Cagdas Eker

Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients

Researchers have reported that serum brain–derived neurotrophic factor (sBDNF) of drug–free depressed patients are lower than those of healthy controls and proposed that low sBDNF levels might reflect failure of neuronal plasticity in depression. In this study, we compared sBDNF levels of depressed patients (n = 28) before and after 8 weeks of antidepressant treatment, with those of healthy controls (n = 18) to test the hypothesis that initially low sBDNF levels of drug–free depressed patients will increase parallel with their clinical response to antidepressant treatment. The severity of depression and response to treatment were assessed with Hamilton Rating Scale for Depression (HAM–D). sBDNF was assayed with the sandwich ELISA method. Baseline sBDNF levels of patients (mean, 20.8 ng/ml; [S.D., 6.7]) were significantly lower than those of controls (mean, 26.8 ng/ml; [S.D., 9.3]; p = 0.015), and were negatively correlated with HAM–D scores (r = –0.49, p = 0.007). After 8 weeks of treatment, sBDNF levels of patients had increased significantly (mean, 33.3 ng/ml; [S.D., 9.9]; p < 0.001) and no longer differed from those of controls. These results support the hypothesis that BDNF might play a critical role in the pathophysiology of major depressive disorder and successful antidepressant treatment increases the attenuated BDNF levels in depressed patients.

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.

Volumetric MRI studies of the hippocampus in major depressive disorder: Meanings of inconsistency and directions for future research.

There are numerous magnetic resonance imaging (MRI) studies investigating the hippocampal volumetric differences between depressed and healthy subjects. Although there are inconsistencies among study results, a smaller hippocampal volume in depressed patients is thought to be related to the pathophysiology of the disease. Many factors appear to affect hippocampal volumes in major depressive disorder patients. Among these factors, recurrency, severity and the individual patient are the most pronounced. Patient groups with a mean age older than 40 years, or samples consisting of patients who have had severe or multiple episodes are more likely to demonstrate smaller hippocampal volumes. The possible causes of this relationship are discussed to give new perspectives to future research.

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.

Altered hippocampal formation shape in first-episode depressed patients at 5-year follow-up.

It is generally accepted that patients with major depressive disorder have smaller hippocampus size compared to healthy people. However, it is still not known if this situation exists before the onset of the disease or is a result of the toxic mechanism created by the depression itself. The findings of the long-term follow-up studies of first-episode depressed patients might contribute to solve the ongoing problem. In this study, the hippocampus of 18 first-episode patients who were followed-up for 5 years, were compared with those of healthy controls. There were no volumetric differences among groups neither at the baseline nor after 5 years of follow-up. However, shape analyses, using high dimensional mapping methods, revealed regional structural changes in the head and tail of the hippocampal formation in CA1 and subiculum regions in patients at the follow-up. Furthermore, a significant negative correlation was found with the number of days in depression without antidepressant treatment in the CA1 region in the head and tail of the hippocampal formation bilaterally. The findings of this study support the hypothesis that pathophysiological processes of depression induce structural alterations in depressed patients.

Cortical thickness and VBM in young women at risk for familial depression and their depressed mothers with positive family history

It has been demonstrated that compared to low-risk subjects, high-risk subjects for depression have structural and functional alterations in their brain scans even before the disease onset. However, it is not known if these alterations are related to vulnerability to depression or epiphenomena. One way to resolve this ambiguity is to detect the structural alterations in the high-risk subjects and determine if the same alterations are present in the probands. In this study, we recruited 24 women with the diagnosis of Major Depressive Disorder (MDD) with recurrent episodes and their healthy daughters (the high-risk for familial depression group; HRFD). We compared structural brain scans of the patients and HRFG group with those of 24 age-matched healthy mothers and their healthy daughters at similar ages to the HRFD group; respectively. Both cortical gray matter (GM) volume and thickness analyses revealed that HRFD daughters and their MDD mothers had similar GM differences in two regions: the right temporoparietal region and the dorsomedial prefrontal cortex. These results suggested that the observed alterations may be related to trait clinical and neurophysiological characteristics of MDD and may present before the onset of illness.

Hippocampal shape alterations in healthy young women with familial risk for unipolar depression

BACKGROUND Although reduced hippocampal volume (HCV) is a common finding in depression, it is unclear whether the structural alterations leading to reduction of HCV are pre-existing risk factors before the onset of clinical symptoms or a cumulative process that begins with the onset of clinical symptoms. The aim of the present study was to understand the anatomical status of the hippocampus prior to the clinical symptoms in subjects with high familial risk for depression. METHODS Twenty-seven young women (mean age: 22.3 ± 2.1 years) who were at high risk for familial unipolar depression and 26 age- and gender-matched healthy controls (mean age: 22.1 ± 2.1 years) with low familial risk for depression were included in the study. Total hippocampal volumes were measured by manual tracing. For 3D shape differences, the spherical harmonic basis functions (SPHARM) software was used. The segmented images were parameterized, and the point-to-point based group difference was compared by the Hotellings T-squared test with total brain volume and Beck Depression Scale as covariates. RESULTS Although there was no difference in overall HCVs, shape analyses revealed a contracted area on the Cornu Ammonis (CA) 1 region of the right hippocampus head in the high-risk group compared to the low-risk group. Cross-sectional design and small sample size, including only females, were the main limitations of this study. CONCLUSION This study with shape analyses provided data suggesting that local structural hippocampal alterations in the CA1 region might be associated with depression vulnerability in women at high risk.

Comparison of atlas based segmentation and manual segmentation of hippocampus

High-resolution Magnetic resonance imaging (MRI) is helpful in diagnosing diseases such as schizophrenia, alzheimer, dementia etc. Brain segmentation is an important preprocess in medical imaging applications. In this study we compare atlas based segmentation and manual segmentation of hippocampus for volumetric measures. A statistically difference was obtained between automatic and manual measurement. We conclude that contemporary techniques are not adequate to obtain sensitive data in some barin structures such as hippocampus core.