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Biomedical subjects

Malek Bajbouj

Publications and source records attributed to Malek Bajbouj.

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

Brain-derived neurotrophic factor serum concentrations in depressive patients during vagus nerve stimulation and repetitive transcranial magnetic stimulation.

BACKGROUND: Vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex are brain stimulation techniques used as therapeutic interventions in major depression. METHODS: In this study, we report the impact of these stimulation techniques on serum concentrations of brain-derived neurotrophic factor (BDNF) in treatment-resistant patients with a diagnosis of major depression. RESULTS: We found no changes of BDNF serum concentrations and no association of neurotrophin concentrations in serum with clinical parameters in our sample. CONCLUSION: Our preliminary results suggest that brain stimulation techniques-in contrast to several antidepressant medications-do not change BDNF serum concentrations.

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

Metabolic alterations in the dorsolateral prefrontal cortex after treatment with high-frequency repetitive transcranial magnetic stimulation in patients with unipolar major depression.

Neuroimaging studies suggest a specific role of anterior cingulate cortex (ACC) and left dorsolateral prefrontal cortex (DLPFC) in major depression. Stimulation of the latter by means of repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the past. The objective of the present study was to examine in vivo neurochemical alterations in both brain regions in 17 patients with unipolar major depression before and after 10 days of high-frequency (20Hz) rTMS of the left DLPFC using 3-tesla proton magnetic resonance spectroscopy. Six out of seventeen patients were treatment responders, defined as a 50% reduction of the Hamilton depression rating scale. No neurochemical alterations in the ACC were detected after rTMS. As compared to the non-responders, responders had lower baseline concentrations of DLPFC glutamate which increased after successful rTMS. Correspondingly, besides a correlation between clinical improvement and an increase in glutamate concentration, an interaction between glutamate concentration changes and stimulation intensity was observed. Our results indicate that metabolic, state-dependent changes within the left DLPFC in major depressive disorder involve the glutamate system and can be reversed in a dose-dependent manner by rTMS.

Adult↗
PubMed2006

Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS).

Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique which had recently been investigated as a putative antidepressant intervention. However, there is little agreement about clinically useful predictors of rTMS outcome. Therefore, the objective of the present study was to determine whether specific biographical, clinical, and psychopathological parameters are associated with the antidepressant response to rTMS in a large sample of 70 depressive patients. We performed a logistic regression analysis in 70 patients with major depressive disorder treated with rTMS of the left dorsolateral prefrontal cortex testing the predictive value of various domains of the depression syndrome as well as the variables episode duration, degree of treatment resistance, and CORE criteria. Response was defined as a 50% reduction of the initial Hamilton score (HAMD). After two weeks of treatment, 21% of the patients showed a response to rTMS. The binary logistic regression model correctly assigned 86.7% of the responders and 96.4% of the non-responders to their final response group. In the model, a high level of sleep disturbances was a significant predictor for treatment response to rTMS. Also, a low score of treatment resistance and a short duration of episode were positive predictors. These findings provide new evidence that especially pronounced sleep disturbances may be a significant clinical predictor of a response to rTMS. Prospective rTMS studies are necessary to validate the predictive value of the derived model.

Antidepressive Agents↗
PubMed2005

Interictal slow-wave focus in left medial temporal lobe during bilateral electroconvulsive therapy.

The interictal state between two electroconvulsive therapy (ECT) sessions is clinically characterised by possible cognitive adverse effects like mild amnestic syndrome. ECT-induced amnestic deficits can persist for several weeks after ECT. Electrophysiologically, slowing of brain electrical activity in the interictal state has often been reported. Especially, for bilateral ECT a correlation between enhanced left frontotemporal theta activity and retrograde amnesia has been demonstrated. This study focuses on the topographic distribution of cortical slow-wave oscillations during the interictal state of a bilateral ECT cycle. Twelve patients with major depression have been investigated with 32-channel resting EEG 24 h after the 6th ECT session. As controls, 8 major depressive patients were investigated prior to antidepressive treatment. The generating sources of slow-wave activity are estimated within the theta frequency band with low-resolution brain electromagnetic tomography. Source analysis revealed a distinct pattern of theta activity in the depth of the left temporal lobe (fusiform and parahippocampal gyri, Brodmann areas 37 and 36, respectively; p< 0.05) during the interictal state. This finding suggests a dysfunction of the left medial temporal lobe memory system during the interictal state of a bilateral ECT cycle. It will further be discussed whether it is possible to obtain information about activity of deep brain structures like the hippocampal formation from scalp-recorded signals.

Adult↗
PubMed2005

Evidence for impaired cortical inhibition in patients with unipolar major depression.

