Understanding how depression physically changes the brain

1. Reduced Activity in the Prefrontal Cortex

In depression, especially major depressive disorder (MDD), people show lower metabolism in the prefrontal cortex, particularly the left dorsolateral prefrontal cortex (DLPFC).

• This region is key for decision-making, planning, and emotional control.

• Decreased activity here correlates with symptoms like indecision, apathy, and low motivation.

2. Overactivity in the Amygdala and Limbic System

The amygdala, which processes fear and emotional salience, often appears overactive in people with depression.

• This heightened response is linked to negative emotional bias and rumination.

• It explains why depressed brains may “lock onto” sad or threatening cues more easily.

3. Disrupted Connectivity Between Regions

Communicatin between emotional and cognitive areas—like between the amygdala and prefrontal cortex—can be disrupted.

• The emotional centers may dominate, while rational regulation from the cortex is reduced.

• This imbalance contributes to mood swings and difficulty calming oneself after stress.

4. Altered Activity in the Anterior Cingulate Cortex (ACC)

The ACC helps integrate emotional and cognitive information.

• Depressed individuals often have either underactivation or hyperactivation, depending on the depression subtype.

• Lower ACC activity is linked with poor response to antidepressants, so brain scans here can sometimes predict treatment outcomes.

5. Changes in the Basal Ganglia and Thalamus

These deep brain structures handle motivation and reward. Depressed people show reduced activity, aligning with anhedonia—the inability to feel pleasure.

In Short

A depressed brain physically shows:

• Less activity in cognitive control regions (prefrontal cortex)

• More activity in emotional alarm centers (amygdala)

• Disrupted communication between them

• Reduced reward circuit engagement

Together, this creates a pattern of heightened emotional sensitivity and weakened emotional regulation—a brain that overreacts to pain and underreacts to reward.