Biomedical subjects

Thomas Frodl

Publications and source records attributed to Thomas Frodl.

17 recordsLinked to original sources

PubMed2006

Amygdala volume and depressive symptoms in patients with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by a high prevalence of comorbid psychiatric disorders, including major depression (MD). The aim of this study was to examine whether a co-occurrence of MD is associated with structural changes in the amygdala of BPD patients. METHODS: Twenty-five right-handed, female patients with BPD and 25 matched healthy control subjects were examined. Diagnoses of BPD and MD were made according to DSM IV. Depressive symptomatology was determined with the Hamilton Depression Scale (HAMD). Magnetic resonance imaging scans were performed with 1.5 T Magnetom Vision (Siemens, Erlangen, Germany). The software program "BRAINS" was applied for brain volumetry and segmentation. The amygdala was delineated as "region of interest." RESULTS: Comparison of amygdala volumes between the whole group of BPD patients and control subjects revealed no significant difference. Amygdala volumes in both hemispheres were significantly larger in BPD patients with MD compared with those without MD. There was a significant correlation in BPD patients between left amygdala volume and depressive symptoms as measured by HAMD. CONCLUSIONS: Correlation of amygdala volume with depression in BPD patients might indicate a causal relationship. Future studies should clarify whether amygdala enlargement is a risk factor for MD in BPD patients or a consequence of the affective disorder.

Adult↗

PubMed2006

Reduced hippocampal volume correlates with executive dysfunctioning in major depression.

OBJECTIVE: Dysfunction of neuronal plasticity or remodelling seems to contribute to the pathopysiology of major depression and may cause the well-documented hippocampal changes in depression. We aimed to investigate whether reduced hippocampal volumes correlate with executive dysfunctioning or memory dysfunctioning or with depression severity. METHODS: We recruited 34 inpatients with a previous or current episode of major depression from the department of psychiatry at the Ludwig-Maximilians University of Munich, Germany. We examined the 34 patients and 34 healthy control subjects with structural high resolution MRI. We assessed cognitive functions with the Wisconsin Card Sorting Test (WCST) and the Rey Auditory Verbal Learning Test (RAVLT) and severity of depression with the Hamilton Depression Rating Scale. RESULTS: Hippocampal volumes and frontal lobe volumes were significantly smaller in patients, compared with healthy control subjects. Furthermore, lower hippocampal volumes were correlated with poorer performance in the WCST. No significant correlations were found between hippocampal volumes and RAVLT performance or severity of depression. CONCLUSIONS: The present findings emphasize that patients with reduced hippocampal volumes show more executive dysfunctions than their counterparts. Thus, the mechanisms resulting in reduced hippocampal volumes seem to be related to the development of major depression.

Adult↗

PubMed2005

D2 receptor occupancy during high- and low-dose therapy with the atypical antipsychotic amisulpride: a 123I-iodobenzamide SPECT study.

UNLABELLED: Amisulpride appears to be an effective agent for treating positive or negative symptoms of schizophrenia, depending on dose. The aim of this study was to assess striatal dopamine D(2) receptor availability by means of (123)I-iodobenzamide (IBZM) SPECT in patients treated with high and low doses of this atypical antipsychotic drug. METHODS: Twenty-nine patients (19 men and 10 women, age range, 19-68 y) with schizophrenia treated with high doses (15 patients; 400-1,200 mg/d; mean dose, 666.7 +/- 219.3 mg/d) or low doses (14 patients; 50-300 mg/d; mean dose, 228.6 +/- 93.5 mg/d) of amisulpride were examined. For assessment of plasma amisulpride concentration, blood samples were taken. Brain SPECT was performed 2 h after intravenous injection of 185 MBq of (123)I-IBZM. For semiquantitative evaluation, transverse slices corrected for attenuation (Chang's first-order method) were used to calculate specific binding in the striatum, with the frontal cortex used as background. RESULTS: In all patients treated with amisulpride, specific binding of (123)I-IBZM to D(2) receptors was significantly lower (P < 0.001) than in healthy controls (0.95). Both groups treated with amisulpride differed significantly in specific binding of (123)I-IBZM to dopamine D(2) receptors (0.20 vs. 0.31, P < 0.05). D(2) receptor blockade correlated well with the administered dose of amisulpride and with amisulpride plasma concentration. CONCLUSION: Our findings suggest that amisulpride treatment leads to a significant occupancy of postsynaptic dopamine D(2) receptors. The blockade of D(2) receptors tends to be significantly lower in patients receiving low-dose amisulpride therapy than in patients receiving high-dose therapy.

