Harald Scherk

Universitätsmedizin Göttingen, Göttingen, Lower Saxony, Germany

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Publications (57)195.74 Total impact

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    ABSTRACT: Recent evidence suggests that deficits of working memory may be a promising neurocognitive endophenotype of bipolar affective disorder. However, little is known about the neurobiological correlates of these deficits. The aim of this study was to determine possible pathophysiological trait markers of bipolar disorder in neural circuits involved in working memory. Functional magnetic resonance imaging was performed in 18 euthymic bipolar patients and 18 matched healthy volunteers using two circuit-specific experimental tasks established by prior systematic neuroimaging studies of working memory. Both euthymic bipolar patients and healthy controls showed working memory-related brain activations that were highly consistent with findings from previous comparable neuroimaging studies in healthy subjects. While these patterns of brain activation were completely preserved in the bipolar patients, only the patients exhibited activation of the right amygdala during the articulatory rehearsal task. In the same task, functional activation in right frontal and intraparietal cortex and in the right cerebellum was significantly enhanced in the patients. These findings indicate that the right amygdala is pathologically activated in euthymic bipolar patients during performance of a circuit-specific working memory task (articulatory rehearsal). This pathophysiological abnormality appears to be a trait marker in bipolar disorders that can be observed even in the euthymic state and that seems to be largely independent of task performance and medication.
    Human Brain Mapping 01/2009; 31(1):115-25. DOI:10.1002/hbm.20849 · 6.92 Impact Factor
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    ABSTRACT: Prefrontal and anterior cingulate cortical regions are assumed to be involved in the pathophysiology of mood regulation. Reduced prefrontal and anterior cingulate function indicated by decreased N-acetyl-aspartate (NAA) levels in patients with bipolar disorder has been reported inconsistently. A positive correlation between lithium serum level and NAA concentrations has been found previously. The aim of this study was to re-investigate prefrontal and anterior cingulate neurochemistry in a sample of euthymic patients with bipolar I disorder. NAA, choline (Cho), creatine (Cr) and myo-inositol (Ins) in left dorsolateral prefrontal cortex and left anterior cingulate cortex were measured in 33 euthymic patients with bipolar I disorder and 29 healthy comparison subjects by using proton magnetic resonance spectroscopy ([(1)H]MRS). Metabolic ratios did not differ between patients with bipolar I disorder and comparison subjects in prefrontal and anterior cingulate cortex neither in the total sample nor in the pairwise matched sub-sample. We could not observe an association between lithium level and NAA ratios. Lithium treated patients demonstrated unchanged NAA or myo-inositol ratios compared to alternatively treated patients. In contrast to prior findings, we could not observe any metabolic alterations in euthymic patients with bipolar disorder.
    The World Journal of Biological Psychiatry 01/2009; 10(4):285-94. DOI:10.3109/15622970701472086 · 4.23 Impact Factor
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    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.
    Journal of Neural Transmission 09/2008; 115(11):1513-8. DOI:10.1007/s00702-008-0103-y · 2.87 Impact Factor
  • Der Nervenarzt 05/2008; 79(4):500-4. DOI:10.1007/s00115-008-2455-9 · 0.86 Impact Factor
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    ABSTRACT: 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. 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. 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. We hypothesize that this NAA/Cr reduction might reflect neuronal dysfunction in the left hippocampus in patients with bipolar disorder.
    Acta Psychiatrica Scandinavica 05/2008; 117(4):283-8. DOI:10.1111/j.1600-0447.2007.01142.x · 5.55 Impact Factor
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    ABSTRACT: 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. 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. 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. With this VBM study we were not able to identify core regions of structural abnormalities in bipolar disorder.
    European Archives of Psychiatry and Clinical Neuroscience 04/2008; 258(6):345-9. DOI:10.1007/s00406-007-0801-8 · 3.36 Impact Factor
  • European Psychiatry 04/2008; 23. DOI:10.1016/j.eurpsy.2008.01.796 · 3.21 Impact Factor
  • European Psychiatry 04/2008; 23. DOI:10.1016/j.eurpsy.2008.01.068 · 3.21 Impact Factor
