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.

Effects of tryptophan depletion and catecholamine depletion on immune parameters in patients with seasonal affective disorder in remission with light therapy.

BACKGROUND: Altered immunologic parameters are found in symptomatic depressed patients relative to remitted depressed patients and healthy controls. We investigated whether tryptophan depletion and catecholamine depletion induce alterations in immunologic parameters in patients with seasonal affective disorder remitted on light therapy, and whether these changes are associated with changes in mood. METHODS: Remitted patients with seasonal affective disorder underwent tryptophan depletion, catecholamine depletion, and sham depletion in a prospective randomized, double-blind crossover design. Measures of depression, plasma levels of tryptophan and catecholamine metabolites, and plasma levels of cytokines (sIL-4, IL-6, neopterin, sTNF-R1 and sTNF-R2) were obtained at baseline, and 7, 24, and 30 hours after monoamine depletion. RESULTS: Tryptophan depletion decreased plasma total and free tryptophan levels; catecholamine depletion decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels. Tryptophan depletion and catecholamine depletion, but not sham depletion, induced a transient exacerbation of depressive symptoms (p <.001); plasma neopterin levels increased during tryptophan depletion and catecholamine depletion (p <.05). Tryptophan depletion and catecholamine depletion induced a transient reduction of plasma sIL-4 levels (p <.05). A significant correlation was found between sIL-4R levels and depression ratings after tryptophan depletion (r = -.61, p <.05). CONCLUSIONS: The monoamine depletion-induced alterations of humoral and cellular immunity suggest a potential role of immunologic parameters in the pathophysiology of seasonal affective disorder; however, the results must be considered preliminary and require further study.

Seasonality of birth in seasonal affective disorder.

BACKGROUND: Season of birth or seasonal changes in putative etiologic factors are thought to influence the development of several psychiatric illnesses. The aim of this investigation was to examine seasonal differences in the frequency of birth in a clinical sample of patients with seasonal affective disorder (SAD). METHOD: 553 outpatients suffering from SAD-DSM-IV-defined depressive disorder with winter-type seasonal pattern-who had been diagnosed and treated at the Department of General Psychiatry (University of Vienna, Austria) between 1994 and 2003, were included in this evaluation. We compared the observed number of births in our sample with expected values calculated from the general population. RESULTS: There was a significant deviation of the observed number of births from the expected values calculated on a monthly basis (p = .009). When comparing quarters (periods of 3 months), we found fewer births than expected in the first quarter of the year and a slight excess of births in the second and third quarters (p = .034). There were also more births in the spring/summer season and fewer than expected in fall and winter (p = .029). Interestingly, patients with melancholic depression were more frequently born in fall/winter and less often in spring/summer compared with patients with atypical depression (p = .008). CONCLUSION: Besides genetic factors, season of birth or seasonal changes in environmental factors also could influence the development of SAD. In addition, birth effects seem to be dependent on the symptom profile of the patients, but further studies are needed to elucidate the underlying mechanisms of these observations.

Bright light therapy in seasonal affective disorder--does it suffice?

Bright light therapy (BLT) has been proposed as treatment of choice for seasonal affective disorder (SAD). However, conventional antidepressants have also been found to be effective in this condition. We examined the psychopharmacologic medication in a clinical sample of 553 SAD patients, who had been treated with BLT, to assess the importance of drug treatment and to critically question the effectiveness of BLT. Forty-nine percent of our patients received psychopharmacologic treatment and about one third (35.4%) was treated with antidepressants, suggesting that BLT does not suffice as only antidepressant regimen for all SAD patients. Furthermore, our results show that only few patients with bipolar affective disorder were willing to accept long-term medication. Opposed to treatment guidelines, patients with several depressive episodes did not receive antidepressant maintenance medication or mood stabilizers more often than patients with only a few episodes.

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.

Serotonin transporter promoter gene polymorphic region (5-HTTLPR) and personality in female patients with seasonal affective disorder and in healthy controls.

Serotonergic pathways have been related to altered personality patterns in seasonal affective disorder (SAD). The short allele (s) of a polymorphism in the serotonin transporter promoter gene (5-HTTLPR) has been associated with neuroticism and anxiety-related personality traits in healthy volunteers. We investigated personality and 5-HTTLPR in female SAD patients using the Temperament and Character Inventory (TCI). TCI was completed by 56 female patients and 76 age-matched female controls. DNA was genotyped using polymerase chain reaction methods. Subjects homozygous for the long allele (l) were compared to s carriers. Females with SAD had higher scores in Harm Avoidance and lower scores in Novelty Seeking, Self-Directedness and Cooperativeness when compared to controls. Patients carrying the s allele had lower Self-Directedness scores. Our data indicate that females with SAD show altered personality traits. The s allele was associated with lower Self-Directedness scores in SAD patients, whereas there were no significant differences in TCI dimensions between patients and controls in carriers of the long allele.