Adult↗

PubMed2004

Differential effects of reboxetine and citalopram on hand-motor function in patients suffering from major depression.

RATIONALE: Motor dysfunctions might be a more common side effect of serotonergic than noradrenergic antidepressants. However, the effects of antidepressants on motor function in depression have rarely been analyzed systematically. Computerized methods allow the objective registration of drug-induced motor dysfunction and were applied in this study. OBJECTIVES: To examine the effects of a selective noradrenaline re-uptake inhibitor (NARI) (reboxetine) and a selective serotonin re-uptake inhibitor (SSRI) (citalopram) on hand-motor function in patients with major depression. METHODS: Different types of hand movements (drawing of circles and handwriting probes) were recorded and analyzed in 16 acutely depressed inpatients receiving citalopram (30-60 mg/day) and 12 acutely depressed inpatients treated with reboxetine (4-8 mg/day), using a digitizing tablet for the analysis of movement dynamics. Both groups were comparable regarding mean age (42-43 years), gender, handedness (preponderance of right-handers) and the mean baseline HAMD score (about 27). Five kinematical parameters reflecting velocity, regularity and degree of automation of hand movements have been computed. RESULTS: Reboxetine had significantly more favorable effects on fine motor function (increased velocity of rapid hand movements) in depressed patients than citalopram. These differences became obvious when patients conducted more complex tasks and are not explained by differential antidepressant effects. CONCLUSIONS: Our findings are in line with the hypothesis that SSRI tend to have small, but more pronounced negative effects on motor function than NARI.

Acute Disease↗

PubMed2004

Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression.

BACKGROUND: Substantial evidence supports a role for dysfunction of the serotonin transporter in the pathogenesis of major depression. Several studies have found reciprocal interactions between the serotonergic system and both brain-derived neurotrophic factor and glutamate, which are known to modulate or affect hippocampal morphologic characteristics. OBJECTIVE: To examine the influence of a polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene on hippocampal volumes in patients with major depression and healthy controls. DESIGN: Baseline investigation of a prospective magnetic resonance imaging study with a 4-year follow-up period. PATIENTS: We examined 40 inpatients with major depression as well as 40 healthy controls matched for age, sex, and handedness. MAIN OUTCOME MEASURES: Subjects underwent high-resolution magnetic resonance imaging. Furthermore, genotyping for the 5-HTTLPR biallelic polymorphism was performed, which consists of a 44-base pair insertion (L allele) or deletion (S allele). RESULTS: Patients with the L/L homozygous genotype had significantly smaller hippocampal gray matter (left hemisphere: P=.003; right hemisphere: P=.01) and white matter volumes (left hemisphere: P=.001; right hemisphere: P=.002) than controls with this genotype. No significant differences were found between patients and controls with the L/S or S/S genotype. Moreover, patients with the L/L genotype had significantly smaller hippocampal white matter volumes than those with the L/S or S/S genotype (P=.03). CONCLUSIONS: These findings suggest that homozygosity for the L allele is associated with decreased hippocampal volumes in patients with major depression but not in healthy controls. A possible explanation is that the interaction between the serotonergic system and neurotrophic factors as well as excitatory amino acid neurotransmission may affect hippocampal morphologic characteristics.

Adult↗

PubMed2004

The septum pellucidum and its variants. An MRI study.

PURPOSE: Increased prevalence of cavum septi pellucidi (CSP) in schizophrenic patients in comparison to healthy subjects was reported previously. Our purpose was to evaluate the prevalence of variants of the septum pellucidum in healthy subjects in three different age groups. METHODS: 151 healthy subjects, including 46 children (age 6 +/- 4 years), 72 young adults (age 31 +/- 8 years) and 33 elderly adults (age 59 +/- 7 years) were examined with high-resolution MRI. Three observers analysed the images using a standardised protocol. We evaluated the incidences of CSP, cavum vergae (CV) and their length. RESULTS: CSP was detected in 80% of the cases in the paediatric group and 68% of young adults and in 72% of the elderly adults. A cavum vergae (CV) was noted in 22% of the children, in 39% of the young adults and in 36% of the elderly subjects. There was no significant difference between the age-related groups. CONCLUSION: We detected a high prevalence of cavum septi pellucidi without a significant age dependence. Enlarged cava septi pellucidi are rare in healthy subjects.