BACKGROUND: Several lines of evidence suggest that central cortical inhibitory mechanisms, especially associated with gamma-aminobutyric acid (GABA) neurotransmission, may play a role in the pathophysiology of major depression. Transcranial magnetic stimulation is a useful tool for investigating central cortical inhibitory mechanisms associated with GABAergic neurotransmission in psychiatric and neurological disorders. METHODS: By means of transcranial magnetic stimulation, different parameters of cortical excitability, including motor threshold, the cortical silent period, and intracortical inhibition/facilitation, were investigated in 20 medication-free depressed patients and 20 age- and gender-matched healthy volunteers. RESULTS: Silent period and intracortical inhibition were reduced in depressed patients, consistent with a reduced GABAergic tone. Moreover, patients showed a significant hemispheric asymmetry in motor threshold. CONCLUSIONS: This study provides evidence of reduced GABAergic tone and motor threshold asymmetry in patients with major depression.

Adult↗
PubMed2005

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex and cortical excitability in patients with major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex is a relatively non-invasive technique with putative therapeutic effects in major depression. However, the exact neurophysiological basis of these effects needs further clarification. Therefore, we studied the impact of ten daily sessions of left, dorsolateral prefrontal rTMS on motor cortical excitability, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 30 patients. As compared to the non-responders, responders (33%) showed changes in parameters pointing towards a reduced cortical excitability. These results suggest that repetitive transcranial magnetic stimulation of the dorsolateral, prefrontal cortex may have inhibitory effects on motor cortical neuronal excitability in patients with major depressive disorder. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of antidepressant stimulation techniques like rTMS.

Adult↗
PubMed2005

Effects of right unilateral electroconvulsive therapy on motor cortical excitability in depressive patients.

Electroconvulsive therapy (ECT) is a widely acknowledged effective treatment for severe major depression. ECT produces considerable anticonvulsant effects that may be related to an increased GABA-ergic neurotransmission. We aimed to explore whether motor cortical excitability as assessed with single and paired pulse transcranial magnetic stimulation (TMS) could be used to investigate these anticonvulsant effects. Therefore, parameters of motor cortical excitability were investigated in 10 patients before and after 10 sessions of right unilateral ECT. After 10 sessions of right unilateral ECT, an enhanced activity of inhibitory circuits in human motor cortex had been observed, as measured by both increased intracortical inhibition and cortical silent period duration, whereas intracortical facilitation and resting motor threshold remained unchanged. The reduction of seizure duration in the course of ECT was associated with clinical improvement and an increase in intracortical inhibition. We interpret this finding as further indirect evidence for changes in inhibitory circuits in the course of ECT in patients with major depression.

Antidepressive Agents↗
PubMed2005

Cerebral blood flow during vagus nerve stimulation--a transcranial Doppler study.

BACKGROUND AND OBJECTIVES: Vagus nerve stimulation (VNS) is an approved treatment of partial onset seizures and has recently shown antidepressant effects in patients with treatment-resistant depression. This study was conducted to investigate whether acute VNS has an influence on cerebral blood flow (CBF) in humans. METHODS: This investigation was designed as an add-on study. In 10 patients with an implanted stimulator who participated in a multicenter clinical trial to evaluate the efficacy of VNS in depression, CBF was investigated by functional transcranial Doppler at baseline (before the stimulator was turned on for the first time) and during stimulation with three different stimulation intensities in a randomized order. RESULTS: Immediately after every increase of the current, CBF velocity showed a nonsignificant increase. Otherwise, no change of CBF above standard deviation could be registered. CONCLUSION: Acute VNS does not have an influence on CBF velocity in depressive patients.

Adult↗
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

Cognitive function over the treatment course of depression in middle-aged patients: correlation with brain MRI signal hyperintensities.

INTRODUCTION: It has been proposed that the often found hyperintensities on MRI representing vascular changes might be correlated with a worse outcome of cognitive malfunction in depression. The purpose of this study was to evaluate neuropsychological status in the acute depressed state and following remission and to investigate the potential relationship between MRI hyperintensities and neuropsychological functioning through the treatment course in a group of middle-aged depressed patients. MATERIALS AND METHODS: Twenty-seven depressed patients were assessed by a series of neuropsychological tests at the beginning of the depressive episode and again after an euthymic phase of 6 months following treatment. Thirty healthy controls were tested at comparable intervals. In all patients and controls a MRI was performed to identify hyperintensities representing a possible correlation with test performance during treatment course. RESULTS: At the onset of a depressive episode patients performed significantly worse than the controls in all tests. After sustained remission the patient group still performed significantly worse in verbal memory and verbal fluency compared to controls. There were no significant correlations between number of presence of vascular risk factors, or presence of hyperintensities on MRI, and cognitive abilities at either time point. DISCUSSION: These findings favor the hypothesis that some neuropsychological deficits might persist following treatment for depression, even in middle-aged patients. We found, however, that any residual cognitive deficit is not associated with MRI-hyperintensities in this age-group.

Adult↗