Biomedical subjects

Jürgen Gallinat

Publications and source records attributed to Jürgen Gallinat.

At least 19 recordsLinked to original sources

PubMed2007

Abnormal hippocampal neurochemistry in smokers: evidence from proton magnetic resonance spectroscopy at 3 T.

OBJECTIVE: In animals, nicotine, the primary psychoactive constituent of tobacco smoke, reduces neurogenesis and increases cell loss in both hippocampus and cortex. Accordingly, tobacco smoking has been linked to reduced performance on cognitive paradigms requiring attention and working memory in humans. However, few prior studies have tested for evidence of structural brain alterations in human tobacco smokers. In this study, proton magnetic resonance spectroscopy was used to assess the effects of chronic smoking on neuronal integrity of the hippocampus and anterior cingulate cortex (ACC). METHODS: Absolute concentrations of N-acetylaspartate, total choline (tCho), and total creatine were measured in the left hippocampus and ACC in 13 chronic tobacco smokers and 13 nonsmokers matched for age, sex, and education. RESULTS: The N-acetylaspartate concentration was significantly reduced in smokers relative to nonsmokers in the left hippocampus but not in the ACC. There were no group differences in the tCho and total creatine concentrations in either voxel. However, ACC tCho concentration was positively correlated with magnitude of lifetime exposure to tobacco smoke (pack-years). CONCLUSION: The results are consistent with prior observations of hippocampal neuronal damage in rodents receiving nicotine and working memory deficits in human tobacco smokers. The positive relationship between tCho and lifetime tobacco exposure suggests that a component of tobacco smoke, presumably nicotine, may increase cortical membrane turnover or modify cell density. Together, these results add to growing evidence that nicotine exerts neurotoxic effects in human brain, although an a priori nature of the findings cannot be ruled out.

Adult↗

PubMed2007

Genetic variations of the NR3A subunit of the NMDA receptor modulate prefrontal cerebral activity in humans.

INTRODUCTION: Recently, a novel N-methyl-D-aspartate (NMDA) receptor subunit, NR3A, has been discovered in the brain. This subunit decreases NMDA receptor activity by modulating the calcium permeability of the receptor channel and current density in cortical cells. Because the NR3A is expressed in the human prefrontal cortex, we hypothesized that genetic variations of the NR3A subunit modulate prefrontal activation. METHODS: Electromagnetic activity during selective attention (auditory oddball task with target processing) was measured in 281 healthy subjects. Genotyping of a missense variation (rs10989591, Val362Met) of the NR3A gene was performed. RESULTS: Individuals carrying Val/Val genotype showed significantly reduced frontal P300 amplitudes compared with Met/Met subjects. Subsequent low-resolution electromagnetic source analysis revealed that this group difference is likely caused by reduced activation in the inferior frontal gyrus. CONCLUSIONS: It was shown for the first time that the genetic constitution of the subunit composition of NMDA receptor regulation might be relevant for prefrontal information processing in humans. The results underline the pivotal role of glutamate in frontal lobe function and indicate that the NR3A subunit could be a plausible candidate gene for diseases with prefrontal dysfunctions.

Adult↗

PubMed2006

Association of the met66 allele of brain-derived neurotrophic factor (BDNF) with smoking.

RATIONALE: It has been suggested that a susceptibility locus near the gene encoding the brain-derived neurotrophic factor (BDNF) contributes to individual differences in human addiction vulnerability. BDNF modulates several behaviors that are associated with addictive drugs, and upregulation of BDNF was found to be associated with several drugs of abuse such as amphetamine, cocaine, and nicotine. In this study, we addressed the question if a common BDNF missense variation (Val66Met) influences the risk for smoking behavior in otherwise healthy human volunteers. MATERIALS AND METHODS: In total, 320 healthy unrelated volunteers (155 male, 165 female, mean age: 38.4 +/- 14.1 years) consisting of 43.3% never smokers, 20.9% former smokers, and 35.6% current smokers were investigated. RESULTS: The frequency of both Met/Met genotype and Met allele was significantly increased in current and in former smokers when compared to never smokers (chi (2) = 10.856, df = 2, p = 0.004 and chi (2) = 4.350, df = 1, p = 0.045, respectively). CONCLUSIONS: Our results suggest that humans who carry the Met allele of the BDNF missense polymorphism might be more vulnerable to initiate and also maintain smoking.

