Narrow‐band blue‐light treatment of seasonal affective disorder in adults and the influence of additional nonseasonal symptoms

Background: Bright visible‐spectrum light therapy has proven effective in the treatment of seasonal affective disorder (SAD) and recent basic research suggests that blue wavelengths ～470 nm account for that effectiveness. To more stringently test the importance of these wavelengths, bright red‐light was used for the placebo (control) condition. Methods: Thirty subjects meeting DSM‐IV criteria for SAD were randomized to narrow‐band light‐emitting diode panels emitting blue‐ or red‐light in this 3‐week, parallel, double‐blind trial. Twenty‐five subjects participated in an open‐label blue‐light follow‐up. Subjects were divided in a blinded, post hoc manner into two groups: SAD only and those experiencing depression with seasonal intensification. The outcome was assessed using Hamilton Depression Rating Scale–17 item version (HAMD‐17) and the Structured Interview Guide for the Hamilton Depression Rating Scale—SAD version. Responders were defined by Clinical Global Impression—Improvement scale. Results: HAMD‐17 scores improved more under the blue‐light condition (51%) than under the red‐light condition (32%) (P=.05). Further, in the blue arm 60% of subjects responded compared with 13% in the red arm (P=.01). During the open‐label phase, subjects from both double‐blind arms improved over baseline. SAD alone patients responded numerically better to treatment than those experiencing depression with seasonal intensification during both treatment periods. Conclusions: Narrow bandwidth blue‐light therapy proved superior to red‐light therapy. Blue‐light therapy produced results similar to both previous 10,000 lux visible‐spectrum light studies and many medication studies. The use of bright red panels supported claims that wavelengths of ～470 nm account for the documented effectiveness of light therapy. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.     

Escitalopram in seasonal affective disorder: results of an open trial

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of escitalopram in the treatment of seasonal affective disorder (SAD, fall-winter depression). METHODS: Twenty SAD patients were included in an 8-week drug surveillance. Patients were treated with open-label escitalopram at a dosage of 10 to 20 mg per day. Efficacy assessments included the Structured Interview Guide for the Hamilton Depression Rating Scale (SAD version; SIGH-SAD), the Clinical Global Impression (CGI) and the Social Adaptation Self Evaluation Scale (SASS). Side effects were monitored with the UKU Side Effect Rating Scale. RESULTS: From week 2 onwards, escitalopram significantly reduced SIGH-SAD score and CGI severity score (p<0.001). From week 4 onwards, the SASS score was also significantly improved (p<0.05). The response rate (SIGH-SAD<50% of baseline value) after treatment for 8 weeks was 95%, the rate of remission (SIGH-SAD < or =7) was 85%. Side effects were mild to moderate and did not lead to cessation of therapy. CONCLUSION: These results suggest that escitalopram is an efficacious and altogether safe treatment for seasonal depression.     

Lux vs. wavelength in light treatment of Seasonal Affective Disorder

Objective: Published dosing guidelines for treatment of Seasonal Affective Disorder (SAD) refer to photopic lux, which is not appropriate for short‐wavelength light. Short wavelengths are most potent for many non‐visual responses to light. If SAD therapy were similarly mediated, standards utilizing lux risk overestimating necessary dose. We investigated antidepressant responses to light using two light‐emitting diode (LED) sources, each emitting substantial short‐wavelength light, but <2500 lux. Method: A randomized, double‐blind trial investigated 3‐week 45 min/day out‐patient treatment with blue‐appearing (goLITE^®) or blue‐enriched white‐appearing light in 18 moderately‐depressed adults (12F, 49.1 ± 9.5 years). Equivalent numbers of photons within the short‐wavelength range were emitted, but the white source emitted twice as many photons overall and seven‐fold more lux. Results: Depression ratings (SIGH‐ADS; http://www.cet.org ) decrease averaged 82% (SD = 17%) from baseline (P < 0.0001) in both white‐ and blue‐light groups. Both sources were well tolerated. Conclusion: Short‐wavelength LED light sources may be effective in SAD treatment at fewer lux than traditional fluorescent sources.     

Dawn simulation and bright light in the treatment of SAD: a controlled study.

