The monoamine hypothesis of depression proposes that major depressive disorder arises primarily from deficiencies or dysregulation of key neurotransmitters, especially serotonin, norepinephrine, and dopamine, within critical brain circuits governing mood, motivation, and cognition. This theory emerged in the mid-20th century following observations that the antihypertensive drug reserpine could induce depressive symptoms by depleting monoamines and that drugs like iproniazid and imipramine alleviated depression by increasing synaptic monoamine availability, with foundational contributions from researchers such as Arvid Carlsson (1950s research on monoamines and mood), Joseph J. Schildkraut(1965 catecholamine hypothesis paper), and Alec Coppen (1967 work emphasising serotonin’s role), whose work helped shape modern psychopharmacology and the development of antidepressants such as selective serotonin reuptake inhibitors. Biologically, reduced monoaminergic transmission in pathways linking the brainstem (e.g., raphe nuclei and locus coeruleus) to the limbic system and prefrontal cortex is thought to impair emotional regulation, stress resilience, and reward processing, although contemporary research recognises that receptor sensitivity, neuroplasticity, and stress hormones also play essential roles beyond simple “chemical imbalance” explanations.

From a Christian theological perspective, this biological account does not negate the spiritual dimension of human suffering but rather reflects the integrated unity of body and soul affirmed in Scripture (Genesis 2:7), acknowledging that despair and sorrow, so vividly expressed in the Psalms (e.g., Psalm 42:11), can have embodied correlates within a fallen creation (Romans 8:22), while also affirming Christ’s compassion for the suffering (Matthew 11:28–30) and legitimising medical treatment as a gift of common grace (cf. Luke 10:34). Thus, the monoamine hypothesis can be seen as part of humanity’s God-given mandate to steward knowledge for healing (Proverbs 24:5).

For personal wellbeing, this framework reduces stigma by grounding depression in neurobiology rather than moral weakness, encouraging evidence-based treatment and holistic care. For societal health, it has catalysed pharmaceutical innovation, improved public understanding of mental illness, and supported policies that integrate medical, psychological, and pastoral responses, promoting communities that respond to suffering with both scientific insight and compassionate love.