Introduction

Depression is one of the most common forms of mental disorder in the general population, and associated with high risk of death by suicide [1]. The amygdala is almond shape structure lies within the temporal lobe that has long been known to play a key role in emotional responses and emotional memory in both humans and animals [2]. Advance in neuroimaging techniques and methods used to extract the cortex and amygdala have allowed measurement of different structures continuously across the whole parts of the brain [3]. Magnetic resonance imaging (MRI) is the most appropriate technique used for anatomical evaluation of human brain structures; due to detailed resolution and its non-invasive properties. In many studies the Brain Suite tools allow excellent approach for measurement of amygdala from T1 weighted MRI images [4,5]. Different neuroimaging studies on patients with depression showed abnormalities in both hipocampus and amygdala [6,7]. Other studies proved that no structural change can occur [8-11]. The recurrences and the course of the disease have direct effect on the size of the amygdala as well as whole brain specifically gray matter [12]. Patients with recurrent depression episodes and young age onset had significant impact on the size left and right hipocampus and amygdala [13-16]. In contrast different studies show that the change had been just of the left side on hipocampus only [17]. The aim of this study is to detect structural alterations of the amygdala [18].

In this article we quantitated and evaluated the gray matter volume of amygdala changes using automatic segmentation tool (brain Suite).

Materials and Methods

The study comprised 50 patients with depression (25 male 25 female) Sudanese and 50 subjects control (25 male and 25 female) and, the total number of volunteers was 100 and their ages were ranging between 20- 40 years mean age 24 years. Sudanese adults clinically diagnosed as patients with depression by psychiatrists. All patients with depression should meet ICD/10 criteria. All patients with depression were or were not receive regular antidepressants medication.

The patients were selected from: Tigani Almahi and Taha Bashar Psychiatric Hospital. The control group has no history of: Psychiatric disorders drug abuse medication, head trauma, neurological diseases and congenital malformation related to the brain. Control subjects were matched with patients on the basis of gender and age. The Beck Depression Rating Scale and is also administered to the depressed patients.

MRI acquisitions

Structural MRI was done to both patients and healthy controls in the MRI section of the department of radiology in the AlAmal National Hospital. The scanner was Philips 1.5 Tesla Magnetom Avanto Vision System. T1- weighted images were obtained using three-dimensional acquisition by Magnetization Prepared Rapid Acquisition (MPRA); which produced good gray/white matter contrast in a very short acquisition time. Slice distance is 1.0 mm, the field of view was 250 read, 192 mm phase, TR=1657 ms, TE=2.95 ms, bandwidth 180 Hz/pixel, flip angle 30°, ECHO spacing=7.5ms, phase resolution=100%, slice resolution=50%, and acquisition time=5 minutes and 18 seconds. The images were in coronal sections. This T1-weighted sequence is part of the standard clinical protocol for qualitative and quantitative analysis of the whole brain in patients with epilepsy. All subjects were scanned in the supine position. The MR images scanner locked like a tunnel about 1.6 meters long surrounded by a large circular magnet. The subject lay on a couch without any metals and then entered into the scanner. When each picture was being taken the subject needed to keep still for a few minutes otherwise the scan picture may be blurred. The scan itself is painless. The whole procedure tacks six minutes, without contrast media.

Approval for the study was obtained from the ethics committee of the National Ribat University, AlAmal Hospital, Taha Bashar, Tigani Almahi Psychiatric Hospital.

MR images analysis tools

Analyses of images were performed on researcher’s computer after downloaded and setup of three programs: RadiAnt Dicom Viewer which was downloaded from www.radiantviewer.com;ImageJ which was downloaded from http://rsb.info.nih.gov/ij; and Brainsuite which was downloaded from http://brainsuite.org. Before analyzing MR images, the images must be manipulated by two programs RadiAnt Dicom Viewer and Image J.

Results

Student T. test revealed the mean volume of gray matter of right, left and total amygdala of patients with depression and controls were 1.77 cm3 , 1.78 cm3and 3.35 cm3 (± SD 2.13, 2.10 and 4.22) and 0.41 cm3 ,0.40 cm3 and 0.81cm3 (± SD 1.30, 1.52 and 2.82), respectively. There was significant difference between patients with depression and control group. P. Value<0.05 in Table 1

Table 1: Comparison of the mean of the gray matter volumes of amygdala between patients with depression and control.

