Enlightened: addressing circadian and seasonal changes in photoperiod in animal models of bipolar disorder

Abstract

Bipolar disorders (BDs) exhibit high heritability and symptoms typically first occur during late adolescence or early adulthood. Affected individuals may experience alternating bouts of mania/hypomania and depression, with euthymic periods of varying lengths interspersed between these extremes of mood. Clinical research studies have consistently demonstrated that BD patients have disturbances in circadian and seasonal rhythms, even when they are free of symptoms. In addition, some BD patients display seasonal patterns in the occurrence of manic/hypomanic and depressive episodes as well as the time of year when symptoms initially occur. Finally, the age of onset of BD symptoms is strongly influenced by the distance one lives from the equator. With few exceptions, animal models useful in the study of BD have not capitalized on these clinical findings regarding seasonal patterns in BD to explore molecular mechanisms associated with the expression of mania- and depression-like behaviors in laboratory animals. In particular, animal models would be especially useful in studying how rates of change in photoperiod that occur during early spring and fall interact with risk genes to increase the occurrence of mania- and depression-like phenotypes, respectively. Another unanswered question relates to the ways in which seasonally relevant changes in photoperiod affect responses to acute and chronic stressors in animal models. Going forward, we suggest ways in which translational research with animal models of BD could be strengthened through carefully controlled manipulations of photoperiod to enhance our understanding of mechanisms underlying seasonal patterns of BD symptoms in humans. In addition, we emphasize the value of incorporating diurnal rodent species as more appropriate animal models to study the effects of seasonal changes in light on symptoms of depression and mania that are characteristic of BD in humans.

Early-life scarcity adversity biases behavioral development toward a bipolar-like phenotype in mice heterozygous for CNTNAP2

“…The time-dependency of symptoms is an integral component of psychopathology(50,51). Especially in mood disorders, symptoms cycles on multiple time-scales, from seasonal(52), to circadian(53) up to milliseconds differences in reaction times(54) and discrepancies in time-perception(55). In this work we chose to investigate arbitrary time-bins to obtain a behavioral redout of characteristics such as impulsivity or stereotypies, which proved an effective strategy to harness the complexity of some deviant traits.…”

The neurons that drive infradian sleep-wake and mania-like behavioral rhythms

“…This in turn would then suggest that NAc-projecting DA neurons not only serve as substrate for murine infradian rhythm production, but also 48 hr cycling in BD. While there exists a considerable number of mouse models for mania or depression 41-43 , animal models for cycling or mood switching are scarce 44 . Yet understanding state switching mechanistically is considered the ‘holy grail’ of bipolar disorder 45 .…”

Bipolar Chronobiology in Men and Mice: A Narrative Review

“…These disturbances encompass a range from symptoms to prodromal signs to treatment targets [2]. Rodent models for BD therefore also often show CRD or are even generated by specifically manipulating the circadian rhythm [3,4].…”