Receptor and transporter imaging studies in schizophrenia, depression, bulimia and Tourette's disorder--implications for psychopharmacology.

Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. To determine patterns of brain dysfunction and to uncover the mechanism of action of centrally active compounds we used single photon emission computerized tomography (SPECT) as well as positron emission tomography (PET) in patients diagnosed with schizophrenia, depression, bulimia and Tourette's disorder. Striatal D2 and 5-HT1A receptors were studied in schizophrenia and 5-HT transporters (5-HTT) in depression and bulimia. Patients were either drug-naïve or drug free, or we studied the influence of specifically acting compounds on receptor/transporter occupancy. We could demonstrate that atypical antipsychotics have a dose-dependent (with the exception of clozapine and quetiapine) lower striatal D2 receptor occupancy rate compared with typical neuroleptics, paralleling the more favourable extrapyramidal side effects of atypical antipsychotics. However, no association between striatal D2 receptor occupancy rates and antipsychotic efficacy has been found. The measurement of 5-HT1A receptors in drug-naïve schizophrenic patients using the in vivo PET methodology revealed an increase of cortical 5-HT1A receptor binding potential in schizophrenia. beta-CIT as a ligand for measurement of 5-HT transporter densities (5-HTT) revealed lower rates in depression compared to age- and sex-matching healthy controls, a measurement that has also been obtained for bulimia. We also documented seasonal variations in brain serotonergic function by our finding of reduced brain 5-HTT availability in winter (compared to summer) in healthy controls. Furthermore, displaceable [123I] beta-CIT binding in the area corresponding to the left striatum (representing predominantly the density of dopamine transporters) was significantly reduced in SAD patients compared to healthy controls. In depression as well as in bulimia, selective serotonin reuptake inhibitors significantly decreased the beta-CIT binding potential, however, no significant dose relationship has been obtained in depression. Genotyping depressed patients for the serotonin transporter promoter gene region (5-HTTLPR) did not provide evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects. In patients suffering from Tourette's disorder (TD) we were unable to detect differences of dopamine transporter densities between psychotropic drug-naïve TD patients and controls. Furthermore, no difference could be found between currently treated (with antipsychotics) and psychotropic drug-naïve TD patients. Our data provide insight into the pathophysiology of neuropsychiatric disorders and may guide future psychopharmacological drug developments.

Season of birth in siblings of patients with seasonal affective disorder. A test of the parental conception habits hypothesis.

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.

Serum lipid levels in seasonal affective disorder.

Previous research has assessed the relationship between blood lipid levels and depression with contradictory results. Several studies have linked low cholesterol levels with impulsive, aggressive and suicidal behaviours. The aim of this pilot study was to examine serum lipids in a sample of patients suffering from seasonal affective disorder (SAD). We conducted a retrospective analysis of data on total serum cholesterol and serum triglycerides in 39 SAD patients and 40 non-seasonally depressed or schizophrenic control subjects. Study subjects had to be free of psychotropic drugs for at least 2 weeks. Analysis of covariance (ANCOVA) was performed to assess group differences. After adjustment for significant covariates SAD patients had significantly lower total cholesterol levels (5.21 +/- 1.14 mmol/l) than control subjects (5.94 +/- 1.11 mmol/l; p = 0.013). Moreover, hypercholesterolemia (total cholesterol > 5.20 mmol/l) was significantly less frequent in the SAD group (46.2%) than in the control group (75.0%; p = 0.012). Total serum triglycerides did not differ significantly between SAD patients (1.54 +/- 1.07 mmol/l) and controls (1.56 +/- 0.96 mmol/l; p = 0.126). The results of this study support the idea that low cholesterol levels may be of pathogenetic importance in SAD. Further study in larger clinical samples is warranted to clarify our findings.

Anger attacks in seasonal affective disorder.

Previous research has linked aggression especially anger attacks with depression. The objective of the present study was to examine the prevalence and clinical picture of anger attacks in seasonal affective disorder (SAD) in comparison to non-seasonal depression. Thirty-six SAD patients and 24 non-seasonally depressed controls were included in this evaluation. Anger attacks were assessed with the Anger Attacks Questionnaire. The prevalence of anger attacks did not differ statistically significantly between seasonally and non-seasonally depressed subjects. However, the monthly number of anger attacks was significantly higher in SAD patients (p=0.009) and they presented with more vegetative symptoms and behavioural outbursts during the anger attacks (p=0.006). SAD patients with anger attacks had significantly lower age of onset (p=0.021) and obtained lower global seasonality scores than SAD patients without anger attacks (p=0.001). Anger attacks are experienced as particularly intense in SAD patients and seem to contribute considerably to their symptomatology.