{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T09:16:12Z","timestamp":1784970972412,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,10,29]],"date-time":"2012-10-29T00:00:00Z","timestamp":1351468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:p>McIntyre RS, Soczynska JK, Woldeyohannes HO, Miranda A, Vaccarino A, MacQueen G, Lewis GF, Kennedy SH. A randomized, double\u2010blind, controlled trial evaluating the effect of intranasal insulin on neurocognitive function in euthymic patients with bipolar disorder. Bipolar Disord 2012: 14: 697\u2013706. \u00a9 2012 John Wiley &amp; Sons A\/S.<\/jats:p><jats:p><jats:bold>Background:\u2002<\/jats:bold> Neurocognitive deficits are prevalent, persistent, and implicated as mediators of functional impairment in adults with bipolar disorder. Notwithstanding progress in the development of pharmacological treatments for various phases of bipolar disorder, no available treatment has been proven to be reliably efficacious in treating neurocognitive deficits. Emerging evidence indicates that insulin dysregulation may be pertinent to neurocognitive function. In keeping with this view, we tested the hypothesis that intranasal insulin administration would improve measures of neurocognitive performance in euthymic adults with bipolar disorder.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Sixty\u2010two adults with bipolar I\/II disorder (based on the Mini International Neuropsychiatric Interview 5.0) were randomized to adjunctive intranasal insulin 40\u2003IU q.i.d. (n\u2003=\u200334) or placebo (n\u2003=\u200328) for eight weeks. All subjects were prospectively verified to be euthymic on the basis of a total score of \u2264 3 on the seven\u2010item Hamilton Depression Rating Scale (HAMD\u20107) and \u2264 7 on the 11\u2010item Young Mania Rating Scale (YMRS) for a minimum of 28 consecutive days. Neurocognitive function and outcome was assessed with a neurocognitive battery.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> There were no significant between\u2010group differences in mean age of the subjects {i.e., mean age 40 [standard deviation (SD)\u2003=\u200310.15] years in the insulin and 39 [SD\u2003=\u200310.41] in the placebo groups, respectively}. In the insulin group, n\u2003=\u200327 (79.4%) had bipolar I disorder, while n\u2003=\u20037 (21.6%) had bipolar II disorder. In the placebo group, n\u2003=\u200325 (89.3%) had bipolar I disorder, while n\u2003=\u20033 (10.7%) had bipolar II disorder. All subjects received concomitant medications; medications remained stable during study enrollment. A significant improvement versus placebo was noted with intranasal insulin therapy on executive function (i.e., Trail Making Test\u2013Part B). Time effects were significant for most California Verbal Learning Test indices and the Process Dissociation Task\u2013Habit Estimate, suggesting an improved performance from baseline to endpoint with no between\u2010group differences. Intranasal insulin was well tolerated; no subject exhibited hypoglycemia or other safety concerns.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Adjunctive intranasal insulin administration significantly improved a single measure of executive function in bipolar disorder. We were unable to detect between\u2010group differences on other neurocognitive measures, with improvement noted in both groups. Subject phenotyping on the basis of pre\u2010existing neurocognitive deficits and\/or genotype [e.g., apolipoprotein E (ApoE)] may possibly identify a more responsive subgroup.<\/jats:p>","DOI":"10.1111\/bdi.12006","type":"journal-article","created":{"date-parts":[[2012,10,29]],"date-time":"2012-10-29T18:03:40Z","timestamp":1351533820000},"page":"697-706","source":"Crossref","is-referenced-by-count":96,"title":["A randomized, double\u2010blind, controlled trial evaluating the effect of intranasal insulin on neurocognitive function in euthymic patients with bipolar disorder"],"prefix":"10.1111","volume":"14","author":[{"given":"Roger S","family":"McIntyre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna K","family":"Soczynska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna O","family":"Woldeyohannes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Vaccarino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda","family":"MacQueen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary F","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney H","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,10,29]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852900028844"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291701004597"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2010.00830.x"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.186.1.32"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000012361"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2010.09101406"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2006.00284.x"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.06.003"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(04)00681-7"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.2174\/156720507780362137"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-2075"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2005.08.017"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2004.04.003"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.03.016"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2008-13309"},{"key":"e_1_2_7_17_2","article-title":"Brain insulin signaling and Alzheimer\u2019s disease: current evidence and future directions","author":"Schi\u00f6th HB","year":"2011","journal-title":"Mol Neurobiol"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2005.00219.x"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.050786"},{"key":"e_1_2_7_20_2","volume-title":"Diagnostic and statistical manual of mental disorders DSM\u2013IV\u2013TR","author":"American Psychiatric Association Task Force on DSM\u2013IV","year":"2000"},{"key":"e_1_2_7_21_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1037\/0278-7393.24.1.3","article-title":"Invariance in automatic influences of memory: toward a user\u2019s guide for the process\u2010dissociation procedure","volume":"24","author":"Jacoby LL","year":"1998","journal-title":"J Exp Psychol Learn Mem Cogn"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1037\/0022-006X.56.1.123"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.2466\/pms.1958.8.3.271"},{"key":"e_1_2_7_24_2","volume-title":"Wechsler Adult Intelligence Scale: WAIS\u2010III. 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