Major depression in adolescent children consecutively diagnosed with mitochondrial disorder

• Published in: Journal of affective disorders Vol. 114; no. 1; pp. 327 - 332
• Main Authors: Koene, S, Kozicz, T.L, Rodenburg, R.J.T, Verhaak, C.M, de Vries, M.C, Wortmann, S, van de Heuvel, L, Smeitink, J.A.M, Morava, E
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.04.2009; Elsevier
• Subjects: Adolescent; Adult and adolescent clinical studies; Aetiology; Biological and medical sciences; Central nervous system; Child; Child, Preschool; Children; Comorbidity; Depression; Depressive Disorder, Major - diagnosis; Depressive Disorder, Major - epidemiology; Depressive Disorder, Major - genetics; DNA, Mitochondrial - genetics; Errors of metabolism; Female; Genetic disorders; Genetic Predisposition to Disease; Genotype; Humans; Lactic acid; Life stress; Magnetic Resonance Imaging; Male; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Mitochondrial Diseases - diagnosis; Mitochondrial Diseases - epidemiology; Mitochondrial Diseases - genetics; Mitochondrial medicine; Mood disorders; Netherlands; Oxidative phosphorylation; PDHC; Phenotype; POLG; Psychiatric Status Rating Scales; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Sequence Deletion; Netherlands; VEP; 3MTYR; polymerase gamma; CNS; OXPHOS; homovanillic acid; PDHC; mitochondrial encephalopathy, lactic acidosis, stroke-like episodes; TRP; CBCL; CSF; mitochondrial encephalopathy, ragged red fibers; 5-hydroxy tryptophane; tryptophane; visual evoked potentials; HDRS; Newcastle Paediatric Mitochondrial Disease Scale; Kearns Sayres syndrome; POLG; Child Behavior Checklist for Children; cerebral spinal fluid; Depression; KSS; NPMDS; brainstem auditory evoked potentials; oxidative phosphorylation; central nervous system; HVA; 5-hydroxyindoleacetic acid; MERRF; Hamilton Depression Rating Scale; BAEP; 3-methoxy-4-hydroxyphenylglycol; 5-HIAA; 5HTP; MHPG; Mitochondrial medicine; sensory evoked potentials; MELAS; 3-methyltyrosine; Lactic acid; SEP; Oxidative phosphorylation; Human; Mood disorder; Metabolic diseases; Enzymopathy; Mitochondrial disorder; Genetic disease; Medicine; Mitochondria; Adolescent; Child
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2008.06.023

Abstract A higher incidence of major depression has been described in adults with a primary oxidative phosphorylation disease. Intriguingly however, not all patients carrying the same mutation develop symptoms of major depression, pointing out the significance of the interplay of genetic and non-genetic factors in the etiology. In a series of paediatric patients evaluated for mitochondrial dysfunction, out of 35 children with a biochemically and genetically confirmed mitochondrial disorder, we identified five cases presenting with major depression prior to the diagnosis. The patients were diagnosed respectively with mutations in MTTK , MTND1 , POLG1 , PDHA1 and the common 4977 bp mtDNA deletion. Besides cerebral lactic acidemia protein and glucose concentrations, immunoglobins, anti-gangliosides and neurotransmitters were normal. No significant difference could be confirmed in the disease progression or the quality of life, compared to the other, genetically confirmed mitochondrial patients. In three out of our five patients a significant stress life event was confirmed. We propose the abnormal central nervous system energy metabolism as the underlying cause of the mood disorder in our paediatric patients. Exploring the genetic etiology in children with mitochondrial dysfunction and depression is essential both for safe medication and adequate counselling.