Die Kraftwerke der Zellen- über die Behandlung von psychiatrischen Symptomen bei Patienten mit Mitochondriopathien

Zusammenfassung

Einleitung Mitochondriopathien sind Erkrankungen der Zellorganellen, welche für die Herstellung des Energieträgers Adenosin-Tri-Phosphat (ATP) essentiell sind. Bei Mutationen entsteht eine mannigfaltige Symptomatik besonders jener Organe, welche auf eine stetige Energieversorgung angewiesen sind- wie zum Beispiel das Nervensystem. Obwohl psychiatrische Symptome bei Mitochondriopathien häufig sind, finden diese im klinischen Alltag kaum Beachtung.

Kasuistik Wir berichten über eine 21-jährige Patientin, welche aufgrund von Panikattacken und Depressionen unsere Akutambulanz aufsuchte. Die Patientin entwickelte im Vorfeld ausgeprägte Nebenwirkungen auf eine niedrigdosierte Sertralin-Therapie.

Schlussfolgerung Mitochondriopathien sind selten, bedürfen jedoch unbedingt einer Anpassung der psychopharmakologischen Therapie. Viele Psychopharmaka können die Atmungskette beeinträchtigen und so zur Entstehung von ausgeprägten Nebenwirkungen führen.

Abstract

Introduction Mitochondriopathies are pathologies of cell organelles, which are essential for the formation of adenosine triphosphate (ATP), which is responsible for cellular energy stock. When mitochondrial mutations occur, symptoms arise frequently in those organs that rely on a continuous energy supply, such as the nervous system. Although psychiatric illness is increasingly prevalent in patients with mitochondrial disease, less attention has been paid to its psychiatric presentations.

Case Report We describe a case of a 21-year-old woman who presented in our outpatient department with panic attacks and depression. The patient experienced major side effects after low-dose sertraline therapy.

Conclusion Mitochondriopathies belong to the class of rare illnesses in psychiatry; nevertheless, they require adaptations of psychopharmacological therapy. Psychotropic drugs are potential respiratory chain inhibitors and could lead to distinct side effects.

Schlüsselwörter

Mitochondriopathie - Panikstörung - Depression - Psychiatrie - Psychopharmakologie

Key words

mitochondriopathy - panic disorder - depression - psychiatry - psychopharmacology

