{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T14:04:18Z","timestamp":1782569058820,"version":"3.54.5"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Ministry of Economy and Industry state of Israel","award":["54780"],"award-info":[{"award-number":["54780"]}]},{"name":"Eshcol Scholarship Israel Ministry of Science"},{"name":"Ministry of Economy and Industry state of Israel","award":["54781"],"award-info":[{"award-number":["54781"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pharmacological treatment of mental disorders is currently decided based on \"trial and error\" strategy. Mitochondrial multifaceted dysfunction is assumed to be a major factor in the pathophysiology and treatment of schizophrenia (SZ) and bipolar disorder (BD). This study aimed to explore the feasibility of using a profile of mitochondrial function parameters as a tool to predict the optimal drug for an individual patient (personalized medicine). Healthy controls (n\u2009=\u200940), SZ (n\u2009=\u200948) and BD (n\u2009=\u200927) patients were recruited. Mental and global state of the subjects, six mitochondrial respiration parameters and 14 mitochondrial function-related proteins were assessed in fresh lymphocytes following in-vitro or in-vivo treatment with five antipsychotic drugs and two mood-stabilizers. In healthy controls, hierarchal clustering shows a drug-specific effect profile on the different mitochondrial parameters following in-vitro exposure. Similar changes were observed in untreated SZ and BD patients with psychosis. Following a month of treatment of the latter patients, only responders showed a significant correlation between drug-induced in-vitro effect (prior to in-vivo treatment) and short-term in-vivo treatment effect for 45% of the parameters. Long- but not short-term psychotropic treatment normalized mitochondria-related parameters in patients with psychosis. Taken together, these data substantiate mitochondria as a target for psychotropic drugs and provide a proof of concept for selective mitochondrial function-related parameters as a predictive tool for an optimized psychotropic treatment in a given patient. This, however, needs to be repeated with an expanded sample size and additional mitochondria related parameters.<\/jats:p>","DOI":"10.1038\/s41598-020-69207-4","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T10:04:12Z","timestamp":1595498652000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Mitochondrial function parameters as a tool for tailored drug treatment of an individual with psychosis: a proof of concept study"],"prefix":"10.1038","volume":"10","author":[{"given":"Tamara","family":"Bar-Yosef","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wessal","family":"Hussein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofer","family":"Yitzhaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odeya","family":"Damri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limor","family":"Givon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmit","family":"Marom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlada","family":"Gurman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Levine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuly","family":"Bersudsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galila","family":"Agam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Ben-Shachar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"69207_CR1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0140-6736(09)60072-6","volume":"373","author":"P Lichtenstein","year":"2009","unstructured":"Lichtenstein, P. et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373, 234\u2013239 (2009).","journal-title":"Lancet"},{"key":"69207_CR2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1176\/appi.ajp.159.4.539","volume":"159","author":"AG Cardno","year":"2002","unstructured":"Cardno, A. G., Rijsdijk, F. V., Sham, P. C., Murray, R. M. & McGuffin, P. A twin study of genetic relationships between psychotic symptoms. Am. J. Psychiatry 159, 539\u2013545 (2002).","journal-title":"Am. J. Psychiatry"},{"key":"69207_CR3","doi-asserted-by":"crossref","unstructured":"International Schizophrenia Consortium et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748\u201352 (2009).","DOI":"10.1038\/nature08185"},{"key":"69207_CR4","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1176\/appi.ajp.2010.09091379","volume":"167","author":"T Insel","year":"2010","unstructured":"Insel, T. et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am. J. Psychiatry 167, 748\u2013751 (2010).","journal-title":"Am. J. Psychiatry"},{"key":"69207_CR5","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1001\/archpsyc.1978.01770300115013","volume":"35","author":"RL Spitzer","year":"1978","unstructured":"Spitzer, R. L., Endicott, J. & Robins, E. Research diagnostic criteria: rationale and reliability. Arch. Gen. Psychiatry 35, 773\u2013782 (1978).","journal-title":"Arch. Gen. Psychiatry"},{"key":"69207_CR6","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1192\/bjp.bp.116.186007","volume":"211","author":"H Takeuchi","year":"2017","unstructured":"Takeuchi, H. et al. One-year symptom trajectories in patients with stable schizophrenia maintained on antipsychotics versus placebo: meta-analysis. Br. J. Psychiatry 211, 137\u2013143 (2017).","journal-title":"Br. J. Psychiatry"},{"key":"69207_CR7","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.biopsych.2017.11.018","volume":"83","author":"L Pei","year":"2018","unstructured":"Pei, L. & Wallace, D. C. Mitochondrial etiology of neuropsychiatric disorders. Biol. Psychiatry 83, 722\u2013730 (2018).","journal-title":"Biol. Psychiatry"},{"key":"69207_CR8","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1177\/0706743716648290","volume":"61","author":"O Bergman","year":"2016","unstructured":"Bergman, O. & Ben-Shachar, D. Mitochondrial oxidative phosphorylation system (OXPHOS) deficits in schizophrenia: possible interactions with cellular processes. Can. J. Psychiatry. 61, 457\u2013469 (2016).","journal-title":"Can. J. Psychiatry."},{"key":"69207_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.03.025","author":"F Du","year":"2017","unstructured":"Du, F. et al. Abnormalities in high-energy phosphate metabolism in first-episode bipolar disorder measured using 31P-magnetic resonance spectroscopy. Biol. Psychiatry https:\/\/doi.org\/10.1016\/j.biopsych.2017.03.025 (2017).","journal-title":"Biol. Psychiatry"},{"key":"69207_CR10","first-page":"136","volume":"2","author":"HK Manji","year":"2003","unstructured":"Manji, H. K. et al. The underlying neurobiology of bipolar disorder. World Psychiatry 2, 136\u2013146 (2003).","journal-title":"World Psychiatry"},{"key":"69207_CR11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.neuron.2006.09.015","volume":"52","author":"CA Ross","year":"2006","unstructured":"Ross, C. A., Margolis, R. L., Reading, S. A. J., Pletnikov, M. & Coyle, J. T. Neurobiology of Schizophrenia. Neuron 52, 139\u2013153 (2006).","journal-title":"Neuron"},{"key":"69207_CR12","first-page":"1","volume":"59","author":"D Ben-Shachar","year":"2003","unstructured":"Ben-Shachar, D. & Laifenfeld, D. Mitochondria, synaptic plasticity, and schizophrenia. Int. Rev. Neurobiol 59, 1 (2003).","journal-title":"Int. Rev. Neurobiol"},{"key":"69207_CR13","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.neubiorev.2016.06.040","volume":"68","author":"G Scaini","year":"2016","unstructured":"Scaini, G. et al. Mitochondrial dysfunction in bipolar disorder: Evidence, pathophysiology and translational implications. Neurosci. Biobehav. Rev. 68, 694\u2013713 (2016).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"69207_CR14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.schres.2016.10.037","volume":"187","author":"T Kato","year":"2017","unstructured":"Kato, T. Neurobiological basis of bipolar disorder: Mitochondrial dysfunction hypothesis and beyond. Schizophr. Res. 187, 62\u201366 (2017).","journal-title":"Schizophr. Res."},{"key":"69207_CR15","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/978-3-030-05542-4_3","volume":"1118","author":"K Iwata","year":"2020","unstructured":"Iwata, K. Mitochondrial involvement in mental disorders: energy metabolism and genetic and environmental factors. Adv. Exp. Med. Biol. 1118, 63\u201370 (2020).","journal-title":"Adv. Exp. Med. Biol."},{"key":"69207_CR16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.schres.2016.10.022","volume":"187","author":"D Ben-Shachar","year":"2017","unstructured":"Ben-Shachar, D. Mitochondrial multifaceted dysfunction in schizophrenia; complex I as a possible pathological target. Schizophr. Res. 187, 3\u201310 (2017).","journal-title":"Schizophr. Res."