Adolescent↗

PubMed2004

Hippocampal and amygdala changes in patients with major depressive disorder and healthy controls during a 1-year follow-up.

BACKGROUND: Although the hippocampus has been found to be smaller in patients with depression, prospective longitudinal in vivo studies are necessary to investigate whether depression can result in a further diminution of hippocampal volumes or whether a smaller hippocampal volume predisposes an individual to the development of depression. METHOD: Thirty patients with DSM-IV major depressive disorder as well as 30 healthy control subjects matched for age, gender, and handedness were examined at admission to the hospital and 1 year later using a documentation of the medical history and high-resolution magnetic resonance imaging (MRI) for the presence of depression and to determine changes in hippocampal as well as amygdala volumes. Patients were enrolled from March 2000 to August 2002. RESULTS: No significant hippocampal and amygdala volume changes were observed in patients or controls between baseline and 1-year follow-up investigations. However, the subgroup of patients who were nonremitted at the time of the follow-up investigation showed significantly reduced left and right hippocampal volumes at both baseline and the 1-year follow-up compared with remitted patients. Moreover, the right hippocampal volumes of nonremitted patients were significantly smaller compared with matched healthy controls. CONCLUSION: These results do not support the hypothesis that hippocampal volumes diminish during the 1-year follow-up period. However, smaller hippocampal volumes may be related to a poor clinical outcome after 1 year.

Adolescent↗

PubMed2003

Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects.

BACKGROUND: The aim of our study was to test the hypothesis that amygdala volumes are reduced in patients with recurrent major depression compared with first episode patients. METHODS: Using structural magnetic resonance imaging, we compared 30 inpatients with first-episode depression and 27 inpatients with recurrent major depression (DSM-IV) with healthy volunteer subjects from the local community matched for age, gender, and handedness. RESULTS: Patients with first-episode depression showed enlarged amygdala volumes compared with patients with recurrent major depression and healthy control subjects. No significant differences were found between patients with recurrent depression and healthy control subjects. No significant correlations were found between amygdala volumes and age of onset, illness duration, or severity of depression. CONCLUSIONS: Larger amygdala volumes in patients with first-episode depression may result from higher amygdala metabolism and blood flow. Additionally, disease progression with stress-related excitotoxic processes during recurrent depressive episodes might result in decreased amygdala volumes. Prospective investigations to investigate amygdala changes during the course of depression are needed.

Adult↗

PubMed2002

Handedness and corpus callosum morphology.

Investigations of a relationship between callosal size and functional behavioral lateralization lead to the hypothesis that, as the size of the corpus callosum (CC) increases, interhemispheric information transfer is facilitated and behavioral laterality effects become smaller. The aim of our in vivo study was to investigate the relationship between functional asymmetry of handedness and CC size in healthy subjects. Magnetic resonance images of the CC and five CC subregions were obtained with a 1.5-T Magnetom using a three-dimensional T1 sequence in 46 healthy men. Handedness was determined using the 'handedness dominance test' (HDT). According to the HDT values, 32 consistent and 14 non-consistent right-handers were identified. No significant difference between handedness subgroups in CC regions and no significant correlations between HDT values and CC areas were detected.

Adolescent↗

PubMed2002

Investigation of a possible diencephalic pathology in schizophrenia.

Absence of the adhesio interthalamica (AI) in schizophrenic first episode patients is suggestive for another marker of early developmental neuropathologic changes. Moreover, findings suggest that schizophrenic patients without AI are characterised by more severe negative symptoms. The study aims to investigate the presence vs. absence of AI in relation to brain measurements and clinical features. Presence or absence of AI and volumetric brain measurements were assessed in 50 patients with schizophrenia and 50 matched controls. No differences in the incidence of AI were found between the groups. Patients without AI revealed a strong trend towards a larger third ventricle and significantly higher scores for negative symptoms. Interestingly, the subgroup of healthy controls without AI also had larger third ventricles. The absence of AI may represent another early developmental marker of cerebral malformation in a clinical subgroup of schizophrenic patients.

