Seasonal Affective Disorder Patients Research Articles

Sleep in seasonal affective disorder patients in forced desynchrony: an explorative study.

The majority of winter-type seasonal affective disorder (SAD) patients complain of hypersomnia and daytime drowsiness. As human sleep is regulated by the interaction of circadian, ultradian and homeostatic processes, sleep disturbances may be caused by either one of these factors. The present study focuses on homeostatic and ultradian aspects of sleep regulation in SAD. Sleep was recorded polysomnographically in seven SAD patients and matched controls subjected to a 120-h forced desynchrony protocol. In time isolation, subjects were exposed to six 20-h days, each comprising a 6.5-h period for sleep. Patients participated while being depressed, while remitted after light therapy and in summer. Controls were studied in winter and in summer. In each condition, the data of each subject were averaged across all recordings. Thus, the influence of the effects of the circadian pacemaker on sleep was excluded mathematically. The comparison of patients with controls and with themselves in the various conditions revealed no abnormalities in homeostatic parameters: sleep stage variables, relative power spectra and time courses of power in various frequency bands across the first three non-rapid eye movement-rapid eye movement (NREM-REM) cycles showed no differences. The data suggest that homeostatic processes are not involved in the disturbance of sleep in SAD.

Polysomnographic sleep effects of fluoxetine and nefazodone on a seasonal affective disorder patient

This reported person met DSM-III-R criteria for seasonal affective disorder. In successive years she had two treatments with fluoxetine and one with nefazodone. Every year regular polysomnographic monitoring was carried out during the critical initial 8 weeks of treatment. The results indicate that on both occasions fluoxetine decreased the patient's sleep quality. Nefazodone had no sleep disturbing effects and on withdrawal no relapse has been seen for 3 years.

A forced desynchrony study of circadian pacemaker characteristics in seasonal affective disorder.

The circadian pacemaker is an endogenous clock that regulates oscillations in most physiological and psychological processes with a near 24-h period. In many species, this pacemaker triggers seasonal changes in behavior. The seasonality of symptoms and the efficacy of light therapy suggest involvement of the circadian pacemaker in seasonal affective disorder (SAD), winter type. In this study, circadian pacemaker characteristics of SAD patients were compared with those of controls. Seven SAD patients and matched controls were subjected to a 120-h forced desynchrony protocol, in which core body temperature and melatonin secretion profiles were measured for the characterization of circadian pacemaker parameters. During this protocol, which enables the study of unmasked circadian pacemaker characteristics, subjects were exposed to six 20-h days in time isolation. Patients participated twice in winter (while depressed and while remitted after light therapy) and once in summer. Controls participated once in winter and once in summer. Between the SAD patients and controls, no significant differences were observed in the melatonin-derived period or in the phase of the endogenous circadian temperature rhythm. The amplitude of this rhythm was significantly smaller in depressed and remitted SAD patients than in controls. No abnormalities of the circadian pacemaker were observed in SAD patients. A disturbance in thermoregulatory processes might explain the smaller circadian temperature amplitude in SAD patients during winter.

A comparison of open treatment of seasonal major and minor depression with light therapy

Background: Although several investigators have described a milder form of seasonal affective disorder (SAD), called subsyndromal SAD, little is known about the effect of light therapy in this group. The current study evaluates 3 weeks of open treatment with light therapy in SAD and subsyndromal SAD patients. Methods: Subjects with major or minor depression according to DSM-IV with a seasonal pattern were recruited during the winter of 1998–1999 from clinic patients and media advertising. Subjects were commenced on open treatment of morning light therapy, for 30 min daily using a new fluorescent light therapy unit that produced approximately 5000 lux at a distance of 12 inches. The treatment lasted 3 weeks and at the end of the first and second week of treatment the duration of exposure could be increased to a maximum of 60 min at the discretion of the clinician. The Structured Interview Guide for the Hamilton Depression Rating Scale-SAD version (SIGH-SAD) was administered weekly to evaluate outcome. Response was defined in a variety of ways to reflect the fact that subsyndromal SAD subjects had milder symptoms. Results: Forty-six subjects entered treatment and 44 (SAD, n=29, subsyndromal SAD, n=15) completed at least 2 weeks. Response rates were generally similar in SAD subjects (64–69%) and subsyndromal SAD (40–67%) patients. There was a trend for longer exposure to be associated with better outcome. Conclusions: Light therapy may be an effective treatment for subjects with both major and minor depression with a seasonal pattern. Optimal duration, for the light therapy unit used in this study, is likely 45–60 min daily.

Changes of clinical pattern in seasonal affective disorder (SAD) over time in a German-speaking sample.

