SOZIALPHOBIE: EPIDEMIOLOGIE, BIOLOGIE UND THERAPIE

Social anxiety disorder (SAD) is considered to be one of the most common anxiety disorders. Despite its high prevalence, the disorder is still considerably underdiagnosed and undertreated. SAD shows a typically early onset in childhood or early adolescence and generally becomes chronic. The disease places a massive burden on patients lives, affecting not only their social interactions but also their educational and professional activities, thereby constituting a severe disability. Although substantial progress in the study of the etiology of SAD has been made, no commonly accepted model has emerged yet. Data from genetic and neuroimaging studies point towards a contribution of several neurotransmitter systems (i.e. norepinephrine, dopamine and serotonin) to the pathophysiology of this disorder. Functional magnetic resonance imaging studies have repeatedly emphasized the central role of the amygdalae and insula in the neural circuitry of the disorder. Selective serotonin reuptake inhibitors (SSRI) are commonly accepted as first line therapy, however other substance classes like serotonin norepineprine reuptake inhibitors (SNRI), monoamine oxidase inhibitors (MAOI), benzodiazepines and several other agents have also proved effective. There is still a substantial lack of data on therapeutic options in cases of non-responsive SAD as well as on add-on therapy. A combined treatment-approach including psychotherapy (e.g. cognitive behavioural therapy) may prove useful.Sozialphobien gehören zu den häufigsten psychiatrischen Erkrankungen. Ungeachtet der hohen Prävalenz wird diese Erkrankung noch immer zu selten erkannt, diagnostiziert und und ausreichend behandelt. Das Krankheitsbild entwickelt sich typischerweise in der Kindheit oder im frühen Adoleszenzalter und zeigt häufig einen chronischen Verlauf. Die Erkrankung stellt eine massive Belastung für die Patienten dar und wirkt nicht nur in sozialen Aspekten, sondern auch im Beruf und der Ausbildung der Betroffenen behindernd. Obwohl in der Erforschung der Ätiologie der Erkrankung bereits große Fortschritte gemacht wurden, hat sich noch kein allgemein akzeptiertes Modell entwickelt. Die Daten aus genetischen Studien und Studien mit bildgebenden Verfahren deuten auf ein Mitwirken des noradrenergen, des dopaminergen und des serotonergen Systems in der Pathophysiologie hin. In funktionellen Magnetresonanztomographiestudien wurde wiederholt die zentrale Rolle von Strukturen wie den Amydalae und der Insula in der neuronalen Grundlage der Sozialphobien gezeigt. In der Therapie der Sozialphobien werden allgemein selekive Serotonin- Wiederaufnahmehemmer als Mittel der ersten Wahl betrachtet. Andere Substanzklassen wie Serotonin-Noradrenalin-Wiederaufnahmehemmer, Monoaminoxidasehemmer, Benzodiazepine und einzelne andere Psychopharmaka haben ebenfalls Therapieeffizienz bewiesen. Zum gegenwärtigen Zeitpunkt gibt es noch immer kaum Daten über Therapieoptionen bei Therapieresistenz oder über add-on Strategien. Eine weitere Möglichkeit stellen kombinierte Therapiestrategien mit psychotherapeutischen Ansätzen (z.B. kognitive Verhaltenstherapie) dar

Cardiovascular Adverse Reactions During Antidepressant Treatment: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2010

