Emanuel Miller Lecture: early onset depressions--meanings, mechanisms and processes.

BACKGROUND: Depressive syndromes in children and adolescents constitute a serious group of mental disorders with considerable risk for recurrence. A more precise understanding of aetiology is necessary to improve treatment and management.
METHODS: Three neuroactive agents are purported to be involved in the aetiology of these disorders: serotonin, brain-derived neurotrophic factor and cortisol. A literature review was conducted to determine their contributions to the emergence of unipolar depressions in the adolescent years.
RESULTS: Serotonin, brain-derived neurotrophic factor and cortisol may operate in concert within two distinct functional frameworks: atypical early epigenesis arising in the first few years of life and resulting in the formation of a vulnerable neuronal network involving in particular the amygdala and ventral prefrontal cortex. Individuals with this vulnerability are likely to show impaired mood regulation when faced with environmental demands during adolescence and over the subsequent decades; and acquired neuroendangerment, a pathological brain process leading to reduced synaptic plasticity, in particular in the hippocampus and perhaps the nucleus accumbens and ventral tegmentum. This may result in motivational, cognitive and behavioural deficits at any point in the lifespan most apparent at times of environmental demand.
CONCLUSIONS: The characteristics, course and outcome of a depressive episode may depend on the extent of the involvement of both atypical early neurogenesis and acquired neuroendangerment.