The goals of this study are to provide estimates of clinical and demographic variables of patients with seasonal affective disorder (SAD) in Germany and Austria, to compare our results with those of previously published SAD studies, and to find out whether the clinical pattern of SAD remained stable over several years. We investigated 610 SAD patients from the outpatient clinics in Bonn (n = 190) and Vienna (n = 420). Patients in Bonn were recruited in the fall-winter season of the years 1989-1992, those in Vienna in the years 1993-2001. We observed a change in the clinical pattern in our patients: patients from Bonn, who were diagnosed and treated about 5 years earlier, were more likely to suffer from melancholic depression, whereas Viennese patients rather suffered from atypical depression (chi(2) = 54.952, df = 2, p < 0.001). The symptoms of hypersomnia, daytime fatigue, increased eating and carbohydrate-craving were more frequent in the Viennese sample, anxiety and deterioration of patients' capacity to perform at work predominated in Bonn. In addition, patients from Vienna obtained a higher GSS (global seasonality score, measured by the SPAQ - Seasonal Pattern Assessment Questionnaire) than those from Bonn (15.7 +/- 3.3 and 14.6 +/- 4.1 respectively; t = 3.104, p = 0.002). Taken together, our results were in good accordance to other published SAD materials, but we were able to demonstrate that our patients reported "feeling worst" (measured by item 13H of the SPAQ) in November and December, whereas SAD patients in the USA clearly had their worst months in January and February. We suggest that an increase in awareness of fall-winter depression in the last decade by both doctors, who referred patients, as well as patients or the entire population must have caused patients to sign up for light therapy at the Viennese SAD clinic because of having heard about the atypical symptom profile. This increased awareness of SAD can also be measured by a statistically significant reduction in the diagnostic latency (from the age of onset to the diagnosis of SAD) when comparing the two study locations.

Role of family history and 5-HTTLPR polymorphism in female seasonal affective disorder patients with and without premenstrual dysphoric disorder

Seasonal affective disorder (SAD) and premenstrual dysphoric disorder (PMDD) share many clinical features, and have been associated with brain serotonin dysfunction. Females with SAD frequently fulfil the diagnostic criteria for PMDD. A polymorphism in the serotonin transporter promoter gene (5-HTTLPR) has been associated with SAD. We investigated the role of family history and 5-HTTLPR in female SAD patients with and without PMDD. Forty-four SAD females with, and 43 SAD females without PMDD, were genotyped for 5-HTTLPR. Family history of affective disorders in first degree relatives was assessed. An association between the presence of PMDD and family history ( P=0.0029) and 5-HTTLPR long/short allele-heterozygosity ( P=0.033) was found in females with SAD. PMDD and SAD may share genetic vulnerability factors, one candidate gene being 5-HTTLPR. The elevated rate of affective disorders in relatives of patients with SAD and PMDD suggests higher genetic vulnerability in this subgroup when compared to patients with SAD alone.

Seasonal affective disorder: spatial organization of EEG power and coherence in the depressive state and in light-induced and summer remission

The present study analyzed EEG power and coherence in subjects with seasonal affective disorder (SAD) during depressive episodes and during light-induced and summer remission. Baseline EEG activity was recorded during the winter period before light treatment (31 SAD patients, 30 control subjects); after 10 days of 2-h morning light treatment (10 SAD subjects); and during the summer period (14 SAD subjects, 27 control subjects). EEG power and coherence were calculated for the delta, theta-1, theta-2, alpha, beta-1 and beta-2 frequency bands. Compared with control subjects, SAD subjects had lower than normal EEG power in most frequency bands; asymmetrical distribution of delta, theta-1, theta-2 and alpha activity in parietal and temporal regions due to increased EEG power over the left electrode sites; and beta activity in the lateral frontal region due to increased beta power over the right electrode site. The foci of decreased EEG coherence were mainly in the right and left frontal and the right posterior regions. Remitted SAD subjects showed normalization of inter-hemispheric asymmetry in lateral frontal areas; increases of delta, theta-2, and alpha activity compared with control values; theta-1 activity in excess of control values; and disappearance of the foci of decreased coherence in anterior areas of the left hemisphere.