Adult↗

PubMed2006

Variations in the vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) are associated with bipolar i disorder.

The vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) maps to the shared bipolar disorder (BPD)/schizophrenia (SZ) susceptibility locus on chromosome 8p21. Vesicular monoamine transporters are involved in transport of monoamine neurotransmitters which have been postulated to play a relevant role in the etiology of BPD and/or SZ. Variations in the VMAT1 gene might affect transporter function and/or expression and might be involved in the etiology of BPD and/or SZ. Genotypes of 585 patients with BPD type I and 563 control subjects were obtained for three missense single nucleotide polymorphisms (SNPs) (Thr4Pro, Thr98Ser, Thr136Ile) and four non-coding SNPs (rs988713, rs2279709, rs3735835, rs1497020). All cases and controls were of European descent. Allele frequencies differed significantly for the potential functional polymorphism Thr136Ser between BPD patients and controls (p=0.003; df=1; OR=1.34; 95% CI: 1.11-1.62). Polymorphisms in the promoter region (rs988713: p=0.005, df=1; OR=1.31; 95% CI: 1.09-1.59) and intron 8 (rs2279709: p=0.039, df=1; OR=0.84; 95% CI: 0.71-0.99) were also associated with disease. Expression analysis confirmed that VMAT1 is expressed in human brain at the mRNA and protein level. Results suggest that variations in the VMAT1 gene may confer susceptibility to BPD in patients of European descent. Additional studies are necessary to confirm this effect and to elucidate the role of VMAT1 in central nervous system physiology.

Adult↗

PubMed2006

Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics.

RATIONALE: Clinical studies in patients with schizophrenia suggest that atypical neuroleptics are more effective than typical neuroleptics in reducing negative symptoms including apathy and anhedonia. Dysfunction of the dopaminergic reward system may contribute to negative symptoms in schizophrenia. OBJECTIVE: We used functional magnetic resonance imaging to assess the blood oxygen level dependency response in the ventral striatum of medicated schizophrenics and healthy control subjects during reward anticipation. METHODS: Twenty schizophrenics [ten medicated with typical (e.g., haloperidol) and ten with atypical (e.g., olanzapine and risperidone) neuroleptics] and ten age-matched healthy volunteers participated in an incentive monetary delay task in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or no consequence. RESULTS: Healthy volunteers and schizophrenics treated with atypical neuroleptics showed ventral striatal activation in response to reward-indicating cues, but schizophrenics treated with typical neuroleptics did not. In patients treated with typical neuroleptics, decrease in activation of the left ventral striatum was correlated with the severity of negative symptoms. CONCLUSIONS: Failure to activate the ventral striatum during reward anticipation was previously associated with the severity of negative symptoms in schizophrenia and was also found in schizophrenics treated with typical neuroleptics in this study. Significant blunting of ventral striatal activation was not observed in patients treated with atypical neuroleptics, which may reflect the improved efficacy of these drugs in treating negative symptoms.

Adult↗

PubMed2006

Persistent dysfunctional frontal lobe activation in former smokers.

OBJECTIVE: Chronic smoking and nicotine exposure are accompanied by impaired cognitive task performance, modulated cerebral activity in brain imaging studies, and neuritic damage in experimental animals. The profile of the described dysfunctions matches frontal lobe circuits which also play a role in reward processing and reinforcement behavior. However, it is largely unknown if cerebral dysfunctions are reversible or persist during long term abstinence. MATERIALS AND METHODS: Cortical activation during auditory target processing (oddball task, P300 component) was recorded with 32-channel EEG in 247 healthy subjects consisting of 84 smokers, 53 former smokers (mean time of abstinence 11.9 years), and 110 never smokers. RESULTS: Both current smokers and former smokers exhibited significantly diminished P300 amplitudes (Cz, Pz) relative to never smokers. Neuroelectric source analysis (low resolution brain electromagnetic tomography) revealed a hypoactivation of the anterior cingulate, orbitofrontal, and prefrontal cortex in smokers compared to never smokers. A similar profile of hypoactivation was observed in former smokers. CONCLUSION: For the first time, evidence is provided that dysfunctional activation of frontal lobe networks in smokers is also present in long term abstainers.