Background: Antidepressants (ADs) are known to have the potential to cause various cardiovascular adverse drug reactions (ADRs). The tricyclic antidepressants (TCAs) were first revealed to be a possible source of cardiovascular ADRs. In recent years, newer classes of ADs were also suggested to have a higher risk of cardiovascular adverse effects. In particular, the selective serotonin reuptake inhibitors (SSRIs) were suspected to have the potential to induce QTc interval prolongation, and therefore increase the risk of ventricular arrhythmia. This descriptive study is based on the continuous pharmacovigilance program of German-speaking countries (Austria, Germany, and Switzerland), the Arzneimittelsicherheit in der Psychiatrie (AMSP), which assesses severe ADRs occurring in clinical routine situations. Methods: Of 169 278 psychiatric inpatients treated with ADs between 1993 and 2010, 198 cases of cardiovascular ADRs (0.12%) were analyzed. Results: Our study showed that the incidence rates of cardiovascular ADRs were highest during treatment with monoamine oxidase inhibitors (0.27%),TCAs (0.15%), and serotonin noradrenaline reuptake inhibitors (0.14%); the risk of occurring during treatment with SSRIs (0.08%) was significantly lower. The noradrenergic and specific serotonergic AD mirtazapine (0.07%) had a significantly lower risk of cardiovascular ADRs than all other ADs. Severe hypotension was the most frequent ADR, followed by hypertension, arrhythmia, and in some rare cases heart failure. Conclusions: Despite certain limitations due to the AMSP study design, our observations on cardiovascular ADRs can contribute to a better knowledge of the cardiovascular risk profiles of antidepressants in the clinical routine setting. However, prospective studies are needed to verify our findings

Electrocardiogram Alterations Associated With Psychotropic Drug Use and CACNA1C Gene Variants in Three Independent Samples

Several antipsychotics and antidepressants have been associated with QTc prolongation or other electrocardiogram (ECG) alterations, but their impact is still debated and other risk factors are known to affect QTc. We investigated the effect of antidepressants and antipsychotics on QTc and other ECG intervals/waves in three samples. Two discovery samples (cross-sectional sample n = 145 and prospective sample n = 68, naturalistic treatment) and a replication prospective sample (Clinical Antipsychotic Trials of Intervention Effectiveness, n = 515, randomized treatment) were analysed. In both prospective samples, baseline/follow-up changes in ECG parameters were analysed in relation to the number of psychotropic drugs stratified according to their known cardiovascular risk. In the cross-sectional sample, ECG parameters were compared among drugs with different risk profile. The possible effect of single nucleotide polymorphisms (SNPs) in the CACNA1C gene on QTc was also investigated. There was no evidence of mean QTc prolongation or increased risk of clinically relevant QTc prolongation ( 6520 msec.) in association with psychotropic drugs stratified according to their known cardiovascular risk. The prescription of drugs with cardiovascular risk was less common in older individuals or individuals with cardiovascular comorbidities. Other factors (gender, baseline QTc, renal function) affected QTc. rs1006737 and SNPs in linkage disequilibrium with it modulated QTc duration/changes in all samples. An association between risk drugs and shorter RR interval or higher heart rate was found in all samples. A relevant effect of psychotropic drugs with cardiovascular risk on QTc duration was not observed. A number of factors other than psychotropic drugs may influence QTc. CACNA1C rs1006737 may modulate QTc in patients treated with psychotropic drugs

Season, weather, and suicide:Further evidence for ecological complexity

Background: easonality in suicide is reported worldwide, and peaks in late spring. Despite the potential connection to the weather, associations between meteorological variables and suicide does not explain seasonality. Studies testing for seasonality while controlling for the weather show patterns that are more complex than a straightforward link between spring-like weather and suicide. Methods: We tested whether seasonality in suicide was due to meteorological variation (hours of sunshine, rainfall, or temperature) in a novel population (Scotland; 2003–2013). We also sought to further explore the ecological complexity demonstrated in previous work by testing associations at a single location (Tay Road Bridge; 1968–2017). RESULTS: We found peaks in suicidal behavior in June at the bridge, but no seasonality for Scotland as a whole. Seasonality was reduced when we controlled for maximum temperature and hours of sunshine. We found patterns to be dependent upon sex, with stronger seasonal and meteorological effects amongst men. Limitations: Our study was exploratory and relies on population-level data. Conclusions: Seasonal and meteorological effects on suicide are dependent upon local and individual context, with significant effects apparent at the Tay Road Bridge and not across Scotland as a whole. Men may be more sensitive to season and weather. In order to determine whether seasonality in suicide is due to meteorological variation, future research should test patterns in small geographical units, in men and women, and for different suicide methods, and seek to identify the social and physical factors which predict variation in patterns