The mean volume of gray matter of right, left and total amygdala of male patients with depression and controls were 1.37 cm³,1.40 cm³ and 2.72 cm³ (± SD 2.69, 2.64 and 5.32) and 0.16 cm3, 0.10 cm3 and 0.27 cm3 (± SD 0.20, 0.11 and 0.29), respectively. There was significant difference between patients with depression and control group. P. Value<0.05 in Table 2.

Table 2: Comparison of the mean of the gray matter volume of amygdala between male patients with depression and control.

The mean volume of gray matter of right, left and total amygdala of female patients with depression and controls were 2.17 cm³, 2.17 cm³and 4.34 cm³ (± SD 1.30, 1.30 and 2.59) and 0.65 cm³, 0.69 cm³ and 1.34 cm³ (± SD 1.82, 2.12 and 3.93), respectively. There was a significant difference between patients with depression and control group. P. Value<0.05 in Table 3.

Table 3: Comparison of the mean of the gray matter volume of amygdala between female patients with depression and
control.

Discussion

The results of the current study revealed that there were significant differences between genders in mean volumes of the gray matter of amygdala. This result is in line with the previous studies [19-21] including meta-analysis [22]. Other reports were in contrast to the present results [23,24]. However, the amygdala is a difficult structure to measure, because in many areas the ‘‘cortical amygdala’’ merges with surrounding structures. Particular boundaries selected can vary widely [25], especially, when it was done manually. However, automated voxel based morphometric studies regarding this issue reveled that there were reduction of gray matter volume of amygdala [26-28], with varying number of samples. The reduction in volume of amygdala due to “glucocorticoid neurotoxic effect” that could lead to neuronal damage [29]. This could be accepted since amygdala has glucocorticoid receptors as hipocampus did, a molecular study confirmed that [30]. However, increased gray matter volume of amygdala could be explained in different ways, firstly; functional magnetic resonance image (fMRI) study on depression has shown a dendritic hypertrophy in the amygdala in first episode of depression[31,32], this expansion could explained by increased reactivity of this brain region in patients with stress-related disorders. Support for this theory comes from animal studies, which showed that acute stress leads to increased dendritic arborization in the amygdala and overall neuronal growth [33].Secondly; genetic influence may play an important role in enlargement of amygdala in depression, especially for those subjects carrying the S-allele of the serotonin transporter promoter polymorphism [34]. Thirdly; Increased amygdala volume in first-episode patients with depression may be consistent with increased glucose metabolism in the amygdala of patients with depression [35]. Finally: enlarged amygdala volumes in first-episode in patients with depression may be due to numerous factors influencing brain volumes (e.g., vascular perfusion, synaptic plasticity, or aging processes) [19-21]. Our data showed that there is increased left side amygdala. Left hypertrophy of amygdala has been associated with depression [36]. It is suggested that this is due to the low glucocorticoid density receptors in left side [37]. The differences between brain structures across gender was the interest of neuroscientist for decades [38]. The results of the current study revealed that there were statistical significance differences between genders in mean volume of the gray matter of amygdala. The male volume is smaller than females in control comparing with depression and that was in line with published literature [39]. This enlargement in female could be explained due to presence of elevated estrogen hormone level in depression, but the mechanism of volume increase remains unclear [40]. Gene evaluations were not including in this study. Gene analysis among patients with depression would help understanding what possible gene might trigger this disease in future studies.

Conclusion

This paper evaluated the volume changes and comparisons between patients with depression and control using the automated segmentation techniques (Brain Suite). Quantitative data obtained allowed the researcher to make statistical comparison between groups. The data obtained in this paper is independent from the observer’s evaluation, therefore it was unbiased.

Our findings introduced a new evidence of abnormalities in amygdala volumes; the gray matter volumes of right, left and total amygdala were statistically different between patients with depression and control. The gray matter volumes of right, left, and total amygdala of males with depression were higher than control males. The gray matter volumes of right, left and total amygdala in females with depression were higher than control females. The gray volumes of right, left and total amygdala in females with depression were higher than males with depression. We can conclude that the disease resulted in a volume decrease in males more than in females.

Acknowledgements

The authors are greatly thanks to the technicians of the department of radiology in the Alamal hospital\ Sudan, for their humble and great contribution to this study and to the subjects who participated in collection of data.

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