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Effects of antipsychotic medication on functional connectivity in major depressive disorder with psychotic features

Neufeld, Nicholas H; Oliver, Lindsay D; Mulsant, Benoit H; Alexopoulos, George S; Hoptman, Matthew J; Tani, Hideaki; Marino, Patricia; Meyers, Barnett S; Rothschild, Anthony J; Whyte, Ellen M; Bingham, Kathleen S; Flint, Alastair J; Voineskos, Aristotle N
The effect of antipsychotic medication on resting state functional connectivity in major depressive disorder (MDD) is currently unknown. To address this gap, we examined patients with MDD with psychotic features (MDDPsy) participating in the Study of the Pharmacotherapy of Psychotic Depression II. All participants were treated with sertraline plus olanzapine and were subsequently randomized to continue sertraline plus olanzapine or be switched to sertraline plus placebo. Participants completed an MRI at randomization and at study endpoint (study completion at Week 36, relapse, or early termination). The primary outcome was change in functional connectivity measured within and between specified networks and the rest of the brain. The secondary outcome was change in network topology measured by graph metrics. Eighty-eight participants completed a baseline scan; 73 completed a follow-up scan, of which 58 were usable for analyses. There was a significant treatment X time interaction for functional connectivity between the secondary visual network and rest of the brain (t = -3.684; p = 0.0004; pFDR = 0.0111). There was no significant treatment X time interaction for graph metrics. Overall, functional connectivity between the secondary visual network and the rest of the brain did not change in participants who stayed on olanzapine but decreased in those switched to placebo. There were no differences in changes in network topology measures when patients stayed on olanzapine or switched to placebo. This suggests that olanzapine may stabilize functional connectivity, particularly between the secondary visual network and the rest of the brain.
PMID: 37258617
ISSN: 1476-5578
CID: 5543342

Computerized cognitive and social cognition training in schizophrenia for impulsive aggression

Khan, Anzalee; Lindenmayer, Jean-Pierre; Insel, Beverly; Seddo, Mary; Demirli, Ecem; DeFazio, Kayla; Sullivan, Mark; Hoptman, Matthew J; Ahmed, Anthony O
BACKGROUND:Schizophrenia is associated with an elevated risk for impulsive aggression for which there are few psychosocial treatment options. Neurocognitive and social cognitive deficits have been associated with aggression with social cognitive deficits seemingly a more proximal contributor. The current study examined the effects of combining cognitive and social cognition treatment on impulsive aggression among inpatients with chronic schizophrenia and schizoaffective disorder and a history of aggression compared to cognitive remediation treatment alone. METHODS:The two-center study randomized 130 participants to receive 36 sessions of either a combination of cognitive remediation and social cognition treatment or cognitive remediation plus a computer-based control. Participants had at least one aggressive incident within the past year or a Life History of Aggression (LHA) score of 5 or more. Participants completed measures of neurocognition, social cognition, symptom severity, and aggression at baseline and endpoint. RESULTS:Study participants were mostly male (84.5 %), had a mean age 34.9 years, and 11.5 years of education. Both Cognitive Remediation Training (CRT) plus Social Cognition Training (SCT) and CRT plus control groups were associated with significant reductions in aggression measures with no group differences except on a block of the Taylor Aggression Paradigm (TAP), a behavioral task of aggression which favored the CRT plus SCT group. Both groups showed significant improvements in neurocognition and social cognition measures with CRT plus SCT being associated with greater improvements. CONCLUSION/CONCLUSIONS:CRT proved to be an effective non-pharmacological treatment in reducing impulsive aggression in schizophrenia inpatient participants with a history of aggressive episodes. The addition of social cognitive training did not enhance this anti-aggression treatment effect but did augment the CRT effect on cognitive functions, on emotion recognition and on mentalizing capacity of our participants.
PMID: 36424289
ISSN: 1573-2509
CID: 5384412

Suicidal ideation and behavior in schizophrenia: The role of negative urgency and psychiatric symptoms [Letter]

Hoptman, Matthew J; Tural, Umit; Arnold, Molly S; Collins, Katherine A; Evans, Kathryn T; Irvin, Molly K; Parincu, Zamfira; Rette, Danielle N; Sparpana, Allison M; Sullivan, Elizabeth F; Iosifescu, Dan V
PMID: 36906943
ISSN: 1573-2509
CID: 5448772

Neural Correlates of Psychopathic Traits in Schizophrenia: fMRI Study of Response Inhibition in Persistently Violent Patients

