structures. Neural activity of the hippocampus, for example, predicts a subsequent decrease in activation of the dorsolateral prefrontal cortex in patients with depression. And, whereas depressive symptoms are associated with abnormally low levels of dorsolateral prefrontal cortex activity, recovery from depression, in response to behavioral therapy or antidepressant medications, is associated with increased activity in this brain region. Again, as dorsolateral prefrontal cortex is linked with executive function, this may help explain some of the observed changes in working memory, cognitive flexibility, attention, and motivation among people who suffer from MDD.

“To date, no universal explanation has been established in terms of anatomy or pharmacology or neurocircuitry, [and] many techniques have been developed in attempts to locate the seat of disease within the brain, but much work remains to be done in this field,” the authors concluded.

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Oakes P, Loukas M, Oskouian RJ, Tubbs RS. The neuroanatomy of depression: a review. Clin Anat. 2016. doi: 10.1002/ca.22781. [Epub ahead of print]