Seasonal and mood independence of low basal prolactin secretion in premenopausal women with seasonal affective disorder

To test hypotheses of opposing roles of dopamine and serotonin in prolactin secretion in seasonal affective disorder, the authors determined basal serum prolactin concentrations for premenopausal women, eight with and 14 without seasonal affective disorder, in late afternoon during the follicular phase of the menstrual cycle (and a subgroup during the luteal phase) in winter and summer. Despite their significantly higher Hamilton depression scale scores in winter than in summer, the patients had significantly lower prolactin concentrations than the control subjects in both seasons. These results suggest that low prolactin secretion may be a trait characteristic in seasonal affective disorder.     

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

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.     

Electroretinography in patients with winter seasonal affective disorder

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

Abnormal ACTH and cortisol responses to ovine corticotropin releasing factor in patients with primary affective disorder

To further explore hypothalamic pituitary adrenal regulation in patients with affective illness, we administered 1 microgram/kg of synthetic ovine corticotropin releasing factor at 2000h to 26 drug-free patients with this disorder and to 15 healthy controls. Compared to controls, depressed patients (N = 12) showed a significant elevation in baseline cortisol and significant reductions in the net ACTH and cortisol responses to corticotropin releasing factor. These findings were normal in manic (N = 6) and improved (N = 8) subjects. An additional finding was that baseline cortisol and net ACTH and cortisol responses to CRF were negatively correlated in the entire group of patients and controls as well as in the patients alone. These data indicate that the reduced ACTH and cortisol responses to CRF in depression reflect normal functioning of the pituitary corticotroph cell (i.e., that the negative feedback effect of cortisol on ACTH secretion in depression is physiologically intact, effectively serving as a brake on the ACTH response to exogenous CRF. Thus, the hypercortisolism of depression may be due to a hypothalamic defect, possibly involving hypersecretion of endogenous CRF. This possibility may be of particular interest in light of clinical observations that depression can often be precipitated by stress and by data in experimental animals that CRF may influence several processes known to be altered in the overall symptom complex of depression.     

Low electrooculographic ratios in patients with seasonal affective disorder

OBJECTIVE: Changes in retinal sensitivity to light have been hypothesized as etiological in seasonal affective disorder. This study was undertaken to investigate sensitivity to light in seasonal affective disorder using electrooculography (EOG), an objective measure of retinal light response. METHOD: In a mood disorders clinic, 19 depressed, drug-free patients with seasonal affective disorder, diagnosed by DSM-III-R criteria, were compared with 19 age- and sex-matched normal comparison subjects. All subjects had identical EOG testing performed during the winter. EOG (Arden) ratios were calculated from the EOG data. RESULTS According to multivariate analysis of variance, the EOG ratios in the patients with seasonal affective disorder were significantly lower than those of the normal comparison subjects, although there was considerable overlap in EOG ratios between patients and comparison subjects. CONCLUSIONS: These results suggest that seasonal affective disorder is associated with subtle retinal abnormalities at the level of the photoreceptor/retinal pigment epithelium complex, consistent with subsensitivity to light. A limitation of this study is that the retinal origins of the EOG response are nonspecific and still not completely elucidated.     

Photopic and scotopic light detection in patients with seasonal affective disorder and control subjects.

BACKGROUND: Retinal sensitivity may play a role in the pathogenesis of seasonal affective disorder (SAD) and response to light therapy. METHODS: Using a dark adaptation procedure, SAD patients and normal control subjects were tested in the winter and summer, with patients retested after light treatment. The eyes were preadapted to bright light followed by 30 min in darkness, during which subjects detected a dim signal titrated around the detection threshold. Photopic (cone-mediated) and scotopic (rod-mediated) components of the data were identified by nonlinear exponential curve fits to successive threshold estimates. RESULTS: Patients (n = 24) showed significantly lower cone and rod thresholds in the summer than winter, while control subjects (n = 12) showed a similar trend. Relative to the control subjects, however, patients were supersensitive in winter (lower cone final threshold, faster rod recovery). Clinical responders to morning light showed a small summer-like increase in cone sensitivity, whereas nonresponders became subsensitive. In comparison to darker-eyed patients, blue-eyed patients showed a larger summertime increase in cone sensitivity and a similar trend after response to morning light. CONCLUSIONS: Heightened retinal sensitivity with increased light exposure, and supersensitivity of patients relative to control subjects in winter, may play roles in the pathogenesis of winter depression and the action of therapeutic light.     

