Neuropeptide S receptor gene - converging evidence for a role in panic disorder

Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn¹⁰⁷Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case-control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli

Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder

Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder

Die Aussichten des Evangeliums in Belgien : Vortrag gehalten bei der XV. Generalversammlung des Evangelischen Bundes zu Hagen i. W. am 8. Oktober 1902

von Pastor Fritz

Multimodal Magnetic Resonance Imaging Data Fusion Reveals Distinct Patterns of Abnormal Brain Structure and Function in Catatonia

Catatonia is a nosologically unspecific syndrome, which subsumes a plethora of mostly complex affective, motor, and behavioral phenomena. Although catatonia frequently occurs in schizophrenia spectrum disorders (SSD), specific patterns of abnormal brain structure and function underlying catatonia are unclear at present. Here, we used a multivariate data fusion technique for multimodal magnetic resonance imaging (MRI) data to investigate patterns of aberrant intrinsic neural activity (INA) and gray matter volume (GMV) in SSD patients with and without catatonia. Resting-state functional MRI and structural MRI data were collected from 87 right-handed SSD patients. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). A multivariate analysis approach was used to examine co-altered patterns of INA and GMV. Following a categorical approach, we found predominantly frontothalamic and corticostriatal abnormalities in SSD patients with catatonia (NCRS total score 65 3; n = 24) when compared to SSD patients without catatonia (NCRS total score = 0; n = 22) matched for age, gender, education, and medication. Corticostriatal network was associated with NCRS affective scores. Following a dimensional approach, 33 SSD patients with catatonia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision were identified. NCRS behavioral scores were associated with a joint structural and functional system that predominantly included cerebellar and prefrontal/cortical motor regions. NCRS affective scores were associated with frontoparietal INA. This study provides novel neuromechanistic insights into catatonia in SSD suggesting co-altered structure/function-interactions in neural systems subserving coordinated visuospatial functions and motor behavior

Genotype×gender interaction analysis of common <i>GAD1</i> alleles associated with panic disorder.

*<p>rs4439928 did not meet the quality criteria in the replication sample.</p><p>Nominally significant results are shown in bold. Abbreviations: OR, odds ratio; p, p-value; SNP, single nucleotide polymorphism.</p

Associations of <i>GAD1</i> candidate SNPs with dimensional anxiety traits.

<p>Nominally significant results are shown in bold. Abbreviations: ACQ, Agoraphobic Cognitions Questionnaire; ASI, Anxiety Sensitivity Index; OR, odds ratio; p, p-value; SNP, single nucleotide polymorphism.</p

Gender-wise association of <i>GAD1</i> polymorphisms displaying gender-specific risk allele enrichment with panic disorder.

<p>Nominally significant results are shown in bold. Abbreviations: OR, odds ratio; p, p-value; SNP, single nucleotide polymorphism.</p