},{"key":"69207_CR17","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/schbul\/sbx077","volume":"44","author":"O Robicsek","year":"2018","unstructured":"Robicsek, O. et al. Isolated mitochondria transfer improves neuronal differentiation of schizophrenia-derived induced pluripotent stem cells and rescues deficits in a rat model of the disorder. Schizophr. Bull. 44, 432\u2013442 (2018).","journal-title":"Schizophr. Bull."},{"key":"69207_CR18","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/j.1399-5618.2009.00729.x","volume":"11","author":"IC Maurer","year":"2009","unstructured":"Maurer, I. C., Schippel, P. & Volz, H.-P. Lithium-induced enhancement of mitochondrial oxidative phosphorylation in human brain tissue. Bipolar Disord. 11, 515\u2013522 (2009).","journal-title":"Bipolar Disord."},{"key":"69207_CR19","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/01.yco.0000218604.63463.cd","volume":"19","author":"G Chen","year":"2006","unstructured":"Chen, G. & Manji, H. K. The extracellular signal-regulated kinase pathway: an emerging promising target for mood stabilizers. Curr Opin Psychiatry 19, 313\u2013323 (2006).","journal-title":"Curr Opin Psychiatry"},{"key":"69207_CR20","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1083\/jcb.200504035","volume":"170","author":"S Sarkar","year":"2005","unstructured":"Sarkar, S. et al. Lithium induces autophagy by inhibiting inositol monophosphatase. J. Cell Biol. 170, 1101\u20131111 (2005).","journal-title":"J. Cell Biol."},{"key":"69207_CR21","first-page":"234","volume":"119","author":"H Kazemi","year":"2018","unstructured":"Kazemi, H., Noori-Zadeh, A., Darabi, S. & Rajaei, F. Lithium prevents cell apoptosis through autophagy induction. Bratisl. Lek. Listy 119, 234\u2013239 (2018).","journal-title":"Bratisl. Lek. Listy"},{"key":"69207_CR22","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.euroneuro.2018.01.004","volume":"28","author":"G Scaini","year":"2018","unstructured":"Scaini, G. et al. Second generation antipsychotic-induced mitochondrial alterations: Implications for increased risk of metabolic syndrome in patients with schizophrenia. Eur. Neuropsychopharmacol. 28, 369\u2013380 (2018).","journal-title":"Eur. Neuropsychopharmacol."},{"key":"69207_CR23","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/BF01952200","volume":"44","author":"A Pletscher","year":"1988","unstructured":"Pletscher, A. Platelets as models: use and limitations. Experientia 44, 152\u2013155 (1988).","journal-title":"Experientia"},{"key":"69207_CR24","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/sj.mp.4001116","volume":"7","author":"N Dror","year":"2002","unstructured":"Dror, N. et al. State dependent alterations in mitochondrial complex I activity in platelets: a potential peripheral marker for schizophrenia. Mol Psychiatry 7, 995\u20131001 (2002).","journal-title":"Mol Psychiatry"},{"key":"69207_CR25","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/ajmg.b.30171","volume":"136B","author":"FA Middleton","year":"2005","unstructured":"Middleton, F. A. et al. Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 136B, 12\u201325 (2005).","journal-title":"Am. J. Med. Genet. B. Neuropsychiatr. Genet."},{"key":"69207_CR26","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/ajmg.b.30272","volume":"141B","author":"PF Sullivan","year":"2006","unstructured":"Sullivan, P. F., Fan, C. & Perou, C. M. Evaluating the comparability of gene expression in blood and brain. Am. J. Med. Genet. Neuropsychiatr. Genet. 141B, 261\u2013268 (2006).","journal-title":"Am. J. Med. Genet. Neuropsychiatr. Genet."},{"key":"69207_CR27","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.lab.2005.10.005","volume":"147","author":"CC Liew","year":"2006","unstructured":"Liew, C. C., Ma, J., Tang, H. C., Zheng, R. & Dempsey, A. A. The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool. J. Lab. Clin. Med. 147, 126\u2013132 (2006).","journal-title":"J. Lab. Clin. Med."},{"key":"69207_CR28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1046\/j.1365-2125.2000.00174.x","volume":"49","author":"PB Mitchell","year":"2000","unstructured":"Mitchell, P. B. Therapeutic drug monitoring of psychotropic medications. Br. J. Clin. Pharmacol. 49, 303\u2013312 (2000).