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Circadian Abnormalities in Depression
CITATION:  Bunney, W. E. & Bunney, B. G. (2000).  Molecular clock genes in man and lower animals:  possible implications for circadian abnormalities in depression.  Neuropsychopharmacology, 22 (4), 335-345. 

ABSTRACT:  The authors of this article discuss the association of circadian rhythm abnormalities and certain types of depression, including seasonal affective disorder (SAD).  Their hypothesis is based on findings that suggest the presence of a clock gene in all organisms, which responds to environmental changes (e.g. light, noise level, temperature) by adjusting physiological mechanisms and behaviors accordingly.  In humans, the most important circadian regulator is the suprochiasmatic nucleus (SCN) found above the optic chiasm in the anterior hypothalamus.  The cells of this nucleus are interconnected and create a rhythmic, autonomic pattern of neural stimulation resulting from the shutting down of protein production once certain levels have been exceeded and turning it back on once levels have fallen sufficiently.   Changes in light activate retinal photoreceptors, which stimulate the SCN directly via the retinohypothalmic tract, or indirectly via the geniculohypothalmic pathway.  Neural interactions between the SCN and pineal gland, then, result in behavioral changes relative to sleep, night-time body temperature, cortisol, as well as the synthesis of melatonin and neuropeptides. 

Current evidence suggest that mutations of the clock gene interfere with protein production and thereby alter the speed of the circadian rhythm and period lengths.  Consequently, the physiological mechanisms and behaviors depending on the clock genes present the symptoms typically associated with SAD,  such as sleep disturbances, increases in night-time temperature, as well as disturbances in the release of melatonin and cortisol.  Similarily, symptoms in certain clinically depressed patients that indicate circadian rhythm aberrations, include changes in temperature and melatonin secretion during sleep, shortened REM latency, and mood swings marked by depression in the morning and near euthymia by evening. 

Therefore, clients presenting with symptoms of depression should be assessed for circadian rhythm disruptions.  For instance, clients with SAD might complain about depressed mood, carbohydrate cravings, overeating, and hypersomnia.  The use of a temperature strip or other non-disruptive means could be used to determine increases in nocturnal temperature.  Clinicians need to pay special attention to clients in high risk groups for SAD, such as women between the ages of 20 to 40 and those living in northern regions.  Clients presenting as clinically depressed should be questioned for symptoms of extreme daily mood swings from very depressed early in the morning to almost euthymic in the evenings.  If circadian rhythm abnormalities are suspected, a sleep clinic assessment might benefit to determine REM latency, early awakening, and elevations in nocturnal temperature.  Similar to SAD, blood tests and urinalysis would be helpful in assessing decreases in melatonin and cortisol release. 

Treatment for clients with SAD should include 2500 lux or higher for two hours per day for at least one week, preferably in the morning.  For clients with clinical depression phase advance treatment of 6 hours for two weeks or a combination treatment of one night of sleep deprivation followed by phase advance treatment might be helpful.  In addition, the SCU has a high density of serontonergic receptors, making SSRIs providing yet another treatment option. 


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