BACKGROUND: Some small controlled studies have found that dawn simulation is effective in treating seasonal affective disorder (SAD). With a larger sample size and a longer duration of treatment, we compared dawn simulation with bright light therapy and a placebo condition in patients with SAD. METHOD: Medication-free patients with SAD were randomly assigned to one of three conditions: bright light therapy (10,000 lux for 30 min, from 6:00 AM to 6:30 AM), dawn simulation (1.5 hour dawn signal from 4:30 AM to 6:00 AM peaking at 250 lux), and a placebo condition, a dim red light (1.5 hour dawn signal from 4:30 am to 6:00 AM peaking at 0.5 lux.) Over the subsequent 6 weeks, the subjects were blindly rated by a psychiatrist using the Structured Interview Guide for the Hamilton Depression Rating-Seasonal Affective Disorder Version (SIGH-SAD). We modeled the profiles of the remissions (SIGH-SAD < or = 8) and response (> or =50% decrease in SIGH-SAD) to treatment over time using Cox proportional hazards models. RESULTS: The sample consisted of 95 subjects who were randomized to the three conditions: bright light (n = 33), dawn simulation (n = 31) and placebo (n = 31). Dawn simulation was associated with greater remission (p <.05) and response (p <.001) rates compared to the placebo. Bright light did not differ significantly from the placebo. Dawn simulation was associated with greater remission (p <.01) and response (p <.001) rates compared to the bright light therapy. The mean daily hours of sunshine during the week before each visit were associated with a significant increase in likelihood of both remission (p <.001) and response (p <.001). CONCLUSIONS: Dawn simulation was associated with greater remission and response rates compared to the placebo and compared to bright light therapy. The hours of sunshine during the week before each assessment were associated with a positive clinical response.     

Effects of light therapy on suicidal ideation in patients with winter depression

BACKGROUND: Recent case reports suggest that some patients with seasonal affective disorder (SAD) may become suicidal after initial treatment with light therapy. This retrospective study sought to determine the effects of light therapy on suicidal ideation in patients with SAD. METHOD: The cases of 191 depressed patients with SAD by DSM-III-R or DSM-IV criteria treated with an open trial of morning light therapy using cool white fluorescent light boxes (2500 lux for 2 hours per day or 10,000 lux for 30 minutes per day) for 2 weeks were retrospectively analyzed. Patients had been rated before and after treatment with the expanded Hamilton Depression Rating Scale (SIGH-SAD). RESULTS: Sixty-seven percent of patients were rated as clinical responders to light therapy. There was significant improvement in the SIGH-SAD suicide item score, with 45% of patients showing a reduction in score. Only 6 patients (3%) had slight worsening of suicide scores. No patients attempted suicide or discontinued light therapy because of emergent suicidality. CONCLUSION: Light therapy relieves suicidal ideation in patients with SAD consistent with overall clinical improvement. Emergence of suicidal ideas or behaviors is very uncommon with light therapy.     

Therapeutic effects of escitalopram and reboxetine in seasonal affective disorder: A pooled analysis

The monoaminergic neurotransmitters serotonin and noradrenaline have both been implicated in the pathogenesis of seasonal affective disorder (SAD). However, the differential therapeutic value of selective serotonin reuptake inhibitors (SSRI) and selective noradrenaline reuptake inhibitors (NARI) in SAD has not been assessed until now. This study compares data from two open-label trials with similar methodology investigating the SSRI escitalopram and the NARI reboxetine. 20 SAD patients were treated with escitalopram (10-20 mg) and 15 patients received treatment with reboxetine (fixed dosage: 8 mg) over 6 weeks. Ratings included the structured interview guide for the Hamilton depression rating scale, SAD version (SIGH-SAD), the clinical global impression of severity (CGI-S) and improvement (CGI-I) and the UKU side effect rating scale. Treatment led to a significant reduction in SIGH-SAD score, CGI-S and CGI-I after one week in the reboxetine group and after two weeks in the escitalopram group. SIGH-SAD score was significantly lower in the reboxetine group at weeks 1, 2 and 4 but not at the end of the study. The response rate (SIGH-SAD <50% of baseline value) and the remission rate (SIGH-SAD <8) were not significantly different after 6 weeks of treatment, but the time to response and to remission was significantly shorter in the reboxetine group. The number and severity of side effects were higher in patients treated with reboxetine at all time points. Thus escitalopram and reboxetine were equally effective in treating SAD on all primary and secondary outcome measures. Reboxetine displayed a faster onset of action, but was associated with more pronounced side effects. Further studies comparing SSRI and NARI in SAD are warranted.     