Adult↗

PubMed2006

Is the loudness dependence of auditory evoked potentials modulated by the selective serotonin reuptake inhibitor citalopram in healthy subjects?

The loudness dependence of auditory evoked potentials (LDAEP) has been discussed as a non-invasive in vivo marker of central serotonergic function. Evidence for this has been found in animal studies, but studies in humans provide less consistent results. In this study, the relationship between LDAEP and directly modulated central serotonergic activity in healthy subjects was investigated. In a single-blind cross-over design, the LDAEP of female participants (age: 24.0 +/- 2.3 years) was measured under two conditions: (1) infusion of 20 mg citalopram diluted in 250 ml 0.9% saline and (2) infusion of 250 ml 0.9% saline as placebo. LDAEP was measured at five different time points before, during and up to 60 min after drug/placebo administration and dipole source analysis was performed. The increase of the central serotonin activity in response to citalopram was not accompanied by a significant change of the LDAEP compared to the placebo condition. The result underlines that the acceptance of LDAEP as a marker of central serotonergic function still needs further discussion.

Acoustic Stimulation↗

PubMed2006

The vulnerability to alcohol and substance abuse in individuals diagnosed with schizophrenia.

Individuals with schizophrenia are at increased risk for developing substance abuse disorders. Here, we consider factors that might elevate their risk for substance abuse. The tendency among schizophrenic individuals to overvalue drug-like rewards and to devalue the potential negative consequences of substance abuse may be a contributing factor to their substance abuse risk. This bias, which may partly reflect the convergence of glutamatergic and dopaminergic input to the limbic striatum, also may contribute to disadvantageous decision-making and other impulsive behavior. This propensity to seek drug-like rewards is augmented by alterations in nicotinic cholinergic, GABAergic, glutamatergic, and cannabinnoid receptor function associated with schizophrenia that increase the abuse liability of low doses of nicotine, ethanol, and perhaps cannabis, and augment the dysphoric effects of higher doses of ethanol and cannabis. The distortions in reward processing and altered response to substances of abuse also increase the likelihood that individuals with schizophrenia will self-medicate their subjective distress with abused substances. The focus on distinctions between motivation and reward with respect to substance abuse risk by schizophrenic patients suggests a need for a reconsideration of the construct of "negative symptoms" for this dually-diagnosed patient group.

Alcoholism↗

PubMed2006

Smoking and structural brain deficits: a volumetric MR investigation.

Growing evidence from animal studies indicates brain-damaging properties of nicotine exposure. Investigations in humans found a wide range of functional cerebral effects of nicotine and cigarette smoking, but studies focusing on brain damage are sparse. In 22 smokers and 23 never-smokers possible differences of the cerebral structures were investigated using magnetic resonance imaging and voxel-based morphometry. Significantly smaller grey matter volume and lower grey matter density (P = 0.05, corrected) were observed in the frontal regions (anterior cingulate, prefrontal and orbitofrontal cortex), the occipital lobe and the temporal lobe including parahippocampal gyrus, in smokers than in never-smokers. Group differences of either grey matter volume or grey matter density were also found in the thalamus, cerebellum and substantia nigra, among other regions. Smokers did not show greater volumes than never-smokers in any cerebral region. Magnitude of lifetime exposure to tobacco smoke (pack-years) was inversely correlated with volume of frontal and temporal lobes and cerebellum (P = 0.001, uncorrected). The data indicate structural deficits of several cortical and subcortical regions in smokers relative to never-smokers. The topographic profile of the group differences show some similarities to brain networks known to mediate drug reinforcement, attention and working memory processing. The present findings may explain in part the frequently reported cognitive dysfunctions in chronic cigarette consumers.

