Agoraphobia.

Panic disorder is an anxiety disorder with an estimated heritability of 48%. Variation in the gene of the nuclear transcription factor "cAMP-responsive element modulator" (CREM) might contribute to its pathogenesis. CREM knock-out mice exhibit significantly less anxiety behavior than wild-type mice and the alternative CREM gene product "inducible cAMP early repressor" (ICER) plays a pivotal role in the hypothalamo-pituitary-adrenal (HPA) axis, which is disturbed in panic disorder. We characterized the genomic organization of the human CREM gene and performed a systematic mutation screening by means of single stranded conformational analysis (SSCA) in a sample of 40 German patients with panic disorder (DSM-III-R). Four novel single nucleotide polymorphisms in CREM promoters P 1 and P 4, one trinucleotide (ATT)-repeat polymorphism in CREM promoter P 2-generating the ICER isoform-and a rare amino acid substitution in CREM exon glut 2 were identified. Association analysis in an extended sample of German patients (n = 88) revealed a significant excess of the shorter CREM P 2 promoter eight-repeat trinucleotide allele and of genotypes containing the eight-repeat trinucleotide allele in panic disorder (P = 0.02), in particular in panic disorder without agoraphobia (P = 0.001). A replication study in independent Italian (n = 76) and Spanish (n = 62) samples, however, failed to confirm this observation. This suggests that the CREM P 2 promoter trinucleotide polymorphism is not a major susceptibility factor in the pathogenesis of panic disorder. Functional analysis of the observed CREM P 2 promoter polymorphism as well as studies in independent panic disorder samples are necessary.

Agoraphobia↗

PubMed2003

Review of the long-term effectiveness of cognitive behavioral therapy compared to medications in panic disorder.

Panic disorder is a recurrent and disabling illness. It is believed that Cognitive Behavioral Therapy (CBT) has a long-term protective effect for this disorder. This would offer CBT considerable advantage over medication management of panic disorder, as patients often relapse when they are tapered off their medications. This is a review of the literature about the long-term effectiveness of CBT. We searched for follow-up studies of panic disorder using CBT. Of the 78 citations produced in the initial search, most had major methodological flaws, including ignoring losses to follow-up, not accounting for interval treatment, and unclear reporting. Three papers met strict methodological criteria, and two of these demonstrated a modest protective effect of CBT in panic disorder patients. We make recommendations for well-designed studies involving comparisons of medications and cognitive behavior therapy.

Agoraphobia↗