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BackgroundClarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.MethodsThe study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].ResultsTotal depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).ConclusionsA history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.

Because longitudinal studies of aging typically lack cognitive data from earlier ages, it is unclear how general cognitive ability (GCA) changes throughout the life course. In 1173 Vietnam Era Twin Study of Aging (VETSA) participants, we assessed young adult GCA at average age 20 and current GCA at 3 VETSA assessments beginning at average age 56. The same GCA index was used throughout. Higher young adult GCA and better GCA maintenance were associated with stronger specific cognitive abilities from age 51 to 73. Given equivalent GCA at age 56, individuals who had higher age 20 GCA outperformed those whose GCA remained stable in terms of memory, executive function, and working memory abilities from age 51 to 73. Thus, paradoxically, despite poorer maintenance of GCA, high young adult GCA still conferred benefits. Advanced predicted brain age and the combination of elevated vascular burden and APOE-ε4 status were associated with poorer maintenance of GCA. These findings highlight the importance of distinguishing between peak and current GCA for greater understanding of cognitive aging.

Introduction: Despite increasing demand for data, little is known about the authorization patterns, safety, and effectiveness of medical cannabis products. Materials and Methods: We conducted a 2 year observational study of adult patients who were legally authorized a medical cannabis product from a single licensed producer; we captured and analyzed authorized cannabis use patterns by cannabinoid profile (tetrahydrocannabinol [THC]-dominant; cannabidiol [CBD]-dominant; and balanced (THC:CBD) and clinical outcomes using standardized outcome measures every 3 months for 12 months at a network of medical cannabis clinics in Quebec, Canada. Results: We recruited 585 patients (average age 56.5 years), of whom 61% identified as female and 85% reported pain as their primary complaint. Over 12 months, there was a significant increase in the number of products authorized (Z=2.59, p=0.01). The proportion of authorizations for a THC-dominant or CBD-dominant product increased relative to the proportion of authorizations for a balanced (THC:CBD) product (all p

Background Tau positron emission tomography (PET) is increasing in popularity for biomarker characterization of Alzheimer’s disease (AD), and recent frameworks rely on tau PET cut-points to stage individuals along the AD continuum. Given the lack of standardization in tau PET thresholding methods, this study sought to systematically canvass and characterize existing studies that have derived tau PET cut-points and then directly assess different methods of tau PET thresholding in terms of their concurrent validity. Methods First, a literature search was conducted in PubMed to identify studies of AD and related clinical phenotypes that used the Flortaucipir (AV-1451) tau PET tracer to derive a binary cut-point for tau positivity. Of 540 articles screened and 47 full-texts reviewed, 23 cohort studies met inclusion criteria with a total of 6536 participants. Second, we derived and compared tau PET cut-points in a 2 × 2 × 2 design that systematically varied region (temporal meta-ROI and entorhinal cortex), analytic method (receiver operating characteristics and 2 standard deviations above comparison group), and criterion/comparison variable (amyloid-beta negative cognitively unimpaired or cognitively unimpaired only) using a sample of 453 older adults from the Alzheimer’s Disease Neuroimaging Initiative. Results For the systematic review, notable variability in sample characteristics, preprocessing methods, region of interest, and analytic approach were observed, which were accompanied by discrepancy in proposed tau PET cut points. The empirical follow-up indicated the cut-point derived based on 2 standard deviations above a either comparison group in either ROI best differentiated tau positive and negative groups on cerebrospinal fluid phosphorylated tau, Mini-Mental State Examination score, and delayed memory performance. Conclusions Given the impact of discrepant thresholds on tau positivity rates, biomarker staging, and eligibility for future clinical treatment trials, recommendations are offered to select cut-point derivations based on the unique goals and priorities of different studies.