Adult↗

PubMed2005

Examining the gateway to the limbic system with diffusion tensor imaging: the perforant pathway in dementia.

Current treatments for Alzheimer's disease (AD) are only able to slow the progression of mental deterioration, making early and reliable diagnosis an essential part of any promising therapeutic strategy. In the initial stages of AD, the first neuropathological alterations occur in the perforant pathway (PP), a large neuronal fiber tract located at the entrance to the limbic system. However, to date, there is no sensitive diagnostic tool for performing in vivo assessments of this structure. In the present bimodal magnetic resonance imaging (MRI) study, we examined 10 elderly controls, 10 subjects suffering from mild cognitive impairment (MCI), and 10 AD patients in order to evaluate the sensitivity of diffusion tensor imaging (DTI), a new MRI technique, for detecting changes in the PP. Furthermore, the diagnostic explanatory power of DTI data of the PP should be compared to high-resolution MRI volumetry and intervoxel coherences (COH) of the hippocampus and the entorhinal cortex, two limbic regions also involved in the pathophysiology of early AD. DTI revealed a marked decrease in COH values in the PP region of MCI (right side: 26%, left side: 29%, as compared to controls) and AD patients (right side: 37%, left side: 43%, as compared to controls). Reductions in COH values of the PP region were significantly correlated with cognitive impairment. DTI data of the PP zone were the only parameter differing significantly between control subjects and MCI patients, while the volumetric measures and the COH values of the hippocampus and the entorhinal cortex did not. DTI of medial temporal brain regions is a promising non-invasive tool for the in vivo diagnosis of the early/preclinical stages of AD.

Aged↗

PubMed2005

Electrophysiological and neuropsychological analysis of a delirious state: the role of the anterior cingulate gyrus.

Functional neuroimaging studies in humans have provided evidence that a frontal network including the anterior cingulate cortex (ACC) plays an important role in attention and awareness. Disturbed attention and awareness are core symptoms of delirium, but imaging studies of attentional dysfunctions in delirium are lacking. However, an increase of slow electroencephalographic (EEG) activity (delta, theta) is a consistent biological finding in delirium. The question whether this slow activity is related to a disturbance in the frontal attentional network has not yet been addressed. The delirium after electroconvulsive therapy (ECT) has been investigated using 32-channel resting EEG before and shortly after ECT in 12 patients with major depressive disorder. During delirium compared with baseline studies, substantial increases of delta and theta power and a decrease of alpha power were observed. The decrease of theta activity at the Fz electrode position in the following 24 h was significantly related to the recovery of awareness and performance of free recall. Source analysis with Low Resolution Electromagnetic Tomography (LORETA) indicated that the main generators of the theta excess during delirium were significantly localized in the anterior cingulate cortex, and additionally in right fronto-temporal brain areas. The results support the concept that a disturbance of attention and awareness during delirium is related to a dysfunction of an attentional network involving the ACC. However, the localization of the theta excess may reflect some motor dysfunctions as well. This dysfunction of the ACC was shown for the first time in patients during a delirious state and may represent an important pathophysiological aspect of delirium.

Attention↗

PubMed2005

Association of human hippocampal neurochemistry, serotonin transporter genetic variation, and anxiety.

The impact of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) on anxiety-related behavior and related cerebral activation has facilitated the understanding of neurobiological mechanisms of anxiety. However, the influence of the 5-HTTLPR genotype on hippocampal neuronal development and neurochemistry, which is relevant to anxiety behavior, has not been investigated. In 38 healthy subjects, absolute concentrations of N-acetylaspartate (NAA) were measured as a main surrogate parameter for hippocampal neurochemistry on a 3-T scanner. A significantly lower hippocampal NAA concentration in s allele carriers was observed as compared to l/l genotype. Other metabolites (choline, creatine + phosphocreatine, glutamate) were unaffected by genotype. The hippocampal NAA concentration was negatively correlated with trait anxiety scores (STAI). Metabolites measured in the anterior cingulate cortex (reference region) were not associated with genotype. The results are in accordance with the recently reported relationship between hippocampal neuronal development and anxiety behavior in adult animals and show an association between human limbic neurochemistry and genetically driven serotonergic neurotransmission relevant to anxiety.

