Arbeitsgedächtnisleistung und genotypische Varianz bei remittierter Depression : eine fMRT-Studie

Background: Cognitive impairments in the acute state of Major Depressive Disorder (MDD) are well documented both in behavioral as well as in fMRI studies (Nair et al. 1999, Harvey et al. 2004). Less well known is, whether cognitive abnormalities remain, when depressive symptoms improve. This study is one of only a few that examine remitted patients. Special interest lies on areas that were activated during working memory tasks in the acute state: The prefrontal cortex and the anterior cingulate cortex (Fossati et al. 2002). Today it is assumed that MDD has a multifactorial genesis. There is evidence that special genetic polymorphisms have influence on the formation of the disease. Candi-date genes are the following polymorphisms: 5HTTLPR (Hariri et al. 2002), 5HT1A (Domschke et al. 2006), MAO-A (Brummett et al. 2007) and COMT (O’Hara et al. 1998). We investigated whether neuronal changes are also verifiable in remission and if there is a connection between MDD and the candidate genes 5HTTLPR, 5HT1A, MAO-A and COMT. Methods and material: 28 fully remitted unipolar MDD patients and 28 healthy control subjects were recruited. They performed a verbal working memory task (0-, 1-, 2-back paradigm) during fMRI measurement. Afterwards a blood sample was taken for genetic analysis. The functional data was analyzed by SPM 5 software. Statistics were per-formed with SPSS 18.0 software. Results: All participants activated a fronto-parietal network during the n-back task and showed intensifying activation with increasing memory load. Patients compared to controls revealed stronger activation in the cingulate cortex. HTTLPR risk allele carriers also showed a hyperactivation in this area. This effect was consistent observing the control group only. The 5HT1A polymorphism did not have a significant effect on the neuronal activation. Analysis of the COMT and MAO-A polymorphisms were stopped because of the dissimilar allelic distribution within our study sample. Conclusion: Compared to patients in the acute episode remitted patients revealed as well a significantly stronger activated cingulate cortex, but no hyperactivation in the PFC. These findings indicate either a different speed of normalization in prefrontal and limbic cortices, or a preexisting neural abnormality or a persisting change. Control subjects with the HTTLPR risk alleles showed similar abnormalities. This suggests that these alleles are risk factors for MDD.