Neuroimaging signatures based on composite scores of cortical thickness and hippocampal volume predict progression from mild cognitive impairment to Alzheimer’s disease. However, little is known about the ability of these signatures among cognitively normal adults to predict progression to mild cognitive impairment. Towards that end, a signature sensitive to microstructural changes that may predate macrostructural atrophy should be useful. We hypothesized that: (i) a validated MRI-derived Alzheimer’s disease signature based on cortical thickness and hippocampal volume in cognitively normal middle-aged adults would predict progression to mild cognitive impairment; and (ii) a novel grey matter mean diffusivity signature would be a better predictor than the thickness/volume signature. This cohort study was part of the Vietnam Era Twin Study of Aging. Concurrent analyses compared cognitively normal and mild cognitive impairment groups at each of three study waves (ns = 246–367). Predictive analyses included 169 cognitively normal men at baseline (age = 56.1, range = 51–60). Our previously published thickness/volume signature derived from independent data, a novel mean diffusivity signature using the same regions and weights as the thickness/volume signature, age, and an Alzheimer’s disease polygenic risk score were used to predict incident mild cognitive impairment an average of 12 years after baseline (follow-up age = 67.2, range = 61–71). Additional analyses adjusted for predicted brain age difference scores (chronological age minus predicted brain age) to determine if signatures were Alzheimer-related and not simply ageing-related. In concurrent analyses, individuals with mild cognitive impairment had higher (worse) mean diffusivity signature scores than cognitively normal participants, but thickness/volume signature scores did not differ between groups. In predictive analyses, age and polygenic risk score yielded an area under the curve of 0.74 (sensitivity = 80.00%; specificity = 65.10%). Prediction was significantly improved with addition of the mean diffusivity signature (area under the curve = 0.83; sensitivity = 85.00%; specificity = 77.85%; P = 0.007), but not with addition of the thickness/volume signature. A model including both signatures did not improve prediction over a model with only the mean diffusivity signature. Results held up after adjusting for predicted brain age difference scores. The novel mean diffusivity signature was limited by being yoked to the thickness/volume signature weightings. An independently derived mean diffusivity signature may thus provide even stronger prediction. The young age of the sample at baseline is particularly notable. Given that the brain signatures were examined when participants were only in their 50 s, our results suggest a promising step towards improving very early identification of Alzheimer’s disease risk and the potential value of mean diffusivity and/or multimodal brain signatures., Among cognitively normal adults in their 50 s, an Alzheimer’s brain signature based on grey matter mean diffusivity—but not cortical thickness—significantly improved prediction of progression to mild cognitive impairment 12 years later. Grey matter mean diffusivity signatures may be sensitive to Alzheimer-related changes as early as middle age., Graphical Abstract Graphical Abstract

Author(s): Elman, Jeremy A; Puckett, Olivia K; Beck, Asad; Fennema-Notestine, Christine; Cross, Latonya K; Dale, Anders M; Eglit, Graham ML; Eyler, Lisa T; Gillespie, Nathan A; Granholm, Eric L; Gustavson, Daniel E; Hagler, Donald J; Hatton, Sean N; Hauger, Richard; Jak, Amy J; Logue, Mark W; McEvoy, Linda K; McKenzie, Ruth E; Neale, Michael C; Panizzon, Matthew S; Reynolds, Chandra A; Sanderson-Cimino, Mark; Toomey, Rosemary; Tu, Xin M; Whitsel, Nathan; Williams, McKenna E; Xian, Hong; Lyons, Michael J; Franz, Carol E; Kremen, William S | Abstract: IntroductionThe locus coeruleus (LC) undergoes extensive neurodegeneration in early Alzheimer's disease (AD). The LC is implicated in regulating the sleep-wake cycle, modulating cognitive function, and AD progression.MethodsParticipants were 481 men (ages 62 to 71.7) from the Vietnam Era Twin Study of Aging. LC structural integrity was indexed by neuromelanin-sensitive magnetic resonance imaging (MRI) contrast-to-noise ratio (LCCNR ). We examined LCCNR , cognition, amnestic mild cognitive impairment (aMCI), and daytime dysfunction.ResultsHeritability of LCCNR was .48. Participants with aMCI showed greater daytime dysfunction. Lower LCCNR was associated with poorer episodic memory, general verbal fluency, semantic fluency, and processing speed, as well as increased odds of aMCI and greater daytime dysfunction.DiscussionReduced LC integrity is associated with widespread differences across cognitive domains, daytime sleep-related dysfunction, and risk for aMCI. These findings in late-middle-aged adults highlight the potential of MRI-based measures of LC integrity in early identification of AD risk.