Krakowski, Menahem I.; Hoptman, Matthew J.; Czobor, Pal
Background and Hypothesis: Psychopathic traits play an important role in schizophrenia, particularly for violent behavior. There have been very few functional imaging studies (fMRI) examining the impact of brain dysfunction on psychopathic traits in schizophrenia. Our goal was to evaluate neural abnormalities underlying these traits through fMRI in violent subjects with schizophrenia (VS) and in 3 comparison groups: healthy controls (HC), nonviolent patients (NV), and nonpsychotic violent subjects (NPV). Study Design: fMRI imaging was used to measure blood-oxygen-level-dependent activation in 95 subjects while they performed a Go/NoGo task: 26 VS, 25 NPV, 26 HC, and 18 NVS. Psychopathy was evaluated through the 2 factors of the Psychopathy Checklist (PCL:SV). The subjects were also evaluated for psychiatric symptoms and for educational achievement. Study Results: Hypoactivation of brain areas involved in response inhibition was related to the severity of psychopathic traits in the violent patients with schizophrenia. These areas included frontal regions, cingulate cortex, insula, precuneus, and basal ganglia. This association was very strong for the first PCL:SV factor, the affective-interpersonal traits, and moderate for the second PCL:SV factor, the antisocial-impulsive traits. The latter traits were also linked to poor educational achievement. Conclusions: The 2 psychopathic factors have different antecedents and are dissociable at the neural level in schizophrenia. Brain dysfunction is more strongly associated with the affective-interpersonal traits while the antisocial traits are associated with various factors. This has important implications for the conceptualization and treatment of violence in patients with schizophrenia.
ISSN: 2632-7899
CID: 5549822

Visual-somatosensory integration (VSI) as a novel marker of Alzheimer's disease: A comprehensive overview of the VSI study

Mahoney, Jeannette R; Blumen, Helena M; De Sanctis, Pierfilippo; Fleysher, Roman; Frankini, Carolina; Hoang, Alexandria; Hoptman, Matthew J; Jin, Runqiu; Lipton, Michael; Nunez, Valerie; Twizer, Lital; Uy, Naomi; Valdivia, Ana; Verghese, Tanya; Wang, Cuiling; Weiss, Erica F; Zwerling, Jessica; Verghese, Joe
Identification of novel, non-invasive, non-cognitive based markers of Alzheimer's disease (AD) and related dementias are a global priority. Growing evidence suggests that Alzheimer's pathology manifests in sensory association areas well before appearing in neural regions involved in higher-order cognitive functions, such as memory. Previous investigations have not comprehensively examined the interplay of sensory, cognitive, and motor dysfunction with relation to AD progression. The ability to successfully integrate multisensory information across multiple sensory modalities is a vital aspect of everyday functioning and mobility. Our research suggests that multisensory integration, specifically visual-somatosensory integration (VSI), could be used as a novel marker for preclinical AD given previously reported associations with important motor (balance, gait, and falls) and cognitive (attention) outcomes in aging. While the adverse effect of dementia and cognitive impairment on the relationship between multisensory functioning and motor outcomes has been highlighted, the underlying functional and neuroanatomical networks are still unknown. In what follows we detail the protocol for our study, named The VSI Study, which is strategically designed to determine whether preclinical AD is associated with neural disruptions in subcortical and cortical areas that concurrently modulate multisensory, cognitive, and motor functions resulting in mobility decline. In this longitudinal observational study, a total of 208 community-dwelling older adults with and without preclinical AD will be recruited and monitored yearly. Our experimental design affords assessment of multisensory integration as a new behavioral marker for preclinical AD; identification of functional neural networks involved in the intersection of sensory, motor, and cognitive functioning; and determination of the impact of early AD on future mobility declines, including incident falls. Results of The VSI Study will guide future development of innovative multisensory-based interventions aimed at preventing disability and optimizing independence in pathological aging.
PMID: 37065459
ISSN: 1663-4365
CID: 5465972

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

Oberlin, Lauren E; Victoria, Lindsay W; Ilieva, Irena; Dunlop, Katharine; Hoptman, Matthew J; Avari, Jimmy; Alexopoulos, George S; Gunning, Faith M
Importance/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:After a 2-week washout period, participants received escitalopram titrated to a target of 20 mg/d for 12 weeks. Main Outcomes and Measures/UNASSIGNED: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/UNASSIGNED: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) (β [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 (β [df] = 0.445 [26]; P = .04) and executive function (β [df] = 0.384 [26]; P = .04). Conclusions and Relevance/UNASSIGNED: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/ Identifier: NCT01728194.
PMID: 35895056
ISSN: 2574-3805
CID: 5276642

P678. Promoting Healthy Sexual Functioning: Exploring the Impact of Gender Role Non-Conformity on Sexual Dysfunction [Meeting Abstract]

