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circadian disruptions, and that both physiological and circadian symptoms
can be ameliorated with timed administration of bright light and/or mela-
tonin (reviewed in Ref. 326 ) . While jetlag and shift work do not necessarily
induce psychotic or major affective disorders, circadian disruption in
humans can lead to relapse of symptoms in people with a history of psychi-
atric illness. 327-330 Moreover, the chronotype and the magnitude of mis-
alignment
in humans correlates with the severity of
symptoms
in
nonseasonal depression 331-337 and seasonal depression. 338,339
4.6.1 Environmental models
Seasonal depression is associated with changes in circadian function caused
by alterations in light exposure, and experimental work has focused on the
nature of this relationship. Entrainment to short photoperiods and decreased
light exposure is associated with depression in diurnal rodents, 340-343
and may be observed in some nocturnal rodent species. 344-346 However,
whether day length influences affective responses of nocturnal rodents can
be markedly influenced by species, strain, type of behavioral test employed,
and time of day tested. 347 Increased exposure to light is also associated with
changes in affective state in nocturnal rodents, with mice held under constant
light displaying behavioral measures of depression and decreased anxiety. 348
Moreover, anxious- and depressive-like behavior is evident in mice exposed
to light at night under both entrained 349-352 and free-running conditions. 56
Under free-running conditions with aberrant light at night, depression-like
behavior can be ameliorated with fluoxetine administration or ablation of
intrinsically photosensitive melanopsin-containing retinal ganglion cells. 56
Lastly, mice exposed to non-24 h LD cycles (20 h) display an increased
impulsivity phenotype when tested under novel environmental condi-
tions. 197 In contrast, anxiety or depressive behavior was not observed inmice
exposed to a weekly 6 h LD shift. 353
4.6.2 Genetic models
Clock gene expression rhythms are evident in a variety of structures impor-
tant for mood, reward processing, and motivation, 354 and these local clocks
may contribute to mood regulation. 355 To date, the strongest association
between clock gene function and mood is provided by studies conducted
with the clock mutant mouse, which has been proposed as a model for mania
due to its hyperactivity, decreased depressive- and anxiety-like behavior,
and increased reward-seeking and goal-directed behavior. 134,356-358 Adding
to the face validity of the clock mutant model for mania, this behavioral
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