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Item Apathy and Anxiety are Related to Poor Function in Persons with Early-Onset Alzheimer’s Disease(Oxford University Press, 2022) Crouch, Adele; Massimo, Lauren; School of NursingNeuropsychiatric symptoms are prevalent in persons with early-onset Alzheimer’s disease (EOAD) and may contribute to the inability to perform instrumental activities of daily living. We examined associations between frequently observed symptoms in persons with EOAD: apathy, anxiety, depression, and patient function. Caregivers of 94 persons with EOAD completed questionnaires including the Neuropsychiatric Inventory and the Functional Activities Questionnaire. Regression analyses were performed for each neuropsychiatric symptom as a predictor with covariates (age, sex disease duration) and our outcome was patient function. We then performed multivariate analysis with the significant predictors. We observed that apathy explained 20.51% [F(4,68)=5.65, adjusted R2=0.2051; p<0.001], anxiety explained 6.63% [F(4,70)=2.31, adjusted R2=0.0663 p<0.05], and depression was not a significant predictor of patient function. In a multivariate model, apathy and anxiety explained 21.03% [F(5,67)=4.83, adjusted R2=0.2103; p<0.001] of the variance in patient function. These results suggest apathy and anxiety contribute to diminished ability to complete functional activities.Item Apathy Is Associated With Ventral Striatum Volume in Schizophrenia Spectrum Disorder(American Psychiatric Association, 2016) Roth, Robert M.; Garlinghouse, Matthew A.; Flashman, Laura A.; Koven, Nancy S.; Pendergrass, J. Cara; Ford, James C.; McAllister, Thomas W.; Saykin, Andrew J.; Psychiatry, School of MedicineApathy is prevalent in schizophrenia, but its etiology has received little investigation. The ventral striatum (VS), a key brain region involved in motivated behavior, has been implicated in studies of apathy. We therefore evaluated whether apathy is associated with volume of the VS on MRI in 23 patients with schizophrenia using voxel-based morphometry. Results indicated that greater self-reported apathy severity was associated with smaller volume of the right VS even when controlling for age, gender, depression, and total gray matter volume. The finding suggests that apathy is related to abnormality of brain circuitry subserving motivated behavior in patients with schizophrenia.Item Clarifying the Overlap Between Motivation and Negative Symptom Measures in Schizophrenia Research: A Meta-Analysis(Elsevier, 2019-04) Luther, Lauren; Fischer, Melanie W.; Firmin, Ruth L.; Salyers, Michelle P.; Psychology, School of ScienceMotivation and negative symptom research has recently been hampered by a series of inconsistent findings, leading to calls for a greater consensus on the type of measures used across studies. To inform this issue, we conducted a meta-analysis that quantified the association between motivation measures (self-report, performance-based) and clinician-rated negative symptom measures as well as a series of moderator analyses to develop a greater understanding of the measurement factors impacting this relationship. Forty-seven eligible studies with people with schizophrenia-spectrum disorders were included. Using a random-effects meta-analytic model, a small but significant overall effect size emerged between motivation and clinician-rated negative symptoms (r = −.18). Several significant moderators were identified, including the generation of negative symptom measures such that there was a significantly stronger relationship between motivation and second-generation (r = −.38) than first-generation negative symptom measures (r = −.17). Further, the type of performance-based measure used moderated the relationship, with effort discounting tasks most strongly related to negative symptoms (r = −.44). The domain of motivation assessed (intrinsic, extrinsic, amotivation) also moderated the relationship. These findings help to identify sources of inconsistencies observed in prior studies and point to both second-generation and effort discounting tasks as the most promising types of measures, particularly for those interested in validating motivation measures or assessing the effectiveness of motivation treatments. Although additional research is needed, our results suggest that using these measures may help to reduce inconsistencies across studies and move the field forward.Item Cognitive Deficits, Apathy, and Hypersomnolence Represent the