Bipolar Disorder: Scherk H

Pfennig A, Weikert B, Falkai P, Gotz T, Kopp I, Sasse J, Scherk H, Strech D, Bauer M. · Klinik und Poliklinik fur Psychiatrie und Psychotherapie, Universitatsklinik-kum Carl Gustav Carus, Technische Universitat Dresden. · Nervenarzt. · Pubmed #18389205 No free full text.

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Scherk H, Pajonk FG, Leucht S. · Department of Psychiatry and Psychotherapy, Georg-August University Goettingen, Goettingen, Germany. · Arch Gen Psychiatry. · Pubmed #17404121 links to  free full text

Abstract: CONTEXT: Recommendations of treatment guidelines concerning the use of second-generation antipsychotic (SGA) agents for acute mania vary substantially across committees or working groups. Meta-analyses addressing the use of SGAs in the treatment of acute mania are lacking. OBJECTIVE: To conduct a meta-analysis of the efficacy and safety of SGAs in the treatment of acute mania. DATA SOURCES: Randomized controlled trials comparing SGAs with placebo, first-generation antipsychotic drugs, or mood stabilizers (MSs) in the treatment of acute mania were searched for in the PsiTri and MEDLINE databases (last search: May 2006). STUDY SELECTION: The abstracts, titles, and index terms of studies were searched using the following key words: aripiprazole, amisulpride, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zotepine in conjunction with mania, manic, and bipolar. DATA EXTRACTION: Data on efficacy, global dropout, dropout due to adverse events, dropout due to inefficacy, weight gain, rate of somnolence, and extrapyramidal symptoms were extracted and combined in a meta-analysis. DATA SYNTHESIS: A total of 24 studies with 6187 patients were included. The SGAs were significantly more efficacious than placebo. The analysis demonstrated that adding antipsychotic agents to MS treatment was significantly more effective than treatment with MSs alone. The SGAs displayed efficacy comparable with that of MSs. Some SGAs seemed to induce more extrapyramidal symptoms than placebo. The SGAs were also associated with higher rates of somnolence than placebo. CONCLUSION: Currently available data suggest that combining SGAs and MSs is the most efficacious treatment of acute mania.

Scherk H, Reith W, Falkai P. · Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum des Saarlandes, Homburg/Saar. · Nervenarzt. · Pubmed #15118824 No free full text.

Abstract: The neurobiological basis of bipolar affective disorders is unknown. However, neuroanatomic circuits of mood regulation have been hypothesized. Neuroimaging revealed volumetric changes of specific brain structures in these circuits. The most prominent abnormality is enlargement of the amygdala. In addition there might be structural changes in the frontal lobe, cerebellum, and pituitary. The findings in bipolar disorder differ from those in unipolar depression and schizophrenia. For further identification of the neurobiological basis of bipolar disorders, structural neuroimaging combined with functional neuroimaging such as magnetic resonance spectroscopy, neuroendocrinological studies, and genetical analyses are required to subgroup patients with bipolar disorder by diagnostic, prognostic, and therapeutic criteria.

Scherk H, Gruber O, Menzel P, Schneider-Axmann T, Kemmer C, Usher J, Reith W, Meyer J, Falkai P. · AMEOS Klinikum Osnabrück, Knollstr. 31, 49088, Osnabrück, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #19224115 No free full text.

Abstract: BACKGROUND: Functional imaging studies in healthy individuals revealed an association between 5-HTTLPR genotype and neuronal activity in the amygdala. The aim of this study was firstly to investigate a possible overall impact of the 5-HTTLPR on amygdala volume in patients with bipolar disorder and healthy individuals and secondly to test a diagnosis specific influence of the 5-HTTLPR on amygdala volume. METHODS: We performed a region of interest analysis of amygdala volume in 37 patients with bipolar I disorder and 37 healthy control subjects. The 5-HTTLPR genotype of each proband was determined and the subjects were separated according to 5-HTTLPR genotype and for statistical analyses the groups SS and SL were combined and compared with the group LL. RESULTS: This study shows that carriers of the short allele (SL or SS) of the 5-HTTLPR polymorphism exhibit a relatively increased volume of the right amygdala compared to homozygous L-allele carriers irrespective of diagnosis status. However, further analyses with the factors genotype and diagnosis were not able to reproduce this result. CONCLUSIONS: The present findings are consistent with the view that the 5-HTTLPR polymorphism might modulate neuronal size or number in the amygdala. It would be worthwhile investigating the relationship between serotonin transporter function and amygdala function and volume in further studies.

Jamrozinski K, Gruber O, Kemmer C, Falkai P, Scherk H. · Department of Psychiatry and Psychotherapy, Georg-August-University Goettingen, Goettingen, Germany. · Acta Psychiatr Scand. · Pubmed #19076115 No free full text.

Abstract: OBJECTIVE: Meta-analytic findings support the hypothesis of specific neurocognitive deficits for bipolar patients in the domains of attention, processing speed, memory and executive functions. This study aims to show neurocognitive impairment in euthymic patients with bipolar I disorder compared with healthy controls while detailing the impact of medication side-effects or illness characteristics on neuropsychological test performance. METHOD: Forty euthymic patients with bipolar I disorder were compared with 40 healthy controls in a cross-sectional design. Clinical features and neuropsychological measures of IQ, psychomotor speed, verbal fluency, learning and memory, executive functions and attention were assessed. RESULTS: Patients without antipsychotic drug use did not differ significantly from healthy controls in any neuropsychological measure. Yet patients treated with antipsychotics showed significant underperformance in the domains of semantic fluency, verbal learning and recognition memory as well as executive functions related to planning abilities, even when clinical features were controlled for. CONCLUSION: The impact of antipsychotic medication needs to be further clarified for euthymic bipolar patients and should be considered when neuropsychological test performance is interpreted.

