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Background: Phenotypic heterogeneity in early language, intellectual, motor, and adaptive functioning (LIMA) features are amongst the most striking features that distinguish different types of autistic individuals. Yet the current diagnostic criteria uses a single label of autism and implicitly emphasizes what individuals have in common as core social-communicative and restricted repetitive behavior difficulties. Subtype labels based on the non-core LIMA features may help to more meaningfully distinguish types of autisms with differing developmental paths and differential underlying biology. Methods: Unsupervised data-driven subtypes were identified using stability-based relative clustering validation on publicly available Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS) data (n = 615; age = 24–68 months) from the National Institute of Mental Health Data Archive (NDA). Differential developmental trajectories between subtypes were tested on longitudinal data from NDA and from an independent in-house dataset from UCSD. A subset of the UCSD dataset was also tested for subtype differences in functional and structural neuroimaging phenotypes and relationships with blood gene expression. The current subtyping model was also compared to early language outcome subtypes derived from past work. Results: Two autism subtypes can be identified based on early phenotypic LIMA features. These data-driven subtypes are robust in the population and can be identified in independent data with 98% accuracy. The subtypes can be described as Type I versus Type II autisms differentiated by relatively high versus low scores on LIMA features. These two types of autisms are also distinguished by different developmental trajectories over the first decade of life. Finally, these two types of autisms reveal striking differences in functional and structural neuroimaging phenotypes and their relationships with gene expression and may highlight unique biological mechanisms. Limitations: Sample sizes for the neuroimaging and gene expression dataset are relatively small and require further independent replication. The current work is also limited to subtyping based on MSEL and VABS phenotypic measures. Conclusions: This work emphasizes the potential importance of stratifying autism by a Type I versus Type II distinction focused on LIMA features and which may be of high prognostic and biological significance. [ABSTRACT FROM AUTHOR]

Objective: There is a dearth of research about the aging process among individuals with bipolar disorder (BD). One potential strategy to overcome the challenge of interpreting findings from existing limited older‐age bipolar disorder (OABD) research studies is to pool or integrate data, taking advantage of potential overlap or similarities in assessment methods and harmonizing or cross‐walking measurements where different measurement tools are used to evaluate overlapping construct domains. This report describes the methods and initial start‐up activities of a first‐ever initiative to create an integrated OABD‐focused database, the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE‐BD) project. Methods: Building on preliminary work conducted by members of the International Society for Bipolar Disorders OABD taskforce, the GAGE‐BD project will be operationalized in four stages intended to ready the dataset for hypothesis‐driven analyses, establish a consortium of investigators to guide exploration, and set the stage for prospective investigation using a common dataset that will facilitate a high degree of generalizability. Results: Initial efforts in GAGE‐BD have brought together 14 international investigators representing a broad geographic distribution and data on over 1,000 OABD. Start‐up efforts include communication and guidance on meeting regulatory requirements, establishing a Steering Committee to guide an incremental analysis strategy, and learning from existing multisite data collaborations and other support resources. Discussion: The GAGE‐BD project aims to advance understanding of associations between age, BD symptoms, medical burden, cognition and functioning across the life span and set the stage for future prospective research that can advance the understanding of OABD. [ABSTRACT FROM AUTHOR]

Background: Large-scale brain networks such as the default mode network (DMN) are often disrupted in Alzheimer's disease (AD). Numerous studies have examined DMN functional connectivity in those with mild cognitive impairment (MCI), a presumed AD precursor, to discover a biomarker of AD risk. Prior reviews were qualitative or limited in scope or approach.Objective: We aimed to systematically and quantitatively review DMN resting state fMRI studies comparing MCI and healthy comparison (HC) groups.Methods: PubMed was searched for relevant articles. Study characteristics were abstracted and the number of studies showing no group difference or hyper- versus hypo-connnectivity in MCI was tallied. A voxel-wise (ES-SDM) meta-analysis was conducted to identify regional group differences.Results: Qualitatively, our review of 57 MCI versus HC comparisons suggests substantial inconsistency; 9 showed no group difference, 8 showed MCI > HC and 22 showed HC > MCI across the brain, and 18 showed regionally-mixed directions of effect. The meta-analysis of 31 studies revealed areas of significant hypo- and hyper-connectivity in MCI, including hypoconnectivity in the posterior cingulate cortex/precuneus (z = -3.1, p < 0.0001). Very few individual studies, however, showed patterns resembling the meta-analytic results. Methodological differences did not appear to explain inconsistencies.Conclusions: The pattern of altered resting DMN function or connectivity in MCI is complex and variable across studies. To date, no index of DMN connectivity qualifies as a useful biomarker of MCI or risk for AD. Refinements to MCI diagnosis, including other biological markers, or longitudinal studies of progression to AD, might identify DMN alterations predictive of AD risk. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is one of the most disabling psychiatric disorders with increased morbidity and mortality. Both schizophrenia and oxidative stress have been associated with accelerated aging. Previous studies found increased oxidative stress in individuals with schizophrenia, though only one study measured F2-isoprostanes and did so in urine. To our knowledge, the present study is the first to assess plasma F2-isoprostane levels, the putative gold standard measure of systemic oxidative stress in vivo, in schizophrenia.Methods: We compared plasma F2-isoprostane levels in 134 stable outpatients with schizophrenia and 120 age- and gender-matched healthy comparison (HC) subjects. Sociodemographic and clinical data were collected in both groups.Results: Plasma F2-isoprostane levels were significantly higher in the schizophrenia group than in the HC group. Women had higher F2-isoprostane levels compared to men, and those with higher body mass index (BMI) had higher levels, within each group. F2-isoprostane levels correlated with BMI, physical functioning, and medical comorbidity but not with severity of psychopathology or executive function. Linear models showed significant effects of diagnosis, gender, and BMI on F2-isoprostane levels, but no interactions.Discussion: Our finding of increased oxidative stress in schizophrenia is consistent with reports of increased morbidity and mortality as well as accelerated aging in schizophrenia. The significant associations between F2-isoprostane levels and both gender and BMI warrant further study. [ABSTRACT FROM AUTHOR]