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"69207_CR29","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.ejcb.2010.05.002","volume":"89","author":"SPP Yaniv","year":"2010","unstructured":"Yaniv, S. P. P., Lucki, A., Klein, E. & Ben-Shachar, D. Dexamethasone enhances the norepinephrine-induced ERK\/MAPK intracellular pathway possibly via dysregulation of the alpha2-adrenergic receptor: implications for antidepressant drug mechanism of action. Eur J Cell Biol 89, 712\u2013722 (2010).","journal-title":"Eur J Cell Biol"},{"key":"69207_CR30","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.bbrc.2011.06.005","volume":"410","author":"R Hnasko","year":"2011","unstructured":"Hnasko, R., Lin, A., McGarvey, J. A. & Stanker, L. H. A rapid method to improve protein detection by indirect ELISA. Biochem. Biophys. Res. Commun. 410, 726\u2013731 (2011).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"69207_CR31","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/s41386-018-0090-0","volume":"44","author":"L Holper","year":"2019","unstructured":"Holper, L., Ben-Shachar, D. & Mann, J. J. J. Multivariate meta-analyses of mitochondrial complex I and IV in major depressive disorder, bipolar disorder, schizophrenia, Alzheimer disease, and Parkinson disease. Neuropsychopharmacology 44, 837\u2013849 (2019).","journal-title":"Neuropsychopharmacology"},{"key":"69207_CR32","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1176\/appi.ajp.161.1.109","volume":"161","author":"LF Jarskog","year":"2004","unstructured":"Jarskog, L. F., Selinger, E. S., Lieberman, J. A. & Gilmore, J. H. Apoptotic proteins in the temporal cortex in schizophrenia: high Bax\/Bcl-2 ratio without caspase-3 activation. Am J Psychiatry 161, 109\u2013115 (2004).","journal-title":"Am J Psychiatry"},{"key":"69207_CR33","doi-asserted-by":"crossref","first-page":"6399","DOI":"10.1038\/s41598-018-24546-1","volume":"8","author":"D Odeya","year":"2018","unstructured":"Odeya, D., Galila, A. & Lilah, T. The observed alteration in BCL2 expression following lithium treatment is influenced by the choice of normalization method. Sci. Rep. 8, 6399 (2018).","journal-title":"Sci. Rep."},{"key":"69207_CR34","doi-asserted-by":"crossref","first-page":"e1111","DOI":"10.1038\/tp.2017.83","volume":"7","author":"G Scaini","year":"2017","unstructured":"Scaini, G. et al. Perturbations in the apoptotic pathway and mitochondrial network dynamics in peripheral blood mononuclear cells from bipolar disorder patients. Transl. Psychiatry 7, e1111\u2013e1111 (2017).","journal-title":"Transl. Psychiatry"},{"key":"69207_CR35","doi-asserted-by":"crossref","unstructured":"Rosenfeld, M., Brenner-Lavie, H., Ari, S. G.-B. G. B., Kavushansky, A. & Ben-Shachar, D. Perturbation in mitochondrial network dynamics and in complex I dependent cellular respiration in schizophrenia. Biol. Psychiatry 69, 980\u2013988 (2011).","DOI":"10.1016\/j.biopsych.2011.01.010"},{"key":"69207_CR36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/bdi.07_12616","volume":"20","author":"Mitochondrial Dysfunction in Bipolar Disorder","year":"2018","unstructured":"Mitochondrial Dysfunction in Bipolar Disorder. Evidence, pathophysiology and translational implications. Bipolar Disord. 20, 19\u201320 (2018).","journal-title":"Bipolar Disord."},{"key":"69207_CR37","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/mp.2013.174","volume":"20","author":"A Merenlender-Wagner","year":"2015","unstructured":"Merenlender-Wagner, A. et al. Autophagy has a key role in the pathophysiology of schizophrenia. Mol. Psychiatry 20, 126\u2013132 (2015).","journal-title":"Mol. Psychiatry"},{"key":"69207_CR38","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1038\/s41386-018-0293-4","volume":"44","author":"G Scaini","year":"2019","unstructured":"Scaini, G. et al. TSPO upregulation in bipolar disorder and concomitant downregulation of mitophagic proteins and NLRP3 inflammasome activation. Neuropsychopharmacology 44, 1291\u20131299 (2019).","journal-title":"Neuropsychopharmacology"},{"key":"69207_CR39","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1176\/appi.ajp.2017.17050550","volume":"175","author":"MM Juki\u0107","year":"2018","unstructured":"Juki\u0107, M. M., Haslemo, T., Molden, E. & Ingelman-Sundberg, M. Impact of CYP2C19 genotype on escitalopram exposure and therapeutic failure: a retrospective study based on 2,087 patients. Am. J. Psychiatry 