Irvin, M; Arnold, M; Sparpana, A; Sullivan, E; Collins, K; Hoptman, M; Iosifescu, D
Background: Uncertainty remains about psychological and sexual implications of gender role non-conformity (GRNC) defined as men endorsing or performing femininity, and women endorsing or performing masculinity. Previous studies have indicated that variance in gender presentation is associated with negative psychological consequences. Homophobic stigmatization and internalized homophobia partially mediate this association, suggesting it is not the practice of GRNC that causes distress but subjective or perceived reactions to it. Here, we test the hypothesis that people reporting sexual dysfunction have higher levels of GRNC.
Method(s): We analyzed data from the Nathan Kline Institute Rockland Sample. 797 subjects (age=48.4 +/- 17.7, sex=66% female) completed the Sex Role Identity Scale (SRIS) and the Trauma Symptom Checklist (TSC-40). GRNC was quantified by SRIS questions-subjective GRNC (S-GRNC) was assessed using the question "How feminine/masculine do you think you are?" and perceived GRNC (P-GRNC) was assessed with "How feminine/masculine do you think you appear and come across to others?" Sexual dysfunction was measured with a TSC-40 subscale. We performed sex-specific stepwise linear regressions to explore the relationships between S-GRNC, P-GRNC, and sexual dysfunction.
Result(s): In male subjects, a model including only S-GRNC significantly predicted sexual dysfunction, F(1, 267)=5.027, p=0.026, adj. R2=0.015. In female subjects, a model including only P-GRNC significantly predicted sexual dysfunction, F(1, 526)=14.854, p<0.001, adj. R2=0.026.
Conclusion(s): GRNC significantly predicts sexual dysfunction; different aspects of GRNC are more relevant for male vs. female subjects. While limited, these results highlight the clinical significance of understanding GRNC to promote healthy sexual functioning for all individuals. Keywords: Sexual Dysfunction, Sex Differences, Gender
ISSN: 1873-2402
CID: 5240702

Replicability in Brain Imaging [Editorial]

Kelly, Robert E; Hoptman, Matthew J
In the early 2010s, the "replication crisis" and synonymous terms ("replicability crisis" and "reproducibility crisis") were coined to describe growing concerns regarding published research results too often not being replicable, potentially undermining scientific progress [...].
PMID: 35326353
ISSN: 2076-3425
CID: 5220442

Estimated Regional White Matter Hyperintensity Burden, Resting State Functional Connectivity, and Cognitive Functions in Older Adults

Jaywant, Abhishek; Dunlop, Katharine; Victoria, Lindsay W; Oberlin, Lauren; Lynch, Charles J; Respino, Matteo; Kuceyeski, Amy; Scult, Matthew; Hoptman, Matthew J; Liston, Conor; O'Dell, Michael W; Alexopoulos, George S; Perlis, Roy H; Gunning, Faith M
OBJECTIVE:White matter hyperintensities (WMH) are linked to deficits in cognitive functioning, including cognitive control and memory; however, the structural, and functional mechanisms are largely unknown. We investigated the relationship between estimated regional disruptions to white matter fiber tracts from WMH, resting state functional connectivity (RSFC), and cognitive functions in older adults. DESIGN/METHODS:Cross-sectional study. SETTING/METHODS:Community. PARTICIPANTS/METHODS:Fifty-eight cognitively-healthy older adults. MEASUREMENTS/METHODS:Tasks of cognitive control and memory, structural MRI, and resting state fMRI. We estimated the disruption to white matter fiber tracts from WMH and its impact on gray matter regions in the cortical and subcortical frontoparietal network, default mode network, and ventral attention network by overlaying each subject's WMH mask on a normative tractogram dataset. We calculated RSFC between nodes in those same networks. We evaluated the interaction of regional WMH burden and RSFC in predicting cognitive control and memory. RESULTS:The interaction of estimated regional WMH burden and RSFC in cortico-striatal regions of the default mode network and frontoparietal network was associated with delayed recall. Models predicting working memory, cognitive inhibition, and set-shifting were not significant. CONCLUSION/CONCLUSIONS:Findings highlight the role of network-level structural and functional alterations in resting state networks that are related to WMH and impact memory in older adults.
PMID: 34412936
ISSN: 1545-7214
CID: 5066902

What Do These Findings Tell Us? Comment on Tinella et al. Cognitive Efficiency and Fitness-to-Drive along the Lifespan: The Mediation Effect of Visuospatial Transformations. Brain Sci. 2021, 11, 1028

Kelly, Robert E; Ahmed, Anthony O; Hoptman, Matthew J
Tinella et al.'s recent article [...].
PMID: 35203929
ISSN: 2076-3425
CID: 5167822