Cortical surface area (CSA) has particular relevance for understanding development, behavior, and the connection between brain structure and function. Little is known about genetic and environmental determinants of CSA during development. We utilized bivariate twin methods to identify global and regionally specific genetic factors which influence CSA in a preliminary sample of typically-developing adolescents, with hypotheses based on findings in middle-aged adults. Similar to previous findings, we observed high heritability for total CSA. There was also significant evidence for genetic influences on regional CSA, particularly when these were not adjusted for total CSA, with highest heritability in frontal cortex and relatively fewer genetic contributions to medial temporal cortical structures. Adjustment for total CSA reduced regional CSA heritability dramatically, but a moderate influence of genetic factors remained in some regions. Both global and regionally-specific genetic factors influence regional CSA during adolescence. [ABSTRACT FROM AUTHOR]

Objective: The current literature on employment in older adults with bipolar disorder (OABD) is limited. Using the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE‐BD), we examined the relationship of occupational status in OABD to other demographic and clinical characteristics. Methods: Seven hundred and thirty‐eight participants from 11 international samples with data on educational level and occupational status were included. Employment status was dichotomized as employed versus unemployed. Generalized linear mixed models with random intercepts for the study cohort were used to examine the relationship between baseline characteristics and employment. Predictors in the models included baseline demographics, education, psychiatric symptom severity, psychiatric comorbidity, somatic comorbidity, and prior psychiatric hospitalizations. Results: In the sample, 23.6% (n = 174) were employed, while 76.4% were unemployed (n = 564). In multivariable logistic regression models, less education, older age, a history of both anxiety and substance/alcohol use disorders, more prior psychiatric hospitalizations, and higher levels of BD depression severity were associated with greater odds of unemployment. In the subsample of individuals less than 65 years of age, findings were similar. No significant association between manic symptoms, gender, age of onset, or employment status was observed. Conclusion: Results suggest an association between educational level, age, psychiatric severity and comorbidity in relation to employment in OABD. Implications include the need for management of psychiatric symptoms and comorbidity across the lifespan, as well as improving educational access for people with BD and skills training or other support for those with work‐life breaks to re‐enter employment and optimize the overall outcome. [ABSTRACT FROM AUTHOR]

Objectives Affective dysregulation is a core feature of bipolar disorder (BD). Abnormalities in neural circuits underlying affect regulation have been observed in BD, specifically in the structure and function of the amygdala and orbital frontal cortex (OFC). Fear extinction is an automatic affect regulatory process relying on neural circuits that are abnormal in BD. Thus, fear extinction might be useful in probing automatic affect regulation deficits in BD. We tested the hypothesis that BD is associated with reduced ability to extinguish fear responses. Methods We examined fear conditioning, extinction, and extinction memory recall in a sample of stable, euthymic participants with BD ( n =19) vs. healthy comparison participants ( n =32). A limited number of subjects (BD: n =12; healthy comparison: n =11) underwent structural MRI scanning to examine cortical size associations with extinction recall. Results Both healthy comparison and BD participants were successful in acquiring a fear response, but BD participants responded with greater startle to both threat and safety cues. Both groups showed significant extinction. The BD group showed superior extinction recall. Extinction recall was associated with right rostral middle frontal cortex thickness across groups, whereas right OFC surface area was associated with recall only in healthy comparisons. Limitations Limitations include use of a stable, highly screened sample and a relatively small number of participants available for MRI analysis. Conclusions Increased fear reactivity may be related to a “trait” disruption in BD patients similar to that previously described in anxiety disorders. This task may be useful for probing automatic affect regulatory processes in BD, and understanding treatment response. [ABSTRACT FROM AUTHOR]

Right-left regional cerebral differences are a feature of the human brain linked to functional abilities, aging, and neurodevelopmental and mental disorders. The role of genetic factors in structural asymmetry has been incompletely studied. We analyzed data from 515 individuals (130 monozygotic twin pairs, 97 dizygotic pairs, and 61 unpaired twins) from the Vietnam Era Twin Study of Aging to answer three questions about genetic determinants of brain structural asymmetry: First, does the magnitude of heritability differ for homologous regions in each hemisphere? Despite adequate power to detect regional differences, heritability estimates were not significantly larger in one hemisphere versus the other, except left > right inferior lateral ventricle heritability. Second, do different genetic factors influence left and right hemisphere size in homologous regions? Interhemispheric genetic correlations were high and significant; in only two subcortical regions (pallidum and accumbens) did the estimate statistically differ from 1.0. Thus, there was little evidence for different genetic influences on left and right hemisphere regions. Third, to what extent do genetic factors influence variability in left-right size differences? There was no evidence that variation in asymmetry (i.e., the size difference) of left and right homologous regions was genetically determined, except in pallidum and accumbens. Our findings suggest that genetic factors do not play a significant role in determining individual variation in the degree of regional cortical size asymmetries measured with MRI, although they may do so for volume of some subcortical structures. Despite varying interpretations of existing data, we view the present results as consistent with previous findings. [ABSTRACT FROM AUTHOR]