Light treatment for seasonal Winter depression in African-American vs Caucasian outpatients

AIM: To compare adherence, response, and remission with light treatment in African-American and Caucasian patients with Seasonal Affective Disorder.METHODS: Seventy-eight study participants, age range 18-64 (51 African-Americans and 27 Caucasians) recruited from the Greater Baltimore Metropolitan area, with diagnoses of recurrent mood disorder with seasonal pattern, and confirmed by a Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV, were enrolled in an open label study of daily bright light treatment. The trial lasted 6 wk with flexible dosing of light starting with 10000 lux bright light for 60 min daily in the morning. At the end of six weeks there were 65 completers. Three patients had Bipolar II disorder and the remainder had Major depressive disorder. Outcome measures were remission (score ≤ 8) and response (50% reduction) in symptoms on the Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-SAD) as well as symptomatic improvement on SIGH-SAD and Beck Depression Inventory-II. Adherence was measured using participant daily log. Participant groups were compared using t-tests, chi square, linear and logistic regressions.RESULTS: The study did not find any significant group difference between African-Americans and their Caucasian counterparts in adherence with light treatment as well as in symptomatic improvement. While symptomatic improvement and rate of treatment response were not different between the two groups, African-Americans, after adjustment for age, gender and adherence, achieved a significantly lower remission rate (African-Americans 46.3%; Caucasians 75%; P = 0.02).CONCLUSION: This is the first study of light treatment in African-Americans, continuing our previous work reporting a similar frequency but a lower awareness of SAD and its treatment in African-Americans. Similar rates of adherence, symptomatic improvement and treatment response suggest that light treatment is a feasible, acceptable, and beneficial treatment for SAD in African-American patients. These results should lead to intensifying education initiatives to increase awareness of SAD and its treatment in African-American communities to increased SAD treatment engagement. In African-American vs Caucasian SAD patients a remission gap was identified, as reported before with antidepressant medications for non-seasonal depression, demanding sustained efforts to investigate and then address its causes.     

Early response to light therapy partially predicts long-term antidepressant effects in patients with seasonal affective disorder

OBJECTIVE: To determine if the antidepressant effect of 1 hour of light therapy is predictive of the response after 1 and 2 weeks of treatment in patients with seasonal affective disorder (SAD). PATIENTS: Twelve patients with SAD. SETTING: National Institutes of Health Clinical Center, Bethesda, Md. INTERVENTIONS: Light therapy for 2 weeks. OUTCOME MEASURES: Scores on the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale (SIGH-SAD) on 4 occasions (before and after 1 hour of light therapy and after 1 and 2 weeks of therapy) in the winter when the patients were depressed. Change on typical and atypical depressive scores at these time points were compared. RESULTS: Improvement of atypical depressive symptoms after 1 hour of light therapy positively correlated with improvement after 2 weeks of therapy. CONCLUSION: In patients with SAD, the early response to light therapy may predict some aspects of long-term response to light therapy, but these results should be treated with caution until replicated.     

Treatment of seasonal affective disorder with duloxetine: an open-label study

OBJECTIVE: The aim of this observational study was to evaluate the effects of duloxetine in the treatment of seasonal affective disorder (SAD). PATIENTS AND METHODS: 26 SAD patients were treated with open-label duloxetine 60-120 mg per day over 8 weeks. Ratings included the Structured Interview Guide for the Hamilton Depression Rating Scale (SAD version; SIGH-SAD) and the Clinical Global Impression (CGI). To estimate treatment effects on social functioning in SAD we employed the Social Adaptation Self Evaluation Scale (SASS), the Sheehan Disability Scale (SDS), and assessments of days lost due to illness and days with reduction in productivity. RESULTS: Duloxetine led to a significant improvement (p<0.001) of SIGH-SAD, CGI severity, SASS, and SDS scores. Days lost due to illness and days with reduction in productivity were significantly diminished during treatment (p<0.001). Treatment with duloxetine over 8 weeks yielded a response rate (SIGH-SAD<50% of baseline value) of 80.8% and a remission rate (SIGH-SAD<8) of 76.9% in the intention to treat sample. The drop-out rate due to side effects was 15.4%. CONCLUSIONS: Our preliminary results indicate that duloxetine might be effective and able to ameliorate the negative social consequences of SAD.     