Core Brain Symptoms of Adult-Onset Myotonic Dystrophy Type 1(Frontiers Media, 2021-07) Miller, Jacob N.; Kruger, Alison; Moser, David J.; Gutmann, Laurie; van der Plas, Ellen; Koscik, Timothy R.; Cumming, Sarah A.; Monckton, Darren G.; Nopoulos, Peggy C.; Neurology, School of MedicineMyotonic dystrophy type 1 is the most common form of muscular dystrophy in adults, and is primarily characterized by muscle weakness and myotonia, yet some of the most disabling symptoms of the disease are cognitive and behavioral. Here we evaluated several of these non-motor symptoms from a cross-sectional time-point in one of the largest longitudinal studies to date, including full-scale intelligence quotient, depression, anxiety, apathy, sleep, and cerebral white matter fractional anisotropy in a group of 39 adult-onset myotonic dystrophy type 1 participants (27 female) compared to 79 unaffected control participants (46 female). We show that intelligence quotient was significantly associated with depression (P < 0.0001) and anxiety (P = 0.018), but not apathy (P < 0.058) or hypersomnolence (P = 0.266) in the DM1 group. When controlling for intelligence quotient, cerebral white matter fractional anisotropy was significantly associated with apathy (P = 0.042) and hypersomnolence (P = 0.034), but not depression (P = 0.679) or anxiety (P = 0.731) in the myotonic dystrophy type 1 group. Finally, we found that disease duration was significantly associated with apathy (P < 0.0001), hypersomnolence (P < 0.001), IQ (P = 0.038), and cerebral white matter fractional anisotropy (P < 0.001), but not depression (P = 0.271) or anxiety (P = 0.508). Our results support the hypothesis that cognitive deficits, hypersomnolence, and apathy, are due to the underlying neuropathology of myotonic dystrophy type 1, as measured by cerebral white matter fractional anisotropy and disease duration. Whereas elevated symptoms of depression and anxiety in myotonic dystrophy type 1 are secondary to the physical symptoms and the emotional stress of coping with a chronic and debilitating disease. Results from this work contribute to a better understanding of disease neuropathology and represent important therapeutic targets for clinical trials.Item Diagnostic criteria for apathy in neurocognitive disorders(Wiley, 2021) Miller, David S.; Robert, Philippe; Ereshefsky, Larry; Adler, Lawrence; Bateman, Daniel; Cummings, Jeff; DeKosky, Steven T.; Fischer, Corinne E.; Husain, Masud; Ismail, Zahinoor; Jaeger, Judith; Lerner, Alan J.; Li, Abby; Lyketsos, Constantine G.; Manera, Valeria; Mintzer, Jacobo; Moebius, Hans J.; Mortby, Moyra; Meulien, Didier; Pollentier, Stephane; Porsteinsson, Anton; Rasmussen, Jill; Rosenberg, Paul B.; Ruthirakuhan, Myuri T.; Sano, Mary; Zucchero Sarracini, Carla; Lanctôt, Krista L.; Psychiatry, School of MedicineIntroduction: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed. Methods: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. Results: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies. Discussion: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.Item Metacognition Is Necessary for the Emergence of Motivation in People With Schizophrenia Spectrum Disorders: A Necessary Condition Analysis(Wolters Kluwer, 2017-12) Luther, Lauren; Bonfils, Kelsey A.; Firmin, Ruth L.; Buck, Kelly D.; Choi, Jimmy; Dimaggio, Giancarlo; Popolo, Raffaele; Minor, Kyle S.; Lysaker, Paul H.; Psychology, School of ScienceMetacognition deficits are a putative cause of reduced motivation in people with schizophrenia spectrum disorders. However, it is unclear whether certain levels of metacognition are necessary for motivation to emerge. This study used a Necessary Condition Analysis (NCA) to test whether metacognition was necessary for the presence of motivation and to identify the minimum level of metacognition necessary for high motivation to be possible in people with schizophrenia spectrum disorders (N=175). Participants completed clinician-rated measures of metacognition and motivation. NCA revealed that metacognition is a necessary condition for motivation and that high levels of motivation were only possible, although not guaranteed, when at least a basic level of metacognition was present. Findings suggest that metacognition is a necessary building block for the development of motivation. Results suggest that targeting metacognition may be essential for improving motivation among people with schizophrenia spectrum disorders who do not meet this metacognition threshold.