Voxel-based morphometric brain comparison between healthy subjects and major depressive disorder patients in Japanese with the s/s genotype of 5-HTTLPR

Abstract

Individuals with s/s genotype of serotonin transporter gene-linked promotor region (5-HTTLPR), which appear with a high frequency in Japanese, exhibit more diagnosable depression in relation to stressful life events than those with the s/l or l/l genotype. We prospectively investigated the brain volume changes in first-episode and medication naïve major depression disorder patients (MDD) with the s/s genotype in Japanese. We assessed the differences between 27 MDD with the s/s genotype and 44 healthy subjects (HS) with the same genotype using a whole-brain voxel-by-voxel statistical analysis of MRI. Gray matter volume in a brain region with significant clusters obtained via voxel-based morphometry analysis were measured and, as an exploratory analysis, evaluated for relationships to the subcategory scores (core, sleep, activity, psychic, somatic anxiety, delusion) of the Hamilton Depression Rating Scale (HAM-D) and the Social Readjustment Rating Scale (SRRS). The brain volume in the left insula lobe was significantly smaller in the MDD than in the HS. The left insula lobe volume correlated negatively with the “psychic” score of HAM-D and the SRRS. In a Japanese population with the s/s genotype, we found an atrophy of the insula in the MDD, which might be associated with “psychic” symptom and stress events.

Relationship between interleukin (IL)-6 and brain morphology in drug-naïve, first-episode major depressive disorder using surface-based morphometry

“…More recently, Igata et al . reported that the serotonin transporter genotype was associated with the volume of the gray matter in MDD patients 37 . Thus, further studies are required to explain the physiological systems in which IL-6 might be related to gray matter changes.…”

Volumetric Deficit Within the Fronto-Limbic-Striatal Circuit in First-Episode Drug Naïve Patients With Major Depression Disorder

“…An fMRI study detected increased insular activation to facial expressions of disgust in MDD ( 46 ), reflecting an emotion processing bias. Local connectivity reduction ( 47 ) and GMV reduction ( 48 ) in the insula was positively correlated with the magnitude of anxiety in MDD. Besides, depressed patients with increased appetite had a lower anterior insular surface area, substantiating insula's role in interoceptive awareness as well as reward processing and emotion regulation ( 49 ).…”

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

“…At the same time, during the analysis of separate polymorphisms, this link was earlier detected. For example, such association was detected for 5-HTTLPR variable number tandem repeat (VNTR) polymorphism in the promoter region of the serotonin transporter gene SLC6A4 [ 86 ]. Besides, for one of alleles of this polymorphism, was found an association between stress and anxiety symptoms, which is moderated by 5-HTTLPR [ 87 ].…”

“…A group of researchers Igata, N. et al, Caspi, A. et al, Zammit, S. et al, Karg, K. et al found that a short ‘S’ allele of the 5-hydroxytryptamine-linked polymorphic region polymorphism (5-HTTLPR) is associated with increased depression in a high-stress context [ 86 , 87 , 106 , 107 , 108 , 109 ]. Insertion deletion polymorphism (5-HTTLPR) is located in the promoter part of the serotonin transporter gene ( SLC6A4 ).…”

“…Insertion deletion polymorphism (5-HTTLPR) is located in the promoter part of the serotonin transporter gene ( SLC6A4 ). A possible cause of depression in a high-stress context may be the association of allele “S” with a deletion [ 86 , 87 , 110 , 111 ]. Often this occurs in patients in response to adverse environmental influences in childhood [ 106 , 111 , 112 ].…”