Action spectra of the lateral eyes recorded from mammalian pineal glands

Single neuronal units from the pineal stalk and the pineal body of hamsters, guinea pigs and rats were recorded during photic stimulation of the lateral eyes in order to identify the retinal photoreceptor that mediates the environmental control of the mammalian pineal. Two cell types could be distinguished: one type was characterized by spontaneous spike discharges that were irresponsive to light stimulation of the eyes and the pineal body; the other, also spontaneously active, responded to flash stimulation of the lateral eye with On- and Off-discharges. With increasing light intensity, the spike frequency of the second response type followed a sigmoidal function up to a saturation level. Spectral sensitivity curves of all dark-adapted animals peaked at 500 nm. During light adaptation (18 microW/cm2) action spectra exhibited an additional maximum in the red (560 nm, rats and hamsters) and in the blue (450 nm, guinea pigs) light, respectively. Chromatic adaptation to orange light diminished the sensitivity at longer wavelengths, whereas adaptation to blue-green light enhanced the sensitivities at longer wavelengths. Thus, the spectral sensitivity recorded from pineal units of hamsters, guinea pigs and rats corresponds to those described for retinal ganglion cells, which indicates that both rods and cones contribute to the light-sensitivity of the mammalian pineal gland. Direct illumination of the pineal gland did not influence the activity of pineal units.     

Open study of effects of alprazolam on seasonal affective disorder

Seasonal affective disorder (SAD) differs from depression with melancholic features in atypical symptoms, such as hyperphagia, hypersomnia and weight gain. Moreover, SAD is confined to a certain season of the year. We examined the pharmacological efficacy of alprazolam for treatment of patients with SAD. Six patients with SAD were treated with alprazolam at doses of 1.2 mg/day or 1.2 mg/day first and then 2.4 mg/day for 2 weeks. The improvement was evaluated by the change of total score of the SIGH-SAD (with both 21 items HAMD and eight items atypical symptoms) and the clinical global impression (CGI). Although only two patients showed a remarkable improvement by SIGH-SAD, all patients showed a higher than moderate improvement with CGI. Our findings suggest that alprazolam might be efficacious for certain SAD patients.     

Blue light stress in retinal neuronal (R28) cells is dependent on wavelength range and irradiance

The aim of our study was to elucidate the role of wavelength and irradiance in blue light retinal damage. We investigated the impact of blue light emitted from light-emitting diode (LED) modules with peaks at either 411nm (half bandwidth 17nm) or 470nm (half bandwidth 25nm) at defined irradiances of 0.6, 1.5 and 4.5W/m(2) for 411nm and 4.5W/m(2) for 470nm on retinal neuronal (R28) cells in vitro. We observed a reduction in metabolic activity and transmembrane potential of mitochondria when cells were irradiated at 411nm at higher irradiances. Furthermore, production of mitochondrial superoxide radicals increased significantly when cells were irradiated with 411nm light at 4.5W/m(2) . In addition, such irradiation caused an activation of the antioxidative glutathion system. Using vital staining, flow cytometry and western blotting, we were able to show that apoptosis only took place when cells were exposed to 411nm blue light at higher irradiances; necrosis was not observed. Enhanced caspase-3 cleavage product levels confirmed that this effect was dependent on light irradiance. Significant alterations of the above-mentioned parameters were not observed when cells were irradiated with 471nm light despite a high irradiance of 4.5W/m(2) , indicating that the cytotoxic effect of blue light is highly dependent on wavelength. The observed phenomena in R28 cells at 411nm (4.5W/m(2) ) point to an apoptosis pathway elicited by direct mitochondrial damage and increased oxidative stress. Thus, light of 411nm should act via impairment of mitochondrial function by compromising the metabolic situation of these retinal neuronal cells.     

Depressive symptomatology differentiates subgroups of patients with seasonal affective disorder

