Depression is associated with low levels of which neurotransmitters?

• A. Dopamine and GABA
• B. Acetylcholine
• C. Glutamate
• D. Serotonin and/or Norepinephrine

Answer: (D)

Depression has long been linked to reduced activity of monoamine transmitters in the brain, especially serotonin and norepinephrine. Serotonin helps regulate mood, sleep, and appetite, while norepinephrine influences arousal, energy, and focus. When signaling by these two systems is diminished, depressive symptoms commonly arise. Pharmacologic evidence supports this: antidepressants that boost serotonin (SSRIs), norepinephrine (SNRIs), or both (TCAs, MAO inhibitors) can alleviate symptoms by increasing their availability at synapses, which reinforces why low levels of these particular neurotransmitters are the classic association.

Dopamine is tied to motivation and reward, and its dysfunction can contribute to anhedonia, but it’s not the primary, universally observed deficit described in the classic view of depression. GABA and glutamate play roles in mood regulation and have therapeutic implications (e.g., glutamatergic modulation with ketamine), but they are not the traditional primary deficit linked to depressive states. Acetylcholine is less central to the mood disturbances defining depression.

So the best answer reflects the well-supported link between depression and reduced serotonin and/or norepinephrine signaling.