Harald Scherk

Hippocampal plasticity in response to exercise in schizophrenia.

CONTEXT Hippocampal volume is lower than expected in patients with schizophrenia; however, whether this represents a fixed deficit is uncertain. Exercise is a stimulus to hippocampal plasticity. OBJECTIVE To determine whether hippocampal volume would increase with exercise in humans and whether this effect would be related to improved aerobic fitness. DESIGN Randomized controlled study. SETTING Patients attending a day hospital program or an outpatient clinic. PATIENTS OR OTHER PARTICIPANTS Male patients with chronic schizophrenia and matched healthy subjects. INTERVENTIONS Aerobic exercise training (cycling) and playing table football (control group) for a period of 3 months. MAIN OUTCOME MEASURES Magnetic resonance imaging of the hippocampus. Secondary outcome measures were magnetic resonance spectroscopy, neuropsychological (Rey Auditory Verbal Learning Test, Corsi block-tapping test), and clinical (Positive and Negative Syndrome Scale) features. RESULTS Following exercise training, relative hippocampal volume increased significantly in patients (12%) and healthy subjects (16%), with no change in the nonexercise group of patients (-1%). Changes in hippocampal volume in the exercise group were correlated with improvements in aerobic fitness measured by change in maximum oxygen consumption (r = 0.71; P = .003). In the schizophrenia exercise group (but not the controls), change in hippocampal volume was associated with a 35% increase in the N-acetylaspartate to creatine ratio in the hippocampus. Finally, improvement in test scores for short-term memory in the combined exercise and nonexercise schizophrenia group was correlated with change in hippocampal volume (r = 0.51; P < .05). CONCLUSION These results indicate that in both healthy subjects and patients with schizophrenia hippocampal volume is plastic in response to aerobic exercise.

Effects of antipsychotics on brain structure

Purpose of review This review highlights the recent findings of different effects of typical and atypical antipsychotics on brain structure. Recent findings Studies examining the effect of treatment with typical antipsychotics on brain structure revealed a significant increase in basal ganglia volumes and decreased grey matter volume in different cortical regions. These volume changes were detectable even after a 12-week treatment. In contrast to these results, treatment with atypical antipsychotics does not seem to change basal ganglia volumes in neuroleptic-naïve patients. Moreover, switching from typical to atypical antipsychotic treatment reduces the increased basal ganglia volume to normal values compared with healthy controls. Only the volumes of thalamus and cortical grey matter increased after atypical antipsychotic treatment. Summary Currently, there is growing evidence that atypical antipsychotics might ameliorate structural changes caused by the disease process underlying schizophrenia and effects of typical antipsychotics. Further studies have to investigate the mechanism leading to these varying effects on brain structure.

Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder

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.

Grey matter differences in bipolar disorder: a meta-analysis of voxel-based morphometry studies

Selvaraj S, Arnone D, Job D, Stanfield A, Farrow TFD, Nugent AC, Scherk H, Gruber O, Chen X, Sachdev PS, Dickstein DP, Malhi GS, Ha TH, Ha K, Phillips ML, McIntosh AM. Grey matter differences in bipolar disorder: a meta‐analysis of voxel‐based morphometry studies. Bipolar Disord 2012: 14: 135–145.

Grey matter differences in bipolar disorder

Selvaraj S, Arnone D, Job D, Stanfield A, Farrow TFD, Nugent AC, Scherk H, Gruber O, Chen X, Sachdev PS, Dickstein DP, Malhi GS, Ha TH, Ha K, Phillips ML, McIntosh AM. Grey matter differences in bipolar disorder: a meta‐analysis of voxel‐based morphometry studies. Bipolar Disord 2012: 14: 135–145.

Proton magnetic resonance spectroscopy in subjects at risk for schizophrenia

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.

Cognitive impairment of executive function as a core symptom of schizophrenia

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.

Neurocognitive functions in euthymic bipolar patients

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.

No change to grey and white matter volumes in bipolar I disorder patients

BackgroundStructural 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.MethodsThirty-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.ResultsWe 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.ConclusionsWith this VBM study we were not able to identify core regions of structural abnormalities in bipolar disorder.

Pathological amygdala activation during working memory performance: Evidence for a pathophysiological trait marker in bipolar affective disorder

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. Hum Brain Mapp, 2010.