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

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.

Photoperiodic regulation of dopamine signaling regulates seasonal changes in retinal photosensitivity in mice.

At high latitudes, approximately 10% of people suffer from depression during the winter season, a phenomenon known as seasonal affective disorder (SAD). Shortened photoperiod and/or light intensity during winter season are risk factors for SAD, and bright light therapy is an effective treatment. Interestingly, reduced retinal photosensitivity along with the mood is observed in SAD patients in winter. However, the molecular basis underlying seasonal changes in retinal photosensitivity remains unclear, and pharmacological intervention is required. Here we show photoperiodic regulation of dopamine signaling and improvement of short day-attenuated photosensitivity by its pharmacological intervention in mice. Electroretinograms revealed dynamic seasonal changes in retinal photosensitivity. Transcriptome analysis identified short day-mediated suppression of the Th gene, which encodes tyrosine hydroxylase, a rate-limiting enzyme for dopamine biosynthesis. Furthermore, pharmacological intervention in dopamine signaling through activation of the cAMP signaling pathway rescued short day-attenuated photosensitivity, whereas dopamine receptor antagonists decreased photosensitivity under long-day conditions. Our results reveal molecular basis of seasonal changes in retinal photosensitivity in mammals. In addition, our findings provide important insights into the pathogenesis of SAD and offer potential therapeutic interventions.

Photoperiodic changes in hippocampal neurogenesis and plasma metabolomic profiles in relation to depression-like behavior in mice.

Photoperiod alters affective behaviors and brain neuroplasticity in several mammalian species. We addressed whether neurogenesis and signaling pathways of insulin-like growth factor-I (IGF-I), a key modulator of neuroplasticity, are regulated by photoperiod in C57BL/6 J mice, a putative model of seasonal affective disorder. We also examined the effects of photoperiod on plasma metabolomic profiles in relation to depression-like behavior to understand a possible linkage between peripheral metabolism and behavior. Mice that were maintained under long-day conditions (LD) exhibited a higher number of 5-bromo-2'-deoxyuridine-positive cells and higher levels of astrocyte marker in the dentate gyrus of the hippocampus compared to that of mice under short-day conditions (SD). Plasma IGF-I levels and levels/expression of IGF-I signaling molecules in the hippocampus (Brn-4, NeuroD1, and phospho-Akt) involved in neuronal proliferation and differentiation were higher in the mice under LD. Metabolome analysis using plasma of the mice under LD and SD identified several metabolites that were highly correlated with immobility in the forced swim test, a depression-like behavior. Negative correlations with behavior occurred in the levels of 23 metabolites, including metabolites related to neurogenesis and antidepressant-like effects of exercise, metabolites in the biosynthesis of arginine, and the occurrence of branched chain amino acids. Three metabolites had positive correlations with the behavior, including guanidinosuccinic acid, a neurotoxin. Taken together, photoperiodic responses of neurogenesis and neuro-glial organization in the hippocampus may be involved in photoperiodic alteration of depression-like behavior, mediated through multiple pathways, including IGF-I and peripheral metabolites.

The effect of age and chronotype on seasonality, sleep problems, and mood.

Seasonal affective disorder has been associated with sleep problems, young age, and an evening chronotype. A chronotype refers to an individual's preference in the timing of their sleep-wake cycle, as well as the time during the sleep-wake cycle when a person is most alert and energetic. Seasonality refers to season-dependent fluctuations in sleep length, social activity, mood, weight, appetite, and energy level. Evening chronotype is more common in young adults and morning chronotype more common in the elderly. This study aimed to estimate the differential contribution of chronotype and age on seasonality. A sample of n=410 participants were included in the study. The age groups showed significantly different results according to sleep parameters, depression, anxiety, stress, seasonality, and chronotype. The oldest group (>59 years) showed the lowest scores on all of these scales. According to a path analysis, chronotype and age predict propensity for seasonality. However, sleep problems were linked to chronotype but not to age. Older adults seem to be more resistant to seasonal changes that are perceived as a problem than young and middle aged adults. Future studies would benefit from considering cultural aspects and examine seasonality, chronotype, depression, and insomnia in longitudinal designs.

