[The power plants of the cell: Treatment of psychiatric symptoms in patients with mitochondriopathy]. / Die Kraftwerke der Zellen- über die Behandlung von psychiatrischen Symptomen bei Patienten mit Mitochondriopathien.

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.

Transcranial low-level laser therapy improves brain mitochondrial function and cognitive impairment in D-galactose-induced aging mice.

Mitochondrial function plays a key role in the aging-related cognitive impairment, and photoneuromodulation of mitochondria by transcranial low-level laser therapy (LLLT) may contribute to its improvement. This study focused on the transcranial LLLT effects on the D-galactose (DG)-induced mitochondrial dysfunction, apoptosis, and cognitive impairment in mice. For this purpose, red and near-infrared (NIR) laser wavelengths (660 and 810 nm) at 2 different fluencies (4 and 8 J/cm2) at 10-Hz pulsed wave mode were administrated transcranially 3 d/wk in DG-received (500 mg/kg/subcutaneous) mice model of aging for 6 weeks. Spatial and episodic-like memories were assessed by the Barnes maze and What-Where-Which (WWWhich) tasks. Brain tissues were analyzed for mitochondrial function including active mitochondria, adenosine triphosphate, and reactive oxygen species levels, as well as membrane potential and cytochrome c oxidase activity. Apoptosis-related biomarkers, namely, Bax, Bcl-2, and caspase-3 were evaluated by Western blotting method. Laser treatments at wavelengths of 660 and 810 nm at 8 J/cm2 attenuated DG-impaired spatial and episodic-like memories. Also, results showed an obvious improvement in the mitochondrial function aspects and modulatory effects on apoptotic markers in aged mice. However, same wavelengths at the fluency of 4 J/cm2 had poor effect on the behavioral and molecular indexes in aging model. This data indicates that transcranial LLLT at both of red and NIR wavelengths at the fluency of 8 J/cm2 has a potential to ameliorate aging-induced mitochondrial dysfunction, apoptosis, and cognitive impairment.

Chrysin exerts neuroprotective effects against 3-Nitropropionic acid induced behavioral despair-Mitochondrial dysfunction and striatal apoptosis via upregulating Bcl-2 gene and downregulating Bax-Bad genes in male wistar rats.

3-Nitropropionic acid (3-NP) is an irreversible inhibitor of mitochondrial complex-II that causes transcriptional dysregulation, bioenergetics failure, protein aggregation and oxidative damage similar to Huntington's disease (HD) pathogenesis. Chrysin, a bioactive flavonoid reported to have anti-inflammation, antioxidant, vasorelaxant and neuroprotective property. The present study was framed to determine the neuroprotective efficiency of chrysin upon 3-NP induced oxidative stress, mitochondrial dysfunctions and neurodegeneration. 3-NP (10mg/kg b.w. i.p.) administration for 14days exhibited significant (P<0.01) behavioral alterations, mitochondrial dysfunction and oxidative damages to biomolecules, finally causes cell death. Chrysin at 50mg/kg b.w. orally for 14days improved all the behavioral performances and regulated the complex activities in mitochondria. Further, chrysin diminished the oxidative stress markers (lipid peroxidation, nitrite and protein carbonyls) by significantly (P<0.01) improving the antioxidant status (superoxide dismutase, catalase and reduced glutathione) in striatal mitochondria. Indeed, chrysin prevents apoptosis by upregulating the Bcl-2 mRNA expression and downregulating the pro-apoptotic (Bax, Bad) mRNAs in 3-NP induced condition. Furthermore, the survival of striatal neurons against 3-NP toxicity was enhanced upon chrysin treatment which was evidenced by observing histopathological studies. Hence, the present study collectively suggests that the chrysin can serve as a potential therapeutic agent on 3-NP induced mitochondrial deficits and subsequent apoptosis.

Psychiatric disorders and mitochondrial dysfunctions.

BACKGROUND: Mitochondria play a key role in the production of the cell energy. The final product of this process is adenosine triphosphate (ATP), used as a source of chemical energy. Besides this major role, mithocondria have been shown to be involved in other functions, such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth. The aim of this paper is to highlight the relationships between psychiatric disorders, especially schizophrenia, bipolar disorder (BD), autism, attention deficit-hyperactivity disorder (ADHD) and Alzheimer's dementia. RESULTS: The review of the available literature indicate that different mitochondrial dysfunctions may accompany and/or be part of the clinical picture of some neuropsychiatric disorders. CONCLUSIONS: Different data would indicate that mitochondrial dysfunctions may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in the cell energy metabolism. Moreover, they would greatly contribute to the process of neural apoptosis that should be at the basis of neurodegenerative disorders, such as schizophrenia, Alzheimer's dementia and the most severe forms of BD. In addition, data are available that mithocondrial abnormalities are present also in developmental disorders, such as autism and ADHD, although the studies aiming at elucidating the role of mithocondria in the onset and pathophysiology of all these conditions should be considered preliminary. In any case, taken together, these scattered findings would suggest novel drugs targeting protecting mitochondria from oxidative stress.

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis.

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (≈ 0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD.

Psychiatric comorbidity in 36 adults with mitochondrial cytopathies.

INTRODUCTION: Mitochondria are intracellular organelles involved in adenosine triphosphate production. The literature has established the presence of mitochondrial dysfunction in some subjects with psychiatric disorders. Also, there are multiple reports of patients with mitochondrial dysfunction who have various psychiatric disorders. Although the literature on mitochondrial dysfunction and its relation to psychiatric disorders is growing, there remain many unanswered questions. OBJECTIVE: To review subjects with mitochondrial cytopathies for prevalence of psychiatric comorbidity. METHODS: For this study, 36 adults were interviewed. The Mini International Neuropsychiatric Interview and the Short-Form 36 Health Survey, version 1 were used. RESULTS: Lifetime diagnoses included 54% major depressive disorder, 17% bipolar disorder, and 11% panic disorder. These prevalence rates are compared with the general population and subjects with cancer and epilepsy. Subjects with a comorbid psychiatric diagnosis were older (P=.05), had more hospital admissions (P=.02), more medical conditions (P=.01), and lower quality of life (P=.01) than subjects with mitochondrial disease alone. CONCLUSION: Clinicians caring for persons with mitochondrial cytopathies should note the high prevalence of psychiatric problems. Also, this comorbidity might have etiological and therapeutic implications.