What Happens to Your Brain Chemistry During Depression?

It's not just serotonin

Serotonin is involved in mood, sleep, appetite and many other brain functions, but depression cannot be explained simply as a serotonin deficiency. The older shorthand of a "chemical imbalance" was a useful simplification; it is not an accurate description of what research now shows.

Depression involves interactions among multiple neurotransmitter systems, the brain networks that connect mood with attention and memory, the body's stress-response machinery, genetic vulnerability, life circumstances and the brain's capacity to adapt — neuroplasticity. Our page on mood, anxiety and brain function in midlife puts those threads together.

What happens to dopamine?

Dopamine is involved in motivation, reward and pleasure. Changes in brain reward circuits may contribute to anhedonia — the loss of interest or pleasure that can occur with depression. This can help explain why someone with depression may say:

• "I don't enjoy anything anymore."
• "I know I should want to do things, but I just don't."
• "I don't feel like myself."

Dopamine also matters for attention and working memory, which is part of why reduced motivation and difficulty concentrating so often travel together. The same signaling comes up in ADHD symptoms during perimenopause.

Your stress system can change too

Depression can also involve the brain's stress-response system, including communication between the hypothalamus, the pituitary gland and the adrenal glands. Chronic stress, poor sleep and mood interact with one another and can influence how these systems function.

That two-way traffic is easy to see in daily life: stress during menopause affects emotional regulation, and a mind that won't shut off at night costs the sleep that mood depends on.

Why can depression cause brain fog?

Depression doesn't only affect mood. It can also cause:

• difficulty concentrating
• slower thinking
• forgetfulness
• difficulty making decisions
• problems maintaining attention
• fatigue
• sleep disturbances

This is one reason some people experiencing depression describe having "brain fog." Because those symptoms overlap with other explanations, our pages on menopause brain fog, sleep and brain function and when cognitive symptoms deserve evaluation are worth reading alongside this one.

What does menopause have to do with this?

During perimenopause, fluctuating ovarian hormones interact with brain systems involved in mood, sleep, cognition and stress regulation. Some women experience new or worsening mood symptoms during this transition, and how estrogen affects the brain explains why that is biologically plausible.

However, depression during perimenopause or menopause should not automatically be blamed on hormones. Mood symptoms can have multiple biological, psychological and social contributors and deserve appropriate evaluation. Our page on hormone therapy and mood covers what hormone therapy can and cannot be expected to do here.

Can treatment change the brain?

Depression is treatable. Depending on the individual, care may include psychotherapy, medications, exercise, improving sleep, addressing medical contributors such as thyroid disease or nutritional deficiencies, and other approaches.

It would be inaccurate to say that antidepressants simply "replace missing serotonin." Their effects on brain signaling, receptor function and plasticity are considerably more complex, and the right approach for any one person is an individualized decision with a clinician.