EEG mapping in seasonal affective disorder

Given that the nature of hemispheric dysfunction is different in heterogeneous disorders, in the present investigation EEG power mapping was applied to establish neurophysiological profiles that might potentially discriminate patients with seasonal affective disorder (SAD) among other affective disorders. The baseline resting EEG activity was recorded from 31 depressed SAD patients and 30 controls. Power in the delta, theta-1, theta-2, alpha, beta-1 and beta-2 frequency bands was extracted by Fourier transformation. Patients were found to have a lower delta (in central, parietal, occipital, temporal, posterior-temporal areas), theta-1 (in central and parietal), theta-2 (in anterior-frontal, parietal, occipital) and alpha activity (in anterior-frontal, midfrontal, central, parietal and occipital areas) than controls. SAD subjects showed, compared to controls, an asymmetrical distribution of delta, theta-1, theta-2 and alpha activity in parietal and temporal regions due to an increase of EEG power over the right electrode sites, and beta activity in the lateral frontal region due to an increase of beta power over the right electrode site. It is assumed that differential hemispheric contributions of EEG spectra may discriminate between the varieties of depression or different depressive states.

Seasonal Affective Disorder and Serotonin-Related Polymorphisms

Disturbances in central serotonergic systems have been hypothesized to be involved in seasonal affective disorder (SAD). Association between SAD and the shorter allele of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR) has been reported in an American sample. We have genotyped 82 SAD patients and 82 healthy controls from Sweden, Finland, and Germany for this and five other polymorphisms in the genes coding for serotonin receptors 5-HT2A and 5-HT2C, tryptophan hydroxylase and white. No associations with SAD or seasonality (seasonal variations in mood and behavior) were detected. Although minor effects cannot be excluded, our results suggest that these polymorphisms do not play a major role in the pathogenesis of SAD in the northern European population.

The Seasonal Health Questionnaire: a preliminary validation of a new instrument to screen for Seasonal Affective Disorder

Background: The main screening tool for Seasonal Affective Disorder (SAD) is the Seasonal Pattern Assessment Questionnaire, but its reliability and validity have been thrown into doubt by several studies. Method: In this study we developed a new questionnaire, the Seasonal Health Questionnaire (SHQ), which is scored by computer to derive the four main operational criteria for diagnosis of SAD. A group of clinically diagnosed SAD patients was contrasted with a group of patients with recurrent non-seasonal depressive disorder using the SPAQ and the SHQ. Results: The SHQ could be completed without difficulty by patients with long histories of recurrent mood disorder. The SPAQ and the Rosenthal Criteria were the least specific of the criteria for identifying SAD — misclassifying many non-seasonal patients. Conclusions: After further development the SHQ may be a more appropriate screening instrument for SAD. The SPAQ should no longer be used for this purpose as it gives misleadingly high estimates of prevalence.

Genetic studies of seasonal affective disorder and seasonality.

Genetic studies of seasonal affective disorder (SAD) and seasonality have received considerable attention over the past several years. Studies of the prevalence of SAD and nonseasonal mood disorders among relatives of patients with SAD suggested a familial contribution to the development of SAD. Two twin studies demonstrated a substantial role of genetic variation in seasonality. Two genetic variants related to serotonergic transmission, the 5-HTTLPR and the 5-HT(2A)-1438G/A gene promoter polymorphisms, have been found to be associated with SAD. 5-HTTLPR is also associated with seasonality in SAD patients and in the general population. It is not clear whether SAD is inherited as a distinct entity or whether seasonality and depression are separate heritable traits that happen to coincide in certain individuals. Vulnerability to SAD and disease pathology may be influenced by many genes, perhaps on several chromosomes.

Immune–inflammatory markers in patients with seasonal affective disorder: effects of light therapy

Background: There is increasing evidence that an activation of the immune–inflammatory system is involved in the pathophysiology of depressive disorders. The purposes of this study were to (1) compare immune–inflammatory markers in patients with seasonal affective disorder (SAD) with those in matched normal controls; and (2) examine the effects of light therapy on the immune–inflammatory markers in patients with SAD. Methods: Plasma concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble IL-2 receptor (sIL-2R) were measured in 15 patients with SAD and 15 age- and sex-matched normal controls. Of the 15 patients, 14 had repeated blood sampling for these variables following 2 weeks of light therapy. Results: We found that patients with SAD had significantly increased IL-6 levels compared to normal controls ( P<0.0005). There was a trend toward increased sIL-2R in patients with SAD ( P=0.09). There was no significant difference in sIL-6R level between the two diagnostic groups ( P=0.18), but the product term (IL-6×sIL-6R) was significantly higher in patients with SAD than that in normal control controls ( P<0.0003). Furthermore, all 14 patients who completed the study improved with 2 weeks of light therapy and nine of them (64%) had 50% reduction in score of the Hamilton Depression Rating Scale–SAD version post-treatment compared to baseline. However, the initially increased immune markers in SAD patients were not significantly altered by the therapeutic light therapy. Limitations: This study was limited to a small sample size and other immune inflammatory markers should be measured for further evidence of immune activation in seasonal depression. Conclusions: Our results of increased IL-6, IL-6×sIL-6R, and sIL-2R in patients with SAD suggest an activation of the immune–inflammatory system in winter depression, which is not altered by 2 weeks of successful light therapy.

