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Mitochondria psychiatric

Akiko Shimamoto, Virginie Rappeneau
The prevalence of some mental illnesses, including major depression, anxiety-, trauma-, and stress-related disorders, some substance use disorders, and later onset of schizophrenia, is higher in women than men. While the higher prevalence in women could simply be explained by socioeconomic determinants, such as income, social status, or cultural background, extensive studies show sex differences in biological, pharmacokinetic, and pharmacological factors contribute to females' vulnerability to these mental illnesses...
March 6, 2017: Schizophrenia Research
R Norkett, S Modi, J T Kittler
Ion transport during neuronal signalling utilizes the majority of the brain's energy supply. Mitochondria are key sites for energy provision through ATP synthesis and play other important roles including calcium buffering. Thus, tightly regulated distribution and function of these organelles throughout the intricate architecture of the neuron is essential for normal synaptic communication. Therefore, delineating mechanisms coordinating mitochondrial transport and function is essential for understanding nervous system physiology and pathology...
January 10, 2017: Schizophrenia Research
George B Stefano, Joshua Samuel, Richard M Kream
Clinical usage of several classes of antibiotics is associated with moderate to severe side effects due to the promotion of mitochondrial dysfunction. We contend that this may be due to perturbation of unique evolutionary relationships that link selective biochemical and molecular aspects of mitochondrial biology to conserved enzymatic processes derived from bacterial progenitors. Operationally, stereo-selective conformational matching between mitochondrial respiratory complexes, cytosolic and nuclear signaling complexes appears to support the conservation of a critically important set of chemical messengers required for existential regulation of homeostatic cellular processes...
January 7, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
T M Murphy, B Crawford, E L Dempster, E Hannon, J Burrage, G Turecki, Z Kaminsky, J Mill
Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25))...
January 3, 2017: Translational Psychiatry
Prakash Devaraju, Stanislav S Zakharenko
Mitochondrial ATP synthesis, calcium buffering, and trafficking affect neuronal function and survival. Several genes implicated in mitochondrial functions map within the genomic region associated with 22q11.2 deletion syndrome (22q11DS), which is a key genetic cause of neuropsychiatric diseases. Although neuropsychiatric diseases impose a serious health and economic burden, their etiology and pathogenesis remain largely unknown because of the dearth of valid animal models and the challenges in investigating the pathophysiology in neuronal circuits...
February 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Nancy Monroy-Jaramillo, Elena Dyukova, Consuelo Walss-Bass
Objectives Psychiatric and substance use disorders have been associated with premature biological ageing. Telomere length (TL), considered an ageing marker, has been analyzed in psychiatric disorders, and to a lesser extent in substance use disorders, with recent findings suggesting TL may be related to disease pathology. Methods We conducted a critical and non-systematic literature search of TL studies published up to June 2016 in psychiatric and substance use disorders, focusing on studies describing mechanisms, including studies linking telomere biology with genetic factors, stress, and mitochondrial alterations (104 studies selected)...
December 21, 2016: World Journal of Biological Psychiatry
Erik A Ehli, Abdel Abdellaoui, Iryna O Fedko, Charlie Grieser, Sahar Nohzadeh-Malakshah, Gonneke Willemsen, Eco Jc de Geus, Dorret I Boomsma, Gareth E Davies, Jouke J Hottenga
As an example of optimizing population-specific genotyping assays using a whole-genome sequence reference set, we detail the approach that followed to design the Axiom-NL array which is characterized by an improved imputation backbone based on the Genome of the Netherlands (GoNL) reference sequence and, compared with earlier arrays, a more comprehensive inclusion of SNPs on chromosomes X, Y, and the mitochondria. Common variants on the array were selected to be compatible with the Illumina Psych Array and the Affymetrix UK Biobank Axiom array...
February 2017: European Journal of Human Genetics: EJHG
Rodrigo A Quintanilla, Cheril Tapia, María José Pérez
Huntington disease (HD) is a devastating neurological disorder that affects the striatum and cortex of patients. HD patients develop progressive motor dysfunction and psychiatric disturbances with gradual dementia. HD is caused by a pathological expansion of CAG repeats in the huntingtin gene that codifies for a protein called huntingtin (Htt), which principal function is not completely understood. Accumulative evidence shows that this pathological expansion modifies Htt function affecting different neuronal targets, including mitochondrial function which is an important factor that contributes to HD...