Adolescent↗

PubMed2002

Enlargement of the amygdala in patients with a first episode of major depression.

BACKGROUND: The amygdala plays a crucial role in the mediation of affective behavior in humans and is implemented in the limbic-thalamic-cortical network that is supposed to modulate human mood. The aim of the present study was to measure the amygdala volumes in patients with a first episode of major depression. METHODS: Thirty inpatients with a first episode of depression were compared with 30 healthy volunteers matched for age, gender, handedness, and education by performing structural magnetic resonance imaging (MRI) measures of the amygdala. RESULTS: Patients showed increased amygdala volumes in both hemispheres as compared to healthy control subjects. No significant correlations were found between amygdala volumes and age, age of onset, illness duration, or severity of depression in the patient group. CONCLUSIONS: Enlarged amygdala volumes in patients with a first episode of major depression might be due to enhanced blood flow in the amygdala rather than to a neurodevelopmental structural predisposition to major depression.

Adolescent↗

PubMed2002

P300 subcomponents and clinical symptoms in schizophrenia.

A small P300 component of the auditory event-related potential has been found to predict poor clinical outcome with a higher amount of thought disorders in schizophrenia and has been proposed as a marker for an underlying neurodevelopmental disorder with prominent thought disorders, early age of onset, prominent negative symptoms and positive family history. The present study was designed to confirm our previous findings with subcomponent analysis. Using dipole source analysis a temporo-basal (TB) P300 as well as a temporo-superior (TS) P300 and LP potential were separated. Fifty patients with schizophrenia (DSM-IV) were included in the study. Late auditory event-related P300 potentials were recorded to infrequent auditory stimuli after treatment psychopathology and family history were assessed. The TB-P300 amplitudes were significantly negatively correlated with thought disorders remaining after treatment and were positively correlated with age of onset. Illness duration was significantly correlated to TB-P300 and TS-P300 amplitudes in the group of patients with late onset. No significant correlations were found with negative symptoms. Family history did not show significant effects on P300. A smaller P300 in patients with more thought disorder remaining after stabilization on medication and an earlier age of onset support the hypothesis that P300 characterizes schizophrenic patients with an underlying neurodevelopmental disorder with specific clinical symptom clusters. On the other hand, diminished P300 with illness duration in the group of patients with later age of onset supports an underlying neurodegenerative progressive process in this subgroup of patients.

Adolescent↗

PubMed2002

Identification of a naturally occurring polymorphism in the promoter region of the norepinephrine transporter and analysis in major depression.

Disturbances in the noradrenergic neurotransmission system have been implicated in the etiology of mood disorders. The norepinephrine transporter (NET) is a main target of antidepressant action and was shown to be dysregulated in major depression. Despite the clinical and physiological significance of NET gene regulation, little is known about the transcriptional control mechanisms governing its expression. Since it is well established that affective disorders have a genetic component with many genes of small effect contributing to the genetic susceptibility of depression, the NET gene is an interesting candidate gene for affective disorders. In a search for polymorphisms or mutations in the 5' flanging region of the NET gene we sequenced approximately 1000 bp upstream of the first codon in the NET gene promoter in 100 patients with major depression and 100 healthy controls. We identified a so far unknown T --> C polymorphism 182 bp upstream of the start codon in a transcriptional relevant region. In a case control association study we investigated the newly identified T-182C polymorphism and an already known G1287A polymorphism in exon 9 of the NET gene in a sample of 193 patients with major depression and 136 healthy, non-related controls. No statistical significant differences between patients and controls were found for any of the analyzed polymorphisms, either in the genotype distribution or in the allele frequencies. Our results suggest that the investigated polymorphisms are not major susceptibility factors in the etiology of major depression.

Adult↗

PubMed2002

Value of event-related P300 subcomponents in the clinical diagnosis of mild cognitive impairment and Alzheimer's Disease.