R4230 --> 632.22 --> The adoption of humanistic practices in anatomical education is increasing with studies identifying educational practices that foster empathetic responses as a crucial aspect of pre‐clinical education. However, there has been little research evaluating the implementation of novel curriculum in pre‐clinical anatomy courses that help students maintain empathy during cadaveric dissections. Specifically, we hypothesize that implementing compassion training (CT) offered by trained professionals during a pre‐clinical anatomy course will help students maintain their empathy towards body donors. We implemented five training sessions run by the Sanford Institute of Empathy and Compassion in the pre‐clinical anatomy thread at the University of California, San Diego in this IRB‐approved study. We sought to assess baseline empathy and prior experience with meditation/mental training among both first and second‐year medical students. We specifically used the Jefferson Scale of Empathy (JSE) to evaluate empathy, which is broadly used in medical professions to assess this attribute. Interestingly, prior to the start of the course, the mean experience with contemplative compassion practices was 0.840 ± 1.042 (n=81) with zero being no experience, but the mean interest in participating in compassion exercises was 2.954 ± 1.422 (n=87) with five being highly interested. Among the 137 students that initially responded to the pre‐survey, 47 students chose to participate in a longitudinal study where students' connection to the body donor was assessed with the Inclusion of Other in Self (IOS) scale. The emotional state of students was assessed using self‐reported scales of both pleasure and arousal. Students in the longitudinal study completed 10 anatomy sessions with five including CT. There was no significant difference in IOS scores between anatomy labs with CT and those without intervention. However, there was a significant difference between total mean levels of engagement during compassion practices with students showing higher levels of engagement in laboratory sessions with CT (With CT: 2.509 ± 1.089 n=106; Without CT: 1.500 ± 0.927 n=54, p<0.001). In conclusion, students are more likely to engage in compassion practices when training is incorporated into laboratory sessions. The question remains how engaging in these exercises affects students' ability to navigate complex emotions during cadaveric dissection. Further investigation is needed to determine if higher levels of engagement are associated with increased empathy towards body donors. In the future, we plan to evaluate whether increased engagement with compassion practices correlates to increased empathy after completion of pre‐clinical anatomy. We ultimately hope that this research will help educators design educational initiatives that help students navigate between empathy and clinical detachment during cadaveric dissection. [ABSTRACT FROM AUTHOR]

Abstract: Prefrontal cortex (PFC) mediated cognitive and emotional processing deficits in bipolar disorder lead to functional limitations even during periods of mood stability. Alterations of sleep and circadian functioning are well-documented in bipolar disorder, but there is little research directly examining the mechanistic role of sleep and/or circadian rhythms in the observed cognitive and emotional processing deficits. We systematically review the cognitive and emotional processing deficits reliant upon PFC functioning of euthymic patients with bipolar disorder and in healthy individuals deprived of sleep. The evidence from two parallel lines of investigation suggests that sleep and circadian rhythms may be involved in the cognitive and emotional processing deficits seen in bipolar disorder through overlapping neurobiological systems. We discuss current models of bipolar highlighting the PFC–limbic connections and discuss inclusion of sleep-related mechanisms. Sleep and circadian dysfunction is a core feature of bipolar disorder and models of neurobiological abnormalities should incorporate chronobiological measures. Further research into the role of sleep and circadian rhythms in cognition and emotional processing in bipolar disorder is warranted. [Copyright &y& Elsevier]

Understanding the genetic and environmental contributions to measures of brain structure such as surface area and cortical thickness is important for a better understanding of the nature of brain-behavior relationships and changes due to development or disease. Continuous spatial maps of genetic influences on these structural features can contribute to our understanding of regional patterns of heritability, since it remains to be seen whether genetic contributions to brain structure respect the boundaries of any traditional parcellation approaches. Using data from magnetic resonance imaging scans collected on a large sample of monozygotic and dizygotic twins in the Vietnam Era Twin Study of Aging, we created maps of the heritability of areal expansion (a vertex-based area measure) and cortical thickness and examined the degree to which these maps were affected by adjustment for total surface area and mean cortical thickness. We also compared the approach of estimating regional heritability based on the average heritability of vertices within the region to the more traditional region-of-interest (ROI)-based approach. The results suggested high heritability across the cortex for areal expansion and, to a slightly lesser degree, for cortical thickness. There was a great deal of genetic overlap between global and regional measures for surface area, so maps of region-specific genetic influences on surface area revealed more modest heritabilities. There was greater inter-regional variability in heritabilities when calculated using the traditional ROI-based approach compared to summarizing vertex-by-vertex heritabilities within regions. Discrepancies between the approaches were greatest in small regions and tended to be larger for surface area than for cortical thickness measures. Implications regarding brain phenotypes for future genetic association studies are discussed. [ABSTRACT FROM PUBLISHER]

Failure to develop normal language comprehension is an early warning sign of autism, but the neural mechanisms underlying this signature deficit are unknown. This is because of an almost complete absence of functional studies of the autistic brain during early development. Using functional magnetic resonance imaging, we previously observed a trend for abnormally lateralized temporal responses to language (i.e. greater activation on the right, rather than the expected left) in a small sample (n = 12) of sleeping 2–3 year olds with autism in contrast to typically developing children, a finding also reported in autistic adults and adolescents. It was unclear, however, if findings of atypical laterality would be observed in a larger sample, and at even earlier ages in autism, such as around the first birthday. Answers to these questions would provide the foundation for understanding how neurofunctional defects of autism unfold, and provide a foundation for studies using patterns of brain activation as a functional early biomarker of autism. To begin to examine these issues, a prospective, cross-sectional design was used in which brain activity was measured in a large sample of toddlers (n = 80) during the presentation of a bedtime story during natural sleep. Forty toddlers with autism spectrum disorder and 40 typically developing toddlers ranging in age between 12–48 months participated. Any toddler with autism who participated in the imaging experiment prior to final diagnosis was tracked and diagnoses confirmed at a later age. Results indicated that at-risk toddlers later diagnosed as autistic display deficient left hemisphere response to speech sounds and have abnormally right-lateralized temporal cortex response to language; this defect worsens with age, becoming most severe in autistic 3- and 4-year-olds. Typically developing children show opposite developmental trends with a tendency towards greater temporal cortex response with increasing age and maintenance of left-lateralized activation with age. We have now demonstrated lateralized abnormalities of temporal cortex processing of language in autism across two separate samples, including a large sample of young infants who later are diagnosed with autism, suggesting that this pattern may reflect a fundamental early neural developmental pathology in autism. [ABSTRACT FROM PUBLISHER]

