{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:18:05Z","timestamp":1773415085204,"version":"3.50.1"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24tm0424224"],"award-info":[{"award-number":["JP24tm0424224"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24wm0425006"],"award-info":[{"award-number":["JP24wm0425006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["JP23K07021"],"award-info":[{"award-number":["JP23K07021"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>\n                    Bipolar disorder is a psychiatric disorder marked by recurrent mood episodes and a strong genetic component. Despite widespread use of mood stabilizers and atypical antipsychotics, effective treatments remain limited, highlighting the need for mechanistic insights. Early studies revealed decreased phosphocreatine and increased mitochondrial DNA (mtDNA) deletions in the brains of bipolar disorder patients, leading to the mitochondrial dysfunction hypothesis. This framework proposes that mtDNA mutations impair Ca\n                    <jats:sup>2+<\/jats:sup>\n                    buffering, producing neuronal dysfunction and mood instability. Supporting evidence spans neuroimaging, postmortem, genetic, and cellular studies, as well as therapeutic responses to mitochondrial modulators. Large\u2010scale genomic analyses implicate both rare and common variants affecting Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling and mitochondrial\u2013endoplasmic reticulum function, while somatic mtDNA mutations further link mitochondrial pathology to bipolar disorder. Animal and induced pluripotent stem cell models converge on neuronal hyperexcitability as a downstream effect of impaired Ca\n                    <jats:sup>2+<\/jats:sup>\n                    regulation. Recent work highlights the paraventricular thalamic nucleus (PVT) as a critical site of pathology. The PVT integrates serotonergic and limbic circuits, regulates salience, and exhibits the highest burden of mtDNA deletions in mutant\n                    <jats:italic>Polg<\/jats:italic>\n                    (mtDNA polymerase) mice. In humans, single\u2010nucleus RNA sequencing reveals a\u2009~50% reduction of PVT neurons in bipolar disorder, with marked transcriptional dysregulation enriched for bipolar disorder risk loci in PVT, with additional changes in microglia. Neuropathological studies further suggest neurodegenerative changes in PVT, particularly in late\u2010onset bipolar disorder. Collectively, these findings position PVT pathology at the core of bipolar disorder pathophysiology, offering a framework that integrates genetic risk, neuronal hyperexcitability, and circuit\u2010level dysregulation and guiding future therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1111\/pcn.70015","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T05:35:14Z","timestamp":1768887314000},"page":"159-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The emerging role of the paraventricular thalamic nucleus in bipolar disorder: Lessons from mitochondrial dysfunction"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7856-3952","authenticated-orcid":false,"given":"Tadafumi","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Psychiatry &amp; Behavioral Science Juntendo University Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mie","family":"Kubota\u2010Sakashita","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Behavioral Science Juntendo University Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Shima","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disorders Collaborative Laboratory RIKEN Center for Brain Science  Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Nishioka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Behavioral Science Juntendo University Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12852"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)01140-7"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.13724"},{"key":"e_1_2_18_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(92)90099-R"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(94)90116-3"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1993.61"},{"key":"e_1_2_18_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115856"},{"key":"e_1_2_18_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(97)00012-7"},{"key":"e_1_2_18_10_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-5618.2000.020305.x"},{"key":"e_1_2_18_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301671"},{"key":"e_1_2_18_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470661277.ch18"},{"key":"e_1_2_18_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3229"},{"key":"e_1_2_18_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780199797608.003.0094"},{"key":"e_1_2_18_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2018.7606"},{"key":"e_1_2_18_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-85519-1_15"},{"key":"e_1_2_18_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0721327.x"},{"key":"e_1_2_18_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.61.5.450"},{"key":"e_1_2_18_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.61.3.300"},{"key":"e_1_2_18_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.22"},{"key":"e_1_2_18_21_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852900015303"},{"key":"e_1_2_18_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-011-0901-0"},{"key":"e_1_2_18_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-9081-8-9"},{"key":"e_1_2_18_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-323632"},{"key":"e_1_2_18_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15526"},{"key":"e_1_2_18_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-019-1257-1"},{"key":"e_1_2_18_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004867412449303"},{"key":"e_1_2_18_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/13554794.2012.690421"},{"key":"e_1_2_18_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0129-y"},{"key":"e_1_2_18_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08468-9"},{"key":"e_1_2_18_31_1","unstructured":"Liao CobotBECB.Rare variant discovery in bipolar disorder. 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