175, 463\u2013470 (2018).","journal-title":"Am. J. Psychiatry"},{"key":"69207_CR40","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1038\/mp.2017.128","volume":"22","author":"AB Niculescu","year":"2017","unstructured":"Niculescu, A. B. et al. Precision medicine for suicidality: from universality to subtypes and personalization. Mol. Psychiatry 22, 1250\u20131273 (2017).","journal-title":"Mol. Psychiatry"},{"key":"69207_CR41","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.cppeds.2017.12.003","volume":"48","author":"AM Wehry","year":"2018","unstructured":"Wehry, A. M., Ramsey, L., Dulemba, S. E., Mossman, S. A. & Strawn, J. R. Pharmacogenomic testing in child and adolescent psychiatry: an evidence-based review. Curr. Probl. Pediatr. Adolesc. Health Care 48, 40\u201349 (2018).","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"69207_CR42","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/tpj.2014.85","volume":"15","author":"CA Altar","year":"2015","unstructured":"Altar, C. A. et al. Clinical validity: Combinatorial pharmacogenomics predicts antidepressant responses and healthcare utilizations better than single gene phenotypes. Pharmacogenomics J. 15, 443\u2013451 (2015).","journal-title":"Pharmacogenomics J."},{"key":"69207_CR43","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s11920-007-0038-2","volume":"9","author":"CU Nnadi","year":"2007","unstructured":"Nnadi, C. U. & Malhotra, A. K. Individualizing antipsychotic drug therapy in schizophrenia: the promise of pharmacogenetics. Curr. Psychiatry Rep. 9, 313\u2013318 (2007).","journal-title":"Curr. Psychiatry Rep."},{"key":"69207_CR44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1055\/s-0043-116492","volume":"51","author":"C Hiemke","year":"2018","unstructured":"Hiemke, C. et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry 51, 9\u201362 (2018).","journal-title":"Pharmacopsychiatry"},{"key":"69207_CR45","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S2215-0366(15)00471-X","volume":"3","author":"AM Chekroud","year":"2016","unstructured":"Chekroud, A. M. et al. Cross-trial prediction of treatment outcome in depression: a machine learning approach. Lancet Psychiatry 3, 243\u2013250 (2016).","journal-title":"Lancet Psychiatry"},{"key":"69207_CR46","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S2215-0366(16)30171-7","volume":"3","author":"N Koutsouleris","year":"2016","unstructured":"Koutsouleris, N. et al. Multisite prediction of 4-week and 52-week treatment outcomes in patients with first-episode psychosis: a machine learning approach. The Lancet Psychiatry 3, 935\u2013946 (2016).","journal-title":"The Lancet Psychiatry"},{"key":"69207_CR47","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1001\/jamapsychiatry.2018.0834","volume":"75","author":"GS Zubenko","year":"2018","unstructured":"Zubenko, G. S., Sommer, B. R. & Cohen, B. M. On the marketing and use of pharmacogenetic tests for psychiatric treatment. JAMA Psychiatry 75, 769 (2018).","journal-title":"JAMA Psychiatry"},{"key":"69207_CR48","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nrn3229","volume":"13","author":"H Manji","year":"2012","unstructured":"Manji, H. et al. Impaired mitochondrial function in psychiatric disorders. Nat Rev Neurosci 13, 293\u2013307 (2012).","journal-title":"Nat Rev Neurosci"},{"key":"69207_CR49","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/ana.410330516","volume":"33","author":"C Burkhardt","year":"1993","unstructured":"Burkhardt, C., Kelly, J. P., Lim, Y. H., Filley, C. M. & Parker, W. D. Neuroleptic medications inhibit complex I of the electron transport chain. Ann. Neurol. 33, 512\u2013517 (1993).","journal-title":"Ann. Neurol."},{"key":"69207_CR50","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.bcp.2009.03.024","volume":"78","author":"H Brenner-Lavie","year":"2009","unstructured":"Brenner-Lavie, H., Klein, E. & Ben-Shachar, D. Mitochondrial complex I as a novel target for intraneuronal DA: modulation of respiration in intact cells. Biochem Pharmacol 78, 85\u201395 (2009).","journal-title":"Biochem Pharmacol"},{"key":"69207_CR51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tibs.2014.10.010","volume":"40","author":"SH Payne","year":"2015","unstructured":"Payne, S. H. The utility of protein and mRNA correlation. Trends Biochem. Sci. 40, 1\u20133 (2015).","journal-title":"Trends Biochem. Sci."