Preserved cognitive performance is a key feature of successful aging. Several theoretical models have been proposed to explain the putative underlying relationship between brain function and performance. We aimed to review imaging studies of the association between brain functional response and cognitive performance among healthy younger and older adults to understand the neural correlates of successful cognitive aging. MEDLINE-indexed articles published between January 1989 and December 2009 and bibliographies of these articles and related reviews were searched. Studies that measured brain function with functional magnetic resonance imaging or positron emission tomography, evaluated cognitive performance, analyzed how cognitive performance related to brain response, and studied healthy older individuals were included. Eighty of 550 articles met these criteria. Seventy percent of the studies reported some brain regions in which greater activation related to better cognitive performance among older participants. This association was not universal, however, and was seen mainly in frontal cortex brain response and seemed to be more common among older compared with younger individuals. This review supports the notion of compensatory increases in brain activity in old age resulting in better cognitive performance, as suggested by hemispheric asymmetry reduction and posterior–anterior shift models of functional brain aging. However, a simple model of bigger structure → greater brain response → better cognitive performance might not be accurate. Suggestions for future research are discussed. [ABSTRACT FROM AUTHOR]

The article presents a study that investigated the possible correlation between genetic factors and the volumes of subcortical brain structures. Several models for genetic factors namely a Basal Ganglia/Thalamus factor, a Ventricular factor, a Limbic factor, and a Nucleus Accumbens factor are found to fit the data generated. Genetic patterning among structures that differentiate between brain, different subcortical regions, and cerebrospinal fluid spaces was observed.

Abstract: Patients with schizophrenia often show verbal learning deficits that have been linked to the pathophysiology of the disorder and result in functional impairment. This study examined the biological basis of these deficits by comparing the brain response of patients with schizophrenia (n =17) to that of healthy comparison participants (n =14) during a verbal paired-associates learning task using functional magnetic resonance imaging (fMRI). Brain response during new word learning was examined within and between groups in two a priori regions of interest, the inferior frontal gyrus and hippocampus, and across the whole brain. In regions of group difference, we also examined the relationship of brain response during learning to later recall of the word pairs. Despite successful matching of levels of word-pair recall, patients'' brain response during new learning was abnormal in bilateral regions within the inferior frontal gyrus, a small region in left posterior hippocampus, and other areas within the frontal, parietal and temporal cortex compared with healthy individuals. In some regions, but not in the hippocampus, patients with the most normal brain response also remembered the most word pairs following scanning. Thus, verbal learning deficits found among patients with schizophrenia appear to be related to hypofunction of distributed brain networks. [Copyright &y& Elsevier]

This article reviews the extant twin studies employing magnetic resonance imaging data (MRI), with an emphasis on studies of population-based samples. There have been approximately 75 twin reports using MRI, with somewhat under half focusing on typical brain structure. Of these, most are samples of adults. For large brain regions such as lobar volumes, the heritabilities of large brain volumes are consistently high, with genetic factors accounting for at least half of the phenotypic variance. The role of genetics in generating individual differences in the volumes of small brain regions is less clear, mostly due to a dearth of information, but rarely because of disagreement between studies. Multivariate analyses show strong genetic relationships between brain regions. Cortical regions involved in language, executive function, and emotional regulation appear to be more heritable than other areas. Studies of brain shape also show significant, albeit lower, genetic effects on population variance. Finally, there is evidence of significant genetically mediated relationships between intelligence and brain structure. At present, the majority of twin imaging studies are limited by sample sizes small by the standards of behavioral genetics; nevertheless the literature at present represents a pioneering effort in the pursuit of answers to many challenging neurobiological questions. [ABSTRACT FROM AUTHOR]

Concern about limitations in the ability to give valid informed consent among certain groups of individuals has led to increased interest in defining, measuring, and enhancing consent-related decision-making. In this overview, we summarize issues related to the definition of decision-making capacity, discuss methods that have been used to assess decision-making abilities and other aspects of informed consent, and briefly describe studies that aim to understand variation in different elements of informed consent. We then review strategies that have been used with the intent of improving aspects of the informed consent process. Finally, we provide an outline of areas that are in need of future studies in order to reach the ultimate goal of preserving as much autonomy as possible in at-risk populations, while still achieving valuable research and treatment goals. Published in 2006 by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Growing recognition of the inadequacy of traditional methods of providing informed consent, especially for individuals vulnerable to impaired decisional capacity, has spurred recent interest in how to assess and improve components of consent-related decision making. In this preliminary study, we aimed to compare different methods of interactive questioning during presentation of research consent information among patients with schizophrenia. Patients were randomized to receive either standard administration (SA) of a consent form or one of two interactive questioning methods: Corrective Feedback (CF), in which the correct answer was provided following the participant''s response, or Errorless Learning (EL), in which correct answers were provided just prior to the question. The MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) was used to measure understanding, appreciation, reasoning, and expression of a choice following presentation of the consent form. There was no significant effect of condition (SA vs. EL vs. CF) on any of the components of decisional capacity. Understanding scores measured during the consent process were higher than those measured afterward, but the two scores were highly correlated. Thus, the results of this randomized study suggest that interactive questioning neither helped nor harmed understanding, appreciation, or reasoning among patients with schizophrenia. Other considerations, however, may favor use of such methods in the consenting process. [Copyright &y& Elsevier]