Objective:Iraq and Afghanistan Veterans with posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) history have high rates of performance validity test (PVT) failure. The study aimed to determine whether those with scores in the invalid versus valid range on PVTs show similar benefit from psychotherapy and if psychotherapy improves PVT performance.Method:Veterans (N = 100) with PTSD, mild-to-moderate TBI history, and cognitive complaints underwent neuropsychological testing at baseline, post-treatment, and 3-month post-treatment. Veterans were randomly assigned to cognitive processing therapy (CPT) or a novel hybrid intervention integrating CPT with TBI psychoeducation and cognitive rehabilitation strategies from Cognitive Symptom Management and Rehabilitation Therapy (CogSMART). Performance below standard cutoffs on any PVT trial across three different PVT measures was considered invalid (PVT-Fail), whereas performance above cutoffs on all measures was considered valid (PVT-Pass).Results:Although both PVT groups exhibited clinically significant improvement in PTSD symptoms, the PVT-Pass group demonstrated greater symptom reduction than the PVT-Fail group. Measures of post-concussive and depressive symptoms improved to a similar degree across groups. Treatment condition did not moderate these results. Rate of valid test performance increased from baseline to follow-up across conditions, with a stronger effect in the SMART-CPT compared to CPT condition.Conclusion:Both PVT groups experienced improved psychological symptoms following treatment. Veterans who failed PVTs at baseline demonstrated better test engagement following treatment, resulting in higher rates of valid PVTs at follow-up. Veterans with invalid PVTs should be enrolled in trauma-focused treatment and may benefit from neuropsychological assessment after, rather than before, treatment.

Author(s): Lopez, Francesca V; Eglit, Graham ML; Schiehser, Dawn M; Pirogovsky-Turk, Eva; Litvan, Irene; Lessig, Stephanie; Filoteo, J Vincent | Abstract: BackgroundThe Apathy Scale (AS), a popular measure of apathy in Parkinson's disease (PD), has been somewhat limited for failing to characterize dimensions of apathy, such as those involving cognitive, behavioral, and emotional apathy symptoms. This study sought to determine whether factors consistent with these apathy dimensions in PD could be identified on the AS, examine the associations between these factors and disease-related characteristics, and compare PD patients and healthy control (HCs) on identified factors.MethodsConfirmatory (CFA) and exploratory factor analysis (EFA) were conducted on AS scores of 157 nondemented PD patients to identify AS factors. These factors were then correlated with important disease-related characteristics, and PD and HC participants were compared across these factors.ResultsPreviously proposed AS models failed to achieve an adequate fit in CFA. A subsequent EFA revealed two factors on the AS reflecting joint cognitive-behavioral aspects of apathy (Motivation-Interest-Energy) and emotional apathy symptoms (Indifference). Both factors were associated with anxiety, depression, health-related quality of life, and independent activities of daily living, with Indifference associated more with the latter. In addition, only the Indifference factor was associated with cognitive functioning. PD patients reported higher levels of symptoms than HCs on both factors, with the group difference slightly larger on the Motivation-Interest-Energy factor.ConclusionThe AS can be decomposed into two factors reflecting Motivation-Interest-Energy and Indifference symptoms. These factors are differentially associated with clinical variables, including cognition and independent activities of daily living, indicating the importance of evaluating apathy from a multidimensional perspective.

Introduction Our goal was to determine whether cognitive and cerebrospinal fluid (CSF) markers of tau and amyloid beta 1‐42 (Aβ42) differ between Vietnam‐era veterans with and without history of traumatic brain injury (TBI) and whether TBI moderates the association between CSF markers and neurocognitive functioning. Methods A total of 102 male participants (52 TBI, 50 military controls [MCs]; mean age = 68) were included. Levels of CSF Aβ42, tau phosphorylated at the threonine 181 position (p‐tau), and total tau (t‐tau) were quantified. Group differences in CSF markers and cognition as well as the moderating effect of TBI on CSF and cognition associations were explored. Results Relative to MCs, the TBI group showed significantly higher p‐tau (P = .01) and t‐tau (P = .02), but no differences in amyloid (P = .09). TBI history moderated the association between CSF tau and performance on a measure of processing speed (t‐tau: P = .04; p‐tau: P = .02). Discussion Tau accumulation may represent a mechanism of dementia risk in older veterans with remote TBI.

