Jürgen Deckert

Adenosine A_2A receptors have been implicated in the pathophysiology of schizophrenia by clinical, anatomical, biochemical and genetic studies. We hypothesized that a genetically determined low number of adenosine A_2A receptors could be a vulnerability factor for the development of the disease. The density of adenosine A_2A receptors was investigated in human postmortem striatum of patients with schizophrenia (n = 9) and matched controls (n = 9) using [³H)CGS 21680 as a radioligand probe. The maximum number of binding sites (B_max) was 70% higher in patients with schizophrenia than in matched controls (609.4 ± 259.1 vs 354.0 ± 156.4 fmol/mg protein, p=0.04). No significant difference could be discerned for the affinity of caffeine for adenosine A_2A receptors between patients and controls. The increase in receptor density correlated with the dose of antipsychotic medication in chlorpromazine equivalents (r²=0.61, p = 0.014). We failed to provide evidence for a genetically determined reduction of adenosine A_2A receptors in schizophrenia. Instead, consistent with findings from animal experiments, our observation supports a role of adenosine A_2A receptors in the molecular effects of antipsychotic drugs.

Candidate genes for association studies in panic disorder are often selected on the basis of molecular mechanisms of drugs utilized in challenge tests such as m-chlorophenylpiperazine (mCPP), a non-selective 5-HT_2C receptor agonist. Two novel, adjacent polymorphisms [(GT)12–18 and (CT)4–5] in the 5Ȳ-reory region of the X-chromosomal 5-HT_2C receptor gene have recently been reported. We determined the allele frequency of long vs. short polymorphism haplotypes in a German and an Italian sample (combined n = 211) of panic disorder patients (DSM-III-R) and compared it with allele frequencies in two ethnically matched control samples (combined n = 226). In the German sample, a comparison of female genotypes containing the short haplotype vs. female genotypes containing only long haplotypes showed a significant difference (p = 0.01, ϰ² analysis). In the Italian sample, however, this observation could not be replicated (p = 0.54, ϰ² analysis). This argues against a major role for these promoter-associated 5-HT_2C receptor gene length polymorphisms in the aetiopathogenesis of panic disorder.

Panic disorder is an anxiety disorder with an estimated heritability of up to 48%. Pharmacological and genetic studies suggest that genes coding for p