Deficits of attention are common among individuals with schizophrenia (SZ) and are related both to genetic liability to the disorder and to functional outcome among patients. To explore the brain systems underlying these attentional abnormalities, we compared the response of nine patients with chronic SZ or schizoaffective disorder to that of 10 matched healthy individuals performing a simple visual vigilance task during functional magnetic resonance imaging. The two groups performed equivalently on the task. When the blood oxygen level dependent (BOLD) signal during identification of a target letter among similar-looking letters was compared to the response during fixation trials, both groups showed multiple clusters of significant brain response in widespread cortical regions. Compared with healthy participants, SZ patients showed a diminished response in the inferior frontal cortex and an abnormally enhanced response in right postcentral gyrus, right medial temporal lobe and left cerebellum. The results suggest that abnormalities of functional brain response to attentional tasks can be observed among patients with SZ even when behavioral performance is unimpaired, and provide further evidence that brain systems related to attention are likely to be involved in the pathophysiology of the disorder. [Copyright &y& Elsevier]

To compare the prevalence of physical morbidities between older aged patients with bipolar disorder (OABD) and non-psychiatric comparisons (NC), and to analyze sex differences in prevalence. OABD was defined as bipolar disorder among adults aged ≥50 years. Outcomes analyzed were the prevalence of diseases affecting the cardiovascular, respiratory, gastrointestinal, genitourinary, renal, musculoskeletal, and endocrine systems. The analysis used cross-sectional data of OABD participants (n = 878; mean age 60.9 ± 8.0 years, n = 496 (56%) women) from the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) dataset and NC participants recruited at the same sites (n = 355; mean age 64.4 ± 9.7 years, n = 215 (61%) women). After controlling for sex, age, education, and smoking history, the OABD group had more cardiovascular (odds ratio [95% confidence interval]: 2.12 [1.38–3.30]), renal (5.97 [1.31–43.16]), musculoskeletal (2.09 [1.30–3.43]) and endocrine (1.90 [1.20–3.05]) diseases than NC. Women with OABD had more gastrointestinal (1.56 [0.99–2.49]), genitourinary (1.72 [1.02–2.92]), musculoskeletal (2.64 [1.66–4.37]) and endocrine (1.71 [1.08–2.73]) comorbidities than men with OABD, when age, education, smoking history, and study site were controlled. This replication GAGE-BD study confirms previous findings indicating that OABD present more physical morbidities than matched comparison participants, and that this health burden is significantly greater among women. [ABSTRACT FROM AUTHOR]

In people with schizophrenia (PwS), inflammation and metabolic issues significantly increase morbidity and mortality. However, our ability to understand inflammatory-metabolic mechanisms in this population has been limited to cross-sectional studies. This study involved 169 PwS and 156 non-psychiatric comparisons (NCs), aged 25–65, observed between 2012 and 2022 with 0 to 5 follow-ups post-baseline. High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, was measured via a particle-enhanced immuno-turbidimetric assay. Body mass index (BMI) was used as a proxy for metabolic function. The measurement intervals for hs-CRP and BMI ranged between 6 and 48 months. Linear mixed models (LMM) results revealed that at all time points, PwS has a higher hs-CRP (t (316) = 4.73, p <.001) and BMI (t (315) = 4.13, p <.001) than NCs; however, for BMI, this difference decreased over time (t (524) = −5.15, p <.001). To study interrelationships between hs-CRP and BMI, continuous time structural equational modeling (CTSEM) was used, accounting for uneven measurement intervals. CTSEM results showed that both hs-CRP predicted future BMI (Est. = 12.91, 95 % CI [7.70; 17.88]) and BMI predicted future hs-CRP (Est. = 1.54, 95 % CI [1.00; 2.04]), indicating a bidirectional relationship between inflammation and metabolic function. Notably, the influence of hs-CRP on future BMI was more robust than the other lagged relationship (p =.015), especially in PwS (Est. = 2.43, 95 % CI [0.39; 0.97]). Our study highlights the important role of inflammation in metabolic function and offers insights into potential interventions targeting inflammation in PwS. [ABSTRACT FROM AUTHOR]

We examined how brain reserve in midlife, measured by brain-predicted age difference scores (Brain-PADs), predicted executive function concurrently and longitudinally into early old age, and whether these associations were moderated by young adult cognitive reserve or APOE genotype. 508 men in the Vietnam Era Twin Study of Aging (VETSA) completed neuroimaging assessments at mean age 56 and six executive function tasks at mean ages 56, 62, and 68 years. Results indicated that greater brain reserve at age 56 was associated with better concurrent executive function (r =.10, p =.040) and less decline in executive function over 12 years (r =.34, p =.001). These associations were not moderated by cognitive reserve or APOE genotype. Twin analysis suggested associations with executive function slopes were driven by genetic influences. Our findings suggest that greater brain reserve allowed for better cognitive maintenance from middle- to old age, driven by a genetic association. The results are consistent with differential preservation of executive function based on brain reserve that is independent of young adult cognitive reserve or APOE genotype. • Brain reserve was related to executive function at baseline and across 12 years. • Cognitive reserve or APOE genotype did not moderate the associations. • Twin data reveal genetic influences underlie brain reserve-EF change associations. • Brain reserve-EF associations persisted when removing amnestic MCI individuals. • Similar associations were observed with measures of whole brain volume. [ABSTRACT FROM AUTHOR]

