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The darkness and the light: diurnal rodent models for seasonal affective disorder

ABSTRACT: ABSTRACT The development of animal models is a critical step for exploring the underlying pathophysiological mechanisms of major affective disorders and for evaluating potential therapeutic approaches. Although most neuropsychiatric research is performed on nocturnal rodents, differences in how diurnal and nocturnal animals respond to changing photoperiods, combined with a possible link between circadian rhythm disruption and affective disorders, has led to a call for the development of diurnal animal models. The need for diurnal models is most clear for seasonal affective disorder (SAD), a widespread recurrent depressive disorder that is linked to exposure to short photoperiods. Here, we briefly review what is known regarding the etiology of SAD and then examine progress in developing appropriate diurnal rodent models. Although circadian disruption is often invoked as a key contributor to SAD, a mechanistic understanding of how misalignment between endogenous circadian physiology and daily environmental rhythms affects mood is lacking. Diurnal rodents show promise as models of SAD, as changes in affective-like behaviors are induced in response to short photoperiods or dim-light conditions, and symptoms can be ameliorated by brief exposure to intervals of bright light coincident with activity onset. One exciting avenue of research involves the orexinergic system, which regulates functions that are disturbed in SAD, including sleep cycles, the reward system, feeding behavior, monoaminergic neurotransmission and hippocampal neurogenesis. However, although diurnal models make intuitive sense for the study of SAD and are more likely to mimic circadian disruption, their utility is currently hampered by a lack of genomic resources needed for the molecular interrogation of potential mechanisms. Summary: We review the potential neural mechanisms by which light influences seasonal depression, focusing on research using diurnal rodent models.

SUBMITTER: Shankar A

PROVIDER: S-EPMC7859703 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Project description:Despite widely published speculation regarding a potential potency advantage of short-wavelength (blue-appearing) light for Seasonal Affective Disorder (SAD) treatment, there have been few systematic studies. Those comparing short-wavelength to broad-wavelength (white) light under actual clinical conditions suggest equivalent effectiveness. This multicenter, parallel-group design trial was undertaken to compare the effects of light therapy on SAD using blue (~465 nm) versus blue-free (595-612 nm) LED lights. Fifty-six medication-free subjects aged 21-64 years who met DSM-IV-TR criteria for recurrent major depression with winter-type seasonal pattern were enrolled in this blinded study at five participating centers between January and March 2012. Thirty-five subjects met the criteria for randomization to 30 min of either blue (~465 nm) or blue-free (595-612 nm) daily morning light therapy. Twenty-nine subjects completed the study; three subjects withdrew due to treatment-related adverse events, including migraines, and three withdrew for non-study-related reasons. The primary effectiveness variable was depression score (SIGH-ADS) after six weeks of daily light treatment. Secondary effectiveness variables included quality-of-life (QoL) and suicidality ratings. Using an intent-to-treat analysis, mean depression scores were different at baseline for the blue group (29 ± 5 versus 26 ± 5, p = 0.05 blue versus blue-free, respectively), and the initial score was used as a covariate. Baseline scores were not significantly different between treatment groups among those who completed the study, and no significant differences in depression scores were observed after 6 weeks (mean ± SD scores at 6 weeks: 5.6 ± 6.1 versus 4.5 ± 5.3, p = 0.74, blue versus blue-free, respectively). In addition, the proportion of subjects who met remission criteria, defined as a depression score ≤8, was not significantly different between the two groups (p = 0.41); among the 29 subjects who completed the study, 76% of subjects experienced remission by the end of the trial, which coincided with the beginning of spring. The QoL and suicidality ratings were also significantly improved from pre- to post-treatment, with no significant difference between treatments. No subject experienced worsening or non-improved symptoms over the 6-week trial. The main finding of this study is that subjects treated with blue light did not improve more than subjects treated with blue-free light; both showed substantial improvement on multiple measures. Failure to find differences may have resulted from methodological constraints, including a small sample size. Recruitment began mid-winter during an unusually mild season, and the trial was terminated earlier than planned by the study sponsor due to a failure to detect a difference. However, if confirmed in a larger randomized sample, these results suggest that blue wavelengths are not necessary for successful SAD treatment.

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The darkness and the light: diurnal rodent models for seasonal affective disorder

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