Author(s): Eglit, Graham ML; Lopez, Francesca; Schiehser, Dawn M; Pirogovsky-Turk, Eva; Litvan, Irene; Lessig, Stephanie; Filoteo, J Vincent | Abstract: BackgroundApathy is a prevalent, multidimensional neuropsychiatric condition in Parkinson's disease (PD). Several authors have proposed apathy subtypes in PD, but no study has examined the classification of PD patients into distinct apathy subtypes, nor has any study examined the clinical utility of doing so.ObjectivesThe current study used a data-driven approach to explore the existence and associated clinical characteristics of apathy subtypes in PD.MethodThe Apathy Scale (AS) was administered to 157 non-demented individuals with PD. Participants were classified into apathy subgroups through cluster analysis. Differences among apathy subtypes on external clinical indicators were explored across apathy subgroups.ResultsIndividuals with PD were classified into three subgroups: a Non-Apathetic group with low levels of apathy symptoms, a Low Interest/Energy group, characterized by elevated symptoms of low interest/energy and minimal low initiation/emotional indifference symptoms, and a Low Initiation group, characterized by an absence of low interest/energy symptoms and elevated levels of low initiation/emotional indifference symptoms. Both Low Interest/Energy and Low Initiation groups exhibited worse depression, fatigue, anxiety, health-related quality of life, and caregiver burden than the Non-Apathetic subgroup. The Low Initiation group exhibited worse overall cognition, emotional well-being, state anxiety, communicative ability, and functional ability than the Low Interest/Energy group. Importantly, disease-related characteristics did not differ across apathy symptom subgroups.ConclusionsNon-demented PD patients can be separated into distinct apathy symptom subgroups, which are differentially associated with important clinical variables. Apathy subgroup membership may reflect disruption to different neural systems independent of disease progression.

Importance Wisdom is a neurobiological personality trait made up of specific components, including prosocial behaviors, emotional regulation, and spirituality. It is associated with greater well-being and happiness. Objective To evaluate the effectiveness of interventions to enhance individual components of wisdom. Data Sources MEDLINE and PsycINFO databases were searched for articles published through December 31, 2018. Study Eligibility Criteria Randomized clinical trials that sought to enhance a component of wisdom, used published measures to assess that component, were published in English, had a minimum sample size of 40 participants, and presented data that enabled computation of effect sizes were included in this meta-analysis. Data Extraction and Synthesis Random-effect models were used to calculate pooled standardized mean differences (SMDs) for each wisdom component and random-effects meta-regression to assess heterogeneity of studies. Main Outcomes and Measures Improvement in wisdom component using published measures. Results Fifty-seven studies (N = 7096 participants) met review criteria: 29 for prosocial behaviors, 13 for emotional regulation, and 15 for spirituality. Study samples included people with psychiatric or physical illnesses and from the community. Of the studies, 27 (47%) reported significant improvement with medium to large effect sizes. Meta-analysis revealed significant pooled SMDs for prosocial behaviors (23 studies; pooled SMD, 0.43 [95% CI, 0.22-0.3];P = .02), emotional regulation (12 studies; pooled SMD, 0.67 [95% CI, 0.21-1.12];P = .004), and spirituality (12 studies; pooled SMD, 1.00 [95% CI, 0.41-1.60];P = .001). Heterogeneity of studies was considerable for all wisdom components. Publication bias was present for prosocial behavior and emotional regulation studies; after adjusting for it, the pooled SMD for prosocial behavior remained significant (SMD, 0.4 [95% CI, 0.16-0.78];P = .003). Meta-regression analysis found that effect sizes did not vary by wisdom component, although for trials on prosocial behaviors, large effect sizes were associated with older mean participant age (β, 0.08 [SE, 0.04]), and the reverse was true for spirituality trials (β, −0.13 [SE, 0.04]). For spirituality interventions, higher-quality trials had larger effect sizes (β, 4.17 [SE, 1.07]), although the reverse was true for prosocial behavior trials (β, −0.91 [SE 0.44]). Conclusions and Relevance Interventions to enhance spirituality, emotional regulation, and prosocial behaviors are effective in a proportion of people with mental or physical illnesses and from the community. The modern behavioral epidemics of loneliness, suicide, and opioid abuse point to a growing need for wisdom-enhancing interventions to promote individual and societal well-being.