Objects: Studies of older age bipolar disorder (OABD) have mostly focused on "younger old" individuals. Little is known about the oldest OABD (OOABD) individuals aged ≥70 years old. The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE‐BD) project provides an opportunity to evaluate the OOABD group to understand their characteristics compared to younger groups. Methods: We conducted cross‐sectional analyses of the GAGE‐BD database, an integrated, harmonized dataset from 19 international studies. We compared the sociodemographic and clinical characteristics of those aged <50 (YABD, n = 184), 50–69 (OABD, n = 881), and ≥70 (OOABD, n = 304). To standardize the comparisons between age categories and all characteristics, we used multinomial logistic regression models with age category as the dependent variable, with each characteristic as the independent variable, and clustering of standard errors to account for the correlation between observations from each of the studies. Results: OOABD and OABD had lower severity of manic symptoms (Mean YMRS = 3.3, 3.8 respectively) than YABD (YMRS = 7.6), and lower depressive symptoms (% of absent = 65.4%, and 59.5% respectively) than YABD (18.3%). OOABD and OABD had higher physical burden than YABD, especially in the cardiovascular domain (prevalence = 65% in OOABD, 41% in OABD and 17% in YABD); OOABD had the highest prevalence (56%) in the musculoskeletal domain (significantly differed from 39% in OABD and 31% in YABD which didn't differ from each other). Overall, OOABD had significant cumulative physical burden in numbers of domains (mean = 4) compared to both OABD (mean = 2) and YABD (mean = 1). OOABD had the lowest rates of suicidal thoughts (10%), which significantly differed from YABD (26%) though didn't differ from OABD (21%). Functional status was higher in both OOABD (GAF = 63) and OABD (GAF = 64), though only OABD had significantly higher function than YABD (GAF = 59). Conclusions: OOABD have unique features, suggesting that (1) OOABD individuals may be easier to manage psychiatrically, but require more attention to comorbid physical conditions; (2) OOABD is a survivor cohort associated with resilience despite high medical burden, warranting both qualitative and quantitative methods to better understand how to advance clinical care and ways to age successfully with BD. Key points: Limited knowledge of older and oldest older age bipolar disorder derived from limited sample sizes.The Global Aging and Geriatric Experiments in Bipolar Disorder consortium provided international data to compare younger age, older age, and oldest older age people with BDInternational sites (n = 14) provided data on patients aged <50 (n = 184 YABD), 50–69 (n = 881 OABD), and ≥70 (n = 304 OOABD) to assess differences among three groupsOABD and OOABD represent distinct cohorts within BD and differ in sociodemographic and clinical characteristics from YABD in general. OOABD individuals may be easier to manage psychiatrically but require more attention to their comorbid physical conditions. OOABD likely is a survivor cohort associated with resilience despite high medical burden, warranting future study using both qualitative and quantitative methods to better understand what makes OOABD resilient, how to advance clinical care and age successfully with BD. [ABSTRACT FROM AUTHOR]

Evidence to date indicates that compassion and empathy are health-enhancing qualities. Research points to interventions and practices involving compassion and empathy being beneficial, as well as being salient outcomes of contemplative practices such as mindfulness. Advancing the science of compassion and empathy requires that we select measures best suited to evaluating effectiveness of training and answering research questions. The objective of this scoping review was to 1) determine what instruments are currently available for measuring empathy and compassion, 2) assess how and to what extent they have been validated, and 3) provide an online tool to assist researchers and program evaluators in selecting appropriate measures for their settings and populations. A scoping review and broad evidence map were employed to systematically search and present an overview of the large and diverse body of literature pertaining to measuring compassion and empathy. A search string yielded 19,446 articles, and screening resulted in 559 measure development or validation articles reporting on 503 measures focusing on or containing subscales designed to measure empathy and/or compassion. For each measure, we identified the type of measure, construct being measured, in what context or population it was validated, response set, sample items, and how many different types of psychometrics had been assessed for that measure. We provide tables summarizing these data, as well as an open-source online interactive data visualization allowing viewers to search for measures of empathy and compassion, review their basic qualities, and access original citations containing more detail. Finally, we provide a rubric to help readers determine which measure(s) might best fit their context. [ABSTRACT FROM AUTHOR]

Background Childhood disadvantage is a prominent risk factor for cognitive and brain aging. Childhood disadvantage is associated with poorer episodic memory in late midlife and functional and structural brain abnormalities in the default mode network (DMN). Although age-related changes in DMN are associated with episodic memory declines in older adults, it remains unclear if childhood disadvantage has an enduring impact on this later-life brain–cognition relationship earlier in the aging process. Here, within the DMN, we examined whether its cortical microstructural integrity—an early marker of structural vulnerability that increases the risk for future cognitive decline and neurodegeneration—is associated with episodic memory in adults at ages 56–66, and whether childhood disadvantage moderates this association. Methods Cortical mean diffusivity (MD) obtained from diffusion magnetic resonance imaging was used to measure microstructural integrity in 350 community-dwelling men. We examined both visual and verbal episodic memory in relation to DMN MD and divided participants into disadvantaged and nondisadvantaged groups based on parental education and occupation. Results Higher DMN MD was associated with poorer visual memory but not verbal memory (β = −0.11, p =.040 vs β = −0.04, p =.535). This association was moderated by childhood disadvantage and was significant only in the disadvantaged group (β = −0.26, p =.002 vs β = −0.00, p =.957). Conclusions Lower DMN cortical microstructural integrity may reflect visual memory vulnerability in cognitively normal adults earlier in the aging process. Individuals who experienced childhood disadvantage manifested greater vulnerability to cortical microstructure-related visual memory dysfunction than their nondisadvantaged counterparts who exhibited resilience in the face of low cortical microstructural integrity. [ABSTRACT FROM AUTHOR]

