Traute Demirakca

Diminished gray matter in the hippocampus of cannabis users: possible protective effects of cannabidiol.

BACKGROUND Chronic cannabis use has been associated with memory deficits and a volume reduction of the hippocampus, but none of the studies accounted for different effects of tetrahydrocannabinol (THC) and cannabidiol (CBD). METHODS Using a voxel based morphometry approach optimized for small subcortical structures (DARTEL) gray matter (GM) concentration and volume of the hippocampus were measured in 11 chronic recreational cannabis users and 13 healthy controls, and correlated with THC and CBD from hair analyses. GM volume was calculated by modulating VBM using Jacobian determinants derived from the spatial normalization. RESULTS Cannabis users showed lower GM volume located in a cluster of the right anterior hippocampus (P(uncorr)=0.002; effect size Cohens d=1.34). In a regression analysis an inverse correlation of the ratio THC/CBD with the volume of the right hippocampus (P(uncorr) p<0.001, Cohens d=3.43) was observed. Furthermore Cannabidiol correlated positively with GM concentration (unmodulated VBM data), but not with GM volume (modulated VBM) in the bilateral hippocampus (P=0.03 after correction for hippocampal volume; left hippocampus Cohens d=4.37 and right hippocampus 4.65). CONCLUSIONS Lower volume in the right hippocampus in chronic cannabis users was corroborated. Higher THC and lower CBD was associated with this volume reduction indicating neurotoxic effects of THC and neuroprotective effects of CBD. This confirms existing preclinical and clinical results. As a possible mechanism the influence of cannabinoids on hippocampal neurogenesis is suggested.

In vivo voxel based morphometry: Detection of increased hippocampal volume and decreased glutamate levels in exercising mice☆

Voluntary exercise has tremendous effects on adult hippocampal plasticity and metabolism and thus sculpts the hippocampal structure of mammals. High-field (1)H magnetic resonance (MR) investigations at 9.4 T of metabolic and structural changes can be performed non-invasively in the living rodent brain. Numerous molecular and cellular mechanisms mediating the effects of exercise on brain plasticity and behavior have been detected in vitro. However, in vivo attempts have been rare. In this work a method for voxel based morphometry (VBM) was developed with automatic tissue segmentation in mice using a 9.4 T animal scanner equipped with a (1)H-cryogenic coil. The thus increased signal to noise ratio enabled the acquisition of high resolution T2-weighted images of the mouse brain in vivo and the creation of group specific tissue class maps for the segmentation and normalization with SPM. The method was used together with hippocampal single voxel (1)H MR spectroscopy to assess the structural and metabolic differences in the mouse brain due to voluntary wheel running. A specific increase of hippocampal volume with a concomitant decrease of hippocampal glutamate levels in voluntary running mice was observed. An inverse correlation of hippocampal gray matter volume and glutamate concentration indicates a possible implication of the glutamatergic system for hippocampal volume.

Effects of Alcoholism and Continued Abstinence on Brain Volumes in Both Genders

BACKGROUND Alcohol abuse has detrimental effects on cerebral function, metabolism, and volume. Some of these effects were found to be at least partially reversible with continued abstinence. Furthermore, it has been reported that there are different effects of alcohol on brain volumes for women compared with men, but the results concerning the interaction between alcohol dependence and gender are inconsistent. With this study, we aimed to further investigate this question by examining the global gray matter (GM) and white matter (WM) changes as well as regional and local GM changes detected by voxel-based morphometry (VBM) in male and female alcoholic patients a few weeks after detoxification and the corresponding changes in a subgroup of these patients 3 months later. METHODS A total of 50 patients, consecutively admitted for alcohol withdrawal treatment, participated in this study and were followed up for at least 3 months into abstinence. High-resolution structural images were processed with SPM8 using an optimized VBM protocol. RESULTS Global cerebrospinal fluid (CSF) volume was increased and WM and GM volume decreased equally in male and female patients. A gender by diagnosis interaction was found neither for global nor for regional volumes or VBM data. VBM whole brain analysis yielded a significant GM volume loss in the patient group in the cingulate gyrus and the insula in both hemispheres. Region of interest analysis for the initial and 3 months follow-up scans yielded significant gains in regional volumes, particularly the cingulate gyrus and the insula in the group of abstinent patients, whereas no volume change at all is found in the patients who had relapsed. CONCLUSIONS Our study confirms widespread cerebral volume loss in recently detoxified alcoholics. The effects of alcohol dependence seem to have equally adverse effects on brain morphometry in males and females.

