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J Affect Disord. 2018 May;232:283-290. doi: 10.1016/j.jad.2018.02.024. Epub 2018 Feb 17.

High levels of mitochondrial DNA are associated with adolescent brain structural hypoconnectivity and increased anxiety but not depression.

Author information

1
Department of Radiology & Biomedical Imaging, University of California San Francisco, United States. Electronic address: Olga.Tymofiyeva@ucsf.edu.
2
Department of Psychiatry and Weill Institute for Neurosciences, University of California San Francisco, United States; Department of Clinical Sciences/ Child, and Adolescent Psychiatry, Umeå University, Umeå, Sweden.
3
Department of Psychiatry and Weill Institute for Neurosciences, University of California San Francisco, United States; Department of Psychology, Stanford University, United States.
4
Department of Psychiatry and Weill Institute for Neurosciences, University of California San Francisco, United States.
5
Department of Psychiatry and Weill Institute for Neurosciences, University of California San Francisco, United States; Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Psychiatry, Lund, Sweden.
6
Department of Biochemistry and Biophysics, University of California San Francisco, United States.
7
Department of Psychiatry and Behavioral Sciences, Stanford University, United States.
8
Department of Psychiatry, Amsterdam Neuroscience, VU University Medical Center, GGZ inGeest, Amsterdam Public Health research institute, Amsterdam, The Netherlands.
9
Department of Radiology & Biomedical Imaging, University of California San Francisco, United States.

Abstract

BACKGROUND:

Adolescent anxiety and depression are highly prevalent psychiatric disorders that are associated with altered molecular and neurocircuit profiles. Recently, increased mitochondrial DNA copy number (mtDNA-cn) has been found to be associated with several psychopathologies in adults, especially anxiety and depression. The associations between mtDNA-cn and anxiety and depression have not, however, been investigated in adolescents. Moreover, to date there have been no studies examining associations between mtDNA-cn and brain network alterations in mood disorders in any age group.

METHODS:

The first aim of this study was to compare salivary mtDNA-cn between 49 depressed and/or anxious adolescents and 35 well-matched healthy controls. The second aim of this study was to identify neural correlates of mtDNA-cn derived from diffusion tensor imaging (DTI) and tractography, in the full sample of adolescents.

RESULTS:

There were no diagnosis-specific alterations in mtDNA-cn. However, there was a positive correlation between mtDNA-cn and levels of anxiety, but not depression, in the full sample of adolescents. A subnetwork of connections largely corresponding to the left fronto-occipital fasciculus had significantly lower fractional anisotropy (FA) values in adolescents with higher than median mtDNA-cn.

LIMITATIONS:

Undifferentiated analysis of free and intracellular mtDNA and use of DTI-based tractography represent this study's limitations.

CONCLUSIONS:

The results of this study help elucidate the relationships between clinical symptoms, molecular changes, and neurocircuitry alterations in adolescents with and without anxiety and depression, and they suggest that increased mtDNA-cn is associated both with increased anxiety symptoms and with decreased fronto-occipital structural connectivity in this population.

KEYWORDS:

Adolescent depression; Anxiety; Brain connectivity; DTI; MRI; Mitochondrial DNA

PMID:
29500956
PMCID:
PMC5864120
[Available on 2019-05-01]
DOI:
10.1016/j.jad.2018.02.024
[Indexed for MEDLINE]

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