Based on the results from functional neuroimaging studies, lesion patient studies and brain stimulation studies two important brain areas play an important role in the pathophysiology of depression. These two brain area s are the ventromedial prefrontal cortex and the dorsolateral prefrontal cortex. The ventromedial prefrontal cortex is depicted in red on the picture above and the dorsolateral prefrontalcortex in blue. The red part is in the forehead on the inside of the two brain half’s (hemispheres) (A) and the blue part is on the outside of the frontal part of both brain parts (B).
The funny thing is that with functional neuroimaging these centers show opposite changes during recovery. While depressed the ventromedial part of the brain is hyperactive and activity decreases during remission of depression and the dorsolateral part is hypoactive during depression and becomes more active during remission of symptoms. This makes it plausible that during depression there is an imbalance in activity between these two brain areas. However, from these studies it is not possible to point to cause and effect. These changes can be the cause of depression but it could also be a consequence of the disease.
Lesion studies demonstrate opposite effects of damage to these areas on depression: dorsolateral prefrontal cortex lesions exacerbate depressive symptoms whereas ventromedial prefrontal cortex lesions diminish depressive symptoms
The ventromedial prefrontal cortex plays an important role in negative affect. Damage to this brain area results in a reduction of negative affect such as guilt, shame, embarrassment and regret. Disturbances of activity of this brain area is believed to lead to these “depressed symptoms”.
The dorsolateral prefrontal cortex is important for “cognitive” and “executive” functions such as working memory, intention formation, goal-directed action, abstract reasoning, and attentional control. Moreover, this brain area is believed to be important for the regulation of negative affect. This brain area is important for the reappraisal/suppression of negative affect. A defect in this regulation of negative affect due to dysfunction of this brain area could be involved depression.
a large and growing body of research implicates the ventromedial and dorsolateral sectors of prefrontal cortex as key neural substrates underlying depression
In a recent study comparing nonrefractory depressed patients with refractory depressed patients and healthy controls the decreased activity in the prefrontal areas in the non refractory patients was mainly on the left frontal areas and in the refractory patients on both prefrontal areas (left and right, bilateral).
In the nonrefractory depressed patients the researchers also found over activity of the bilateral limbic system. They suggest that
Our study provides evidence of different neuropathophysiology in refractory depressive disorder and nonrefractory depressive disorder, which had been suggested in previous studies
This conclusion leaves the possibility that refractory depression might also be a more serious type of depression, due to lack of proper treatment or the consequence of more episodes resulting in brain changes or longer episode duration. More as a continuum instead of separate kind of depressions.
In a recent study published online in PLos ONE 37 patients with major depressive disorder (mean age 43.2 years), medication-free, in an acute depressive episode, and 37 healthy individuals were scanned with MRI scan. Following the MRI scan, 30 patients underwent treatment with the antidepressant medication fluoxetine or cognitive behavioural therapy (CBT). After treatment they were scanned again with MRI scans. Of the patients who subsequently achieved clinical remission with antidepressant medication, the whole brain structural neuroanatomy predicted 88.9% of the clinical response, prior to the initiation of treatment. Brain structure did not aid diagnosis. Changes after CBT were not related to remission status.
The structural neuroanatomy of depression shows high predictive potential for clinical response to antidepressant medication, while its diagnostic potential is more limited.
Koenigs, M., & Grafman, J. (2009). The functional neuroanatomy of depression: Distinct roles for ventromedial and dorsolateral prefrontal cortex Behavioural Brain Research, 201 (2), 239-243 DOI: 10.1016/j.bbr.2009.03.004
Lui, S., Parkes, L., Huang, X., Zou, K., Chan, R., Yang, H., Zou, L., Li, D., Tang, H., Zhang, T., Li, X., Wei, Y., Chen, L., Sun, X., Kemp, G., & Gong, Q. (2009). Depressive Disorders: Focally Altered Cerebral Perfusion Measured with Arterial Spin-labeling MR Imaging Radiology, 251 (2), 476-484 DOI: 10.1148/radiol.2512081548
Costafreda, S., Chu, C., Ashburner, J., & Fu, C. (2009). Prognostic and Diagnostic Potential of the Structural Neuroanatomy of Depression PLoS ONE, 4 (7) DOI: 10.1371/journal.pone.0006353
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