Functioning and neuronal viability of the anterior cingulate neurons following antipsychotic treatment: MR-spectroscopic imaging in chronic schizophrenia

Magnetic resonance spectroscopic imaging provides a non-invasive approach for testing the hypothesis that neuronal function can improve under atypical antipsychotic medication leading to improvement in cognitive function. We studied two groups of schizophrenic patients, one treated exclusively with typical neuroleptics, the other with atypical medications. 1H MR-spectroscopic imaging of the anterior cingulate gyrus was performed in all patients. Perseveration errors in the Wisconsin Card Sorting Test (WCST) served as an additional marker for cingulate gyrus function. Our results showed that N-acetylaspartate (NAA), a measure of neuronal function, was closely correlated with perseveration errors seen on the WCST. Patients treated with atypical medications had fewer errors on the WCST and higher NAA levels than those on typical medications, and there was a correlation between the time treated with atypical medication, higher NAA levels and better test performance. These results suggest that atypical antipsychotics modify the function of anterior cingulate neurons in a specific manner.

Differential effects of long-term treatment with clozapine or haloperidol on GABAA receptor binding and GAD67 expression.

One of the most consistent findings in postmortem studies of schizophrenia is increased GABAA receptor binding and reduced glutamic acid decarboxylase (GAD67) expression. Due to long-term antipsychotic treatment before death, these findings may reflect not only the consequences of schizophrenia but also medication effects. To differentiate between these options, we used an animal model and evaluated long-term effects of typical (haloperidol) and atypical (clozapine) antipsychotic drugs on the GABAergic system. A total of 33 adult male rats were treated in three cohorts over a period of 6 months. One cohort of 11 animals received clozapine (45 mg/kg/day), another one received haloperidol (1.5 mg/kg/day) and a third one received pH-adapted minimal concentrations of HCl in the drinking water. Receptor autoradiography of the GABAA receptor ([3H]-muscimol binding) and in situ hybridization in adjacent sections with 35S-labeled cRNA probes of the y-aminobutyric acid (GABA)-producing enzyme, GAD67, was performed. While haloperidol increased GABAA receptor binding in striatum and nucleus accumbens (NA), it suppressed GABAA receptor binding in temporal (TEMPC) and parietal (PARC) cortex. Clozapine induced GABAA receptor binding in infralimbic cortex (ILC) and similar like haloperidol in anterior cingulate cortex (ACC), two regions of the limbic cortex. In addition, either drug increased gene expression of GAD67. It is concluded that antipsychotic drugs differentially alter the GABAergic system, strongly suggesting that drug effects are partially responsible for the up-regulation of GABAA receptor binding in certain brain regions as observed in postmortem brains of schizophrenic patients. However, the reduced GAD67 expression seen in postmortem brains does not appear to reflect drug effects, since our animal model demonstrated increased gene expression.

Abnormal amygdala activation profile in pedophilia

Despite considerable public interest research in neurobiological correlates of pedophilia is scarce. Since amygdala activation is central for emotional valuation, arousal, and salience, we investigated the activation profile of this structure in 10 male subjects with pedophilia (exclusively attracted to boys), all convicted sex-offenders and sentenced to forensic psychiatric treatment along with ten male heterosexual matched controls. We used a sexually non-explicit functional Magnetic Resonance Imaging (fMRI) paradigm with images of men, women, boys or girls randomly embedded in neutral target/non-target geometrical symbols. We applied statistical parametric mapping (SPM2) and SPSS 14 for image processing and analysis. While controls activated significantly less to pictures of children compared to adults, the activation profile was reversed in subjects with pedophilia, who exhibited significantly more activation to children than adults. The highest activation was observed for boys in the patient group, and for women in control participants. Our data show enhanced activation to children’s pictures even in an incidental context and suggest the provocative hypothesis that a normally present mechanism for reduced emotional arousal for children relative to adults is reversed in pedophilia, suggesting a neural substrate associated with deviant sexual preference in this condition. More extensive research in this field would be of benefit for both the victims and the offenders.Despite considerable public interest research in neurobiological correlates of pedophilia is scarce. Since amygdala activation is central for emotional valuation, arousal, and salience, we investigated the activation profile of this structure in 10 male subjects with pedophilia (exclusively attracted to boys), all convicted sex-offenders and sentenced to forensic psychiatric treatment along with ten male heterosexual matched controls. We used a sexually non-explicit functional Magnetic Resonance Imaging (fMRI) paradigm with images of men, women, boys or girls randomly embedded in neutral target/non-target geometrical symbols. We applied statistical parametric mapping (SPM2) and SPSS 14 for image processing and analysis. While controls activated significantly less to pictures of children compared to adults, the activation profile was reversed in subjects with pedophilia, who exhibited significantly more activation to children than adults. The highest activation was observed for boys in the patient group, and for women in control participants. Our data show enhanced activation to children’s pictures even in an incidental context and suggest the provocative hypothesis that a normally present mechanism for reduced emotional arousal for children relative to adults is reversed in pedophilia, suggesting a neural substrate associated with deviant sexual preference in this condition. More extensive research in this field would be of benefit for both the victims and the offenders.