• Literatur

• 1 Larsson N-G, Clayton DA. Molecular genetic aspects of human mitochondrial disorders. Annual review of genetics 1995; 29: 151-178
• 2 Schaefer AM, McFarland R, Blakely EL. et al. Prevalence of mitochondrial DNA disease in adults. Annals of neurology 2008; 63: 35-39
• 3 Bernier F, Boneh A, Dennett X. et al. Diagnostic criteria for respiratory chain disorders in adults and children. Neurology 2002; 59: 1406-1411
• 4 Chinnery PF. Mitochondrial disorders overview. 2014
• 5 te Riele M, Schreuder T, van Alfen N. et al. The yield of diagnostic work-up of patients presenting with myalgia, exercise intolerance, or fatigue: A prospective observational study. Neuromuscular Disorders. 2016 DOI: 10.1016/j.nmd.2016.12.002
• 6 Smits B, van den Heuvel L, Knoop H. et al. Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome. Mitochondrion 2011; 11: 735-738
• 7 Van Adel BA, Tarnopolsky MA. Metabolic myopathies: update 2009. Journal of clinical neuromuscular disease 2009; 10: 97-121
• 8 Fattal O, Link J, Quinn K. et al. Psychiatric comorbidity in 36 adults with mitochondrial cytopathies. CNS spectrums 2007; 12: 429-438
• 9 Amemiya S, Hamamoto M, Goto Y. et al. Psychosis and progressing dementia: presenting features of a mitochondriopathy. Neurology 2000; 55: 600-601
• 10 Anglin RE, Tarnopolsky MA, Mazurek MF. et al. The psychiatric presentation of mitochondrial disorders in adults. The Journal of neuropsychiatry and clinical neurosciences 2012; 24: 394-409
• 11 Anglin RE, Rosebush PI, Mazurek MF. Treating psychiatric illness in patients with mitochondrial disorders. Psychosomatics 2010; 51: 179
• 12 Fattal O, Budur K, Vaughan AJ. et al. Review of the literature on major mental disorders in adult patients with mitochondrial diseases. Psychosomatics 2006; 47: 1-7
• 13 Wallace DC, Singh G, Lott MT. et al. Mitochondrial DNA mutation associated with Leber‘s hereditary optic neuropathy. Science 1988; 242: 1427
• 14 DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. New England Journal of Medicine 2003; 348: 2656-2668
• 15 Toker L, Agam G. Mitochondrial dysfunction in psychiatric morbidity: current evidence and therapeutic prospects. Neuropsychiatric disease and treatment 2015; 11: 2441
• 16 Sequeira A, Rollins B, Magnan C. et al. Mitochondrial mutations in subjects with psychiatric disorders. PloS one. 2015 10. e0127280
• 17 Clay HB, Sillivan S, Konradi C. Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia. International Journal of Developmental Neuroscience 2011; 29: 311-324
• 18 Gershon ES, Badner JA, Detera-Wadleigh SD. et al. Maternal inheritance and chromosome 18 allele sharing in unilineal bipolar illness pedigrees. American Journal of Medical Genetics Part A 1996; 67: 202-207
• 19 Amar S, Shamir A, Ovadia O. et al. Mitochondrial DNA HV lineage increases the susceptibility to schizophrenia among Israeli Arabs. Schizophrenia research 2007; 94: 354-358
• 20 Shimamoto A, Rappeneau V. Sex-dependent mental illnesses and mitochondria. Schizophrenia Research. 2017 DOI: 10.1016/j.schres.2017.02.025
• 21 Wang Q, Dwivedi Y. Transcriptional profiling of mitochondria associated genes in prefrontal cortex of subjects with major depressive disorder. The World Journal of Biological Psychiatry. 2016 DOI: 10.1080/15622975.2016
• 22 Chang C-C, Jou S-H, Lin T-T. et al. Mitochondria DNA change and oxidative damage in clinically stable patients with major depressive disorder. PloS one 2015; 10: e0125855
• 23 Boles RG, Burnett BB, Gleditsch K. et al. A high predisposition to depression and anxiety in mothers and other matrilineal relatives of children with presumed maternally inherited mitochondrial disorders. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 2005; 137: 20-24
• 24 Su YA, Wu J, Zhang L. et al. Dysregulated mitochondrial genes and networks with drug targets in postmortem brain of patients with posttraumatic stress disorder (PTSD) revealed by human mitochondria-focused cDNA microarrays. International journal of biological sciences 2008; 4: 223
• 25 Kim HK, Mendonça KM, Howson PA. et al. The link between mitochondrial complex I and brain-derived neurotrophic factor in SH-SY5Y cells–The potential of JNX1001 as a therapeutic agent. European journal of pharmacology 2015; 764: 379-384
• 26 Callaly E, Walder K, Morris G. et al. Mitochondrial dysfunction in the pathophysiology of bipolar disorder: effects of pharmacotherapy. Mini reviews in medicinal chemistry 2015; 15: 355-365
• 27 Machado AK, Andreazza AC, da Silva TM. et al. Neuroprotective Effects of Açaí (Euterpe oleracea Mart.) against Rotenone In Vitro Exposure. Oxidative medicine and cellular longevity 2016; 2016
• 28 Nussbaumer M, Asara JM, Teplytska L. et al. Selective mitochondrial targeting exerts anxiolytic effects in vivo. Neuropsychopharmacology 2016; 41: 1751-1758
• 29 de Oliveira MR. Fluoxetine and the mitochondria: A review of the toxicological aspects. Toxicology Letters 2016; 258: 185-191
• 30 Abdel-Razaq W, Kendall D, Bates T. The effects of antidepressants on mitochondrial function in a model cell system and isolated mitochondria. Neurochemical research 2011; 36: 327-338
• 31 Hroudova J, Fisar Z. Activities of respiratory chain complexes and citrate synthase influenced by pharmacologically different antidepressants and mood stabilizers. Neuroendocrinol Lett 2010; 31: 336-342
• 32 Li Y, Couch L, Higuchi M. et al. Mitochondrial dysfunction induced by sertraline, an antidepressant agent. Toxicological Sciences. 2012 DOI: 10.1093/toxsci/kfs100
• 33 Woynillowicz AK, Raha S, Nicholson CJ. et al. The effect of smoking cessation pharmacotherapies on pancreatic beta cell function. Toxicology and applied pharmacology 2012; 265: 122-127
• 34 Burkhardt C, Kelly JP, Lim YH. et al. Neuroleptic medications inhibit complex I of the electron transport chain. Annals of neurology 1993; 33: 512-517
• 35 Ponchaut S, Veitch K. Valproate and mitochondria. Biochemical pharmacology 1993; 46: 199-204
• 36 Finsterer J. Toxicity of antiepileptic drugs to mitochondria. 2016 DOI: 10.1007/164_2016_2
• 37 Klopstock T, Jaksch M, Gasser T. Age and cause of death in mitochondrial diseases. Neurology 1999; 53: 855-855
• 38 Rodriguez MC, MacDonald JR, Mahoney DJ. et al. Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders. Muscle & nerve 2007; 35: 235-242
• 39 Tarnopolsky M. The mitochondrial cocktail: rationale for combined nutraceutical therapy in mitochondrial cytopathies. Advanced drug delivery reviews 2008; 60: 1561-1567
• 40 Wright D, Renoir T, Smith Z. et al. N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington‘s disease. Translational psychiatry 2015; 5: e492
• 41 Srinivasan V, Spence DW, Pandi-Perumal SR. et al. Melatonin in mitochondrial dysfunction and related disorders. International Journal of Alzheimer’s Disease 2011; 2011