Lifetime and 12-month prevalence estimates for mental disorders in northeastern Germany: findings from the Study of Health in Pomerania.

Few epidemiological studies presented 12-month and lifetime prevalence estimates for DSM-IV mental disorders in the adult general population by sex and age up to very old age. From 2007 to 2010, DSM-IV mental disorders were assessed with the DIA-X/M-CIDI among N = 2400 participants (aged 29-89 years) from the Study of Health in Pomerania, an epidemiological study based on a two-stage stratified cluster sample randomly drawn from the adult general population in northeastern Germany. 36.3% of the sample was affected by any 12-month and 54.8% by any lifetime mental disorder. The most frequent diagnostic groups were anxiety (12-month: 14.8%, lifetime: 23.4%), substance use (12-month: 14.5%, lifetime: 25.0%), somatoform (12-month: 12.9%, lifetime: 20.4%) and depressive (12-month: 7.3%, lifetime: 18.6%) disorders. Except for substance use (higher prevalence in men) and bipolar disorders (comparable prevalence in men and women), higher 12-month and lifetime prevalence estimates were found in women vs. men. Moreover, lower 12-month and lifetime prevalence estimates were found in older (aged 60-74 or 75-89 years) vs. younger (aged 29-44 or 45-59 years) age groups. 22.6% (men: 21.1%, women: 23.9%) of those affected by any 12-month disorder met criteria for two and 13.6% (men: 9.6%, women: 16.9%) for three or more 12-month diagnoses. Similarly, 26.4% (men: 25.7%, women: 26.9%) of those affected by any lifetime disorder met criteria for two and 22.7% (men: 19.6%, women: 25.2%) for three or more lifetime diagnoses. Our findings demonstrate the frequency of mental disorders in northeastern Germany and emphasize the need for continued prevention and intervention efforts.

Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing.

Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis. Binding to its receptor CRHR1 triggers the downstream release of the stress response-regulating hormone cortisol. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here we aimed to evaluate CRHR1 as a risk factor for panic disorder (PD). Allelic variation of CRHR1 was captured by 9 single-nucleotide polymorphisms (SNPs), which were genotyped in 531 matched case/control pairs. Four SNPs were found to be associated with PD, in at least one sub-sample. The minor allele of rs17689918 was found to significantly increase risk for PD in females after Bonferroni correction and furthermore decreased CRHR1 mRNA expression in human forebrains and amygdalae. When investigating neural correlates underlying this association in patients with PD using functional magnetic resonance imaging, risk allele carriers of rs17689918 showed aberrant differential conditioning predominantly in the bilateral prefrontal cortex and safety signal processing in the amygdalae, arguing for predominant generalization of fear and hence anxious apprehension. Additionally, the risk allele of rs17689918 led to less flight behavior during fear-provoking situations but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus reduced gene expression driven by CRHR1 risk allele leads to a phenotype characterized by fear sensitization and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder.

Assessing the interplay of childhood adversities with more recent stressful life events and conditions in predicting panic pathology among adults from the general population.

BACKGROUND: Although research suggests that (a) childhood adversities and more recent stressful life events/conditions are risk factors for panic pathology and that (b) early life stress increases vulnerability to later psychopathology, it remains unclear whether childhood adversities amplify the association between more recent stressful life events/conditions and panic pathology. METHODS: Data were derived from a general population sample (Study of Health in Pomerania, SHIP). Lifetime panic pathology was assessed with the Munich Composite International Diagnostic Interview (M-CIDI). Childhood adversities (emotional, physical and sexual abuse; emotional and physical neglect) were assessed with the Childhood Trauma Questionnaire (CTQ). More recent separation/loss events and long-lasting stressful conditions were assessed with the Stralsund Life Event List (SEL). Individuals with lifetime panic pathology (fearful spell, panic attack or panic disorder, N = 286) were compared to controls without any psychopathology (N = 286, matched for sex and age). RESULTS: Conditional logistic regressions revealed that childhood adversities as well as more recent separation/loss events and long-lasting stressful conditions were associated with panic pathology (OR 1.1-2.5). Moreover, more recent separation/loss events - but not long-lasting stressful conditions - interacted statistically with each of the examined childhood adversities except for sexual abuse in predicting panic pathology (OR 1.1-1.3). That is, separation/loss events were associated more strongly with panic pathology among individuals with higher childhood adversities. LIMITATIONS: Data were assessed retrospectively and might be subject to recall biases. CONCLUSIONS: Findings suggest that early childhood adversities amplify the risk of developing panic pathology after experiencing separation or loss events.

A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety.

Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.