Applying experimental therapeutics to examine cognitive and chronological vulnerabilities as mediators of acute outcomes in cognitive-behavioral therapy and light therapy for winter depression.

OBJECTIVE: We applied the experimental therapeutics approach to test whether acute treatment outcomes for winter seasonal affective disorder (SAD) are mediated by a cognitive mechanism in cognitive-behavioral therapy (CBT-SAD) versus a chronobiologic mechanism in light therapy (LT). METHOD: Currently depressed adults with major depression, recurrent with seasonal pattern (N = 177; 83.6% female, 92.1% non-Hispanic White, M age = 45.6) were randomized to 6 weeks of LT or group CBT-SAD. SAD symptoms were assessed weekly on the Structured Clinical Interview for the Hamilton Rating Scale for Depression-SAD Version. At pre-, mid-, and posttreatment, participants completed measures of general depressogenic cognitions (Dysfunctional Attitudes Scale; DAS); SAD-specific negative cognitions (Seasonal Beliefs Questionnaire; SBQ); chronotype (Morningness-Eveningness Questionnaire; MEQ); and depressive symptoms (Beck Depression Inventory-Second Edition). RESULTS: Parallel-process growth models showed evidence for hypothesized mechanisms. For SAD-specific negative cognitions (SBQ), both symptom measures showed (1) an effect of treatment group on the slope of the mediator, with CBT-SAD demonstrating greater decreases, and (2) an effect of the slope of the mediator on the slope of the outcome. These effects held for the SBQ but not the broader measure of depressogenic cognitions (DAS). For the chronotype measure (MEQ), treatment assignment affected change, whereby LT was associated with reduced "eveningness," but this was unrelated to change in symptoms. CONCLUSIONS: CBT-SAD promoted decreases in SAD-specific negative cognitions, and these changes were related to decreases in symptoms. Consistent with the theory that LT corrects misaligned circadian rhythms, LT reduced eveningness, but this did not correspond to symptom improvement. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Does photoperiodism involve a seasonal and non-pathological Warburg effect?

The precise means whereby mammals recognize and respond to changing day length so as to adjust their physiology to the seasons (photoperiodism) remains enigmatic. We present a new hypothesis according to which aerobic glycolysis (AG) within selected astrocytic syncytia plays a central role in photoperiodism. We focus on the response of the mammal breeding in longer days (LD) to the shorter days (SD) of autumn. It is posited that AG in the brain of the SD organism is activated within a specified circuitry and temporal window. The circuitry involves regions targeted by the medullary norepinephrine (NE) system including but not limited to the anterior bed nucleus of the stria terminalis; the temporal window in question is defined by the autumnal extension of darkness into a segment of the organism's circadian activity cycle that was illuminated on the previous day. Lactate generated from glucose during SD serves primarily as a signaling entity as opposed to a fuel, instructing astrocytes, for example, gradually to replace the LD genome with one specific to SD. The requirement to provision glucose to the brain for AG through SD accounts for the frequent findings of mild autumnal hyperglycemia and elevated carbohydrate appetite across many different mammalian species including human beings. So long as the sidereal environment enveloping life on earth featured its extraordinarily predictable pattern of photoperiodic change, the dangers of exposing the organism to augmented glucose and lactate within a strictly delimited window were easily outweighed by the benefits of a precision mechanism ensuring the alignment of the animal's reproductive cycle with the seasonal one. With "light pollution," that delicate balance may now be at risk.

Has the sun set for seasonal affective disorder and HPA axis studies? A systematic review and future prospects.