Patients with seasonal affective disorder (SAD) may vary in symptoms of their depressed winter mood state, as we showed previously for nondepressed (manic, hypomanic, hyperthymic, euthymic) springtime states [Goel et al., 1999]. Identification of such differences during depression may be useful in predicting differences in treatment efficacy or analyzing the pathogenesis of the disorder. In a cross-sectional analysis, we determined whether 165 patients with Bipolar Disorder (I, II) or Major Depressive Disorder (MDD), both with seasonal pattern, showed different symptom profiles while depressed. Assessment was by the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD), which includes a set of items for atypical symptoms. We identified subgroup differences in SAD based on categories specified for nonseasonal depression, using multivariate analysis of variance and discriminant analysis. Patients with Bipolar Disorder (I and II) were more depressed (had higher SIGH-SAD scores) and showed more psychomotor agitation and social withdrawal than those with MDD. Bipolar I patients had more psychomotor retardation, late insomnia, and social withdrawal than bipolar II patients. Men showed more obsessions/compulsions and suicidality than women, while women showed more weight gain and early insomnia. Whites showed more guilt and fatigability than blacks, while blacks showed more hypochondriasis and social withdrawal. Darker-eyed patients were significantly more depressed and fatigued than blue-eyed patients. Single and divorced or separated patients showed more hypochondriasis and diurnal variation than married patients. Employed patients showed more atypical symptoms than unemployed patients, although most of the subgroup distinctions lay on the Hamilton Scale. These results comprise a set of biological and sociocultural factors-including race, gender, and marital and employment status-which contribute to depressive symptomatology in SAD. Significant mood and sociocultural factors, in contrast to biological factors of gender and eye color, were similar to those reported for nonseasonal depression. Lightly pigmented eyes, in particular, may serve to enhance photic input during winter and allay depressive symptoms in vulnerable populations.     

Platelet [3H]paroxetine and [3H]lysergic acid diethylamide binding in seasonal affective disorder and the effect of bright light therapy.

BACKGROUND: Seasonal affective disorder (SAD) has been regarded as a melatonin disorder, but the pathophysiological mechanisms of SAD are to a large extent unclarified. Serotonergic mechanisms have also been studied, but they have shown inconsistent results. METHODS: We have compared [3H]paroxetine and [3H]lysergic acid diethylamide (LSD) binding in platelets from 23 SAD patients and 23 controls. Then SAD patients had 4 weeks of light therapy. On the last treatment day new blood samples were drawn. Symptoms before and after light treatment were measured by SIGH-SAD. RESULTS: Bmax for paroxetine binding before light treatment was higher in SAD patients compared to controls and also higher in responders than in nonresponders. Bmax decreased significantly during light treatment. We also found a negative correlation between the two Bmax values before but not after light treatment. There was a negative correlation between Bmax for paroxetine binding before treatment and clinical status after treatment. Patients with reduced Bmax for LSD binding after treatment had a better clinical treatment response. CONCLUSIONS: The present study indicates that serotonin receptor parameters might be suitable in the prediction of clinical response to light treatment.     

Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales

OBJECTIVE: To investigate the use of bright light therapy as an adjunct treatment to sertraline in non-seasonal major depression. METHOD: In a randomised double-blind trial, 102 patients were treated for 5 weeks with either white bright light (10 000 lux, 1 h daily) or red dim light (50 lux, 30 min daily). All patients were treated with sertraline in a fixed dose of 50 mg daily. The clinician-rated depression scales used were the Hamilton Depression Rating Scale (HAM-D17), Hamilton six-item subscale (HAM-D6), Melancholia Scale (MES) and the seven 'atypical' items from the SIGH-SAD. RESULTS: One-hundred and two patients were included in the study. Analyses showed that the reduction in depression scores in the bright light group was statistically significantly larger than in the dim light group on all scales. The scale most sensitive at endpoint was the HAM-D(6), which includes the core symptoms of depression. CONCLUSION: The study results support the use of bright light as an adjunct treatment to antidepressants in non-seasonal depression.     

Preliminary evidence for spectral opponency in the suppression of melatonin by light in humans

Human adult males were exposed to light from blue light emitting diodes (18 lux; 29 microW/cm) and from clear mercury vapor lamps (450 lux; 170 microW/cm) during night-time experimental sessions. Both conditions suppressed nocturnal melatonin concentrations in blood plasma with the blue light more effective than mercury at melatonin suppression. No additive model incorporating opsin photopigments either alone or in combination could explain the results, but a model incorporating an opponent mechanism was consistent with the present data as well as data from previously published studies.     