Rapid Partial Regeneration of Brain Volume During the First 14 Days of Abstinence from Alcohol

BACKGROUND Chronic alcohol abuse leads to severe damage of the nervous system, including a change in cerebral metabolism and brain morphology. Global volume reductions of gray matter (GM) and white matter and an increase in cerebrospinal fluid (CSF) occur after severe alcohol consumption, but abstinent alcoholics also demonstrate a brain volume recovery. The aim of this study was to investigate whether volumetric amelioration takes place already within the first 2 weeks of abstinence. METHODS All 49 alcohol-dependent patients included in this study were scanned within the first 24 hours of detoxification and after 2 weeks of supervised abstinence. Amelioration of volumetric brain loss in alcohol-dependent patients has been investigated, and brain volumes have been compared with 55 healthy control subjects using whole-brain segmentation and a voxel-based morphometric approach. RESULTS On the first day of abstinence, the global CSF volume was larger and the GM volume was smaller in alcohol-dependent patients compared with healthy controls. The largest clusters with significant volumetric differences were in the cingulate gyrus, precentral and middle frontal gyrus, cerebellum, and insula. Already after 2 weeks of abstinence, a significant albeit partial recovery of GM volume occurred in several brain regions. CONCLUSIONS Our results show that recovery of GM volume in alcohol-dependent patients starts within a few days after detoxification but varies between brain regions. This suggests that the general ability to recover and the rate as well as onset of the recovery diverges for different brain regions.

Disturbance in the neural circuitry underlying positive emotional processing in post-traumatic stress disorder (PTSD) : An fMRI study

AbstractThis study was designed to investigate the circuitry underlying movie–induced positive emotional processing in subjects with chronic PTSD. Ten male subjects with chronic PTSD and ten matched controls were studied. In an fMRI–paradigm a sequence of a wellknown Walt Disney cartoon with positive emotional valence was shown. PTSD subjects showed an increased activation in the right posterior temporal, precentral and superior frontal cortex. Controls recruited more emotion–related regions bilateral in the temporal pole and areas of the left fusiform and parahippocampal gyrus. This pilot study is the first to reveal alterations in the processing of positive emotions in PTSD possibly reflecting a neuronal correlate of the symptom of emotional numbness in PTSD.

Voxel-Based Morphometry in Women with Borderline Personality Disorder with and without Comorbid Posttraumatic Stress Disorder

Patients with Borderline Personality Disorder (BPD) showed reduced volume of amygdala and hippocampus, but similar findings are evident in Posttraumatic Stress Disorder (PTSD). Applying voxel-based morphometry (VBM) in a larger cohort of patients with BPD, we sought to extend earlier findings of volume abnormalities in limbic regions and to evaluate the influence of co-occurring PTSD in BPD patients. We used voxel-based morphometry to study gray matter volume (GMV) in 60 healthy controls (HC) and 60 patients with BPD. Subgroup analyses on 53 patients concerning the role of co-occurring PTSD were conducted. Additionally, regression analyses were calculated to assess the relation between borderline symptom severity as well as dissociative experiences and GMV. Differences in local GMV between patients with BPD and HC were observed in the amygdale and hippocampus as well as in the fusiform and cingulate gyrus. Co-occurring PTSD was accompanied by increased GMV in the superior temporal gyrus and dorsolateral prefrontal cortex. Independent of co-occurring PTSD, severity of BPD symptoms predicted smaller GMV in the amygdala and dorsal ACC. Dissociation was positively related to GMV in the middle temporal gyrus. We could replicate earlier findings of diminished limbic GMV in patients with BPD and additionally show that patients with co-morbid PTSD feature increased GMV in prefrontal regions associated with cognitive control.

Alcohol consumption significantly influences the MR signal of frontal choline-containing compounds

The aim of this work was to evaluate the relationship between the amount of alcohol consumption of a group of social drinkers and the magnetic resonance spectroscopy signal of choline-containing compounds (Cho) in the frontal lobe. Two independent long echo (TE = 135 ms) (1)H MRSI studies, the first comprising 24 subjects with very low alcohol consumption, the second 18 subjects with a more widespread alcohol consumption were conducted. Significant correlations of Cho measures from frontal white matter and from the anterior cingulate gyrus with alcohol consumption in the last 90 days prior to the MR examination were found. Age, gender, and smoking did not show significant effects on the metabolite measures. Partialling out the effect of the voxel white matter content did not change the correlation of choline measures with alcohol consumption. The main conclusion from the repeated finding of a positive correlation of alcohol consumption and frontal Cho signals is that monitoring for alcohol consumption is mandatory in MRS studies where pathology depended Cho changes are hypothesized.