The two-process model of sleep regulation: a reappraisal

In the last three decades the two-process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time-courses derived from physiological and behavioural variables. The model simulates successfully the timing and intensity of sleep in diverse experimental protocols. Electrophysiological recordings from the suprachiasmatic nuclei (SCN) suggest that S and C interact continuously. Oscillators outside the SCN that are linked to energy metabolism are evident in SCN-lesioned arrhythmic animals subjected to restricted feeding or methamphetamine administration, as well as in human subjects during internal desynchronization. In intact animals these peripheral oscillators may dissociate from the central pacemaker rhythm. A sleep/fast and wake/feed phase segregate antagonistic anabolic and catabolic metabolic processes in peripheral tissues. A deficiency of Process S was proposed to account for both depressive sleep disturbances and the antidepressant effect of sleep deprivation. The model supported the development of novel non-pharmacological treatment paradigms in psychiatry, based on manipulating circadian phase, sleep and light exposure. In conclusion, the model remains conceptually useful for promoting the integration of sleep and circadian rhythm research. Sleep appears to have not only a short-term, use-dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24-h cycle

Cardiovascular Adverse Reactions During Antidepressant Treatment: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2010

Background: Antidepressants (ADs) are known to have the potential to cause various cardiovascular adverse drug reactions (ADRs). The tricyclic antidepressants (TCAs) were first revealed to be a possible source of cardiovascular ADRs. In recent years, newer classes of ADs were also suggested to have a higher risk of cardiovascular adverse effects. In particular, the selective serotonin reuptake inhibitors (SSRIs) were suspected to have the potential to induce QTc interval prolongation, and therefore increase the risk of ventricular arrhythmia. This descriptive study is based on the continuous pharmacovigilance program of German-speaking countries (Austria, Germany, and Switzerland), the Arzneimittelsicherheit in der Psychiatrie (AMSP), which assesses severe ADRs occurring in clinical routine situations. Methods: Of 169 278 psychiatric inpatients treated with ADs between 1993 and 2010, 198 cases of cardiovascular ADRs (0.12%) were analyzed. Results: Our study showed that the incidence rates of cardiovascular ADRs were highest during treatment with monoamine oxidase inhibitors (0.27%),TCAs (0.15%), and serotonin noradrenaline reuptake inhibitors (0.14%); the risk of occurring during treatment with SSRIs (0.08%) was significantly lower. The noradrenergic and specific serotonergic AD mirtazapine (0.07%) had a significantly lower risk of cardiovascular ADRs than all other ADs. Severe hypotension was the most frequent ADR, followed by hypertension, arrhythmia, and in some rare cases heart failure. Conclusions: Despite certain limitations due to the AMSP study design, our observations on cardiovascular ADRs can contribute to a better knowledge of the cardiovascular risk profiles of antidepressants in the clinical routine setting. However, prospective studies are needed to verify our findings

The impact of BDNF polymorphisms on suicidality in treatment-resistant major depressive disorder: A European multicenter study

Background: Numerous studies have reported associations between the brain-derived neurotrophic factor (BDNF) gene and psychiatric disorders, including suicidal behavior, although with conflicting results. Methods: A total of 250 major depressive disorder patients were collected in the context of a European multicenter resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and Hamilton Rating Scale for Depression, and treatment response using the HAM-D. Genotyping was performed for the functional Val66Met polymorphism (rs6265) and 7 additional tagging single nucleotide polymorphisms within the BDNF gene. Results: Neither BDNF single markers nor haplotypes were found to be associated with suicide risk and lifetime history of suicide attempts. Gender-specific analyses revealed nonsignificant single marker (rs908867) and haplotypic association with suicide risk in males after multiple testing correction. Analyzing treatment response phenotypes, the functional Val66Met polymorphism as well as rs10501087 showed significant genotypic and haplotypic association with suicide risk in remitters (n = 34, 13.6%). Conclusions: Considering the sample size, the present findings need to be replicated in larger samples to confirm or refute a role of BDNF in the investigated suicidal behavior phenotypes