Electroretinography in patients with winter seasonal affective disorder

A retinal sensitivity abnormality has been hypothesized in seasonal affective disorder (SAD). To explore this hypothesis, the electroretinogram (ERG) was used to assess retinal sensitivity at the level of the rod photoreceptor system. We examined 27 depressed patients who met DSM-III-R criteria for major depression, recurrent, with a seasonal (winter) pattern and 23 normal control subjects who were age-paired and sex-matched as much as possible with the SAD patients. ERG testing was performed in dark-adapted, dilated eyes in winter between 10:00 and 15:00 h. Retinal sensitivity was based on the light stimulus intensity necessary to reach a 50-microV amplitude threshold. We found that retinal sensitivity was significantly lower (0.21 log units) in SAD patients compared with normal control subjects and that 55% of the patients had a retinal sensitivity value one standard deviation lower than the mean value of the control subjects. These results are consistent with a retinal hyposensitivity hypothesis for SAD, but the explanation for lower rod photoreceptor sensitivity in SAD is not known. We hypothesize that brain neurotransmitter dysregulation may be at the origin of both the mood disorder and retinal sensitivity change.     

The influence of different light spectra on the suppression of pineal melatonin content in the syrian hamster

The purpose of this study was to test the capacity of different visible wavelengths of light to suppress nocturnal levels of pineal melatonin in hamsters. It was found that the visible wavelengths vary in their ability to perturb pineal melatonin. During the period of peak pineal melatonin production, animals were exposed to fluorescent light sources having half-peak bandwidths of 339–371 nm (near-ultraviolet), 435–500 nm (blue), 510–550 nm (green), 558–636 nm (yellow) and 653–668 nm (red). In each experiment, animals were exposed to equal irradiances of each light source. The different irradiances used were 0.928, 0.200, 0.186, 0.074 and 0.019 μW/cm². The resultant data demonstrated that blue fluorescent light was the most efficient in suppressing pineal melatonin. Green fluorescent light was found to be the next most efficient light for inhibiting pineal melatonin followed by yellow fluorescent light. Near-ultraviolet and red light were the least capable of suppressing pineal melatonin. These observations suggest that the retinal photopigment responsible for mediating the pineal gland's response to light in the hamster may be either rhodopsin or another blue-sensitive chromophore.     

Dimensions of temperament and bright light response in seasonal affective disorder

Scale scores on the Tridimensional Personality Questionnaire (TPQ)-novelty seeking (NS), harm avoidance (HA), and reward dependence (RD)-can predict response to antidepressants. This study examined 89 patients with Bipolar Disorder (I, II) or Major Depressive Disorder, both with recurrent winter seasonal pattern. The TPQ was administered while the patients were depressed, following 10-14 days of bright light therapy (30 min, 10,000 lux) and after spontaneous springtime remission. The Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD) assessed the severity of depression. At baseline, there were no significant differences between diagnostic subgroups or responders and non-responders on the TPQ or SIGH-SAD scales, though baseline RD scores were significantly higher in women than men. Furthermore, neither severity of depression nor magnitude of post-treatment clinical improvement was significantly correlated with baseline TPQ scores. Only HA scores decreased after treatment, with responders showing the greatest effect. HA scores also decreased from the baseline to springtime assessments for the group as a whole, with no difference between responders and non-responders. This is the first study to demonstrate that HA is state- rather than trait-dependent in seasonal affective disorder. The TPQ dimensions of temperament do not predict response to light therapy.     

Potential animal models of seasonal affective disorder

Seasonal affective disorder (SAD) is characterized by depressive episodes during winter that are alleviated during summer and by morning bright light treatment. Currently, there is no animal model of SAD. However, it may be possible to use rodents that respond to day length (photoperiod) to understand how photoperiod can shape the brain and behavior in humans. As nights lengthen in the autumn, the duration of the nightly elevation of melatonin increase; seasonally breeding animals use this information to orchestrate seasonal changes in physiology and behavior. SAD may originate from the extended duration of nightly melatonin secretion during fall and winter. These similarities between humans and rodents in melatonin secretion allows for comparisons with rodents that express more depressive-like responses when exposed to short day lengths. For instance, Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a depressive-like phenotype when exposed to short days. Current research in depression and animal models of depression suggests that hippocampal plasticity may underlie the symptoms of depression and depressive-like behaviors, respectively. It is also possible that day length induces structural changes in human brains. Many seasonally breeding rodents undergo changes in whole brain and hippocampal volume in short days. Based on strict validity criteria, there is no animal model of SAD, but rodents that respond to reduced day lengths may be useful to approximate the neurobiological phenomena that occur in people with SAD, leading to greater understanding of the etiology of the disorder as well as novel therapeutic interventions.