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Objective: There is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide sequence of NPY (Leu7Pro variation) was previously found to protect against depression. Our study aimed at replicating this association in a large Danish population with major depression. Method: Leu7Pro was studied in a sample of depressed patients and ethnically matched controls, as well as psychiatric disease controls with schizophrenia. Possible functional consequences of Leu7Pro were explored in vitro. Results: In contrast to previous studies, Pro7 appeared to be a risk allele for depression, being significantly more frequent in the depression sample (5.5%, n = 593; p = 0.009; odds ratio, OR: 1.46) as compared to ethnically matched controls (3.8%, n = 2912), while schizophrenia patients (4.1%, n = 503) did not differ. In vitro, the Pro7 substitution appeared to be associated with reduced levels of NPY without affecting its mRNA level. Conclusion: The Leu7Pro variation may increase the risk of major depression, possibly by affecting the biosynthesis of NPY. Pernille

Udgivelsesdato: 2010, OBJECTIVES: Panic disorder (PD) is a common psychiatric disease occurring more frequently in women than men. Multiple common and/or rare variants in the genome contribute to the complex etiology of the disorder. The neuropeptide cholecystokinin (CCK) and its receptors (the CCK system) have been suggested to be involved in the pathogenesis of PD. METHODS: We examined the promoter, exon, and exon-intron boundaries of the genes encoding CCK and its receptors (CCKAR and CCKBR) for variations in 187 patients with PD and 277 screened control individuals. Up to 1342 additional healthy population controls were examined for some of the variations. One CCK gene intron variation was analyzed for alternative splicing using an exon-trapping assay. RESULTS: The promoter variant (-36C > T; rs1799923) and an intron 1 polymorphism (IVS1-7C > G; rs754635) in the CCK gene were found to protect against PD (P<0.05). The intron 1 variation did not seem to alter the splicing of the gene. None of the other variations found were associated with PD, but a 2-marker haplotype (rs1800855/rs1800857) in the CCKAR gene protected women against PD (P=0.004). In addition, we found two novel rare missense variations in the CCKBR gene (Lys329Asn and Pro446Leu) in two and one patient, respectively. CONCLUSION: The results suggest that the CCK system may play a role in the pathogenesis of PD, with susceptibility alleles both protecting and contributing to the disease. Both common and rare variants seem to be involved. The involvement of the CCK system may also contribute to the increased prevalence of PD in women.

Udgivelsesdato: 2008/4

Udgivelsesdato: 2008

Udgivelsesdato: 2006/6

SUMMARY: We describe three cases of nonconvulsive status epilepticus induced by electroconvulsive therapy (ECT). Nonconvulsive status epilepticus is an important differential diagnosis in patients who develop prolonged confusion after ECT. The present cases exemplify the difficulty in defining the diagnosis on the basis of the clinical manifestations. The application of electroencephalography is recommended in monitoring patients with prolonged confusion following ECT. Concurrent drug therapy and ECT is discussed.

The generation of new neurons in the adult mammalian brain has been documented in numerous recent reports. Studies undertaken so far indicate that adult hippocampal neurogenesis is related in a number of ways to hippocampal function.Here, we report that subjecting adult rats to fractionated brain irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21 days after irradiation, the animals with blocked neurogenesis performed poorer than controls in a hippocampus-dependent place-recognition task, indicating that the presence of newly generated neurons may be necessary for the normal function of this brain area. The animals were never impaired in a hippocampus-independent object-recognition task. These results are in line with other reports documenting the functional significance of newly generated neurons in this region. As our irradiation procedure models prophylactic cranial irradiation used in the treatment of different cancers, we suggest that blocked neurogenesis contributes to the reported deleterious side effects of this treatment, consisting of memory impairment, dysphoria and lethargy.

Parkinson's disease; major depression; registries