The complex interrelation and interdependence of neurochemical systems involving critical neurotransmitters, synaptic regulation, nerve cell mediation and modulation, neuropeptides and neuroendocrine systems are poorly understood. In the past four decades, explorations of these mechanisms have focused on simpler hypotheses derived from clinical observations of drug effects. The interaction of these multiple systems has been difficult to investigate in the laboratory.
Recent studies challenging the simpler paradigm of cat-echolamine deficit or excess in depression have focused upon neurotransmitter modulation of nerve cell regulation as well as effects of neurotransmitter systems on receptor sensitivity. Addi-tional studies show that patients with depression as well as those who have died by suicide are reported to have lower levels of the serotonin transporter (SERT) than in control subjects (Owens and Nemeroff, 1998). As the pharmacology of the neurotransmitters and receptors is further explicated, receptor changes leading to effects on second messenger systems and the generation of new proteins affecting gene expression will become the focus of the neurobiology of MDD.
Specific abnormalities in sleep and circadian rhythms are among the most consistent findings in biological psychiatry. Clinical observations of insomnia and hypersomnia are commonly noted as a central feature of depressive disorder. Polysomnography (PSG) demonstrates that the progression of sleep from nonrapid eye movement (nonREM) stages 1 to 4 to rapid eye movement (REM) sleep is disrupted in MDD. EEG recordings demonstrate a shorter than normal onset of REM sleep termed reduced or shortened REM latency. The frequency of eye movements during REM sleep is greater, termed increased REM density. During the sleep laboratory evaluation, increased awakening during sleep leads to the reduction in total sleep time in MDD. NonREM abnormalities include prolonged sleep latency, increased wakefulness, decreased arousal threshold and early morning awakening. Giles and colleagues (1989) have suggested that sleep EEG parameters are more trait-like and that some sleep EEG alterations may precede the onset of clinical depression.
Biological rhythm abnormalities include advances in the timing of daily rhythms such as REM sleep, cortisol and body temperature. Endogenous processes within a day (approximately 25 hours) are circadian rhythms. Episodic recurrences of the ill-ness over days, months, or years are called infradian rhythms (a period of more than a day). Ultradian rhythms are oscillations that occur more than once daily and occur at the cellular and neu-rohormonal level. Mechanisms which explain the alterations in oscillation of biological rhythms in depression are not well deline-ated. Clearly, homeostatic regulation of cellular, biochemical and psychological phenomenon is necessary to maintain euthymia. Seasonal variation in mood disorders represents the effect of change in light and temperature on the individual’s biological vulnerability to depression. Treatments involving light manipula-tion have begun to address the impact of seasonal change on those individuals vulnerable to depression with seasonal pattern.