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The introduction of a German ("German") DRG system (G-DRG) by 01.01.2003 is to improve efficiency and transparency of hospital performance and to terminate the presently implausible variability of costs. For the first time world wide the attempt is undertaken to finance by a DRG-system--supplemented by certain additional charges and rebates--hospital costs completely. Institutions submitted to the psychiatry personnel regulation (PsychPV) are excluded. As the basis for the G-DRG-system self-administration authorities have selected the Australian AR-DRG system. The adjustment to German conditions is an extraordinary challenge: Compatibility must be achieved between the German classification of diagnoses (CGD-10) and procedures (OPS-301) and pertinent coding standards and the Australian classification systems. In the hospitals a unit cost accounting must be established, which at least approximately allows a strictly case-related calculation of actual costs. The relative cost weights of the DRGS and thus in the long run, their prices will be calculated on the basis the costs of a complete sample of cases of a representative subset of hospitals. The full-scale DRG system will confront with new risks. One is the transfer of treatment components and thus costs to Institutions not covered by the DRG system (e.g. rehabilitation hospitals, psychiatry). Thus, psychiatry will be at least indirectly involved. In addition, psychiatric patients will be directly affected if they are treated--possibly due to misallocation--in non-psychiatric institutions (e.g. internal medicine, neurology) or in psychosomatic departments not covered by the PsychPV.

Panic disorder like other neuropsychiatric disorders is believed to be caused by multiple psychosocial and biological factors. Several lines of evidence point to a role for the peptide neurotransmitter cholecystokinin in the pathogenesis of panic disorder. We therefore determined the allele and genotype frequencies of a single nucleotide polymorphism in the CCK gene (-36CT) and one CT repeat polymorphism in the CCK-B-receptor gene in a German panic disorder sample (n = 115 for CCK gene polymorphism, n = 111 for CCK-B-receptor polymorphism) and compared them with gender and age matched controls. The length of the polymorphic CT repeat alleles varies between 146 bp and 180 bp. We first analysed the results by a permutation test which provided evidence for heterogeneity between patients and controls (p=0.002). We then analysed the data as a di-allelic polymorphism with a short (146-162bp) and a long (164-180bp) allele and as a tetra-allelic polymorphism with 4 alleles (146-154bp, 156-162bp, 164-170bp, 172-180bp). In the di-allelic analysis as well as in the tetra-allelic analysis there was an excess of the longer allele (p = 0.001) or the two longer alleles (p = 0.041) respectively in patients with panic disorder. No difference between groups was observed for the -36CT polymorphism. Our findings are consistent with the notion that genetic variation in the CCK neurotransmitter system contributes to the pathogenesis of panic disorder.

The biochemical effects of antidepressant drugs generated the hypothesis of disturbances in the noradrenergic system in the pathogenesis of affective disorders. However, interference with the cholinergic system also yields psychotropic sequelae. Central cholinomimetics revealed antimanic properties as opposed to antidepressant effects of anticholinergics. Therefore, in extension of the catecholamine hypothesis and again based on the paradigm of pharmacological isomorphism, a cholinergic-adrenergic balance hypothesis has been suggested for affective disorders. This postulates a cholinergic predominance relative to noradrenergic activity in depression and the converse in mania. Although there are indications of inverse behavioural effects of cholinergic as opposed to catecholaminergic stimulation in man and animal, there is only few evidence at the neurophysiological and biochemical level in favour of the net effects depending on such a balance. However, only the direct demonstration of a biochemical defect can prove the balance hypothesis. More probably, interindividually different defects must be expected. They need not necessarily involve the synaptic signal transduction directly. Strategies and findings which might demonstrate biochemical disturbances are presented and discussed.

With the tricyclics, selective serotonin reuptake inhibitors (SSRIs) and other substances, we now have available a range of medications for the treatment of depression and other psychological disorders (e.g. anxiety, panic). Nevertheless, only some of the patients experience a remission of their depressive symptoms. The occurrence of side effects and the only modest level of effectiveness result in inadequate compliance on the part of the patient. With venlafaxine and duloxetine two representatives of the selective serotonin and noradrenaline reuptake inhibitor (SSNRI) class of antidepressants are now available. SSNRIs have a dual effect coupled with high selectivity. The present article the extent to which this particular action mechanism results in an improved clinical efficacy and tolerability profile of the SSNRIs, in particular in comparison with SSRIs.

Summary: Recurrent panic attacks, anticipatory anxiety and phobic avoidance characterise panic disorder. The influence of genetic factors on liability to the disease has been the object of several linkage and association studies and appears to relate to an oligo-or polygenic rather than a monogenic mode of inheritance. Recently, an excess of high activity monoamine oxidase A (MAO-A) gene promoter alleles was found in female patients with panic disorder. An analysis of possible synergistic effects of the MAO-A gene promoter variant and the short serotonin transporter (5-HTT) gene promoter variant in panic disorder was performed in a German and an Italian sample (combined panic disorder n = 144, combined controls n = 175). There was no significant difference in odds ratios, suggesting that the observed increase of genetic liability by the long MAO-A gene promoter allele is not modified by the 5-HTT gene promoter polymorphism.

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-HT2C receptor agonist. Two novel, adjacent polymorphisms [(GT)12-18 and (CT)4-5] in the 5'-regulatory region of the X-chromosomal 5-HT2C 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, chi (2) analysis). In the Italian sample, however, this observation could not be replicated (p = 0.54, chi (2) analysis). This argues against a major role for these promoter-associated 5-MT,, receptor gene length polymorphisms in the aetiopathogenesis of panic disorder.

A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene. In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for association with panic disorder in two independent samples (German sample, n = 80; Italian sample, n = 129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles. Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) were more active than allele 3. Among females of both the German and the Italian samples of panic disorder patients (combined, n = 209) the longer alleles (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df = 1, P = 0.001). Together with the observation that inhibition of monoamine oxidase A is clinically effective in the treatment of panic disorder these findings suggest that increased monoamine oxidase A activity is a risk factor for panic disorder in female patients.