Alleles↗

PubMed2005

Association of a functional BDNF polymorphism and anxiety-related personality traits.

RATIONALE: Converging lines of evidence point to brain-derived neurotrophic factor (BDNF) as a factor in the pathophysiology of depression. Recently, it was shown that the Val allele of the BDNF Val66Met substitution polymorphism showed a significant association with higher mean neuroticism scores of the NEO-Five Factor Inventory (NEO-FFI) in healthy subjects, and previous studies suggested the Val allele to be increased in bipolar disorder families. The association to anxiety-related traits has not been investigated so far. METHODS: We tested a total of 343 unrelated subjects of German descent (171 male, 172 female, age: 39.0+/-14.6 years) who were carefully screened for psychiatric health. The self-ratable State-Trait Anxiety Inventory (STAI), which allows anxiety to be quantified as a comparatively stable personality trait, and the NEO-Five Factor Inventory (NEO-FFI) was applied. RESULTS: In the trait-related anxiety score, a significant (F=3.2, df=2, p<0.042) effect of the genotype was observed with higher levels of trait anxiety in Val/Val (35.0+/-7.4) compared to Val/Met (33.4+/-6.5) and Met/Met (32.0+/-4.6) genotypes. The NEO neuroticism scores were also higher in Val/Val (29.5+/-7.0) than in Val/Met (28.4+/-6.5) or Met/Met (26.8+/-5.8) genotype, but not at a significant rate. CONCLUSIONS: Our findings support the hypothesis that anxiety- and depression-related personality traits are associated with the BDNF polymorphism although the explained variance is low.

Adult↗

PubMed2005

Association of BDNF serum concentrations with central serotonergic activity: evidence from auditory signal processing.

Disturbances of serotonergic neurotransmission in the brain have been implicated in the pathogenesis and maintenance of several psychiatric disorders. According to recent preclinical and clinical studies, the loudness dependence of auditory evoked potentials (LD) is related to the central serotonergic neurotransmission in humans. As the serotonergic phenotype has been reported to be associated with brain-derived neurotrophic factor (BDNF), we studied whether BDNF serum concentrations are related to LD in 109 healthy human volunteers (62 male, 47 female, age: 42.5+/-13.1 years). Pearson correlation showed a significant negative correlation between the BDNF serum concentrations and the LD measured at Fz (r=-0.259, p=0.007) and a trend for the Cz electrode (r=-0.185, p=0.055). Although this association needs to be replicated, the results are in line with the assumption that low serum BDNF levels reflect low central serotonergic neurotransmission as indicated by a strong LD.

Adult↗

PubMed2004

The amygdala in schizophrenia: a trimodal magnetic resonance imaging study.

In schizophrenic psychoses, structural and functional alterations of the amygdala have been demonstrated by several neuroimaging studies. However, postmortem examinations on the brains of schizophrenics did not confirm the volume changes reported by volumetric magnetic resonance imaging (MRI) studies. In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed a trimodal MRI design including high-resolution volumetry, diffusion tensor imaging (DTI), and quantitative magnetization transfer imaging (qMTI) in a sample of 14 schizophrenic patients and 14 matched controls. Three-dimensional MRI volumetry revealed a significant reduction of amygdala raw volumes in the patient group, while amygdala volumes normalized for intracranial volume did not differ between the two groups. The regional diffusional anisotropy of the amygdala, expressed as inter-voxel coherence (COH), showed a marked and significant reduction in schizophrenics. Assessment of qMTI parameters yielded significant group differences for the T2 time of the bound proton pool and the T1 time of the free proton pool, while the semi-quantitative magnetization transfer ratio (MTR) did not differ between the groups. The application of multimodal MRI protocols is diagnostically relevant for the differentiation between schizophrenic patients and controls and provides a new strategy for the detection and characterization of subtle structural alterations in defined regions of the living brain.

