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

Tymofiyeva, Olga; Henje Blom, Eva; Ho, Tiffany C.; Connolly, Colm G.; Lindqvist, Daniel LU ; Wolkowitz, Owen M.; Lin, Jue; LeWinn, Kaja Z.; Sacchet, Matthew D. and Han, Laura K.M., et al. (2018) In Journal of Affective Disorders 232. p.283-290
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... (More)

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.

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published
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keywords
Adolescent depression, Anxiety, Brain connectivity, DTI, Mitochondrial DNA, MRI
in
Journal of Affective Disorders
volume
232
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:85042678947
ISSN
0165-0327
DOI
10.1016/j.jad.2018.02.024
language
English
LU publication?
yes
id
21048067-0a9e-4cc5-b5e0-2ed0d8ee1d62
date added to LUP
2018-03-28 10:55:01
date last changed
2019-02-20 11:12:15
@article{21048067-0a9e-4cc5-b5e0-2ed0d8ee1d62,
  abstract     = {<p>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.</p>},
  author       = {Tymofiyeva, Olga and Henje Blom, Eva and Ho, Tiffany C. and Connolly, Colm G. and Lindqvist, Daniel and Wolkowitz, Owen M. and Lin, Jue and LeWinn, Kaja Z. and Sacchet, Matthew D. and Han, Laura K.M. and Yuan, Justin P. and Bhandari, Sarina P. and Xu, Duan and Yang, Tony T.},
  issn         = {0165-0327},
  keyword      = {Adolescent depression,Anxiety,Brain connectivity,DTI,Mitochondrial DNA,MRI},
  language     = {eng},
  pages        = {283--290},
  publisher    = {Elsevier},
  series       = {Journal of Affective Disorders},
  title        = {High levels of mitochondrial DNA are associated with adolescent brain structural hypoconnectivity and increased anxiety but not depression},
  url          = {http://dx.doi.org/10.1016/j.jad.2018.02.024},
  volume       = {232},
  year         = {2018},
}