February 19, 2017: Biochemical and Biophysical Research Communications
Miroslav Adzic, Zeljka Brkic, Sonja Bulajic, Milos Mitic, Marija B Radojcic
Preclinical Research Mitochondria are cell organelles crucial to the production of cellular energy. Several lines of evidence have indicated that mitochondrial dysfunction could be related to the pathophysiology of CNS diseases including bipolar disorder, major depressive disorder, and schizophrenia. These changes include impaired energy metabolism in the brain, co-morbidity with mitochondrial diseases, the effects of psychotropics on mitochondrial function, increased mitochondrial DNA (mtDNA) deletion in the brain, and association with mtDNA polymorphisms...
November 2016: Drug Development Research
Oded Bergman, Dorit Ben-Shachar
Mitochondria are key players in the generation and regulation of cellular bioenergetics, producing the majority of adenosine triphosphate molecules by the oxidative phosphorylation system (OXPHOS). Linked to numerous signaling pathways and cellular functions, mitochondria, and OXPHOS in particular, are involved in neuronal development, connectivity, plasticity, and differentiation. Impairments in a variety of mitochondrial functions have been described in different general and psychiatric disorders, including schizophrenia (SCZ), a severe, chronic, debilitating illness that heavily affects the lives of patients and their families...
August 2016: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
Giselli Scaini, Gislaine T Rezin, Andre F Carvalho, Emilio L Streck, Michael Berk, João Quevedo
Bipolar disorder (BD) is a chronic psychiatric illness characterized by severe and biphasic changes in mood. Several pathophysiological mechanisms have been hypothesized to underpin the neurobiology of BD, including the presence of mitochondrial dysfunction. A confluence of evidence points to an underlying dysfunction of mitochondria, including decreases in mitochondrial respiration, high-energy phosphates and pH; changes in mitochondrial morphology; increases in mitochondrial DNA polymorphisms; and downregulation of nuclear mRNA molecules and proteins involved in mitochondrial respiration...
September 2016: Neuroscience and Biobehavioral Reviews
Roghaiyeh Safari, Reza Salimi, Zeliha Tunca, Aysegul Ozerdem, Deniz Ceylan, Meral Sakizli
Calcium signaling is important for synaptic plasticity, generation of brain rhythms, regulating neuronal excitability, data processing and cognition. Impairment in calcium homeostasis contributed to the development of psychiatric disorders such as bipolar disorder (BP). MCU is the most important calcium transporter in mitochondria inner membrane responsible for influx of Ca[Formula: see text]. MICU1 is linked with MCU and has two canonical EF hands that are vital for its activity and regulates MCU-mediated Ca[Formula: see text] influx...
June 2016: Journal of Integrative Neuroscience
Qingzhong Wang, Yogesh Dwivedi
OBJECTIVES: Recent evidences suggest that mitochondrial dysfunction maybe involved in the pathophysiology of major depressive disorder (MDD); however, the role of mitochondrial genes in this disorder has not been studied systematically. In the present study, we profiled expression of mitochondrial genes in dorsolateral prefrontal cortex (dlPFC) of MDD and non-psychiatric control subjects. METHODS: Human mitochondrial RT(2) profile PCR array plates were used to examine differentially expressed genes in dlPFC of 11 MDD and 11 control subjects...
July 11, 2016: World Journal of Biological Psychiatry
Gretchen Hermes, David Nagy, Michael Waterson, Attila Zsarnovszky, Luis Varela, Mihaly Hajos, Tamas L Horvath
BACKGROUND/PURPOSE: Major psychiatric illnesses, affecting 36% of the world's population, are profound disorders of thought, mood and behavior associated with underlying impairments in synaptic plasticity and cellular resilience. Mitochondria support energy demanding processes like neural transmission and synaptogenesis and are thus points of broadening interest in the energetics underlying the neurobiology of mental illness. These experiments interrogated the importance of mitochondrial flexibility in behavior, synaptic and cortical activity in a mouse model...
