[Current biochemical hypotheses of endogenous depression].

Area of Science:

• Neuroscience
• Biochemistry
• Psychiatry

Context:

• Depression is a complex mood disorder with debated biochemical underpinnings.
• Existing hypotheses focus on neurotransmitters like noradrenaline and serotonin.
• Novel antidepressants show varied effects, suggesting multifaceted mechanisms.

Purpose:

• To critically evaluate current working hypotheses of depression.
• To explore recent unified and brain-area-specific imbalance hypotheses.
• To highlight the need for in vivo studies of neurotransmission in depression.

Summary:

• The noradrenaline and serotonin hypotheses of depression are reviewed, noting limitations and complexities.
• Factors like neuropeptide co-modulation, variable re-uptake influences, and receptor system interactions suggest a complex pathobiochemistry.
• Recent hypotheses propose noradrenaline-sensitive adenylate cyclase subsensitivity, beta-receptor downregulation, and brain-area-specific neurotransmitter imbalances.

Impact:

• Understanding the complex pathobiochemistry of depression is crucial for developing effective treatments.
• Future research should consider adaptation and tolerance in neurotransmission.
• Defining basal neurotransmission activity and functional changes post-therapy is essential for advancing depression research.