Nikolaus Thierry

A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder

Serotonergic mechanisms are thought to play an important role in the pathogenesis of seasonal affective disorder (SAD). The expression of the serotonin transporter (5-HTT) is regulated in part by an insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality. We genotyped 138 SAD patients and 146 healthy volunteers with low seasonality for 5-HTTLPR. No difference between patients and controls was found for genotype distribution and s-allele frequency. However, genotype distribution and allele frequencies were strongly associated with DSM-IV depression subtypes. Melancholic depression was associated with the 5-HTTLPR long (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fishers exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our data are compatible with the hypothesis of a disease process that is not causally related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere on its way to phenotypic disease expression.

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

Decreased synaptic serotonin during depressive episodes is a central element of the monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT turnover rate, a measure for the number of inward transport events per minute, and tyramine-induced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of bright light therapy, and in summer using a case–control design in a consecutive sample of 73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients were drug-naive or medication-free for at least 6 months prior to study inclusion, females patients were studied in the follicular phase of the menstrual cycle. All participants were genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p=0.014) and outward (p=0.003) transport was enhanced in depressed patients. Both measures normalized toward control levels after therapy and in natural summer remission. Changes in outward transport showed a clear correlation with treatment response (ρ=0.421, p=0.001). Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission.

Prevalence of premenstrual dysphoric disorder in female patients with seasonal affective disorder

BACKGROUND Both seasonal affective disorder/winter type (SAD) and premenstrual dysphoric disorder (PMDD) are cyclical disorders characterized by so-called atypical depressive symptoms. In the present study we compared the point prevalence rates of PMDD between a sample of premenopausal female patients suffering from SAD and healthy female controls. METHODS Forty-six female patients with SAD and 46 healthy controls were included in our study. All subjects underwent a semistructured clinical interview according to DSM IV criteria and completed the Seasonal Pattern Assessment Questionnaire. PMDD was diagnosed in a self-rating interview for PMDD according to DSM IV criteria. To verify the diagnosis of PMDD, all patients were followed up in stable summer remission using daily self-rating scales for two full menstrual cycles. RESULTS Patients with SAD fulfilled significantly more often the diagnostic criteria for PMDD than female healthy controls (46% vs. 2%, respectively; chi-square: P<0.001). CONCLUSIONS These results provide preliminary evidence for a high point prevalence rate of PMDD in premenopausal females with SAD. CLINICAL IMPLICATIONS It would be worthwhile to investigate whether an additional diagnosis of PMDD has an impact on the clinical outcome and the response to bright light therapy in female patients with SAD.

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.

Saisonal abhängige Depression in zwei deutschsprachigen Universitätszentren: Bonn, Wien Klinische und demographische Charakteristika

Zusammenfassung610 Patienten mit einer saisonal abhängigen Depression (SAD) wurden an den Universitätskliniken für Psychiatrie in Bonn (1989–1992) und Wien (1993–2001) behandelt. Ziel der vorliegenden Erhebung ist einerseits der Vergleich unserer Patientenstichprobe mit anderen pub-lizierten SAD-Populationen, andererseits eine Untersuchung in Hinblick auf Unterschiede zwischen den beiden Standorten. Wir fanden ein Geschlechtsverhältnis von 5,0:1 (Frauen:Männer) unter unipolar Depressiven und von 1,5:1 unter Patienten mit bipolarer affektiver Störung. Der Anteil von Patienten mit Bipolar-II-Störung betrug 21,7%, Bipolar-I-Patienten waren mit 1,3% in unserem Sample vertreten. Der mittlere globalen Saisonalitäts-Score (GSS) betrug 15,4. Frauen hatten höhere GSS-Werte als Männer (t=2,127, p=0,035) und Wiener Patienten hatten höhere Scores als die in Bonn (t=3,104, p=0,002). 66,3% aller Patienten zeigten Symptome einer atypischen, 17,8% die einer melancholischen Depression (nach DSM). Patienten mit atypischer Depression waren in Wien häufiger anzutreffen, solche mit melancholischer in Bonn (χ2=54,952, df=2, p<0,001). Die demographischen und klinischen Charakteristika der beschriebenen Patienten bestätigen die Ergebnisse anderer epidemiologischer Untersuchungen, die in nichtdeutschsprachigen Populationen durchgeführt wurden.SummarySix hundred ten patients with seasonal affective disorder (SAD) were diagnosed and treated at the university hospitals for psychiatry in Bonn, Germany (1989–1992) and Vienna, Austria (1993–2001). The aim of this study was to compare our sample with other SAD populations in the literature and to investigate differences between the two study locations. We found female:male sex ratios of 5.0:1.0 in unipolar depressives and 1.5:1.0 in patients with bipolar affective disorder. Of our patients, 21.7% suffered from bipolar II disorder, and 1.3% were diagnosed as having bipolar I. Our patients obtained a mean global seasonality score (GSS) of 15.4. Women had a higher GSS than men (t=2.127, P=0.035), and Viennese patients had higher scores than patients in Bonn (t=3.104, P=0.002). Totals of 66.3% of all patients suffered from atypical depression and 17.8% from melancholic depression. Patients with atypical depression were more frequent in Vienna, whereas patients with melancholic depression predominated in Bonn (χ2=54.952, df=2, P<0.001). The demographic and clinical characteristics of the patients described in this article confirm the findings of other epidemiological investigations obtained in non-German-speaking samples.