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    ABSTRACT: The anterior limb of the internal capsule (ALIC), connecting cortical and subcortical structures, is involved in functional important circuits. To detect volumetric changes in ALIC, including the influence of genetic factors, a magnetic resonance imaging (MRI) study of families affected with schizophrenia was performed. The study sample comprised 22 family members with schizophrenia (FM-SZ), 34 family members without schizophrenia (FM-NSZ), and 43 control subjects. In addition to manual tracing of ALIC, subjects underwent proton magnetic resonance spectroscopy in the left prefrontal cortex, psychopathological rating, and neuropsychological assessment of frontal lobe function. Compared with controls, a significant reduction of right ALIC volume was seen in all family members (12%-16% reduction, p < .01) and a reduction of left ALIC volume in FM-NSZ (10% reduction, p = .028) was also observed. Both groups of family members showed a bilateral reduction in maximal cross sectional area of the ALIC. FM-SZ performed significantly worse on neurocognitive measures (Subject Ordered Pointing Task [SOPT] and Wisconsin Card Sorting Test), and performance correlated negatively with the ALIC volume (SOPT, r = -.6, p = .03). A reduced volume of ALIC in affected families supports the hypothesis of disturbed frontothalamic connectivity in schizophrenia and demonstrates functional relevance by an association with reduced neurocognitive performance.
    Biological psychiatry 02/2008; 63(1):65-71. DOI:10.1016/j.biopsych.2007.02.026 · 9.47 Impact Factor
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    ABSTRACT: Cognitive dysfunction is a common finding in schizophrenia. Nevertheless the specific pattern of neuropsychological impairment in schizophrenia compared to other severe mental illnesses has not been intensively studied. Twenty-four patients with schizophrenia belonging to different stages of the disease (11 first-episode patients, 13 patients with multiple episodes), 18 patients with bipolar disorder and 23 healthy control subjects underwent standardized neuropsychological assessment. Statistical analysis of covariance (ANCOVA) demonstrated that, compared to control subjects, patients with schizophrenia performed significantly worse in the trail-making test (P = 0.012), verbal fluency (category letter, P = 0.004), verbal learning/memory (P = 0.005), and the Wisconsin Card Sorting Test (WCST) (P = 0.004 for administered trials; P = 0.025 for perseverative responses, T value) indicating significant deficits in attention and psychomotor performance, and in particular in verbal working memory and cognitive flexibility for schizophrenic patients. A significant difference between schizophrenic and bipolar patients was found only in the WCST. Schizophrenic patients made significantly more perseverative responses (P = 0.002, ANCOVA), indicating a more pronounced and specific deficit in cognitive flexibility and frontally based executive function. In conclusion, these results may suggest a cognitive endophenotype in schizophrenia and underline the role of the prefrontal cortex in schizophrenic pathophysiology.
    The World Journal of Biological Psychiatry 02/2008; 10(4 Pt 2):442-51. DOI:10.1080/15622970701849986 · 4.23 Impact Factor
  • Schizophrenia Research 02/2008; 98:38-38. DOI:10.1016/j.schres.2007.12.081 · 4.43 Impact Factor
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    ABSTRACT: Dopaminergic activity in the brain is modulated by the dopamine transporter (DAT). Several lines of evidence suggest that a variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene (SLC6A3) influences its gene expression. The aim of this study was to determine whether the DAT1VNTR polymorphism alters the metabolic ratios NAA/Cho, NAA/Cr, Cho/Cr and Ins/Cr in the left dorsolateral prefrontal cortex, anterior cingulate cortex, and putamen in healthy subjects and psychiatric patients irrespective of clinical diagnosis. Sixty-four individuals (30 patients with bipolar disorder, 18 patients with obsessive-compulsive disorder, and 16 healthy subjects) participated in the study. The 3'-UTR VNTR polymorphism of DAT1 (SLC6A3) gene was genotyped in all individuals. (1)H-MRS was performed in the above-mentioned brain regions. The individuals with the homozygous DAT1 10-repeat genotype presented significantly higher ratios of NAA/Cho and NAA/Cr in the left putamen compared to the group of individuals with the 9/9-repeat or 9/10-repeat genotype. The VNTR polymorphism of the DAT1-gene modulates NAA/Cho and NAA/Cr in the left putamen independent of psychiatric diagnosis status. These results suggest an association of DAT1 VNTR polymorphism, dopaminergic activity, and neuronal function in putamen.
    The World Journal of Biological Psychiatry 11/2007; 10(4 Pt 2):524-30. DOI:10.1080/15622970701586349 · 4.23 Impact Factor
  • Pharmacopsychiatry 09/2007; 40(05). DOI:10.1055/s-2007-991691 · 2.17 Impact Factor
  • Pharmacopsychiatry 09/2007; 40(05). DOI:10.1055/s-2007-991786 · 2.17 Impact Factor
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    ABSTRACT: Prospective studies of children with ADHD have shown a high level of substance use disorder comorbidity, particularly when associated with social maladaptation and antisocial behavior. Conversely, studies of drug abusing participants and delinquents revealed a high prevalence of ADHD comorbidity. In this study 129 young male prison inmates were systematically examined for ADHD and substance use disorders. 64,3 % showed harmful alcohol consumption. 67,4 % fulfilled DSM-IV criteria for any drug abuse or dependence. 28,8 % of these participants were diagnosed with ADHD, combined type, other 52,1 % showed ADHD residual type. Opioid dependence was more common in delinquents without ADHD. Addicted delinquents with ADHD showed worse social environment and a higher degree of psychopathology, including externalizing and internalizing behavior, compared to addicted delinquents without ADHD. Neuroticism and conscientiousness ratings of the addicted ADHD group, but not of those without ADHD, differed from non-addicted delinquents. The results underline the need of adequate therapeutic programs for addicted young prison inmates considering ADHD comorbidity, which is associated with additional psychopathology and social problems.