Adult↗

PubMed2004

New evidence for involvement of the entorhinal region in schizophrenia: a combined MRI volumetric and DTI study.

Postmortem examinations and magnetic resonance imaging (MRI) studies suggest involvement of the entorhinal cortex (EC) in schizophrenic psychoses. However, the extent and nature of the possible pathogenetical process underlying the observed alterations of this limbic key region for processing of multimodal sensory information remains unclear. Three-dimensional high-resolution MRI volumetry and evaluation of the regional diffusional anisotropy based on diffusion tensor imaging (DTI) were performed on the EC of 15 paranoid schizophrenic patients and 15 closely matched control subjects. In schizophrenic patients, EC volumes showed a slight, but not significant, decrease. However, the anisotropy values, expressed as inter-voxel coherences (COH), were found to be significantly decreased by 17.9% (right side) and 12.5% (left side), respectively, in schizophrenics. Reduction of entorhinal diffusional anisotropy can be hypothesized to be functionally related to disturbances in the perforant path, the principal efferent EC fiber tract supplying the limbic system with neuronal input from multimodal association centers. Combinations of different MRI modalities are a promising approach for the detection and characterization of subtle brain tissue alterations.

Adult↗

PubMed2004

Pharmacogenetic insights to monoaminergic dysfunction in alcohol dependence.

RATIONALE: Alcohol dependence is characterized by the development of tolerance, withdrawal symptoms, and craving for alcohol. Chronic alcohol consumption causes neuroadaptive changes in the central dopaminergic and serotonergic system, which are partially reversible after detoxification. The severity and time-course of recovery of these neuroadaptive changes may depend on the genetic constitution of monoamine transporters and receptors and contribute to the relapse risk of alcoholics. OBJECTIVES: To assess the interaction between the genetic constitution and the in vivo availability of dopamine and serotonin transporters and receptors, chronic alcohol intake, alcohol craving and withdrawal. METHODS: Review of brain imaging studies that assess the genotype and availability of dopamine and serotonin transporters in detoxified alcoholics and healthy control subjects. RESULTS: Chronic alcohol intake induced neuroadaptive reductions in striatal dopamine transporter (DAT) availability, which were reversible during early abstinence. A polymorphism of the DAT gene (SLC6A3) was associated with the in vivo transporter availability and with the severity of alcohol withdrawal. Neurotoxic reductions in 5-HTT protein expression were limited to homozygous carriers of the long allele in the 5-HTT gene (SCL6A4) regulatory region and correlated with negative mood states. CONCLUSION: Genetic constitution interacts with the in vivo availability of central dopamine and serotonin transporters during alcohol detoxification and may affect the severity of alcohol withdrawal and clinical depression.

Alcoholism↗

PubMed2004

[Genetic and pharmacological effects on prefrontal cortical function in schizophrenia].

Brain imaging studies with PET, SPECT, functional magnetic resonance imaging, and spectroscopy provide evidence of prefrontal dysfunction in schizophrenia. Dysfunction of the prefrontal cortex is associated with cognitive impairment and negative symptoms. Combined multimodal imaging shows that a developmentally early disturbance of frontotemporal-limbic neuronal networks is associated with a disinhibition of subcortical dopaminergic neurotransmission. Current studies imply genetic factors in the regulation of dopaminergic neurotransmission and their effects on prefrontal cortex function. Some studies also indicate that atypical neuroleptics may at least partially improve frontal cortex function. We review the literature and discuss genotype and medication effects on frontal dysfunction in schizophrenia. Molecular brain imaging combines imaging techniques with the assessment of genotype effects and represents a powerful tool for the understanding of neuropsychiatric disorders.

Antipsychotic Agents↗