OBJECTIVE: Seasonal Affective Disorder (SAD) is a form of cyclic mood disorder that tends to manifest as winter depression. SAD has anecdotally been described as a hypocortisolemic condition. However, there are no systematic reviews on SAD and Hypothalamic-Pituitary-Adrenal (HPA) axis function. This review intends to summarize these findings. METHODS: Using the PRISMA (2009) guideline recommendations we searched for relevant articles indexed in databases including MEDLINE, EMBASE, PsycINFO, and PsychArticles. The following keywords were used: "Seasonal affective disorder", OR "Winter Depression", OR "Seasonal depression" associated with: "HPA Axis" OR "cortisol" OR "CRH" OR "ACTH". RESULTS: Thirteen papers were included for qualitative analysis. Studies used both heterogeneous methods and populations. The best evidence comes from a recent study showing that SAD patients tend to demonstrate an attenuated Cortisol Awakening Response (CAR) in winter, but not in summer, compared to controls. Dexamethasone Suppression Test (DST) studies suggest SAD patients have normal suppression of the HPA axis. CONCLUSION: There is still insufficient evidence to classify SAD as a hypocortisolemic condition when compared to controls. Heterogeneous methods and samples did not allow replication of results. We discuss the limitations of these studies and provide new methods and targets to probe HPA axis function in this population. SAD can provide a unique window of opportunity to study HPA axis in affective disorders, since it is highly predictable and can be followed before, during and after episodes subsides.

Red white and blue - bright light effects in a diurnal rodent model for seasonal affective disorder.

Despite the common use of bright light exposure for treatment of seasonal affective disorder (SAD), the underlying biology of the therapeutic effect is not clear. Moreover, there is a debate regarding the most efficacious wavelength of light for treatment. Whereas according to the traditional approach full-spectrum light is used, recent studies suggest that the critical wavelengths are within the range of blue light (460 and 484 nm). Our previous work shows that when diurnal rodents are maintained under short photoperiod they develop depression- and anxiety-like behavioral phenotype that is ameliorated by treatment with wide-spectrum bright light exposure (2500 lux at the cage, 5000 K). Our current study compares the effect of bright wide-spectrum (3,000 lux, wavelength 420- 780 nm, 5487 K), blue (1,300 lux, wavelength 420-530 nm) and red light (1,300 lux, wavelength range 600-780 nm) exposure in the fat sand rat (Psammomys Obesus) model of SAD. We report results of experiments with six groups of sand rats that were kept under various photoperiods and light treatments, and subjected to behavioral tests related to emotions: forced swim test, elevated plus maze and social interactions. Exposure to either intense wide-spectrum white light or to blue light equally ameliorated depression-like behavior whereas red light had no effect. Bright wide-spectrum white light treatment had no effect on animals maintained under neutral photoperiod, meaning that light exposure was only effective in the pathological-like state. The resemblance between the effects of bright white light and blue light suggests that intrinsically photosensitive retinal ganglion cells (ipRGCs) are involved in the underlying biology of SAD and light therapy.

Patterns of depressive symptom remission during the treatment of seasonal affective disorder with cognitive-behavioral therapy or light therapy.

BACKGROUND: To elucidate mechanisms related to remission in winter seasonal affective disorder (SAD), we explored the course of individual depressive symptom offset across two distinct treatment modalities that show comparable outcomes at treatment endpoint: cognitive-behavioral therapy for SAD (CBT-SAD) and light therapy (LT). METHOD: One hundred seventy-seven adults with SAD in a depressive episode were randomized to 6-weeks of CBT-SAD (n = 88) or LT (n = 89). Symptoms were assessed via the 29-item Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD Version (SIGH-SAD) at pretreatment and weekly during treatment. Survival analyses were conducted for the 17 SIGH-SAD items endorsed by more than 40 participants at pretreatment. Within each of the included symptoms, data from participants who endorsed the symptom at pretreatment and who had 3 or fewer weeks missing were included. RESULTS: For most (13/17; 76%) symptoms, CBT-SAD and LT did not differ in time to remission. However, for four symptoms (early insomnia, psychic anxiety, hypersomnia, and social withdrawal), LT led to symptom remission more quickly than CBT-SAD. CONCLUSIONS: Symptom remission progressed comparably across CBT-SAD and LT for most symptoms. Despite the fact that the two treatments led to similar remission rates and improvements at treatment endpoint, for early insomnia, psychic anxiety, hypersomnia, and social withdrawal, LT led to symptom remission faster than CBT-SAD. These results suggest different mechanisms and pathways to the same therapeutic end. Speedier remission of early insomnia and hypersomnia is consistent with the theory that SAD is related to a pathological circadian phase-shift that can be corrected with LT.

Decreased retinal sensitivity in depressive disorder: a controlled study.

OBJECTIVE: To compare pupil responses in depressed patients with a seasonal pattern, depressed patients without a seasonal pattern and healthy controls as a function of daylight hours on the testing day. METHOD: Patients suffering from a major depressive episode were included in wintertime. The pupil light reflex was measured at inclusion and in the following summer using a binocular pupillometer. A protocol of low (1 lux) and high (400 lux) intensity red and blue lights was used to assess rod, cone and melanopsin-containing intrinsic photosensitive retinal ganglion cell input to the pupil reflex. RESULTS: The mean group pupil responses associated with a melanopsin-mediated sustained pupil response at 400 lux blue light were significantly reduced in the depressed subjects (N = 39) as compared to the healthy controls (N = 24) (P = 0.023). Across all groups, a reduction in number of daylight hours was significantly associated with a reduction in sustained pupil response (P = 0.007). All groups showed an equal effect of daylight hours on the melanopsin-mediated sustained pupil response. CONCLUSION: The melanopsin-mediated sustained pupil contraction to offset of high-intensity blue light is reduced in depressed patients. These results further emphasize the interaction of light exposure with depression.

Amygdala response to emotional faces in seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is characterized by seasonally recurring depression. Heightened amygdala activation to aversive stimuli is associated with major depressive disorder but its relation to SAD is unclear. We evaluated seasonal variation in amygdala activation in SAD and healthy controls (HC) using a longitudinal design targeting the asymptomatic/symptomatic phases of SAD. We hypothesized increased amygdala activation to aversive stimuli in the winter in SAD individuals (season-by-group interaction). METHODS: Seventeen SAD individuals and 15 HCs completed an implicit emotional faces BOLD-fMRI paradigm during summer and winter. We computed amygdala activation (SPM5) to an aversive contrast (angry & fearful minus neutral) and angry, fearful and neutral faces, separately. Season-by-group and main effects were evaluated using Generalized Least Squares. In SAD individuals, we correlated change in symptom severity, assessed with The Hamilton Rating Scale for Depression - Seasonal Affective Disorder version (SIGH-SAD), with change in amygdala activation. RESULTS: We found no season-by-group, season or group effect on our aversive contrast. Independent of season, SAD individuals showed significantly lower amygdala activation to all faces compared to healthy controls, with no evidence for a season-by-group interaction. Seasonal change in amygdala activation was unrelated to change in SIGH-SAD. LIMITATIONS: Small sample size, lack of positive valence stimuli. CONCLUSIONS: Amygdala activation to aversive faces is not increased in symptomatic SAD individuals. Instead, we observed decreased amygdala activation across faces, independent of season. Our findings suggest that amygdala activation to angry, fearful and neutral faces is altered in SAD individuals, independent of the presence of depressive symptoms.

Seasonality in affective disorders.

Humans retain neurobiological responses to circadian day-night cycles and seasonal changes in daylength in spite of a life-style usually independent of dawn-dusk signals. Seasonality has been documented in many functions, from mood to hormones to gene expression. Research on seasonal affective disorder initiated the first use of timed bright light as therapy, a treatment since extended to non-seasonal major depression and sleep-wake cycle disturbances in many psychiatric and medical illnesses. The growing recognition that sufficient light is important for psychological and somatic well-being is leading to the development of novel lighting solutions in architecture as well as focus on a more conscious exposure to natural daylight.

State- and trait-like variation in morning and evening components of morningness-eveningness in winter depression.

PURPOSE: Evening preference (eveningness) can be a risk factor for depression and a shift toward morning preference (morningness) can occur in response to treatment. A study of winter depression provides possibility to longitudinally evaluate state- and trait-like variation in morningness-eveningness during treatment in winter and remission in summer. MATERIAL AND METHODS: Female patients with winter depression and controls without a psychiatric history (n = 54 and 32 with mean age ± standard deviation of 34.4 ± 11.0 and 35.7 ± 9.5 years, respectively) were treated with two-hour bright light for a week during winter period. Some of them (n = 40 and 19, respectively) were then restudied in summer. Measures obtained during the winter period from patients before and after treatment were compared to those obtained from controls and from the same patients in the summer period. Among compared measures, there were self-assessments of state- and trait-like differences in morning and evening components of morningness-eveningness. RESULTS: The groups of depressed patients and controls differed in self-assessments of morning but not evening component of morningness-eveningness. The difference in state-like variation in morning component became non-significant after treatment and in summer. On the other hand, trait-like variation in this component demonstrated adequate test-retest (winter-summer) reliability, i.e. a shift toward trait-like eveningness persisted in patients in the summer. CONCLUSIONS: The observed normalization of state-like variation in morning component of morning-evening preference can be mainly explained by the disappearance of such depressive symptoms as lack of energy, social withdrawal, loss of interest in once enjoyable activities, etc.

Prediction of outcome of bright light treatment in patients with seasonal affective disorder: Discarding the early response, confirming a higher atypical balance, and uncovering a higher body mass index at baseline as predictors of endpoint outcome.

BACKGROUND: We tested the hypothesis that the early improvement in mood after the first hour of bright light treatment compared to control dim-red light would predict the outcome at six weeks of bright light treatment for depressed mood in patients with Seasonal Affective Disorder (SAD). We also analyzed the value of Body Mass Index (BMI) and atypical symptoms of depression at baseline in predicting treatment outcome. METHODS: Seventy-eight adult participants were enrolled. The first treatment was controlled crossover, with randomized order, and included one hour of active bright light treatment and one hour of control dim-red light, with one-hour washout. Depression was measured on the Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH-SAD). The predictive association of depression scores changes after the first session. BMI and atypical score balance with treatment outcomes at endpoint were assessed using multivariable linear and logistic regressions. RESULTS: No significant prediction by changes in depression scores after the first session was found. However, higher atypical balance scores and BMI positively predicted treatment outcome. LIMITATIONS: Absence of a control intervention for the six-weeks of treatment (only the first session in the laboratory was controlled). Exclusion of patients with comorbid substance abuse, suicidality and bipolar I disorder, and patients on antidepressant medications, reducing the generalizability of the study. CONCLUSION: Prediction of outcome by early response to light treatment was not replicated, and the previously reported prediction of baseline atypical balance was confirmed. BMI, a parameter routinely calculated in primary care, was identified as a novel predictor, and calls for replication and then exploration of possible mediating mechanisms.

Seasonal pattern in bipolar disorders and cardio-vascular risk factors: A study from the FACE-BD cohort.

Seasonal pattern (SP) and metabolic syndrome (MetS) are major contributors to poor outcome in bipolar disorders (BD). Patients with seasonal bipolar depression present increased appetite, carbohydrate cravings, weight gain, and hypersomnia, which can increase the development of MetS. MetS also appears to be associated with seasonal mood changes in the general population. This study examines whether a SP in BD is associated with an increased risk of MetS and its sub-components. One thousand four hundred and seventy-one outpatients with BD were systematically enrolled from 2009 to 2016. Inclusion required a disease duration of at least 5 years, with 486 (33%) patients with SP (SP+) and 985 (67%) without (SP-) according to the DSM IV-TR criteria. When using continuous measures of metabolic components, SP+ patients, as compared to SP-, suffered from higher levels for systolic blood pressure (p = 0.01), low-density lipoprotein cholesterol (p = 0.009), fasting glucose (p = 0.007), triglycerides levels (p = 0.03), a larger abdominal circumference (p = 0.02), and a higher body mass index (p = 0.07). In the covariance analysis, adjusted for gender, age, and bipolar subtype, as well as the number of depressive and hypomanic episode, SP+ patients had a significantly higher level of fasting glucose and higher systolic blood pressure. The frequency of MetS did not differ between groups (21.2% in SP- versus 23.9% in SP+). When using categorical definitions for abnormal metabolic components (International Diabetes Federation criteria), there were no differences between groups, except that SP+ patients were more overweight/obese as compared to SP- patients (55.03% versus 46.7%, respectively; p = 0.002) and tended to have more frequently high fasting glucose (18.2% versus 14.3%, respectively; p = 0.07). MetS was frequent in patients with BD, however not associated with SP. Patients with SP appeared more vulnerable to overweight/obesity and presented with higher levels of MetS subcomponents although these parameters were mainly in the normal range. All patients with BD should benefit from early screening and targeted management of cardio-vascular risk factors.

Secondary to excessive melatonin synthesis, the consumption of tryptophan from outside the blood-brain barrier and melatonin over-signaling in the pars tuberalis may be central to the pathophysiology of winter depression.

Seasonal affective disorder is defined as recurrent episodes of major depression, mania, or hypomania with seasonal onset and remission. In this class of mood disturbances, a unipolar major depressive disorder known as winter depression is common in populations living in northern latitudes far from the equator. Winter depression repeatedly occurs in the autumn or winter and remits in the spring or summer, and its etiopathogenesis is currently unknown. However, one can surmise that excessive melatonin production during the reduced duration of daily sunlight in the autumn and winter plays a role in its pathophysiology. Melatonin is synthesized from tryptophan within the pineal gland, which is located outside the blood-brain barrier, and overproduction of melatonin may lead to augmented consumption of tryptophan, from which serotonin is synthesized. As tryptophan is captured from the blood and excessively utilized by the pineal gland, tryptophan blood levels may decline; as such, it is more difficult for tryptophan to pass through the blood-brain barrier and reach the serotonergic neurons as the ratio of tryptophan to the other amino acids that compete for the same transporter to enter the brain is diminished. As such, less tryptophan is available for serotonin synthesis. Moreover, melatonin is known to modulate thyrotropin expression in the thyrotrophic cells of the pars tuberalis of the pituitary gland, and overproduction of melatonin in the autumn or winter months may cause excessive signaling in the pars tuberalis, diminishing its release of thyrotropin and resulting in central hypothyroidism. Both conditions reduced serotonin production and central hypothyroidism may cause depression. Furthermore, the excessive synthesis of melatonin during the autumn and winter may negatively affect the expression of neuromedin U in the pars tuberalis, causing an increased appetite, which is common in winter depression patients. The hypersomnia common in winter depressive patients can be ascribed to excessive circulating melatonin, a hormone that increases the propensity for sleep. Furthermore, central hypothyroidism may also increase sleepiness, as it is known that hypothyroid patients usually experience excessive somnolence. In this theoretical article, we also propose studies to evaluate winter depression patients with regard to the necessity, or not, of offering them an increased amount of tryptophan in their diets during the autumn and winter. We also suggest that the administration of triiodothyronine to winter depressive patients may mitigate their central hypothyroidism.

[Light and Medicine]. / Licht und Medizin.

There would be no life without light. The rotation of the earth around its axis has introduced the development of biological clocks in all living subjects regulating all functions of the body. The rhythms best described are the 24-hour/circadian and the seasonal rhythms. The rhythmic composition around the body clock has great impact on health and disease, both in diagnostics and treatment. Nowadays, bright light, e.g. in seasonal affective disorder, can be regarded as a drug, being even more effective than selective serotonin reuptake inhibitors.

The relation between chronotype and treatment outcome with light therapy on a fixed time schedule.

BACKGROUND: Seasonal affective disorder (SAD) is characterized by recurrent episodes of major depression in a seasonal pattern. The therapy of choice is light therapy (LT). It is suggested that LT should be administered relative to the chronotype of the patient, with the optimal timing earlier for morning than for evening types. This study aims to retrospectively investigate the relation between chronotype and the effect of LT on a fixed time in the morning in a population of SAD patients. METHODS: Data from four different studies conducted at the University Center of Psychiatry in Groningen, the Netherlands was used. Data from 132 patients was used (103 women). Depression score was determined by a structured interview (SIGH-SAD) prior to LT and after LT. Prior to LT morningness/eveningness preference of the patient was determined by the 'Morningness/Eveningness Questionnaire' (MEQ). All patients received LT at 8:00 AM at the clinic, independent of chronotype. RESULTS: Patients had an average MEQ score of 51.5±8.2. There was no significant relationship between MEQ score and therapy success as measured with the SIGH-SAD (F2,129=0.05, ns). When patients were divided by chronotype (ranging from definite morning to moderate evening) no significant relation between MEQ score and therapy success was found (F2,129=0.02, ns). LIMITATIONS: Retrospective design. CONCLUSIONS: The lack of a significant relationship between chronotype, as measured with the MEQ, and therapy success with LT at a fixed timepoint may indicate that the anti-depressive effect of morning light in SAD patients is not explained by a phase shift of the biological clock.