Accurate and early diagnosis of Alzheimer's Disease (AD) with reliable and noninvasive methods is of great importance for clinical practice as effective and specific antidementive therapies become available. The aim of the study was to evaluate the clinical relevance of event-related P300 in the early diagnosis of AD. Thirty patients with AD, 26 patients with mild cognitive impairment (MCI) from our Memory Clinic and 26 age-matched healthy controls (HC) were studied with event-related P300 potentials. Amplitudes of temporo-basal dipoles (TB-P300) were significantly diminished in AD compared to HC and MCI. Furthermore, latencies of temporo-superior dipoles (TS-P300) were significantly prolonged in AD compared with HC. Sensitivity was 90.0% for the differentiation of patients with AD from HC (specificity 79.1%) using reduced TB-P300 amplitudes and prolonged TS-P300 latencies. Similar results were found using Pz amplitudes as well as Fz latencies. Our data suggest that TB-P300 amplitudes and TS-P300 latencies may be an accurate clinically available, nonexpensive, noninvasive, and reliable marker for AD.

Aged↗

PubMed2002

Hippocampal changes in patients with a first episode of major depression.

OBJECTIVE: Previous work suggests that patients with unipolar depression may have structural as well as functional abnormalities in limbic-thalamic-cortical networks, which are hypothesized to modulate human mood states. A core area in these networks is the hippocampus. In the present study, differences in volumes of hippocampal gray and white matter between patients with a first episode of major depression and healthy comparison subjects were examined. METHOD: Thirty patients with a first episode of major depression and 30 healthy comparison subjects who were matched for age, gender, handedness, and education were examined with high-resolution magnetic resonance imaging. RESULTS: Male patients with a first episode of major depression had significantly smaller hippocampal total and gray matter volumes than healthy male comparison subjects. Both male and female patients showed significant alterations of left-right asymmetry and significant reductions of left and right hippocampal white matter fibers in relation to healthy comparison subjects. Hippocampal measurements were not significantly correlated with clinical variables, such as age at onset of illness, illness duration, or severity of depression. CONCLUSIONS: These results are consistent with findings of structural abnormalities of the hippocampal formation in patients with major depression that were more pronounced in male patients. The authors' findings support the hypothesis that the hippocampus and its connections within limbic-cortical networks may play a crucial role in the pathogenesis of major depression.

Adult↗

PubMed2002

Does the definition of borders of the planum temporale influence the results in schizophrenia?

OBJECTIVE: The planum temporale, a highly asymmetric neocortical area of the temporal lobe, has a possible role in schizophrenia. The authors used three different anatomical definitions of the planum temporale to examine the anterior, posterior, and total planum temporale gray matter volumes simultaneously. METHOD: Magnetic resonance imaging was used to examine 30 male schizophrenic patients and 30 healthy male comparison subjects. The total planum temporale was identical in all three anatomical definitions applied to determine the border between the anterior and posterior planum temporale regions. RESULTS: No significant differences between men with and without schizophrenia were detected with regard to planum temporale volumes and asymmetry coefficients for any of the three definitions. CONCLUSIONS: The authors could not prove the hypothesis that the definition of planum temporale borders influences the results concerning possible disturbances of planum temporale asymmetry in patients with schizophrenia.

Adult↗

PubMedDate not supplied

P300 subcomponents in obsessive-compulsive disorder.

Hyperactivity in the frontal cortex, leading to acceleration of attentional and cognitive processes, is discussed as pathogenetic factor in obsessive-compulsive disorder (OCD), as supported by findings of neuroimaging studies. This dysfunction in patients with OCD could be reflected by the auditory event-related P300 component, since one subcomponent of the P300, the so-called P3a, is mainly generated in frontal regions. The P300 of 21 patients with OCD free of medication and 21 age- and sex-matched healthy controls was studied, and dipole source analysis was used, allowing the separation of the subcomponents P3a and P3b with high reliability. No difference concerning the P3a between OCD and healthy subjects was found. OCD patients, however, showed a larger P3b amplitude and a shorter P3b latency (only right hemisphere) as well as a shorter reaction time to target tones as the healthy controls. Since the P3b, generated mainly in the temporo-parietal junction, is related to attentional and higher cognitive functions, whereas the P3a is more related to unspecific orienting reactions, the P3b abnormalities found in these patients could be an electrophysiological correlate of overfocussed attention and faster cognitive processes in OCD, possibly due to higher arousal and noradrenergic function. Regarding the findings with small P300 amplitudes and long latencies in most of the other psychiatric patients, it is remarkable that OCD is one of the few psychiatric diseases being characterized by larger P3b amplitudes and shorter latencies.

Adult↗