Ozlem Donat Eker

The effect of depression, BDNF gene val66met polymorphism and gender on serum BDNF levels

OBJECTIVE To determine the effect of BDNF gene val66met polymorphism on serum BDNF levels in drug-free patients with major depressive disorder (MDD) and healthy subjects, that differ by gender. METHODS Sixty-six drug-free patients (19 males+47 females) with non-psychotic MDD and fifty-six healthy controls (18 males+38 females) were recruited. Three-way ANOVA was employed to analyze the effect of mental health status, met-carriage and gender on Hamilton Depression Rating Scale (HDRS) scores and serum BDNF levels, by using the MIXED Procedure (SAS). RESULTS Patients had a lower serum BDNF level than healthy subjects (22.47 vs. 27.49; p<0.0001). Met-carrier patients had a higher HDRS score than Val homozygotes (25.99 vs. 22.99, p<0.02). Serum BDNF level for met-carrier subjects (patients+controls) was lower than Val homozygote subjects (23.08 vs. 26.87; p<0.002). However, there were no effects of two-way interactions of met-carriage and mental health status on HDRS scores and serum BDNF levels. There was no gender effect on HDRS scores in the patients. Overall, male subjects (patients+controls) had a higher serum BDNF level than female subjects (26.87 vs. 23.08; p<0.002). However, there were no effects of two-way interactions of gender with mental health status and met-carriage on serum BDNF levels. CONCLUSIONS We replicated the previous findings of lower serum BDNF levels during depression and in females. In addition, we found that met-carriage had an effect in reducing serum BDNF levels, regardless of gender and depression. Further animal and human studies with a larger sample size should investigate whether BDNF val66met polymorphism could alter brain and serum BDNF levels.

Association of the brain-derived neurotrophic factor Val66Met polymorphism with hippocampus volumes in drug-free depressed patients.

Abstract Objectives. Val66Met BDNF gene polymorphism is shown to affect the function of mature BDNF and mature BDNF plays an important role in the hippocampal neurogenesis and neuronal survival. Methods. A relationship of Val66Met BDNF gene polymorphism and hippocampal volumes in 33 MDD patients and 40 healthy controls is investigated. Region of interest analysis was conducted on the images acquired via MRI. Results. Depressed patients had smaller left hippocampal volumes compared to healthy controls. The diagnosis of MDD was not significantly related to hippocampal volumes among Met carriers; however, among Val homozygotes depressed patients had significantly smaller left hippocampal volumes compared to controls. Although both right and left hippocampal volumes showed nearly significant correlation with the duration of illness, this correlation reached (negative) significant levels only in the right hippocampal volume of the Val homozygotes. Conclusions. Val homozygote genotype may serve as a vulnerability factor in MDD regarding hippocampal volume loss. This finding can be considered as a supportive evidence for the neurotrophic factor hypothesis of depression.

Smaller Hippocampus Volume Is Associated with Short Variant of 5-HTTLPR Polymorphism in Medication-Free Major Depressive Disorder Patients

Aim: Serotonin is known for its importance in the pathophysiology of major depressive disorder. Although the hippocampus is one of the key regions in which neurogenesis occurs, and serotonin plays an important role in neurogenesis, results of studies that investigate effect of the 5-HTTLPR polymorphism on hippocampal volumes in major depressive disorder are inconclusive. Method: We looked for a relationship between the 5-HTTLPR polymorphism and hippocampal volumes in 44 depressed patients (mean age ± SD 33.6 ± 9.5 years) and 43 healthy controls (30.4 ± 6.7 years). Region of interest analysis was conducted on the images acquired via MRI. Results: Although hippocampal volumes were similar in healthy and patient groups, there was a significant interaction between genotype and diagnosis on hippocampus volumes. Post-hoc ANCOVA showed that hippocampal volumes of S/S homozygous depressed patients were smaller compared to healthy controls in both hemispheres. Conclusion: The 5-HTTLPR polymorphism has an effect on hippocampal volumes of depressed patients, which is apparent only in S/S genotype. It seems that decreased neurogenesis by effects of reduced serotoninergic transmission may be responsible for smaller hippocampal volumes observed in S/S homozygous depressed patients.

Brain regions associated with risk and resistance for bipolar I disorder: a voxel‐based MRI study of patients with bipolar disorder and their healthy siblings

Bipolar I disorder is a highly heritable disorder but not all siblings manifest with the illness, even though they may share similar genetic and environmental risk factors. Thus, sibling studies may help to identify brain structural endophenotypes associated with risk and resistance for the disorder.

No pituitary gland volume change in medication-free depressed patients

Increased serum cortisol levels and a hyperactive hypothalamo-pituitary-adrenal (HPA) axis have been proposed to play an important role in the pathophysiology of Major Depressive Disorder (MDD). However, there are inconsistent results regarding pituitary gland volume (PGV), which is one of the key elements of the HPA axis evaluated by MRI in depressed patients. In this study, we analyzed the PGV of medication-free moderately depressed MDD patients (N=34) and age and sex matched healthy controls (N=39). PGV did not differ between MDD patients and healthy controls [mean volume+/-S.D.; 0.76+/-0.17 cm3 and 0.75+/-0.14 cm3; ANCOVA, F1,69=1.25 p>0.05; respectively]. Our results confirm that volumetric PGV changes are not crucial for depression pathophysiology among unmedicated, moderately depressed adults.

The relationship between the anterior corpus callosum size and prefrontal cortex volume in drug-free depressed patients

INTRODUCTION An evolving literature suggests a volume reduction and a loss of functional integrity of prefrontal cortex in depressed patients. Interhemispheric prefrontal functional integrity is mediated via the anterior portion of the corpus callosum. Until recently interhemispheric fibers connecting prefrontal cortex have not been well defined. In this study, we compared the corpus callosum area of depressed patients with controls using a novel schema proposed by Hofer and Frahm (2006) which defined a specific anterior callosal area for prefrontal interhemispheric fibers. We further investigated the correlation between callosal area and prefrontal cortical volume. METHODS Thirty-six patients with major depressive disorder and thirty-three healthy controls were recruited. All subjects were psychotropic medication-free and right-handed. The imaging was performed on a 1.5T MR unit (Magnetom Vision Siemens). The images obtained from 3D MP-RAGE sequence were used for analyses. Medical Image Processing, Analyzing and Visualization (MIPAV) software was used for callosal and prefrontal measurements. RESULTS Depressed patients had reduced prefrontal cortical volume and a loss of the normal callosal/gray matter correlation, but normal white matter volume and normal callosal areas. LIMITATIONS It is not known if the observed changes were preexisting or acquired. CONCLUSION Our results indicate that the normal structural relationship between anterior callosal area and prefrontal cortical volume is disrupted in major depressive disorder and that the disruption is due to reduced cortical volume rather than to changes in interhemispheric connections.