The Abnormal Functional Connectivity between the Hypothalamus and the Temporal Gyrus Underlying Depression in Alzheimer's Disease Patients.

Xiaozheng Liu,Guanghui Bai,Hongtao Hou,Yunhai Tu,Xiaoyan Huang,Zhongwei Guo,Xingli Chen,Wei Chen

doi:10.3389/fnagi.2018.00037

Abstract

Hypothalamic communication with the rest of the brain is critical for accomplishing a wide variety of physiological and psychological functions, including the maintenance of neuroendocrine circadian rhythms and the management of affective processes. Evidence has shown that major depressive disorder (MDD) patients exhibit increased functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Neurofibrillary tangles are also found in the hypothalamus of Alzheimer’s disease (AD) patients, and AD patients exhibit abnormal changes in the HPA. However, little is known of how the hypothalamus interacts with other brain regions in AD patients with depression (D-AD). Functional connectivity (FC) analysis explores the connectivity between brain regions that share functional properties. Here, we used resting-state (rs) magnetic resonance imaging (MRI) technology and the FC method to measure hypothalamic connectivity across the whole brain in 22 D-AD patients and 21 non-depressed AD patients (nD-AD). Our results showed that D-AD patients had reduced FC among the hypothalamus, the right middle temporal gyrus (MTG) and the right superior temporal gyrus (STG) compared with the FC of nD-AD patients, suggesting that the abnormal FC between the hypothalamus and the temporal lobe may play a key role in the pathophysiology of depression in AD patients.

Highlights

Symptoms of major depression of varying severity are a common comorbidity in Alzheimer’s disease (AD), with a prevalence of up to 63% in patients with AD (Khundakar and Thomas, 2015)
The D-AD and non-depressed AD patients (nD-AD) groups were well matched in terms of age (t = −1.414, P = 0.165), sex distribution (χ 2 = 0.024, P = 1.000), and years of education (t = 0.757, P = 0.453)
We found that, compared with the nD-AD patients, the D-AD patients exhibited reduced Functional connectivity (FC) among the hypothalamus, the right middle temporal gyrus (MTG) and the right superior temporal gyrus (STG), suggesting that abnormal FC between the hypothalamus and the temporal lobe plays a key role in the pathophysiology of depression in AD patients

Summary

Introduction

Symptoms of major depression of varying severity are a common comorbidity in Alzheimer’s disease (AD), with a prevalence of up to 63% in patients with AD (Khundakar and Thomas, 2015). These symptoms result in more rapid functional decline and loss of independence, and even shorter survival lengths (Lyketsos and Lee, 2004; Chi et al, 2015). Both psychiatric and neurological disorders recognize the occurrence of affective and psychotic symptoms in patients with AD, the underlying mechanisms of depressive symptoms in these patients. With the development of medical imaging, numerous neuroimaging studies have investigated the neurobiological roles of the hypothalamus in MDD patients (Baeken et al, 2009; Gao et al, 2013; Sudheimer et al, 2015)

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