    Fortschritte der Neurologie · Psychiatrie 06/2007; 75(5):285-92. · 0.76 Impact Factor
  • Fortschritte der Neurologie · Psychiatrie 05/2007; 75(5):285-292. DOI:10.1055/s-2005-919080 · 0.76 Impact Factor
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    ABSTRACT: 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. To conduct a meta-analysis of the efficacy and safety of SGAs in the treatment of acute mania. 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). 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 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. 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. Currently available data suggest that combining SGAs and MSs is the most efficacious treatment of acute mania.
    Archives of General Psychiatry 04/2007; 64(4):442-55. DOI:10.1001/archpsyc.64.4.442 · 13.75 Impact Factor
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    ABSTRACT: Gray matter reduction and ventricular enlargement belong to the best replicated findings in schizophrenia. Brain morphologic changes were also found in non-schizophrenic family members (FM). The intention of this study was to examine whether non-psychotic first-degree relatives reveal similar morphologic changes as schizophrenic patients and how state of genetic loading contribute to these abnormalities. Forty-nine schizophrenic patients, 71 non-schizophrenic FM and 48 control subjects took part in this volumetric MRI study. All subjects were between 18 and 59 years old. Dependent variables were gray matter, white matter and total cerebrospinal fluid (CSF) volume, determined by SPM99 segmentation algorithm. As an important part of CSF lateral ventricle volume was determined manually by removing surrounding CSF areas. In schizophrenic patients compared to controls and non-schizophrenic FM total CSF volumes and lateral ventricles were increased. Gray and, to a lesser degree, white matter volumes were decreased as well. For CSF, gray and white matter there was no significant difference between uni- and multiple affected families. CSF correlated significantly negative with gray matter (r=-0.78) and, less intensive, with white matter (r=-0.40). There were negative correlations between gray and white matter volume as well (r=-0.26). These correlations were not significantly different between the diagnostic groups. CSF enlargement and gray matter reductions in schizophrenic patients compared to controls and non-affected FM seem to be interdependent findings. However, this correlation is independent of the factor diagnosis and is therefore not specific for schizophrenia.
    Journal of Psychiatric Research 11/2006; 40(7):646-55. DOI:10.1016/j.jpsychires.2005.04.009 · 4.09 Impact Factor
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    ABSTRACT: We used proton magnetic resonance spectroscopy (1H MRS) to examine biochemical characteristics of the brain tissue in subjects at risk for schizophrenia. Nineteen participants fulfilling research criteria for an early (n=10) or a late (n=9) at-risk syndrome, 21 patients with full disease according to DSM IV and 31 healthy control subjects were included in the study. Single-voxel 1H MRS was performed in the left frontal lobe, the anterior cingulate gyrus and the left superior temporal lobe. Subjects were followed longitudinally to detect conversion to schizophrenia. We observed a significant reduction of the metabolic ratios NAA/Cr and NAA/Cho in the left frontal lobe and of NAA/Cr in the anterior cingulate gyrus in both at-risk groups and in the schizophrenic patients compared with healthy controls. Those at-risk subjects, who converted to schizophrenia within the observation period, had a higher Cho/Cr and a lower NAA/Cho ratio in the anterior cingulate gyrus compared with non-converters. NAA/Cr did not differ between converters and non-converters. Six at-risk subjects were taking antidepressants, two were taking antipsychotics. There was no difference in any metabolic ratio in any region between at-risk subjects with and without medication. We conclude that the reduction of the neuronal marker NAA in the left prefrontal lobe and the anterior cingulate gyrus may represent a vulnerability indicator for schizophrenia in at-risk subjects, while elevated Cho in the anterior cingulate gyrus may be a predictor for conversion from the prodromal state to the full disease.
    Schizophrenia Research 11/2006; 87(1-3):81-8. DOI:10.1016/j.schres.2006.06.011 · 4.43 Impact Factor

Publication Stats

1k Citations
195.74 Total Impact Points

Institutions

  • 2008–2013
    • Universitätsmedizin Göttingen
      • Department of Psychiatry and Psychotherapy
      Göttingen, Lower Saxony, Germany
  • 2012
    • Klinikum Osnabrück
      Osnabrück, Lower Saxony, Germany
  • 2007–2012
    • Georg-August-Universität Göttingen
      • Department of Clinical Psychology and Psychotherapy
      Göttingen, Lower Saxony, Germany
  • 2003–2010
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany
  • 2000–2006
    • University of Bonn
      • • Department of Neurobiology
      • • Institute of Human Genetics
      Bonn, North Rhine-Westphalia, Germany
  • 2004–2005
    • Universitätsklinikum des Saarlandes
      Homburg, Saarland, Germany