Actigraphy in patients with seasonal affective disorder and healthy control subjects treated with light therapy.

BACKGROUND: Abnormalities of the circadian rest-activity cycle are hypothesized to accompany the clinical picture of seasonal affective disorder (SAD). The purpose of this study was to investigate if bright light therapy (BLT) is able to reverse these disturbances. METHODS: Seventeen SAD outpatients and 17 sex- and age-matched healthy control subjects were treated with BLT administered in the morning for 4 weeks. Activity levels were measured with wrist actigraphy. RESULTS: SAD patients had 33% lower total (p = .031) and 43% lower daylight activity (p = .006) in week 1 compared with control subjects. The relative amplitude of the sleep-wake cycle was attenuated by 6% in patients (p = .025); they were phase delayed by 55 minutes (p = .023) and had significantly lower sleep efficiency (p = .030). Total (p = .002) and daylight activity (p = .001) increased after 4 weeks of treatment in SAD patients. Moreover, BLT led to increase of relative amplitude (p = .005), advance of delayed rhythms (p = .036), and improved sleep efficiency (p = .011) in patients. Intradaily stability, measuring the strength of coupling of the rhythm to external zeitgebers, increased by 9% both in patients and healthy control subjects (p = .032). CONCLUSIONS: Treatment with BLT normalizes disturbed activity patterns and restores circadian rhythms in SAD patients. BLT might also stabilize the circadian rhythm in nondepressed individuals during the fall-winter season.     

Season of birth in siblings of patients with seasonal affective disorder

Recently we have published a report on seasonally varying birth rates in 553 patients with seasonal affective disorder (SAD). The present study is aimed to test the hypothesis of an idiosyncratic seasonal conception pattern of the parents of these patients to explain this phenomenon. We conducted a telephone interview with the patients to obtain information on the birth data of their siblings. Using the method of chart review to acquire information on the family history of our patients, we excluded those siblings with psychiatric disorders. We first compared the birth months and the quarters of birth of 435 healthy siblings with the general population. Secondly, we compared the birth distribution of the index SAD patients with that of their siblings. There was a significant deviation between the birth distribution of the siblings and the general population calculated on a monthly basis (p = 0.044). When comparing quarters we found less births than expected in the first (-14.1%) and fourth quarter of the year (-15.1%) and an excess of births in the second (+7.7%) and third quarter (+21.1%; p = 0.018). There were no significant differences between the group of SAD patients and their siblings regarding their birth patterns as calculated by months (p = 0.848) or quarters (p = 0.320). Our study provides support for the hypothesis of specific parental conception habits underlying the birth seasonality in SAD. Further research could be conducted in non-seasonal depression as there is still a lack of studies on seasonality of birth in affective disorders.     

Depressive symptomatology differentiates subgroups of patients with seasonal affective disorder

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

Alcoholism and seasonal affective disorder

Seasonal changes in mood and behavior (seasonality) may be closely related to alcoholism. Some patients with alcoholism have a seasonal pattern to their alcohol misuse. They may be self-medicating an underlying seasonal affective disorder (SAD) with alcohol or manifesting a seasonal pattern to alcohol-induced depression. Both genetic and environmental factors play a role in the etiology and pathogenesis of alcoholism and SAD, operating, at least in part, through the brain serotonergic system. Family and molecular genetic studies suggest that there may be a genetic link between seasonality and alcoholism. Certain environmental and social factors may contribute to the development of seasonality in patients with alcoholism. The fact that SAD and alcoholism may be comorbid shows the importance of a thorough diagnostic interview. Both mental health and drug and alcohol professionals should be provided with education to assist with appropriate identification, management, and referral of patients presenting with comorbid alcoholism and SAD.     

Effects of bright light on resting metabolic rate in patients with seasonal affective disorder and control subjects

Many of the symptoms of seasonal affective disorder (SAD) could be construed as having an energy-conserving function. We predicted that SAD patients would have abnormally low resting metabolic rates (RMR), which would be increased to normal levels by light therapy. To test this hypothesis we measured RMR in 10 patients on and off light treatment and 9 normal controls. Contrary to our prediction we found that SAD patients had significantly higher RMR values compared with the normal population (p less than 0.02) and these values were significantly lowered by light treatment (p less than 0.05). The possible implications of these findings are discussed.     

