Left a-iHyp volume mediates the association between depression and sleep in adolescent depression
Poster No:
520
Submission Type:
Abstract Submission
Authors:
Xinyue Hu1, Ruohan Feng2, Yingxue Gao3, Zilin Zhou4, Weijie Bao5, Guoping Huang6, Xiaoqi Huang3
Institutions:
1West China Hospital, Chengdu,China, 2The Third Hospital of Mianyang, Mianyang, China, 3Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, 4Sichuan University West China Hospital Department of Radiology, Chengdu, SiChuan, 5Sichuan University West China Hospital Department of Radiology, Chengdu, Sichuan, 6Department of Psychiatry, Mianyang, sichuan
First Author:
Co-Author(s):
Yingxue Gao
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan
Xiaoqi Huang
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan
Introduction:
The hypothalamus is a complex and heterogeneous structure and alterations in its subunits play different roles in the pathophysiology of major depressive disorder (MDD)(Otte, Gold et al. 2016). For instance, anterior-superior hypothalamus (a-sHyp), primarily contains the paraventricular nucleus, is involved in modulating the stress response (Daviu, Füzesi et al. 2020). The anterior-inferior hypothalamus (a-iHyp) subunit, comprising the suprachiasmatic nucleus, is involved in regulating circadian rhythms (Xu, Berto et al. 2021). To date, only one study has reported that enlargement of the left hypothalamus does not extend to the mammillary body in unmedicated adult patients with MDD relative to HCs, indicating that MDD may affect certain subunits rather than the whole hypothalamus (Nowak, Schindler et al. 2023). Given age-specific neuroanatomic differences in MDD (Schmaal, Hibar et al. 2017), subunit-level hypothalamic abnormalities in adolescent MDD (aMDD) remain unclear. Research has shown that poor sleep quality, difficult interpersonal relationships and high study pressure are significant risk factors for developing aMDD (Alonzo, Hussain et al. 2021, Steare, Gutiérrez Muñoz et al. 2023). However, how hypothalamic abnormalities may contribute to the interplay of sleep, life events and emotional deficits in aMDD remain undetermined.
Methods:
High-resolution 3D T1-weighted images were obtained with a (MPRAGE) sequence from 83 treatment-naïve patients with aMDD and 59 healthy controls (HCs) matched for age, sex, years of education, and handedness. MRI data were preprocessed and segmented into ten bilateral hypothalamic subunits including bilateral a-iHyp, a-sHyp, posHyp, inferior tubular hypothalamus (infTub), and superior tubular hypothalamus (supTub) with FreeSurfer software (Fig.1A). The HAMD-24 and HAMA-14 scales were used to evaluate the severity of depression and anxiety symptoms of all subjects, respectively. Sleep quality was assessed using the PSQI. The frequency and intensity of stressful life events over the past 12 months were assessed using the ASLEC. A general linear model (GLM) was applied to examine differences in whole hypothalamic volumes and subunit-level volumes between groups for each hemisphere separately. Partial correlation analyses were conducted to examine the relationships between hypothalamic measurements, clinical features and adolescent life events in aMDD patients and HCs separately. All tests were adjusted for the effects of age, sex, education years and intracranial volume (ICV) as covariates. Subsequently, mediation analyses were performed to investigate the interrelationships among hypothalamic volume, PSQI scores, and clinical measures.
Results:
Patients with aMDD exhibited significantly higher HAMD-24 scores compared to HCs, as well as higher HAMA-14 scores, PSQI scores, and scores across the six dimensions of the ASLEC. The left a-iHyp volumes were significantly smaller, whereas the right infTub volumes were significantly larger in patients with aMDD compared with HCs (pFDR-corrected<0.05, Fig. 1B). A significant positive correlation was observed between the HAMD total scores and PSQI total scores in patients with aMDD (pFDR-corrected<0.05, Fig. 2B). The volumes of the left a-iHyp were significantly negatively correlated with both the HAMD scores and the PSQI scores in the patients with aMDD (pFDR-corrected<0.05, Fig. 2B). Additionally, the volumes of left a-sHyp were significantly negatively correlated with punishment scores and lost scores in the HCs (pFDR-corrected<0.05, Fig.2B). Further, mediation analyses showed that the volumes of left a-iHyp partially mediated the effect of HAMD scores on PSQI scores (p <0.05, Fig. 2C).
·fig.1
·fig.2
Conclusions:
The volume of the left a-iHyp has been identified as a potential neural substrate mediating the link between poor sleep quality and depressive severity in aMDD. It also may be a potential target region for guiding clinical treatment of sleep problems in aMDD.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures 2
Keywords:
Affective Disorders
Emotions
Psychiatric Disorders
Sleep
STRUCTURAL MRI
Sub-Cortical
1|2Indicates the priority used for review
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Nowak, M., Schindler, S., Storch, M., Geyer, S., & Schönknecht, P. (2023). Mammillary body and hypothalamic volumes in mood disorders. J Psychiatr Res, 158, 216-225. doi:10.1016/j.jpsychires.2022.12.004
Otte, C., Gold, S. M., Penninx, B. W., Pariante, C. M., Etkin, A., Fava, M., . . . Schatzberg, A. F. (2016). Major depressive disorder. Nat Rev Dis Primers, 2, 16065. doi:10.1038/nrdp.2016.65
Schmaal, L., Hibar, D. P., Sämann, P. G., Hall, G. B., Baune, B. T., Jahanshad, N., . . . Veltman, D. J. (2017). Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group. Mol Psychiatry, 22(6), 900-909. doi:10.1038/mp.2016.60
Steare, T., Gutiérrez Muñoz, C., Sullivan, A., & Lewis, G. (2023). The association between academic pressure and adolescent mental health problems: A systematic review. J Affect Disord, 339, 302-317. doi:10.1016/j.jad.2023.07.028
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