Objective: Black emerging adult women (ages 18-25 years) are among the fastest growing demographics of HIV infection, second only to men who have sex with men. Black women account for nine of 10 new HIV cases, whereas 84% of these cases are reported to be from heterosexual contact with infected male partners. Heterosexual Black college women (BCW) have been nearly ignored in the HIV literature despite having shared (e.g., risky alcohol use, multiple and concurrent sex partnerships, and inconsistent condom use) and unique (e.g., segregating dating practices and high sexually transmitted infection rates) risk factors when compared with broader college student demographics.Method: This conceptual paper uses a multiple risk factor framework to underscore shared and unique risk factors that may work to increase the potential HIV infection risk burden in this understudied population.Conclusions: Prevention and intervention implications and recommendations for future research that have potential to impact the ways in which colleges, universities, and researchers engage this population are presented. (PsycINFO Database Record (c) 2019 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

We examined the role of menopausal status in daily mood and cognitive performance among women with bipolar disorder (BD) compared to healthy comparison women. We analyzed the association of menopausal status, bipolar diagnosis, and their interaction on daily mood assessed by mobile surveys and attentional performance measured multiple times over 2 weeks. Menopausal status was associated with more daily negative affect in women with BD, but not related to attentional performance. [ABSTRACT FROM AUTHOR]

Objective: To determine the clinical and biological characteristics of an exceptionally high functioning index person (IP) with schizophrenia in her mid-50s, which may represent compensatory mechanisms, and potentially, avoidance of the accelerated aging typically associated with schizophrenia.Method: IP, 11 other women with schizophrenia, and 11 non-psychiatric comparison (NC) women were assessed with standard ratings of psychopathology, neurocognitive function, decisional capacity, and functional brain imaging. IP was also compared to a sample of demographically similar NCs (N=45) and persons with schizophrenia (N=42) on a set of blood-based biomarkers of aging related to metabolic function, oxidative stress, and inflammation.Results: IP's scores on working memory, and levels of brain activation during an affective face matching task in the left fusiform, right lingual, and left precentral gyri, exceeded NCs. IP was similar to NCs in severity of negative symptoms, most neurocognitive functions, decisional capacity, and brain activation in the left inferior occipital gyrus during a selective stopping task. IP's levels on 11 of 14 metabolic and inflammatory biomarkers of aging were better than NCs and the schizophrenia group.Conclusion: Although speculative, results suggest a possible model in which superior working memory permits a person to be aware of the potentially psychotic nature of a thought or perception, and adjust response accordingly. Compensatory overactivity of brain regions during affective processing may also reflect heightened meta-awareness in emotional situations. Biomarker levels raise the possibility that IP partially avoided the accelerated biological aging associated with schizophrenia. [ABSTRACT FROM AUTHOR]

Schizophrenia and bipolar disorder are among the leading causes of disability, morbidity, and mortality worldwide. In addition to being serious mental illnesses, these disorders are associated with considerable systemic physiological dysfunction, including chronic inflammation and elevated oxidative stress. The advent of sophisticated sequencing techniques has led to a growing interest in the potential role of gut microbiota in human health and disease. Advances in this area have transformed our understanding of a number of medical conditions and have generated a new perspective suggesting that gut microbiota might be involved in the development and maintenance of brain/mental health. Animal models have demonstrated strong though indirect evidence for a contributory role of intestinal microbiota in psychiatric symptomatology and have linked the microbiome with neuropsychiatric conditions. We present a systematic review of clinical studies of microbiome in schizophrenia and bipolar disorder. The published literature has a number of limitations; however, the investigations suggest that these disorders are associated with reduced microbial diversity and show global community differences compared to non-psychiatric comparison samples. In some reports, specific microbial taxa were associated with clinical disease characteristics, including physical health, depressive and psychotic symptoms, and sleep, but little information on the functional potential of those community changes. Studies also suggest increased intestinal inflammation and permeability, which may be among the principal mechanisms by which microbial dysbiosis impacts systemic physiological functioning. We highlight gaps in the current literature and implications for diagnosis and therapeutic interventions, and outline future directions for microbiome research in psychiatry. [ABSTRACT FROM AUTHOR]

Some evidence suggests a biphasic pattern of changes in cortical thickness wherein higher, rather than lower, thickness is associated with very early Alzheimer's disease (AD) pathology. We examined whether integrating information from AD brain signatures based on mean diffusivity (MD) can aid in the interpretation of cortical thickness/volume as a risk factor for future AD-related changes. Participants were 572 men in the Vietnam Era Twin Study of Aging who were cognitively unimpaired at baseline (mean age = 56 years; range = 51–60). Individuals with both high thickness/volume signatures and high MD signatures at baseline had lower cortical thickness/volume in AD signature regions and lower episodic memory performance 12 years later compared to those with high thickness/volume and low MD signatures at baseline. Groups did not differ in level of young adult cognitive reserve. Our findings are in line with a biphasic model in which increased cortical thickness may precede future decline and establish the value of examining cortical MD alongside cortical thickness to identify subgroups with differential risk for poorer brain and cognitive outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Despite the importance of psychosocial functioning impairment in Bipolar Disorder (BD), its role among Older Adults with BD (OABD) is not well known. The development of guidelines for the assessment of psychosocial functioning helps to facilitate a better understanding of OABD and can lead to better tailored interventions to improve the clinical outcomes of this population. Methods: Through a series of virtual meetings, experts from eight countries in the International Society of Bipolar Disorder (ISBD) on OABD task force developed recommendations for the assessment of psychosocial functioning. Results: We present (1) a conceptualization of functioning in OABD and differences compared with younger patients; (2) factors related to functioning in OABD; (3) current measures of functioning in OABD and their strengths and limitations; and, (4) other potential sources of information to assess functioning. Conclusions: The task force created recommendations for assessing functioning in OABD. Current instruments are limited, so measures specifically designed for OABD, such as the validated FAST‐O scale, should be more widely adopted. Following the proposed recommendations for assessment can improve research and clinical care in OABD and potentially lead to better treatment outcomes. [ABSTRACT FROM AUTHOR]

