PMID- 35895056 OWN - NLM STAT- MEDLINE DCOM- 20220729 LR - 20230301 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 5 IP - 7 DP - 2022 Jul 1 TI - Comparison of Functional and Structural Neural Network Features in Older Adults With Depression With vs Without Apathy and Association With Response to Escitalopram: Secondary Analysis of a Nonrandomized Clinical Trial. PG - e2224142 LID - 10.1001/jamanetworkopen.2022.24142 [doi] LID - e2224142 AB - IMPORTANCE: Apathy is prevalent among individuals with late-life depression and is associated with poor response to pharmacotherapy, including chronicity and disability. Elucidating brain networks associated with apathy and poor treatment outcomes can inform intervention development. OBJECTIVES: To assess the brain network features of apathy among individuals with late-life depression and identify brain network abnormalities associated with poor antidepressant response. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a single-group, open-label nonrandomized clinical trial of escitalopram conducted at an outpatient geriatric psychiatry clinic enrolled 40 adults aged 59 to 85 years with major depressive disorder from July 1, 2012, to July 31, 2019. INTERVENTIONS: After a 2-week washout period, participants received escitalopram titrated to a target of 20 mg/d for 12 weeks. MAIN OUTCOMES AND MEASURES: Baseline and posttreatment magnetic resonance imaging (MRI), clinical, and cognitive assessments were conducted. Functional MRI was used to map group differences in resting state functional connectivity (rsFC) of the salience network, and diffusion MRI connectometry was performed to evaluate pathway-level disruptions in structural connectivity. The Apathy Evaluation Scale was used to quantify apathy, and the Hamilton Depression Rating Scale (HAM-D) was used to quantify the primary outcome of depression severity. RESULTS: Forty participants (26 women [65%]; mean [SD] age, 70.0 [6.6] years [range, 59-85 years]) with depression were included; 20 participants (50%) also had apathy. Relative to nonapathetic participants with depression, those with depression and apathy had lower rsFC of salience network seeds with the dorsolateral prefrontal cortex (DLPFC), premotor cortex, midcingulate cortex, and paracentral lobule and greater rsFC with the lateral temporal cortex and temporal pole (z score >2.7; Bonferroni-corrected threshold of P < .0125). Compared with participants without apathy, those with apathy had lower structural connectivity in the splenium, cingulum, and fronto-occipital fasciculus (t score >2.5; false discovery rate-corrected P = .02). Twenty-seven participants completed escitalopram treatment; 16 (59%) achieved remission (HAM-D score <10). Lower insula-DLPFC/midcingulate cortex rsFC was associated with less symptomatic improvement (HAM-D % change) (beta [df] = 0.588 [26]; P = .001) and a higher likelihood of nonremission (odds ratio, 1.041 [95% CI, 1.003-1.081]; P = .04) after treatment and, in regression models, was a mediator of the association between baseline apathy and persistence of depression. Lower dorsal anterior cingulate-DLPFC/paracentral rsFC was associated with residual cognitive difficulties on measures of attention (beta [df] = 0.445 [26]; P = .04) and executive function (beta [df] = 0.384 [26]; P = .04). CONCLUSIONS AND RELEVANCE: This study suggests that disturbances in connectivity between the salience network and other large-scale networks that support goal-directed behavior may give rise to apathy and may be associated with poor response of late-life depression to antidepressant pharmacotherapy. These network disturbances may serve as targets for novel interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01728194. FAU - Oberlin, Lauren E AU - Oberlin LE AD - Department of Psychiatry, Weill Cornell Medicine, New York, New York. AD - Institute of Geriatric Psychiatry, Weill Cornell Medicine, White Plains, New York. FAU - Victoria, Lindsay W AU - Victoria LW AD - Department of Psychiatry, Weill Cornell Medicine, New York, New York. AD - Institute of Geriatric Psychiatry, Weill Cornell Medicine, White Plains, New York. FAU - Ilieva, Irena AU - Ilieva I AD - Department of Psychiatry, Weill Cornell Medicine, New York, New York. FAU - Dunlop, Katharine AU - Dunlop K AD - Department of Psychiatry, Weill Cornell Medicine, New York, New York. FAU - Hoptman, Matthew J AU - Hoptman MJ AD - Clinical Research Division, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York. AD - Department of Psychiatry, NYU Grossman School of Medicine, New York, New York. FAU - Avari, Jimmy AU - Avari J AD - Department of Psychiatry, Weill Cornell Medicine, New York, New York. AD - Institute of Geriatric Psychiatry, Weill Cornell Medicine, White Plains, New York. FAU - Alexopoulos, George S AU - Alexopoulos GS AD - Department of Psychiatry, Weill Cornell Medicine, New York, New York. AD - Institute of Geriatric Psychiatry, Weill Cornell Medicine, White Plains, New York. FAU - Gunning, Faith M AU - Gunning FM AD - Department of Psychiatry, Weill Cornell Medicine, New York, New York. AD - Institute of Geriatric Psychiatry, Weill Cornell Medicine, White Plains, New York. LA - eng SI - ClinicalTrials.gov/NCT01728194 GR - T32 MH019132/MH/NIMH NIH HHS/United States GR - R01 MH097735/MH/NIMH NIH HHS/United States PT - Clinical Trial PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20220701 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Antidepressive Agents) RN - 4O4S742ANY (Escitalopram) SB - IM MH - Aged MH - Antidepressive Agents/therapeutic use MH - *Apathy MH - Depression/diagnostic imaging/drug therapy MH - *Depressive Disorder, Major/diagnostic imaging/drug therapy/psychology MH - Escitalopram MH - Female MH - Humans MH - Neural Networks, Computer PMC - PMC9331093 COIS- Conflict of Interest Disclosures: Dr Dunlop reported receiving grants from the Canadian Institutes of Health Research outside the submitted work. Dr Hoptman reported receiving grants from a National Institute of Mental Health subcontract award during the conduct of the study; nonfinancial support from Brain Sciences; and grants from the American Foundation for Suicide Prevention outside the submitted work. Dr Alexopoulos reported receiving grants from Weill Cornell Medicine during the conduct of the study and receiving personal fees from Janssen, Eisai, and Otsuka; serving on the speakers bureaus of Takeda, Lundbeck, Otsuka, and Sunovion; and serving on the advisory boards of Janssen and Eisai outside the submitted work. Dr Gunning reported receiving grants from the National Institute of Mental Health during the conduct of the study and grants from Akili Interactive. No other disclosures were reported. EDAT- 2022/07/28 06:00 MHDA- 2022/07/30 06:00 PMCR- 2022/07/27 CRDT- 2022/07/27 11:34 PHST- 2022/07/27 11:34 [entrez] PHST- 2022/07/28 06:00 [pubmed] PHST- 2022/07/30 06:00 [medline] PHST- 2022/07/27 00:00 [pmc-release] AID - 2794700 [pii] AID - zoi220679 [pii] AID - 10.1001/jamanetworkopen.2022.24142 [doi] PST - epublish SO - JAMA Netw Open. 2022 Jul 1;5(7):e2224142. doi: 10.1001/jamanetworkopen.2022.24142.