Biological Basis of Depression

A recent review article in the American Journal of Psychiatry examines data from many functional neuroimaging studies in order to define more clearly the biological basis of depression.

Abnormalities in two sets of neural circuits seem to be the most consistent findings in people with depression:Serotonin Implicit Emotion Circuits

  1. Serotonin anxiety and distress circuits that connect the amygdala and several locations in the medial prefrontal cortex.
  2. Dopamine reward circuits that connect the ventral striatum and medial prefrontal cortex.

dopamine reward circuit

The serotonin circuit is illustrated in the picture to the right.

The amygdala can be thought of as the threat or fear of respondents said of portion of the limbic or emotional brain. Serotonin signalling from the prefrontal cortex to the amygdala seems to reduce emotional response to negative information and a tendency to see threats in the world. Increases in serotonin signaling in the prefrontal cortex areas that connect to the amygdala reduces threat response.

I have described the experience of low serotonin in the circuits as akin to the constant playing of “scary music” from a horror film. It’s like those moments in a horror film when everything seems normal but all of a sudden you hear the scary music and you know that there must be something about to happen. Imagine that feeling continually occurring and I think you have some sense of what abnormalities in this circuit feel like.

People with abnormalities in the serotonin circuit seem to respond better to serotonin antidepressants. The most striking finding from a number of studies designed to evaluate predictors of antidepressant response is an association between hypermetabolism, as measured with PET, or greater activity, measured with fMRI, in the pregenual anterior cingulate cortex (part of the serotonin circuit) and better response to a single serotonin antidepressant (SRI). No such association was found for response to the dopaminergic medication bupropion (Little et al).

The dopamine circuit is illustrated in the picture to the left.

Abnormalities in the dopamine circuit seem to be associated with reduced pleasure and difficulty being motivated to do things because of the loss of anticipatory pleasure. There is less data on treatment outcomes being correlated with abnormalities in this circuit but, as I’ve noted in another post, there is some evidence to suggest that anhedonia or the lack of pleasure correlates with a better response to dopamine antidepressants. Anhedonia may be a predictor of a better response to ketamine and ketamine profoundly affects these dopamine circuits.


Phillips ML, Chase HW, Sheline YI, et al. “Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches.” American Journal of Psychiatry. Volume 172 Issue 2, February 01, 2015, pp. 124-138.

Little JT, Ketter TA, Kimbrell TA, et al: Bupropion and venlafaxine responders differ in pretreatment regional cerebral metabolism in unipolar depression. Biol Psychiatry 2005; 57:220–228

Amygdala Differences in Depressed Individuals

amygdalaThe best way to tackle an illness is to start treatment as early as possible. In the case of depression, recent studies has revealed that there may be a way to identify depression symptoms in children. An fMRI study was conducted on a group of preschool students to see if there were any differences in the brains of depressed and non depressed kids at this early of an age.

The chidlren were shown pictures of faces that had a myriad of different expressions. The faces showed the different emotions of happy, sad, fearful, and neutral. When viewing the photos, the fMRI examined the brain activity of the the different participants. To the researcher’s surprise, there was a difference between children who were and were not depressed!

Preschoolers with depression demonstrated increased blood flow in the amygdala when viewing any facial expression in comparison to preschoolers without depression.

The preschoolers with greater amygdala activity went on to demonstrate a greater negative affect later on in life. These findings are a huge step in a positive direction for treatment of depression. If the depression can be identified at this early of an age, individuals can begin treatment right away and avoid problems caused by the illness that would occur later in life. These individuals could start learning strategies to manage depression much earlier, which may decrease the negative impact of the illness in the future.

Perhaps one of the most exciting components of this research is that there is a difference of brain functioning in individuals who have direction. Finding this difference has sparked investigation of new treatment programs, other brain differences, and has enhanced the overall diagnosis ability of doctors.

To learn more about this research and the battle against depression, get the full story by clicking this link: