Seasonal Affective Disorder

Seasonal Affective Disorder is a subgrouping of major depressive disorder that occurs with seasonal variation.  It is a highly complex, multifactorial illness.

Full MD free SAD article here.

NAMI’s discussion of SAD

Psychoneuroendocrinology. 2010 Dec 8. [Epub ahead of print]

Seasonal differences in the diurnal pattern of cortisol secretion in healthy participants and those with self-assessed seasonal affective disorder.

Thorn L, Evans P, Cannon A, Hucklebridge F, Evans P, Clow A.

Department of Psychology, University of Westminster, 309 Regent Street, London W1B 2UW, UK.


This study compared the daily pattern of free salivary cortisol secretion in winter and in summer between two groups; participants with self-assessed seasonal affective disorder (SAD) and age- and sex-matched healthy controls. Fifty-two participants completed the study with an equal number in each group. The diurnal pattern of cortisol secretion was assessed across two consecutive weekdays in summer, and two in winter, with conditions being counterbalanced. On each study day participants collected multiple saliva samples in the domestic setting to capture the cortisol awakening response (CAR) and declining levels across the day. In addition, perceived stress, anxiety, depression, state stress and state arousal were assessed using validated questionnaires. There was no evidence for any seasonal changes in psychological data or cortisol pattern for the healthy control population. In summer, self-assessed SAD and control participants had similar psychological and cortisol profiles. In winter however, SAD participants reported greater depression, stress and anxiety, and lower levels of arousal. Furthermore, the CAR was significantly attenuated in SAD participants during winter months. There was no difference in cortisol levels during the rest of the day between controls and SAD participants in winter. In line with the above findings and previous research, there was an inverse relationship between the increase in cortisol following awakening and a measure of seasonality in winter. Furthermore in winter, a general dysphoria construct correlated inversely with the CAR, indicating that participants reporting greater depression, stress and anxiety and lower arousal, exhibited lower CARs. In conclusion, during the shortened photoperiod in winter, the cortisol response to awakening is attenuated in participants with self-assessed SAD in comparison to controls. These findings contribute to the understanding of the physiology of SAD.

Copyright © 2010 Elsevier Ltd. All rights reserved

J Psychiatr Pract. 2010 Nov;16(6):387-93.

Light therapy for seasonal affective disorder in a clinical office setting.

Privitera MR, Moynihan J, Tang W, Khan A.University of Rochester Medical Center, Rochester, NY 14642, USA.


OBJECTIVE: To determine predictors of response to light therapy (LT) for seasonal affective disorder, winter version, in a clinical office setting for patients with a spectrum of seasonality defined by the Seasonal Pattern Assessment Questionnaire (SPAQ).

METHOD: A retrospective review was done of charts of 51 patients who had been treated with a 1-week light therapy intervention. Patient self-rated scales applied in a standard manner were used to measure clinical progress. The Beck Depression Inventory (BDI) with added atypical features was used as the primary outcome variable. Sleep patterns were analyzed and the effect of psychotropic medications on outcome was determined. Seven point scales were used to assess expected response and global response. The importance of having LT set up and available in an office setting was evaluated. Retrospective degree of disability was measured based on the SPAQ degree of problem. The severity of the depressive episode was determined based on BDI score at entry.

RESULTS: Seasonality (how a patient’s symptoms vary as a function of the season of the year), degree of disability based on the SPAQ, and severity of depressive episode at entry based on the BDI predicted response to LT. Greater severity at baseline based on BDI score predicted less chance of attaining full remission within 7 days of treatment compared with patients with lower severity scores at entry on the BDI. Sleep patterns relative to a fixed treatment time of 7 AM did not predict LT response. Light therapy was effective on its own, and the results were mixed as to whether adding LT to an existing antidepressant medication produced superior results.

CONCLUSION: Degree of seasonality can be used as a predictor of response to LT and may be clinically useful when suggesting that patients consider a trial of LT.

PMID: 21107143

Aust N Z J Psychiatry. 1997 Apr;31(2):279-84.

Seasonal affective disorder in Australia: is photoperiod critical?

Murray GW, Hay DA.

Department of Psychology, University of Melbourne, Parkville, Victoria, Australia.


OBJECTIVES: Seasonal affective disorder (SAD) is a variant of recurrent depression in which episodes are linked to a particular season, typically winter. SAD is understood as the extreme end of a continuum of seasonality in the general population. Photoperiod (the timing and duration of daylight) has been assumed to be aetiologically critical. The present research used a survey design to investigate the assumed centrality of photoperiod for SAD/seasonality in Australia. Two hypotheses were tested: that self-reported seasonality does not increase further from the equator and that seasonality does not stand alone from non-seasonal neurotic complaints.

METHOD: The sampling frame used was adult females on the Australian Twin Registry roll. A sample of 526 women residing across the latitudes of Australia responded to a survey based around the Seasonal Pattern Assessment Questionnaire (SPAQ). The SPAQ asks respondents to retrospectively report on season-related changes in mood and behaviour. The survey also contained three questionnaire measures of neurotic symptoms of anxiety and depression: the General Health Questionnaire (GHQ), the Community Epidemiological Survey for Depression (CES-D) and the State-Trait Anxiety Inventory-Trait (STAI-T).

RESULTS: Self-reported seasonality did not correlated with latitude (r = 0.01, NS). On the other hand, a substantial relationship was found between seasonality and each of the measures of non-seasonal complaints: GHQ (r = 0.35, p < 0.001); CES-D (r = 0.35, p < 0.001); and STAI-T (r = 0.30, p < 0.001).

CONCLUSIONS: Within the limitations of a design based on retrospective self-report, the findings of the present study suggest that the diathesis for SAD/seasonality may not be photoperiod-specific. At least in Australia, there is provisional support for the proposal that human seasonality may have a broader psychological component. The findings are discussed in terms of established research into normal mood, trait personality and non-seasonal depression.

PMID: 9140637

Ann Clin Psychiatry. 2007 Oct-Dec;19(4):239-46.

Seasonal affective disorder: a clinical update.

Westrin A, Lam RW.

Department of Clinical Sciences, Division of Psychiatry, Lund University Hospital, Lund, Sweden.


BACKGROUND: Seasonal affective disorder (SAD) consists of recurrent major depressive episodes in the fall/winter with remissions in spring/summer.

METHOD: A Medline search was conducted to identify studies relating to clinical management of SAD using the Medical Subject Heading, seasonal affective disorder, and key words, depress* and season*, focusing on studies published in the past 10 years. The Cochrane library of systematic reviews was also searched for relevant studies.

RESULTS: A careful history is important to make the diagnosis and differentiate SAD from other similar conditions such as subsyndromal SAD and atypical depression. Seasonal patterns with winter worsening are also recognized in “nonseasonal” depression as well as many other psychiatric conditions, and comorbidity with SAD is common. The pathophysiology of SAD seems to be heterogeneous as research on circadian, neurotransmitter function and genetic hypotheses have shown discrepant results. A dual vulnerability model with differential loading on separate seasonal and depression factors has been proposed to explain these findings. Recent systematic reviews have shown that light therapy is an efficacious and well-tolerated treatment for SAD. There is also evidence for efficacy of pharmacotherapy to treat and prevent SAD. Clinical studies show equal effectiveness with light and antidepressants, so patient preference should be considered in the selection of initial treatment. Dawn stimulation, negative air ions, exercise and cognitve behaviour therapy are under investigation and may also be helpful treatments for SAD.

CONCLUSIONS: SAD is a common condition with significant psychosocial impairment. Clinicians should be vigilant in recognizing seasonal patterns of depressive episodes because there are effective, evidence-based treatments for SAD.

PMID: 18058281

Soc Psychiatry Psychiatr Epidemiol. 1997 Apr;32(3):149-57.

Seasonal changes in affective state in samples of Asian and white women.

Suhail K, Cochrane R.School of Psychology, University of Birmingham, Edgbaston, UK.


Seasonality of the affective state has been reported to vary in direct proportion to latitude in temperate regions. The frequency of seasonal affective disorder (SAD) and the severity of the symptoms associated with it have been reported to be greater in higher than in lower latitudes. In addition, recent research has suggested a genetic loading for SAD. Most of the research on the seasonality of affect has been done in high latitude areas, seasonal mood cycles have been infrequently investigated in tropical areas, and no study has so far measured and compared seasonal changes in affect and behaviour in indigenous and populations non-indigenous to high latitudes. To rule out the biases associated with retrospective designs, a prospective longitudinal study was designed to investigate seasonal mood variations in indigenous white and non-indigenous Asian populations. Since previous research has indicated the excessive vulnerability of women to winter depression, it was decided to measure seasonality of the affective state only in women. To examine the relative effects of genetic predispositions and physical environment, the Asian group was further divided into “Asian” and “Asian-British”. The former group comprised women who were living in England but who had been born and had spent considerably more time in their country of origin, while the latter group consisted of women who were born in England and who had lived there all their lives. The three groups of 25 women each were matched for age and socio-economic status, and were interviewed every month for 1 year using the Hospital Anxiety and Depression Scale (HAD), a Behavioural Change Inventory (BCI), the Ladder Scale of General Well-being (LSW) and a Monthly Stress Inventory (MSI). One retrospective scale was administered at the end of the study year to compare the extent of seasonal change in affect with that on the HAD-depression subscale. The results showed that seasonal depression peaked in winter in all three groups, with the incidence of winter depression being highest in the Asian group. Seasonal changes on several dimensions of behaviour were in the direction of winter depression for all three groups. States other than depression (anxiety and general well-being) did not show any seasonal variation. Hours of daylight was found to be the best predictor of seasonal variation in mood among environmental and psychosocial variables. There was no evidence to support a genetic hypothesis for SAD.

Am J Geriatr Pharmacother. 2010 Feb;8(1):4-33.

Extraskeletal effects of vitamin D in older adults: cardiovascular disease, mortality, mood, and cognition.

Barnard K, Colón-Emeric C.

Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.


BACKGROUND: Vitamin D insufficiency is prevalent among older adults and may be associated with higher risk for cardiovascular (CV) disease, mortality, depression, and cognitive deficits.

OBJECTIVE: The aim of this article was to review published observational and experimental studies that explored the association between vitamin D insufficiency and CV disease, mortality, mood, and cognition with an emphasis on older adults.

METHODS: PubMed and Web of Science databases were searched for English-language articles from January 1966 through June 2009 relating to vitamin D, using the following MeSH terms: aged, vitamin D deficiency, physiopathology, drug therapy, cardiovascular diseases, blood pressure, mortality, delirium, dementia, cognitive disorders, depression, depressive disorder, seasonal affective disorder, mental disorders, and vitamin D/therapeutic use. Publications had to include patients > or =65 years of age who had > or =1 recorded measurement of 25-hydroxyvitamin D (25[OH]D) or were receiving vitamin D supplementation. All case-control, cohort, and randomized studies were reviewed.

RESULTS: Forty-two case-control, cohort, and randomized trials were identified and included in the review. Based on these publications, the prevalence of vitamin D insufficiency (25[OH]D concentration <30 ng/mL) in communitydwelling older adults (> or =65 years of age) ranged from 40% to 100%. Epidemiologic data and several small randomized trials found a potential association between vitamin D deficiency (25[OH]D concentration <10 ng/mL) and CV disease, including hypertension and ischemic heart disease. Although subgroup analyses of data from the Women’s Health Initiative Randomized Trial (the largest randomized, placebo-controlled trial of vitamin D plus calcium therapy) did not find reductions in blood pressure, myocardial infarction, or CV disease-related deaths, intervention contamination limited the findingsObservational studies and a meta-analysis of randomized controlled trials found a mortality benefit associated with higher serum 25(OH)D concentrations or vitamin D(2) or D(3) supplementation (mean dose, 528 IU/d). Observational and small randomized trials found a potential benefit of sunlight or vitamin D on symptoms of depression and cognition, but the findings were limited by methodologic problems.

CONCLUSIONS: Vitamin D insufficiency appears to be highly prevalent among older adults. Evidence from epidemiologic studies and small clinical trials suggests an association between 25(OH)D concentrations and systolic blood pressure, risk for CV disease-related deaths, symptoms of depression, cognitive deficits, and mortality. The Women’s Health Initiative Randomized Trial did not find a benefit of vitamin D supplementation on blood pressure, myocardial infarction, or mortality in postmenopausal women.

Copyright 2010 Excerpta Medica Inc. All rights reserved. Published by EM Inc USA.. All rights reserved.

PMID: 20226390

J Nutr Health Aging. 2006 Mar-Apr;10(2):151-3.

Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women.

Dumville JC, Miles JN, Porthouse J, Cockayne S, Saxon L, King C.Area 4, Seebohm Rowntree Building, Dept of Health Sciences, University of York, York YO10 5DD.


BACKGROUND: Seasonal Affective Disorder (SAD) is a sub-type of depression that only occurs during the winter months. A reduction in vitamin D may be linked to SAD. Since vitamin D deficiency has been reported to be common in older people, vitamin D supplementation may be expected to reduce seasonal mood disturbance in this group.

OBJECTIVE: To assess the effect of vitamin D supplementation on the mental health of older women.

SETTING: Primary care in three areas of the UK (Herts, Newcastle, York).

SUBJECTS: Women aged 70 years or more recruited to the trial in the months May-October. Intervention: Eligible women were randomised to receive calcium and vitamin D supplementation or no supplementation.

OUTCOME MEASURE: At baseline and the six monthly assessment the mental component score (MCS), calculated from the SF-12 questionnaire was used to assess participants’ subjective psychological well-being.

RESULTS: A total of 2117 women recruited to the trial had their baseline measures taken between the months of May-October (1205 woman in the control group and 912 women in the intervention group). Of these women, 1621 had a MCS score at baseline and six months. Comparison of the six month mean MCS scores, adjusting for baseline MCS score and age, showed there was no significant difference between the two scores (p = 0.262).

CONCLUSIONS: Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores.

PMID: 16554952

J Nutr Health Aging. 1999;3(1):5-7.

Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder.

Gloth FM 3rd, Alam W, Hollis B.The Department of Medicine, The Union Memorial Hospital, Baltimore, Maryland 21218-2895, USA.


Seasonal Affective Disorder (SAD) is prevalent when vitamin D stores are typically low. Broad-spectrum light therapy includes wavelengths between 280-320 nm which allow the skin to produce vitamin D. This study was designed to test the hypothesis that vitamin D deficiency might play a role in SAD. A prospective, randomized controlled trial was conducted in a group of 15 subjects with SAD. Eight subjects received 100,000 I.U. of vitamin D and seven subjects received phototherapy. At the onset of treatment and after 1 month of therapy subjects were administered the Hamilton Depression scale, the SIGH-SAD, and the SAD-8 depression scale. All subjects also had serum levels of 25-hydroxyvitamin D (25-OH D) measured before and 1 week after intervention therapy. All subjects receiving vitamin D improved in all outcome measures. The phototherapy group showed no significant change in depression scale measures.Vitamin D status improved in both groups (74% vitamin D group, p < 0.005 and 36% phototherapy group, p < 0.01). Improvement in 25-OH D was significantly associated with improvement in depression scale scores (r2=0.26; p=0.05). Vitamin D may be an important treatment for SAD. Further studies will be necessary to confirm these findings.

PMID: 10888476

Med Hypotheses. 1998 Sep;51(3):267-8.

Vitamin D and serotonin in winter.

Partonen T.

Department of Psychiatry, University of Helsinki, Finland.


Calcitriol accumulates in the nuclei of adrenal medullary cells, stimulating the tyrosine hydroxylase gene expression. The transcription of the CREM gene is induced by adrenergic input to the pineal gland at night. Depending on the photoperiod of the prior night length, the CREM gene is either subsensitive or supersensitive to induction. Guided by the memory of past photoperiods, the induced changes in melatonin synthesis may mediate either the inhibitory or stimulatory effects on bodily functions. Calcitriol might inhibit the binding of melatonin to the nuclear retinoid Z receptors, which would result in the increased serotonin levels. Serotonin synthesis is hypothesized to be dependent on the duration of light exposure the previous summer.

PMID: 9792205

J Neurosci. 2010 Nov 3;30(44):14691-4.

Seasonal effects on human striatal presynaptic dopamine synthesis.

Eisenberg DP, Kohn PD, Baller EB, Bronstein JA, Masdeu JC, Berman KF.

Section on Integrative Neuroimaging, Clinical Brain Disorders Branch, Genes Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.


Past studies in rodents have demonstrated circannual variation in central dopaminergic activity as well as a host of compelling interactions between melatonin–a scotoperiod-responsive neurohormone closely tied to seasonal adaptation–and dopamine in the striatum and in midbrain neuronal populations with striatal projections. In humans, seasonal effects have been described for dopaminergic markers in CSF and postmortem brain, and there exists a range of affective, psychotic, and substance abuse disorders that have been associated with both seasonal symptomatic fluctuations and dopamine neurotransmission abnormalities. Together, these data indirectly suggest a potentially crucial link between circannual biorhythms and central dopamine systems. However, seasonal effects on dopamine function in the living, healthy human brain have never been tested. For this study, 86 healthy adults underwent (18)F-DOPA positron emission tomography scanning, each at a different time throughout the year. Striatal regions of interest (ROIs) were evaluated for differences in presynaptic dopamine synthesis, measured by the kinetic rate constant, K(i), between fall-winter and spring-summer scans. Analyses comparing ROI average K(i) values showed significantly greater putamen (18)F-DOPA K(i) in the fall-winter relative to the spring-summer group (p = 0.038). Analyses comparing voxelwise K(i) values confirmed this finding and evidenced intrastriatal localization of seasonal effects to the caudal putamen (p < 0.05, false-discovery rate corrected), a region that receives dopaminergic input predominantly from the substantia nigra. These data are the first to directly demonstrate a seasonal effect on striatal presynaptic dopamine synthesis and merit future research aimed at elucidating underlying mechanisms and implications for neuropsychiatric disease and new treatment approaches.

PMID: 21048126

Neurosci Biobehav Rev. 2011 Jan;35(3):669-79. Epub 2010 Aug 26.

Potential animal models of seasonal affective disorder.

Workman JL, Nelson RJ.

Department of Psychology, The Ohio State University, Columbus, OH 43201, USA.


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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID: 20800614

Chronobiol Int. 2010 Aug;27(7):1438-53.

Increased sensitivity to light-induced melatonin suppression in premenstrual dysphoric disorder.

Parry BL, Meliska CJ, Sorenson DL, Lopez A, Martínez LF, Hauger RL, Elliott JA.

Department of Psychiatry, University of California, San Diego, La Jolla, California 92093-0804, USA. bparry@ucsd.eduAbstract

Increased sensitivity to light-induced melatonin suppression characterizes some, but not all, patients with bipolar illness or seasonal affective disorder. The aim of this study was to test the hypothesis that patients with premenstrual dysphoric disorder (PMDD), categorized as a depressive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), have altered sensitivity to 200 lux light during mid-follicular (MF) and late-luteal (LL) menstrual cycle phases compared with normal control (NC) women. As an extension of a pilot study in which the authors administered 500 lux to 8 PMDD and 5 NC subjects, in the present study the authors administered 200 lux to 10 PMDD and 13 NC subjects during MF and LL menstrual cycle phases. Subjects were admitted to the General Clinical Research Center (GCRC) in dim light (<50 lux) to dark (during sleep) conditions at 16:00 h where nurses inserted an intravenous catheter at 17:00 h and collected plasma samples for melatonin at 30-min intervals from 18:00 to 10:00 h, including between 00:00 and 01:00 h for baseline values, between 01:30 and 03:00 h during the 200 lux light exposure administered from 01:00 to 03:00 h, and at 03:30 and 04:00 h after the light exposure. Median % melatonin suppression was significantly greater in PMDD (30.8%) versus NC (-0.2%) women (p = .040), and was significantly greater in PMDD in the MF (30.8%) than in the LL (-0.15%) phase (p = .047). Additionally, in the LL (but not the MF) phase, % suppression after 200 lux light was significantly positively correlated with serum estradiol level (p = .007) in PMDD patients, but not in NC subjects (p > .05).

PMID: 20795885

Psychiatry Res. 2008 Oct 30;161(1):76-86. Epub 2008 Sep 11.

Late, but not early, wake therapy reduces morning plasma melatonin: relationship to mood in Premenstrual Dysphoric Disorder.

Parry BL, Meliska CJ, Martínez LF, López AM, Sorenson DL, Hauger RL, Elliott JA.

Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0804, United States.


Wake therapy improves mood in Premenstrual Dysphoric Disorder (PMDD), a depressive disorder in DSM-IV. We tested the hypothesis that the therapeutic effect of wake therapy in PMDD is mediated by altering sleep phase with melatonin secretion. We measured plasma melatonin every 30 min (18:00-09:00 h) in 19 PMDD and 18 normal control (NC) women during mid-follicular (MF) and late luteal (LL) menstrual cycle phases, and during LL interventions with early wake therapy (EWT) (sleep 03:00-07:00 h)(control condition) vs. late wake therapy (LWT) (sleep 21:00-01:00 h)(active condition). Melatonin offset was delayed and duration was longer in the symptomatic LL vs. asymptomatic MF phase in both NC and PMDD subjects. LWT, but not EWT, advanced offset and shortened duration vs. the LL baseline, although they improved mood equally. Later baseline LL morning melatonin offset was associated with more depressed mood in PMDD patients, and longer melatonin duration in the MF phase predicted greater mood improvement following LWT. That LWT, but not EWT, advanced melatonin offset and shortened duration while they were equally effective in improving mood suggests that decreasing morning melatonin secretion is not necessary for the therapeutic effects of wake therapy in PMDD.

PMID: 18789826

Biol Psychiatry. 2000 Nov 1;48(9):920-31.

Cortisol circadian rhythms during the menstrual cycle and with sleep deprivation in premenstrual dysphoric disorder and normal control subjects.

Parry BL, Javeed S, Laughlin GA, Hauger R, Clopton P.

Department of Psychiatry, University of California, San Diego, California 92093-0804, USA.


BACKGROUND: In this study we extended previous work by examining whether disturbances in the circadian rhythms of cortisol during the menstrual cycle distinguish patients with premenstrual dysphoric disorder (PMDD) from normal control (NC) subjects. In addition, we tested the differential response to the effects of early and late partial sleep deprivation on cortisol rhythms.

METHODS: In 15 PMDD and 15 NC subjects we measured cortisol levels every 30 min from 6:00 PM to 9:00 AM during midfollicular (MF) and late luteal (LL) menstrual cycle phases and also during a randomized crossover trial of early (sleep 3:00 AM-7:00 AM) versus late (sleep 9:00 PM-1:00 AM) partial sleep deprivation administered in two subsequent and separate luteal phases.

RESULTS: In follicular versus luteal menstrual cycle phases we observed altered timing but not quantitative measures of cortisol secretion in PMDD subjects, compared with NC subjects: in the LL versus MF phase the cortisol acrophase was a mean of 1 hour earlier in NC subjects, but not in PMDD subjects. The effect of sleep deprivation on cortisol timing measures also differed for PMDD versus NC subjects: during late partial sleep deprivation (when subjects’ sleep was earlier), the cortisol acrophase was almost 2 hours earlier in PMDD subjects.

CONCLUSIONS: Timing rather than quantitative measures of cortisol secretion differentiated PMDD subjects from NC subjects both during the menstrual cycle and in response to early versus late sleep deprivation interventions.

PMID: 11074230

J Biol Rhythms. 1997 Feb;12(1):34-46.

Temperature circadian rhythms during the menstrual cycle and sleep deprivation in premenstrual dysphoric disorder and normal comparison subjects.

Parry BL, LeVeau B, Mostofi N, Naham HC, Loving R, Clopton P, Gillin JC.

Department of Psychiatry, University of California, San Diego, La Jolla 92093, USA.


The aim of this study was to test the hypothesis that the circadian rhythm of core body temperature is altered in premenstrual dysphoric disorder (PMDD) subjects compared to that in normal comparison (NC) subjects and that it is normalized in PMDD subjects after treatment with early night partial sleep deprivation (ESD) or late night partial sleep deprivation (LSD). A total of 23 subjects meeting DSM-IV criteria for PMDD and 18 NC subjects had 24-h core body temperature recordings taken during the following conditions: (1) baseline midfollicular (preovulatory) and (2) late luteal (postovulatory) menstrual cycle phases and after a randomized crossover trial in subsequent luteal phases of (3) ESD, in which subjects slept from 03:00 to 07:00 h, followed by (4) a night of recovery sleep (ESD-R: sleep 22:30 to 06:30 h), and (5) LSD, in which subjects slept from 21:00 to 01:00 h, also followed by (6) a night of recovery sleep (LSD-R: sleep 22:30 to 06:30 h). Temperature amplitudes were significantly decreased in the luteal phase compared to those in the follicular menstrual cycle phase and increased after nights of recovery sleep. Compared to the baseline late luteal phase, during LSD, temperature amplitude increased in PMDD subjects but decreased in NC subjects. During ESD, the temperature acrophase was delayed in PMDD subjects but was advanced in NC subjects; during LSD, the temperature acrophase was advanced in PMDD subjects but was delayed in NC subjects compared to the late luteal baseline. Nocturnal temperature and temperature maxima and mesors tended to be higher in PMDD subjects than in NC subjects; when not reduced during sleep deprivation interventions, these were not associated with therapeutic effects. Alterations in both phase and amplitude of temperature circadian rhythms characterize PMDD subjects as contrasted with NC subjects in response to sleep deprivation. The changes in phase reflected more shifts in temperature acrophase in response to shifts in sleep in PMDD subjects. This realignment of the timing of sleep and temperature in addition to the enhancement of blunted amplitude rhythms during recovery nights of sleep may provide corrective mechanisms that contribute to the therapeutic effects of sleep deprivation.

PMID: 9104689

Aust Fam Physician. 2010 May;39(5):307-10.

Circadian rhythms and depression.

Boyce P, Barriball E.

Discipline of Psychiatry, University of Sydney and Department of Psychiatry, Westmead Hospital, Sydney, New South Wales, Australia.


BACKGROUND: Depression is a common disorder in primary care. Disruptions to the circadian rhythms associated with depression have received little attention yet offer new and exciting approaches to treatment.

OBJECTIVE: This article discusses circadian rhythms and the disruption to them associated with depression, and reviews nonpharmaceutical and pharmaceutical interventions to shift circadian rhythms.

DISCUSSION: Features of depression suggestive of a disturbance to circadian rhythms include early morning waking, diurnal mood changes, changes in sleep architecture, changes in timing of the temperature nadir, and peak cortisol levels. Interpersonal social rhythm therapy involves learning to manage interpersonal relationships more effectively and stabilisation of social cues, such as including sleep and wake times, meal times, and timing of social contact. Bright light therapy is used to treat seasonal affective disorders. Agomelatine is an antidepressant that works in a novel way by targeting melatonergic receptors.

PMID: 20485718

Psychiatry Res. 2010 Feb 28;175(3):217-20. Epub 2009 Dec 31.

Climatic relationships with specific clinical subtypes of depression.

Radua J, Pertusa A, Cardoner N.

Department of Psychiatry, Bellvitge University Hospital, University of Barcelona, Barcelona, Spain.


Studies on the relationship between climate and unipolar depression rates have yielded mixed results, which could be attributed to the inclusion of heterogeneous clinical samples and the use of admission rather than onset dates. This study aimed to overcome these methodological issues. During an 8-year timeframe, onset rates of unipolar depressive episodes requiring hospitalization from individuals living up to 15 km from a selected meteorological station were stratified by clinical subtypes and modeled as Autoregressive Integrated Moving Average (ARIMA) functions of orthogonal climatic factors obtained by Principal Components Analysis (PCA). For comparison purposes, onset rates stratified by demographic factors and by diagnosis of Seasonal Affective Disorder (SAD) and admission rates were also modeled. The main findings were a negative 1-month delayed relationship between onset rates of episodes with melancholic features and a climatic factor mainly composed of ambient temperature/sunlight, and a negative 1-month delayed relationship between onset rates of episodes with psychotic features and a climatic factor mainly composed of barometric pressure. Results of this study support a climatic-rather than seasonal-influence in specific subtypes of depression. If replicated, they may have nosological and therapeutic implications.