Menstrual disturbances – a rare side-effect of bright-light therapy

Seasonal affective disorder (SAD; autumn–winter depression) is a form of recurrent depressive or bipolar disorder, that affects up to 4% of the general population (Kasper et al., 1989). Bright-light therapy (BLT) has been proven to be an effective and well-tolerated treatment for patients suffering from autumn–winter depression. This report presents the case of a patient experiencing menstrual disturbances during light therapy.

Typical neuroleptics vs. atypical antipsychotics in the treatment of acute mania in a natural setting.

The present retrospective chart review documents the treatment practice of in-patients suffering from acute manic or hypomanic episodes, at the Department of General Psychiatry, Medical University of Vienna between 1997 and 2001. The aim of the study was to compare the efficacy of typical neuroleptics and atypical antipsychotics as add-on therapy to mood stabilizers. A total of 119 episodes of consecutively admitted patients with ICD-10-defined acute mania (n=106) or hypomania (n=13) were included in a retrospective analysis. Two subgroups were separated out of the whole patient sample according to the medication used: (a) mood stabilizer+typical neuroleptic (n=27) and (b) mood stabilizer+atypical antipsychotic (n=39). The treatment patterns of both subgroups during the first 14 d of in-patient treatment were evaluated. The therapeutic effect was measured by the Clinical Global Impression Scale (CGI). Both patient groups showed no differences on CGI at admission. Patients treated with atypical antipsychotics showed a significantly greater clinical improvement after 14 d (p<0.005) and on discharge (p<0.05) than patients treated with typical neuroleptics. Furthermore, patients treated with atypical antipsychotics developed significantly less extrapyramidal side-effects (p<0.01) and were significantly treated less often with benzodiazepines (p<0.05) during the first 14 d compared to the group receiving typical neuroleptics. Based on our evaluation and the data available in the literature atypical antipsychotics can be considered as first choice for the treatment of acute mania as add-on therapy to mood stabilizers because of their better efficacy and side-effect profile compared to typical neuroleptics.

Zur Biologie der Dysthymie

Die Dysthymie stellt eine chronische niederschwellige Form der Depression dar. Trotz ihrer hohen Morbiditatsund Mortalitatsrate, die mit jener der major depression (MD) vergleichbar ist, wurde die Dysthymie als Krankheitsentitat im Vergleich zu anderen affektiven Erkrankungen bislang atiologisch wenig untersucht. Die bisherigen Untersuchungen mit biologischem Ansatz haben in erster Linie eine Nahe zur MD beschrieben. Insbesondere neurobiologische Grundlagenforschung wie Neuroimaging, Neurophysiologie und spezielle Neuropharmakologie dieser Erkrankung lieferten bislang widerspruchliche Ergebnisse. Dennoch weisen einige Forschungsansatze in eine viel versprechende Richtung.