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

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.

SUBMITTER: Tymofiyeva O

PROVIDER: S-EPMC5864120 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Tymofiyeva Olga O Henje Blom Eva E Ho Tiffany C TC Connolly Colm G CG Lindqvist Daniel D Wolkowitz Owen M OM Lin Jue J LeWinn Kaja Z KZ Sacchet Matthew D MD Han Laura K M LKM Yuan Justin P JP Bhandari Sarina P SP Xu Duan D Yang Tony T TT

Journal of affective disorders 20180217

<h4>Background</h4>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 exami ...[more]

PMID: 29500956

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Project description:BACKGROUND:Despite substantial evidence demonstrating numerous parental risk and protective factors for the development of adolescent depression and anxiety disorders, there is currently no single measure that assesses these parenting factors. To address this gap, we developed the Parenting to Reduce Adolescent Depression and Anxiety Scale (PRADAS) as a criterion-referenced measure of parental concordance with a set of evidence-based parenting guidelines for the prevention of adolescent depression and anxiety disorders. In this paper, we used a sample of Australian parents of adolescents to: (1) validate the PRADAS as a criterion-referenced measure; (2) examine parental concordance with the guidelines in the sample; and (3) examine correlates of parental concordance with the guidelines. METHODS:Seven hundred eleven parents completed the PRADAS, as well as two established parenting measures, and parent-report measures of adolescent depression and anxiety symptoms. Six hundred sixty adolescent participants (aged 12-15) also completed the symptom measures. Concordance with the guidelines was assessed via nine subscale scores and a total score. Reliability of the scores was assessed with an estimate of the agreement coefficient, as well as 1-month test-retest reliability. Convergent validity was examined via correlations between the scale and two established parenting measures. RESULTS:One proposed subscale was removed from the final version of the scale, resulting in a total of eight subscales. Reliability was high for the total score, and acceptable to high for seven of the eight subscales. One-month test-retest reliability was acceptable to high for the total score. Convergent validity was supported by moderate to high correlations with two established measures of parenting. Overall, rates of parental concordance with the guidelines were low in our sample. Higher scores were associated with being female and higher levels of parental education. Greater parental concordance with the guidelines was associated with fewer symptoms of depression and anxiety in adolescent participants. DISCUSSION:This initial validation study provides preliminary support for the reliability and validity of the PRADAS. The scale has potential for use in both clinical and research settings. It may be used to identify parents' strengths and potential targets for intervention, and as an outcome measure in studies of preventive parenting interventions.

Project description:BackgroundDepression is the leading cause of disability worldwide with > 50% of cases emerging before the age of 25 years. Large-scale neuroimaging studies in depression implicate robust structural brain differences in the disorder. However, most studies have been conducted in adults and therefore, the temporal origins of depression-related imaging features remain largely unknown. This has important implications for understanding aetiology and informing timings of potential intervention.MethodsHere, we examine associations between brain structure (cortical metrics and white matter microstructural integrity) and depression ratings (from caregiver and child), in a large sample (N = 8634) of early adolescents (9 to 11 years old) from the US-based, Adolescent Brain and Cognitive Development (ABCD) Study®. Data was collected from 2016 to 2018.FindingsWe report significantly decreased global cortical and white matter metrics, and regionally in frontal, limbic and temporal areas in adolescent depression (Cohen's d = -0⋅018 to -0⋅041, β = -0·019 to -0⋅057). Further, we report consistently stronger imaging associations for caregiver-reported compared to child-reported depression ratings. Divergences between reports (caregiver vs child) were found to significantly relate to negative socio-environmental factors (e.g., family conflict, absolute β = 0⋅048 to 0⋅169).InterpretationDepression ratings in early adolescence were associated with similar imaging findings to those seen in adult depression samples, suggesting neuroanatomical abnormalities may be present early in the disease course, arguing for the importance of early intervention. Associations between socio-environmental factors and reporter discrepancy warrant further consideration, both in the wider context of the assessment of adolescent psychopathology, and in relation to their role in aetiology.FundingWellcome Trust (References: 104036/Z/14/Z and 220857/Z/20/Z) and the Medical Research Council (MRC, Reference: MC_PC_17209).

Dataset Information

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

Publications

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

Similar Datasets

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