June 2016: Molecular Metabolism
M J Devine, R Norkett, J T Kittler
The long, asymmetric and specialised architecture of neuronal processes necessitates a properly regulated transport network of molecular motors and cytoskeletal tracks. This allows appropriate distribution of cargo for correct formation and activity of the synapse, and thus normal neuronal communication. This communication is impaired in psychiatric disease, and ongoing studies have proposed that Disrupted in schizophrenia 1 (DISC1) is an important genetic risk factor for these disorders. The mechanisms by which DISC1 dysfunction might increase propensity to psychiatric disease are not completely understood; however, an emerging theme is that DISC1 can function as a key regulator of neuronal intracellular trafficking...
October 1, 2016: Journal of Physiology
Abdülhadi Cihangir Uguz, Kadir Demirci, Javier Espino
Mitochondria play a critical role in regulating cellular functions, such as redox signaling, calcium homeostasis, and apoptosis. Also, mitochondria are crucial for neurogenesis and neuronal functions. Melatonin is an indole analog hormone, which is generally produced by the pineal gland. It plays a vital role in circadian rhythm and act as a powerful antioxidant by scavenging free radicals, immunomodulators, and anticancer agents. Schizophrenia and mood disorders are the two major psychiatric disorders. Disturbances of sleep and circadian rhythms are well-known symptoms of schizophrenia and mood disorders (bipolar disorder, major depression)...
2016: Current Medicinal Chemistry
Dragana Filipović, Nevena Todorović, Rick E Bernardi, Peter Gass
Various stressors may disrupt the redox homeostasis of an organism by causing oxidative and nitrosative stress that may activate stressor-specific pathways and provoke specific responses. Chronic social isolation (CSIS) represents a mild chronic stress that evokes a variety of neurobehavioral changes in rats similar to those observed in people with psychiatric disorders, including depression. Most rodent studies have focused on the effect of social isolation during weaning or adolescence, while its effect in adult rats has not been extensively examined...
March 31, 2016: Brain Structure & Function
Stefania Schiavone, Luigia Trabace
Redox dysregulation occurs following a disequilibrium between reactive oxygen species (ROS) producing and degrading systems, i.e. mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and nitric oxide synthase (NOS) on one hand and the principal antioxidant system, the glutathione, on the other hand. Increasing recent evidence points towards a pathogenetic role of an altered redox state in the development of several mental disorders, such as anxiety, bipolar disorders, depression, psychosis, autism and post-traumaticstress disorders (PTSD)...
May 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Kamaljeet Kaur, Raja Fayad, Arpit Saxena, Norma Frizzell, Anindya Chanda, Suvarthi Das, Saurabh Chatterjee, Shweta Hegde, Manjeshwar Shrinath Baliga, Venkatesh Ponemone, Matthew Rorro, Jennifer Greene, Yasmine Elraheb, Alan J Redd, John Bian, John Restaino, LeAnn B Norris, Zaina P Qureshi, Bryan L Love, Brandon Brookstaver, Peter Georgantopoulos, Oliver Sartor, Dennis W Raisch, Gowtham Rao, Kevin Lu, Paul Ray, William Hrusheshky, Richard Schulz, Richard Ablin, Virginia Noxon, Charles L Bennett
BACKGROUND: The 3 fluoroquinolone (FQ) antibiotics - ciprofoxacin, levofoxacin, and moxifoxacin - are commonly administered to oncology patients. Although these oral antibiotics are approved by the US Food and Drug Administration (FDA) for treatment of urinary tract infections, acute bacterial sinusitis, or bacterial infection in patients with chronic obstructive pulmonary disease, they are commonly prescribed off-label to neutropenic cancer patients for the prevention and treatment of infections associated with febrile neutropenia...
February 2016: Journal of Community and Supportive Oncology
Fumiaki Ogawa, Laura C Murphy, Elise L V Malavasi, Shane T O'Sullivan, Helen S Torrance, David J Porteous, J Kirsty Millar
Mitochondria are essential for neuronal function, providing the energy required to power neurotransmission, and fulfilling many important additional roles. In neurons, mitochondria must be efficiently transported to sites, including synapses, where their functions are required. Neurons, with their highly elongated morphology, are consequently extremely sensitive to defective mitochondrial trafficking which can lead to neuronal ill-health/death. We recently demonstrated that DISC1 associates with mitochondrial trafficking complexes where it associates with the core kinesin and dynein adaptor molecule TRAK1...
May 18, 2016: ACS Chemical Neuroscience
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