Insight in seasonal affective disorder

Lack of insight complicates the evaluation and treatment of patients with psychotic and affective disorders. No studies of insight in seasonal affective disorder (SAD) have been reported. Thirty patients with SAD diagnosed by the Structured Clinical Interview for DSM-III-R but no other axis I conditions were treated short-term with light-therapy. Insight was measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) as modified by the authors to assess the self-report of insight into depressive symptoms. Increasing scores (1 to 5) indicated increasing unawareness of illness (i.e., less insight). SAD patients displayed a moderate amount of insight when depressed (mean SUMD score, 2.5). When recovered, they showed no significant change in insight into past depressive symptoms (mean SUMD score, 2.8). Greater insight into current depressive symptoms correlated with more depressive symptoms on the Hamilton Rating Scale for Depression score ([HRSD] r = .35, P < .05). In conclusion, SAD patients possess a moderate amount of insight into depressive symptoms that does not change after recovery, a result in agreement with studies of insight in psychosis and mania. Further, in SAD, increased severity of illness may be associated with increased insight into depressive symptoms, consistent with the hypothesis of depressive realism.     

Adaptation to dim light in depressed patients with seasonal affective disorder

Supersensitivity to light has been suggested as a possible trait marker for manic-depressive illness. Because winter seasonal affective disorder (SAD) is associated with depressive episodes during dark winter days, the authors postulated that SAD patients would show diminished sensitivity to dim light. Dark-adaptation curves were obtained in 10 medication-free, depressed SAD patients and in 10 age- and sex-matched drug-free healthy controls. Contrary to the hypothesis, patients adapted to dim light more rapidly than controls.     

Circadian rhythms of melatonin,cortisol and prolactin in patients with obsessive-compulsive disorder

Plasma melatonin, cortisol and prolactin (PRL) levels were measured over a 24-h period in 13 drug-free patients with obsessive-compulsive disorder and in matched healthy subjects. The circadian profiles of melatonin and PRL were altered in patients; the circadian rhythm of cortisol was preserved, although at a higher level compared with normal controls. These changes were significantly related to the severity of the obsessive-compulsive symptoms. Further studies need to clarify the state- or trait-dependent character of these abnormalities.     

Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder.

Plasma levels of melatonin and cortisol were measured over a 24-hour period in seven patients with primary obsessive-compulsive disorder (OCD) and seven matched healthy control subjects. In OCD patients, the 24-hour secretion of melatonin was reduced as compared with that in healthy control subjects, whereas its circadian rhythm was preserved. In addition, in OCD patients, the overall secretion of cortisol was higher than that in control subjects, but there was no change in the circadian pattern of cortisol secretion. No correlation was found between clinical parameters and hormone levels.     

Clinical evidence for thyroid dysfunction in patients with seasonal affective disorder.

Of 49 consecutive patients over a 21-mo period satisfying conservative criteria for seasonal affective disorder (SAD), a well-characterized syndrome involving seasonal neurovegetative dysregulation, 17 (35%) were found to have elevated serum TSH compatible with mild primary hypothyroidism (TSH > 4.6 microIU/ml). An additional eight patients (16%) met criteria for "conjectural" hypothyroidism (TSH > 3.5 microIU/ml or exaggerated TSH response to TRH). The frequency of cases with supranormal TSH within the SAD group, both with and without inclusion of the "conjectural" cases, proved statistically significant when compared to that within psychiatric patients not satisfying criteria for SAD (N = 381) or to that within the population at large. The author suggests that SAD may in part represent a reformulation in modern neuropsychiatric terms of a previously noted fall-winter decrement, both biochemical and clinical, among hypothyroid patients.     

Effects of naloxone-HCl on cortisol levels in patients with affective disorder and normal controls

Cortisol levels were measured before and after administration of naloxone-HCl in patients with affective disorder (n = 16) and normal control subjects (n = 8). On two consecutive days, 20 mg of naloxone-HCl or placebo was administered i.v. over 15 minutes in a double-blind crossover design. Blood samples were collected at 30, 15, and l minute(s) both before and after infusion. Cortisol rose from a mean baseline level of 14.8 microgram% to a mean peak level of 23.1 microgram% following the naloxone administration. Significant cortisol increases were found in both the 15- and 30-minute samples during the naloxone session. There were no differences between patient and normal subject samples or between diagnostic groups. A subgroup of manic patients who had responded to naloxone with a reduction of their manic behavior also had an attenuated cortisol response to naloxone. This proved to be an artifact secondary to variability in the cortisol response in these patients.