Introduction Apolipoprotein E (APOE) interacts with Alzheimer's disease pathology to promote disease progression. We investigated the moderating effect of APOE on independent associations of amyloid and tau positron emission tomography (PET) with cognition. Methods For 297 nondemented older adults from the Alzheimer's Disease Neuroimaging Initiative, regression equations modeled associations between cognition and (1) cortical amyloid beta (Aβ) PET levels adjusting for tau and (2) medial temporal lobe (MTL) tau PET levels adjusting for Aβ, including interactions with APOE e4-carrier status. Results Adjusting for tau PET, Aβ was not associated with cognition and did not interact with APOE. In contrast, adjusting for Aβ PET, MTL tau was associated with all cognitive domains. Further, there was a stronger moderating effect of APOE on MTL tau and memory associations in e4-carriers, even among Aβ-negative individuals. Discussion Findings suggest that APOE may interact with tau independently of Aβ and that elevated MTL tau confers negative cognitive consequences in Aβ-negative e4 carriers.

Hypertension is common among older adults and is believed to increase susceptibility to Alzheimer’s disease, but mechanisms underlying this relationship are unclear. Hypertension also promotes circle of Willis atherosclerosis, which contributes to cerebral hypoperfusion and arterial wall stiffening, two potential mechanisms linking hypertension to Alzheimer’s disease. To examine the role of circle of Willis atherosclerosis in the association between hypertension and Alzheimer’s disease neuropathology, we analysed post-mortem neuropathological data on 2198 decedents from the National Alzheimer’s Coordinating Center database [mean (standard deviation) age at last visit 80.51 (1.95) and 47.1% female] using joint simultaneous (i.e. mediation) modelling. Within the overall sample and among Alzheimer’s dementia decedents, hypertension was indirectly associated with increased neuritic plaques and neurofibrillary tangles through its association with circle of Willis atherosclerosis. Similar indirect effects were observed for continuous measures of systolic and diastolic blood pressure. These results suggest that hypertension may promote Alzheimer’s disease pathology indirectly through intracranial atherosclerosis by limiting cerebral blood flow and/or dampening perivascular clearance. Circle of Willis atherosclerosis may be an important point of convergence between vascular risk factors, cerebrovascular changes and Alzheimer’s disease neuropathology., Hypertension increases susceptibility to Alzheimer’s disease, but mechanisms underlying this relationship are unclear. In this sample of 2198 decedents, hypertension was indirectly associated with Alzheimer’s disease neuropathology through its association with circle of Willis atherosclerosis. Intracranial atherosclerosis may promote Alzheimer’s disease by limiting cerebral blood flow and/or dampening perivascular clearance., Graphical Abstract Graphical Abstract

Objective: The D-KEFS Color Word Interference Test (CWIT) is among the most commonly administered measures of verbally mediated processing speed and executive functioning. Previous research...

Author(s): Martin, A'verria; Eglit, Graham ML; Maldonado, Yadira; Daly, Rebecca; Liu, Jinyuan; Tu, Xin; Jeste, Dilip V | Abstract: Background and objectivesNegative age stereotypes can become internalized and contribute to lower levels of physical and mental well-being in older adults, including those with serious illnesses. The main objective of this study was to examine the relationships of attitude toward own aging (ATOA) with health outcomes after controlling for resilience among older cancer survivors and comparison subjects without cancer, aged 50 years or older.MethodsWe examined data in 1,140 adults from the Successful Aging Evaluation (SAGE) study, a structured multi-cohort investigation of community-based adults selected using random digit dialing. There were 219 participants with cancer (excluding skin cancer) and 912 without cancer. ATOA was assessed with the Philadelphia Geriatric Morale Scale, and its relationship with measures of physical, cognitive, and mental health, as well as resilience was evaluated.ResultsIndividuals with cancer reported slightly more pessimistic ATOA than individuals without cancer. ATOA correlated with physical and mental health in individuals with and without cancer. Hierarchical linear multiple regression revealed that ATOA contributed significantly to the prediction of physical and mental health after controlling for socio-demographic variables and resilience.Discussion and implicationsHigher levels of positive ATOA appear to be a protective factor for health in older adults, including those with cancer. Interventions that provide education about positive aspects of aging, modify negative automatic thoughts, and promote optimism may be useful for increasing ATOA and thereby improving physical and mental health in older adults, especially those with cancer.