},{"key":"69207_CR52","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","volume":"13","author":"C Vogel","year":"2012","unstructured":"Vogel, C. & Marcotte, E. M. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat. Rev. Genet. 13, 227\u2013232 (2012).","journal-title":"Nat. Rev. Genet."},{"key":"69207_CR53","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/S0028-3908(98)00215-9","volume":"38","author":"S Balijepalli","year":"1999","unstructured":"Balijepalli, S., Boyd, M. R. & Ravindranath, V. Inhibition of mitochondrial complex I by haloperidol: the role of thiol oxidation. Neuropharmacology 38, 567\u2013577 (1999).","journal-title":"Neuropharmacology"},{"key":"69207_CR54","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.biocel.2004.11.016","volume":"37","author":"C Bastianon","year":"2005","unstructured":"Bastianon, C., Zanoni, R., Miolo, G., Caffieri, S. & Reddi, E. Mitochondria and plasma membrane as targets of UVA-induced toxicity of neuroleptic drugs fluphenazine, perphenazine and thioridazine. Int. J. Biochem. Cell Biol. 37, 901\u2013908 (2005).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"69207_CR55","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1007\/s00702-007-0668-x","volume":"114","author":"KA Newell","year":"2007","unstructured":"Newell, K. A., Zavitsanou, K. & Huang, X.-F. Short and long term changes in NMDA receptor binding in mouse brain following chronic phencyclidine treatment. J. Neural Transm. 114, 995\u20131001 (2007).","journal-title":"J. Neural Transm."},{"key":"69207_CR56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phrs.2017.04.013","volume":"121","author":"AAK Moe","year":"2017","unstructured":"Moe, A. A. K., Medely, G. A., Reeks, T., Burne, T. H. J. & Eyles, D. W. Short- and long-term effects of risperidone on catalepsy sensitisation and acquisition of conditioned avoidance response: adolescent vs adult rats. Pharmacol. Res. 121, 1\u201313 (2017).","journal-title":"Pharmacol. Res."},{"key":"69207_CR57","first-page":"428","volume":"20","author":"CC Abbott","year":"2013","unstructured":"Abbott, C. C., Jaramillo, A., Wilcox, C. E. & Hamilton, D. A. Antipsychotic drug effects in schizophrenia: a review of longitudinal FMRI investigations and neural interpretations. Curr. Med. Chem. 20, 428\u2013437 (2013).","journal-title":"Curr. Med. Chem."},{"key":"69207_CR58","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/mp.2013.67","volume":"18","author":"O Robicsek","year":"2013","unstructured":"Robicsek, O. et al. Abnormal neuronal differentiation and mitochondrial dysfunction in hair follicle-derived induced pluripotent stem cells of schizophrenia patients. Mol. Psychiatry 18, 1067\u20131076 (2013).","journal-title":"Mol. Psychiatry"},{"key":"69207_CR59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/mp.2014.22","volume":"20","author":"K Brennand","year":"2015","unstructured":"Brennand, K. et al. Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia. Mol. Psychiatry 20, 1\u20138 (2015).","journal-title":"Mol. Psychiatry"},{"key":"69207_CR60","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2217\/pgs.10.179","volume":"12","author":"F Mouaffak","year":"2011","unstructured":"Mouaffak, F. et al. Association of an UCP4 (SLC25A27) haplotype with ultra-resistant schizophrenia. Pharmacogenomics 12, 185\u2013193 (2011).","journal-title":"Pharmacogenomics"},{"key":"69207_CR61","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/ajmg.b.30443","volume":"144B","author":"K Yasuno","year":"2007","unstructured":"Yasuno, K. et al. Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia. Am. J. Med. Genet. Part B Neuropsychiatr. Genet. 144B, 250\u2013253 (2007).","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69207-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69207-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69207-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T14:09:01Z","timestamp":1670335741000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69207-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,23]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["69207"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-69207-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,23]]},"assertion":[{"value":"6 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12258"}}