{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:41:32Z","timestamp":1792759292775,"version":"4.5.0"},"reference-count":41,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100009104","name":"Department of Health Research, India","doi-asserted-by":"publisher","award":["HRD\/DHR-ICMR\/PG-2024\/0495"],"award-info":[{"award-number":["HRD\/DHR-ICMR\/PG-2024\/0495"]}],"id":[{"id":"10.13039\/501100009104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recent evidence increasingly links schizophrenia to mitochondrial dysfunction, implicating altered mitochondrial respiratory and metabolic processes in its pathophysiology. Preclinical data suggest that atypical antipsychotics may inhibit mitochondrial respiratory chain complex I (MRCC I), raising concerns regarding mitochondrial impairment despite clinical efficacy. Hence, this study was conducted to evaluate mitochondrial dysfunction associated with schizophrenia and to compare changes during treatment with risperidone and aripiprazole.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this randomized, open-label, clinical trial, 60 patients with schizophrenia were allocated to either risperidone or aripiprazole for 12\u2009weeks. A healthy control group (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200930) was recruited for baseline biochemical comparisons. The outcome measures were the change in platelet MRCC I, serum lactate, pyruvate, lactate:pyruvate (L:P) ratio, creatine kinase, Positive and Negative Syndrome Scale (PANSS), Newcastle Mitochondrial Disease Adult Scale (NMDAS), responder rate, and treatment-emergent adverse events (TEAEs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At baseline, schizophrenia patients exhibited significantly higher levels of MRCC I, lactate, pyruvate, and L:P ratio compared to healthy controls, consistent with underlying mitochondrial dysregulation. After 12\u2009weeks of therapy, both risperidone and aripiprazole significantly reduced MRCC I concentration (\u22122.66 vs \u22123.13\u2009nmol\/10\n                      <jats:sup>8<\/jats:sup>\n                      platelets), with no inter-group difference (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.508). Serum lactate and L:P ratio increased significantly, while serum pyruvate remained unchanged. PANSS scores improved significantly in both groups, with comparable responder rates. NMDAS scores showed no significant change. TEAEs were mostly mild and more frequent with risperidone, though not statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Schizophrenia is associated with alterations in mitochondrial-related biochemical markers suggestive of disrupted cellular bioenergetics. Treatment with risperidone and aripiprazole was associated with changes in these markers, without differences between groups. These findings reflect altered bioenergetic status and warrant further investigation using functional assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov identifier: NCT06236451.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811261453937","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T02:47:14Z","timestamp":1782528434000},"page":"1624-1634","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial dysfunction in schizophrenia and its modulation by atypical antipsychotic drugs: A randomized controlled trial"],"prefix":"10.1177","volume":"40","author":[{"given":"Amiya","family":"Shaju","sequence":"first","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biswa Ranjan","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, All India Institute of Medical Sciences, Bhubaneswar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debadatta","family":"Mohapatra","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, All India Institute of Medical Sciences, Bhubaneswar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4063-9178","authenticated-orcid":false,"given":"Rituparna","family":"Maiti","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40303-014-0006-9"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3229-c1"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-69207-4"},{"key":"e_1_3_2_6_1","doi-asserted-by":"crossref","unstructured":"Bast L Yao S Martinez-Lopez JA et al. 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