The Test of Memory Malingering (TOMM) and the Word Memory Test (WMT) are both performance validity tests (PVTs) that use a two-alternative forced-choice (2AFC) recognition memory format. Several studies have reported that these tests are susceptible to cognitive impairment and that the WMT is more susceptible than the TOMM. The current study explored components of recognition memory (i.e., conscious recollection and familiarity) underlying the TOMM and WMT to identify factors that make them susceptible and resilient to cognitive impairment.Fifty-four nonclinical undergraduate research participants were administered the TOMM and WMT while providing introspective judgments about their recognition memory using the remember/know/guess procedure. In addition, half of participants were administered dual-task interference, a manipulation intended to reduce recollection, during these tests, while the other half completed these tests without interference. Standard cutoffs on the TOMM and WMT were explored, as well as alternative cutoffs based on TOMM Trial 1 scores.The WMT was more impacted by dual-task interference than standard TOMM cutoff trials, while alternative TOMM cutoff trials were equally impacted by dual-task interference relative to the WMT. Dual-task interference reduced recollection on these tests, but spared familiarity. Standard TOMM trials and the WMT were relatively comparable on levels of recollection, but familiarity contributed more to the TOMM than to the WMT. Alternative TOMM trials possessed lower familiarity and recollection than standard TOMM trials and lower recollection than the WMT.Reduced recollection places examinees at risk of failing the TOMM and WMT, while familiarity contributes to the relative resilience of the standard TOMM. Future development of 2AFC recognition memory PVTs should attempt to maximize the contribution of familiarity to their completion.

BACKGROUND: Psychiatry has traditionally focused on studying psychopathology and treating mental illnesses to relieve symptoms and prevent relapse. Positive psychiatry seeks to expand the scope of psychiatry to broader aspects of mental health and well-being among individuals with or without mental illnesses. Positive psychosocial factors such as well-being, resilience, optimism, wisdom, and social support are central to positive psychiatry. AIM: To summarizethe emerging scienceof positive psychiatry, emphasizing the use of measures of positive characteristics and outcomes relevant to mental health. METHODS: Overview of recent research in positive psychiatry, focusing on measurements. RESULTS: Positive psychosocial factorsare associated with better mental and physical health in diverse populations. Among individuals with serious mental illnesses, levels of these factors varyconsiderably, but positive psychiatry interventions can improvewell-being and rates of recovery in at least subsets of the patients. A number of measures of positive factors and outcomes are available; most of them are based on self-reports, which have advantages as well as limitations. CONCLUSIONS: Positive psychiatry has the potential to improve the health and well-being of individuals with or without mental illnesses. Further research is needed to provide clinicians and investigatorswith a full tool-box of validated measures for positive psychosocial factors and outcomes. These measures should be subjected to rigorous psychometric evaluation across populations to help clarify mechanisms underlying positive factors, evaluate their longitudinaltrajectories, and examine the impact of interventions on health and well-beingover the lifespan in different clinical groups.

OBJECTIVE:Making decisions is central to the exercise of control over one's well-being. Many individuals with serious mental illness (SMI) experience limitations in their decision-making capacity. These individuals have often been placed under legal guardianship and substitute decision makers have been appointed to make decisions on their behalf. More recently, supported decision making (SDM) has emerged as a possible alternative in some cases. SDM involves recruitment of trusted supports to enhance an individual's capacity in the decision-making process, enabling him or her to retain autonomy in life decisions. This overview examines issues associated with decision-making capacity in SMI, frameworks of substitute decision making and SDM, and emerging empirical research on SDM. METHOD:This is an overview of the medical and legal literature on decision making capacity and supported decision making for persons with SMI. RESULTS:Many but not all individuals with SMI exhibit decrements in decision-making capacity and skill, in part due to cognitive impairment. There are no published data on rates of substitute decision making/guardianship or SDM for SMI. Only three empirical studies have explored SDM in this population. These studies suggest that SDM is viewed as an acceptable and potentially superior alternative to substitute decision making for patients and their caretakers. CONCLUSIONS:SDM is a promising alternative to substitute decision making for persons with SMI. Further empirical research is needed to clarify candidates for SDM, decisions in need of support, selection of supporters, guidelines for the SDM process, integration of SDM with emerging technological platforms, and outcomes of SDM. Recommendations for implementation of and research on SDM for SMI are provided.