2008 Elsevier Ireland Ltd. All rights reserved.

PMID: 20045197

Aviat Space Environ Med. 2008 Jul;79(7):695-9.

Seasonal levels of melatonin, thyroid hormones, mood, and cognition near the Arctic Circle.

Pääkkönen T, Leppäluoto J, Mäkinen TM, Rintamäki H, Ruokonen A, Hassi J, Palinkas LA.

Department of Biomedicine/Physiology, University of Oulu, Oulu, Finland. tiina.paakkonen@oulu.fiAbstract

INTRODUCTION: The associations between melatonin and thyroid hormones and changes in mood and cognitive performance caused by exposure to cold and darkness were examined in 12 circumpolar residents during winter and summer.

METHODS: Each participant was exposed to three different experimental conditions in random order: 1) 22 degrees C and bright light; 2) 10 degrees C and bright light; and 3) 10 degrees C and dim light. The duration of each exposure was 24 h. RESULTs: Increased serum melatonin and thyrotropin were associated with decreased rectal temperature (r = -0.446 – -0.580) and increased mean skin temperature (r = 0.204-0.519). Higher serum melatonin was associated with increased vigor (r = 0.330) and decreased accuracy on simple cognitive tasks (r = -0.332 – -0.430). Increased serum free triiodothyronine (fT3) was associated with decreased negative mood scores (r = -0.365 – -0.483), decreased response time (RT) on the simple reaction time (SRT) task (r = -0.606), and decreased accuracy on the addition/subtraction task (r = -0.372). Higher serum free thyroxine was associated with decreased fatigue and anger (r = -0.409 – -0.522). Increased serum thyrotropin was associated with decreased accuracy and RT on the SRT task and decreased RT on the grammatical reasoning task (r = -0.315 – -0.415).

CONCLUSIONS: Associations between serum melatonin and thyroid hormones with mood were consistent with the psychological changes associated with the polar triiodothyronine syndrome. Also, serum melatonin and thyrotropin were associated with impaired and fT3 with improved cognitive performance, supporting the decrements in cognitive performance associated with the polar triiodothyronine syndrome.

PMID: 18619130

A critical review of 27 herbal medicines and formulas in treating a broad range of psychiatric disorders (in addition to anxiety and depression), including obsessive-compulsive, seasonal affective, bipolar depressive, psychotic, phobic and somatoform disorders. Ovid Medline, Pubmed and the Cochrane Library were searched for pharmacological and clinical evidence of herbal medicines with psychotropic activity. A forward search of later citations was also conducted. Whilst substantial high-quality evidence exists for the use of kava and St John’s wort in the treatment of anxiety and depression respectively, urgently require more research are Rhodiola rosea (roseroot) and Crocus sativus (saffron) for depression; Passiflora incarnata (passionflower), Scutellaria lateriflora (scullcap) and Zizyphus jujuba (sour date) for anxiety disorders; and Piper methysticum (kava) for phobic, panic and obsessive-compulsive disorders.

 The maintenance of light therapy-induced remission from depression in patients with seasonal mood cycles seems to depend on the functional integrity of the brain serotonin system. 

The decline in melatonin levels correlated with the decline in specific SAD symptoms of hyperphagia and carbohydrate craving.

 Low melatonin levels were seen in bulimia or neuralgia and in women with fibromyalgia; replacement reduced pain, sleeping disorders, and depression in fibromyalgia and bulimia. Melatonin profiles are a diagnostic tool to distinguish between several forms of depression, like major depression, winter depression (SAD), unipolar depression, delayed sleep phase syndrome (DSPS). In patients with a major depression success with antidepressants correlated with an increase in their melatonin profiles but only patients suffering from DSPS can be successfully treated with melatonin. In perimenopausal women melatonin administration did produce a change in LH, FSH and thyroid hormones. 

 A review of the literature showed that melatonin has an inhibiting effect on insulin sensitivity. 


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