Scherk H, Backens M, Zill P, Schneider-Axmann T, Wobrock T, Usher J, Reith W, Falkai P, Möller HJ, Bondy B, Gruber O. · Department of Psychiatry and Psychotherapy, Georg-August-University Goettingen, von-Siebold-Str. 5, 37075, Göttingen, Germany. · J Neural Transm. · Pubmed #18726138 No free full text.

Abstract: The SNAP-25 gene is an integral part of the vesicle docking and fusion machinery that controls neurotransmitter release. Several post mortem studies revealed a reduction of SNAP-25 protein in the hippocampus of patients with schizophrenia and bipolar disorder (BD). Thirty-eight patients with schizophrenia, BD or obsessive-compulsive disorder and 17 healthy controls participated in the study. Proton magnetic resonance spectroscopy in left hippocampus was performed in each individual. Three single nucleotide polymorphisms (SNP) of the SNAP-25 gene were genotyped. Individuals with the homozygous CC genotype of the DdeI SNP presented a significantly higher ratio of N-acetyl-aspartate (NAA)/choline-containing compounds (Cho) in the left hippocampus compared to the group of individuals with the homozygous TT genotype. The SNAP-25 genotype may modulate synaptic plasticity and neurogenesis in the left hippocampus, and altered NAA/Cho ratio may be an indicator for this genetic modulation of neuronal function in the hippocampus.

Scherk H, Kemmer C, Usher J, Reith W, Falkai P, Gruber O. · Department of Psychiatry and Psychotherapy, Georg-August-University of Goettingen, von-Siebold-Str. 5, 37075, Goettingen, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #18347837 No free full text.

Abstract: BACKGROUND: Structural brain imaging is assumed to be a key method to elucidate the underlying neuropathology of bipolar disorder. However, magnetic resonance imaging studies using region of interest analysis and voxel-based morphometry (VBM) revealed quite inconsistent findings. Hence, there is no clear evidence so far for core regions of cortical or subcortical structural abnormalities in bipolar disorder. The aim of this study was to investigate grey and white matter volumes in a large sample of patients with bipolar I disorder. METHODS: Thirty-five patients with bipolar I disorder and 32 healthy controls matched with respect to gender, handedness and education participated in the study. MRI scanning was performed and an optimized VBM analysis was conducted. RESULTS: We could not observe any significant differences of grey or white matter volumes between patients with bipolar disorder and healthy control subjects. Additional analyses did not reveal significant correlations between grey or white matter volume with number of manic or depressive episodes, duration of illness, existence of psychotic symptoms, and treatment with lithium or antipsychotics. CONCLUSIONS: With this VBM study we were not able to identify core regions of structural abnormalities in bipolar disorder.

Scherk H, Backens M, Schneider-Axmann T, Kemmer C, Usher J, Reith W, Falkai P, Gruber O. · Department of Psychiatry and Psychotherapy, Georg-August-University Goettingen, Goettingen, Germany. · Acta Psychiatr Scand. · Pubmed #18205896 No free full text.

Abstract: OBJECTIVE: Subcortical regions such as hippocampus, thalamus and ventral putamen are assumed to be involved in the pathophysiology of mood regulation. Disturbed hippocampal neuronal function indicated by reduced N-acetyl-aspartate (NAA) levels in bipolar patients was shown by several studies. Results in thalamus and putamen are inconsistent. METHOD: N-acetyl-aspartate, choline (Cho), creatine (Cr) and myo-inositol (Ins) were measured in left hippocampus, left thalamus and left putamen using proton magnetic resonance spectroscopy in 13 euthymic patients with bipolar I disorder and 13 pairwise matched healthy control subjects. Metabolic ratios NAA/Cr, NAA/Cho, Cho/Cr and Ins/Cr were calculated. RESULTS: Patients with bipolar I disorder demonstrated significantly reduced NAA/Cr in the left hippocampus compared with healthy control subjects. No alterations were found in thalamus or putamen. CONCLUSION: We hypothesize that this NAA/Cr reduction might reflect neuronal dysfunction in the left hippocampus in patients with bipolar disorder.

Schulze TG, Müller DJ, Krauss H, Scherk H, Ohlraun S, Syagailo YV, Windemuth C, Neidt H, Grässle M, Papassotiropoulos A, Heun R, Nöthen MM, Maier W, Lesch KP, Rietschel M. · Department of Psychiatry, University of Bonn, Bonn, Germany. · Am J Med Genet. · Pubmed #11121185 No free full text.

Abstract: Various polymorphisms of the X-chromosomal monoamine oxidase A (MAO-A) gene were investigated for association with affective disorders. However, none of the studied variants could consistently be associated with either major depressive or bipolar affective disorder. Recently, a positive association between panic disorder and a novel functional repeat polymorphism in the MAO-A gene promoter, with the longer alleles being more active, was reported. Since monoaminergic neurotransmission is supposed to play an important role in affective disorders, we investigated a potential association of this polymorphism with major depressive illness in a sample of 146 unrelated patients of German descent and a control group of 101 individuals with a negative life history for affective disorders. Similarly to the recent findings in panic disorder, we observed a significantly increased frequency of genotypes containing only long alleles in female patients with recurrent major depression in comparison with age- and sex-matched controls. Thus, our data suggest that an excess of high-activity MAO-A gene promoter alleles resulting in an elevated MAO-A activity is a risk factor for major depressive disorder in females. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:801-803, 2000.