Reboxetine in seasonal affective disorder: an open trial

Seasonal affective disorder (SAD), winter type, is a condition characterized by the annual recurrence of depressive episodes during fall/winter, alternating with spring/summer euthymia or hypomania. Various neurotransmitters have been implicated in the etiology of SAD, the strongest evidence involving serotonin. Recently, increasing attention has been paid to the potential role of catecholaminergic pathways in the pathophysiology of SAD. We investigated the efficacy and tolerability of reboxetine, a selective noradrenaline inhibitor, in patients with SAD. Eleven out of sixteen patients who were included in a 6-week drug surveillance during winter season experienced full remission of depressive symptoms. Nine patients reported a rapid relief of preexistent severe atypical depressive symptoms within the first treatment week. Reboxetine might therefore be an effective and well-tolerated treatment option for SAD patients. In conclusion, our preliminary results are in line with evidence from recent studies suggesting that catecholaminergic systems might also be involved in the pathophysiology of SAD.

The role of brain thyroid hormones in the mechanisms of seasonal changes in mood and behavior

Many individuals experience seasonal changes in mood and behavior. Various theories have been suggested to explain the mechanisms of these changes. However, the mechanisms of seasonal mood and behavioral changes remain unclear. The author suggests that brain thyroid hormones may play an important role in seasonal changes in mood and behavior. This suggestion is based on the facts that seasonal changes in light and temperature may affect the metabolism of brain thyroid hormones and that small alterations of the brain thyroid economy, independent of peripheral changes in thyroid status, may produce significant behavioral effects. The author further suggests that there may be a fault in the thyroid metabolism in the brain in seasonal affective disorder patients, and that fault cannot be identified by studying the peripheral thyroid hormone metabolism. Seasonal mood and behavioral changes may also be related to the interaction between thyroid hormones and different neurotransmitter systems in the brain.

Nonverbal interpersonal attunement and extravert personality predict outcome of light treatment in seasonal affective disorder

We investigated whether personality and nonverbal interpersonal processes can predict the subsequent response to light treatment in seasonal affective disorder (SAD) patients. In 60 SAD patients, Neuroticism and Extraversion were assessed prior to light treatment (4 days with 30 min of 10.000 lux). From videotaped clinical interviews, the nonverbal interpersonal attunement (i.e. equalizing durations and frequencies of elements of behaviour between conversation partners) was registered for the patients’ support seeking and the interviewers’ support giving behaviour. The higher Extraversion and the more the patients and the interviewers got attuned over the interview, the more favourable the outcome of light treatment was. Hence, personality and nonverbal interpersonal processes may be involved in the response to light treatment in SAD.

257. Thyroid function tests in patients with seasonal affective disorder and control subjects

Seasonal affective disorder (SAD) is a condition of recurring winter depressions alternating with non-depressed periods in spring and summer. Because some symptoms of SAD, such as decreased energy and weight gain, also occur in hypothyroidism, it is possible that individuals with SAD have a subtle decrease in thyroid function. Multiple lines of evidence suggest that changes in function of the hypothalamo-pituitary-thyroid axis could be responsible for seasonal changes in behavior and physiology. Studies of thyroid function might help to clarify the biological mechanisms involved in the pathogenesis of SAD and seasonality. We studied blood levels of free thyroxine (T4) and thyroid-stimulating hormone (TSH) in 75 SAD patients and 74 matched controls in the winter. Subjects with overt hypothyroidism were excluded from the study population. We found that levels of free T4 were significantly lower in patients than in normal volunteers, but that there was no difference in TSH levels between SAD patients and healthy volunteers. Future research will be needed to clarify the role of the hypothalamo-pituitary-thyroid axis in the pathogenesis of winter depression. Specifically, it will be important to determine whether the difference in thyroid function between SAD patients and controls, if replicated, is an epiphenomenon or is related to the biological mechanisms that cause some of the symptoms of SAD.

