The Limbic System in Youth Depression: Brain Structural and Functional Alterations in Adolescent In-patients with Severe Depression

Abstract

Adolescent-onset major depressive disorder (MDD) is associated with an increased risk of recurrent depressive episodes, suicidal behaviors, and psychiatric morbidity throughout the lifespan. The objective of the present study was to investigate brain structural and functional changes in adolescent patients with MDD. Furthermore, we aimed to clarify the influence of early-life stress on brain function and structure. The study investigated adolescent patients with severe MDD (n=20, mean age=16.0, range=15-18 years) and a control sample of matched healthy adolescents (n=21, mean age=16.6, range=15-18 years). Functional MRI data were obtained using a face-matching paradigm to investigate emotion processing. Structural MRI data were analyzed using voxel-based morphometry (VBM). In line with previous studies on adult MDD, adolescent patients showed elevated amygdala activity to negative and reduced amygdala activity to positive emotional stimuli. Furthermore, MDD patients showed smaller hippocampal volumes compared to healthy adolescents. Higher levels of childhood maltreatment were associated with smaller hippocampal volumes in both depressed patients and healthy controls, whereby no associations between amygdala reactivity and childhood maltreatment were found. Our results suggest that hippocampal alterations in youth MDD patients may at least partly be traced back to higher occurrence of early-life adverse experiences. Regarding the strong morphometric impact of childhood maltreatment and its distinctly elevated prevalence in MDD populations, this study provides an alternative explanation for frequently observed limbic structural abnormalities in depressed patients.

Antidepressant‐Like Effect of Ferulic Acid via Promotion of Energy Metabolism Activity

“…The brain tissues were isolated, washed with ice‐cold PBS, and immediately immersed in liquid nitrogen. As previous studies have pointed out the functional and structural alterations in the limbic area, including cerebral cortex and amygdala, in mouse models of depression and in adult patients with major depressive disorder, the limbic area of mice brain was focused to determine the mechanisms of anti‐depressant‐like effects of FA. The entire limbic area of the mouse brain containing the cortex, hippocampus, and amygdale was quickly dissected on ice and was minced for RNA extraction.…”

Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications

“…Magnesium deficiency has been shown to lead to changes in the functioning of the central nervous system (CNS), especially in the glutamatergic transmission in the limbic system and cerebral cortex [ 54 ]—brain regions that play important roles in the etiopathogenesis of depression [ 96 , 97 , 98 ]. Magnesium is particularly well known for its importance as an antagonist of the NMDA glutamate receptor, which has long been understood as a key player in synaptic potentiation, learning and memory [ 99 , 100 ].…”

The role of BDNF methylation and Val66Met in amygdala reactivity during emotion processing

“…Evidence supporting this hypothesis can also be derived from previous studies. First, higher BDNF DNA methylation has also been found in MDD patients (Kang et al, ), a diagnosis frequently associated with high amygdala reactivity (Redlich et al, ; Redlich et al, ; Stuhrmann et al, ). Second, it has been shown that the intake of epigenetic modifying medicaments like citalopram increases peripheral BDNF levels (Lopez et al, ) which goes along with reduced amygdala reactivity (Murphy, Norbury, O'Sullivan, Cowen, & Harmer, ).…”