EEG and subjective sleepiness during extended wakefulness in seasonal affective disorder: circadian and homeostatic influences

%Background: Seasonal affective disorder (SAD) may reflect a disturbance of circadian phase relationships or a disturbance of sleep–wake dependent processes, both of which change daytime energy and sleepiness levels. Methods: Under the unmasking conditions of a 40-hour constant routine protocol (CR), self-rated sleepiness and waking electroencephalogram (EEG) power density were assessed in women with SAD ( n = 8) and in age-matched healthy control subjects ( n = 9). Results: There was no significant effect of season or light treatment in any of the measures.The time course of subjective sleepiness was characterized by a circadian modulation and an overall increase during extended wakefulness in both SAD patients and control subjects. A prominent circadian rhythm of subjective sleepiness was not different in SAD patients and control subjects; however, the progressive buildup of sleepiness, as quantified by nonlinear regression analysis, was significantly reduced in SAD patients, mainly because they were sleepier than control subjects during the first 12 hours of the CR. The time course of waking EEG theta-alpha activity showed a more rapid increase during the first 10 hours of the CR in SAD patients. In contrast to control subjects who showed a progressive increase in the course of the 40-hour episode of extended wakefulness, EEG theta-alpha activity in SAD patients did not further increase over the remainder of the CR. Conclusions: The data suggest that SAD patients may have a trait (rather than state) deficiency in the homeostatic buildup of sleep pressure during extended wakefulness as indexed by subjective sleepiness and EEG theta-alpha activity.

123I]-β-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder

Background: Numerous findings indicate alterations in brain serotonin systems in seasonal affective disorder (SAD). [ 123I]-2-β-carbomethoxy-3-β-(4-iodophenyl)-tropane ([ 123I]-β-CIT) labels serotonin transporters (5-HTTs) in the midbrain. We performed a [ 123I]-β-CIT single photon emission computer tomography (SPECT) study under the hypothesis of lower [ 123I]-β-CIT binding reflecting reduced central 5-HTT availability in depressed SAD patients. Methods: Depressed SAD patients and healthy control subjects were investigated using [ 123I]-β-CIT SPECT 4 hours and again 24 hours after tracer injection. Subjects had either never used psychotropic medication or had been drug-free for at least 6 months prior to the investigation. Specific-to-nondisplaceable partition coefficient (V 3′′) was calculated for the thalamus-hypothalamus and the midbrain-pons; the cerebellum served as a reference region. Results: Patients showed a reduction in V 3′′ in thalamus-hypothalamus (2.41 ± 0.3 vs. 2.84 ± 0.4; p = .026) 24 hours post tracer injection (p.i.). No difference between patients and control subjects was found in midbrain-pons (1.31 ± 0.2 vs. 1.42 ± 0.2; p = .39). No differences were detected in the SPECT acquisitions 4 hours p.i. Conclusions: Depressed SAD patients showed lower specific-to-nondisplaceable [ 123I]-β-CIT binding in the region of interest (ROI) thalamus-hypothalamus. The small size of the midbrain-pons ROI may have contributed to the failure to show a difference in this ROI as well. Similar to reduced midbrain 5-HTT availability in nonseasonal depression, depression in SAD seems to be associated with reduced 5-HTT availability to the thalamus-hypothalamus.

Body temperature and mood variations during forced desynchronization in winter depression: a preliminary report

Background: It has been suggested that certain abnormalities (e.g., in phase or amplitude) of the circadian pacemaker underlie seasonal affective disorder. Methods: One male seasonal affective disorder patient (blind to the study design) participated in two 120-hour forced desynchrony experiments and was subjected to six 20-hour days, once during a depressive episode and once after recovery. Core body temperature was continuously measured. During wakefulness, the Adjective Mood Scale was completed at 2-hour intervals. Results: Sleep–wake as well as pacemaker-related variations of mood were found, both when the subject was depressed and when he was euthymic. Compared with recovery, during the depressive episode the circadian temperature minimum and the circadian mood variation showed phase delays of approximately 1 and 2 hours, respectively. Conclusions: The data of this first seasonal affective disorder patient, participating in forced desynchrony experiments, may indicate a phase delay of the circadian pacemaker during a seasonal affective disorder episode.

Free thyroxine and thyroid-stimulating hormone levels in patients with seasonal affective disorder and matched controls

Seasonal affective disorder (SAD) is characterized by recurrent episodes of depression in the fall and winter that alternate with nondepressed periods in the spring and summer. Because some symptoms of SAD, such as decreased energy and weight gain, also occur in hypothyroidism, it is possible that individuals with SAD have a subtle decrease in thyroid function. To test this hypothesis, we studied blood levels of free thyroxine (T 4) and thyroid-stimulating hormone (TSH) in SAD patients and matched controls in the winter. We found that free T 4 blood levels were slightly but significantly lower in patients than in healthy volunteers. The difference between TSH levels in SAD patients and controls was not statistically significant. Future research will be needed to determine whether the difference in thyroid function between SAD patients and controls is an epiphenomenon or is related to the biological mechanisms that cause symptoms of SAD.