Severe depression is associated with accelerated brain aging. BrainAge gap, the difference between predicted and observed BrainAge, was investigated in patients with late-life depression (LLD). We aimed to examine BrainAge gap in LLD and its associations with clinical characteristics indexing LLD chronicity, current severity, prior to electroconvulsive therapy (ECT) and ECT outcome. Data was analyzed from the Mood Disorders in Elderly treated with Electroconvulsive Therapy (MODECT) study. A previously established BrainAge algorithm (BrainAge R by James Cole, (https://github.com/james-cole/brainageR)) was applied to pre-ECT T1-weighted structural MRI-scans of 42 patients who underwent ECT. A BrainAge gap of 1.8 years (SD = 5.5) was observed, Cohen's d = 0.3. No significant associations between BrainAge gap, number of previous episodes, current episode duration, age of onset, depression severity, psychotic symptoms or ECT outcome were observed. Limited sample size. Our initial findings suggest an older BrainAge than chronological age in patients with severe LLD referred for ECT, however with high degree of variability and direction of the gap. No associations were found with clinical measures. Larger samples are needed to better understand brain aging and to evaluate the usability of BrainAge gap as potential biomarker of prognosis an treatment-response in LLD. ClinicalTrials.gov identifier: NCT02667353 • This study examines the BrainAgegap of patients with severe late-life depression (LLD) before electroconvulsive therapy (ECT). • A BrainAge gap of 1.8 years (SD = 5.5) was observed. Not associated with clinical measures. • Larger samples are needed to evaluate the potential of BrainAge gap as a biomarker of treatment response. [ABSTRACT FROM AUTHOR]

Analyzing cortical folding may provide insight into the biological underpinnings of neurodevelopmental diseases. A neurodevelopmental subtype of bipolar disorders (BD-ND) has been characterized by the combination of early age of onset and psychotic features. We investigate potential cortical morphology differences associated with this subtype. We analyze, for the first time in bipolar disorders, the sulcal pits, the deepest points in each fold of the cerebral cortex. We extracted the sulcal pits from anatomical MRI among 512 participants gathered from 7 scanning sites. We compared the number of sulcal pits in each hemisphere as well as their regional occurrence and depth between the BD-ND subgroup (N = 184), a subgroup without neurodevelopmental features (BD, N = 77) and a group of healthy controls (HC, N = 251). In whole brain analysis, BD-ND group have a higher number of sulcal pits in comparison to the BD group. The local analysis revealed, after correction for multiple testing, a higher occurrence of sulcal pits in the left premotor cortex among the BD-ND subgroup compared to the BD and the HC groups. Our findings confirm that BD-ND is associated with a specific brain morphology revealed by the analysis of sulcal pits. These markers may help to better understand neurodevelopment in mood disorder and stratify patients according to a pathophysiological hypothesis. • At the whole brain level, BD-ND have a higher number of sulcal pits than BD without neurodevelopmental phenotype. • BD-ND patients differ from both BD and HC in the occurrence of the pit located specifically in the left premotor cortex. • Exploratory results suggest other local differences in the occurrence and the depth of a series of pits between the BD-ND and the BD or the HC group, mostly within the frontal lobe. • Exploratory results suggest other differences of pits between BD-ND, BD and HC group, mostly within the frontal lobe. [ABSTRACT FROM AUTHOR]

Background: Social and language abilities are closely intertwined during early typical development. In autism spectrum disorder (ASD), however, deficits in social and language development are early-age core symptoms. We previously reported that superior temporal cortex, a well-established social and language region, shows reduced activation to social affective speech in ASD toddlers; however, the atypical cortical connectivity that accompanies this deviance remains unknown. Methods: We collected clinical, eye tracking, and resting-state fMRI data from 86 ASD and non-ASD subjects (mean age 2.3 ± 0.7 years). Functional connectivity of left and right superior temporal regions with other cortical regions and correlations between this connectivity and each child's social and language abilities were examined. Results: While there was no group difference in functional connectivity, the connectivity between superior temporal cortex and frontal and parietal regions was significantly correlated with language, communication, and social abilities in non-ASD subjects, but these effects were absent in ASD subjects. Instead, ASD subjects, regardless of different social or nonsocial visual preferences, showed atypical correlations between temporal–visual region connectivity and communication ability (r(49) = 0.55, p < 0.001) and between temporal–precuneus connectivity and expressive language ability (r(49) = 0.58, p < 0.001). Limitations: The distinct connectivity–behavior correlation patterns may be related to different developmental stages in ASD and non-ASD subjects. The use of a prior 2-year-old template for spatial normalization may not be optimal for a few subjects beyond this age range. Conclusions: Superior temporal cortex is known to have reduced activation to social affective speech in ASD at early ages, and here we find in ASD toddlers that it also has atypical connectivity with visual and precuneus cortices that is correlated with communication and language ability, a pattern not seen in non-ASD toddlers. This atypicality may be an early-age signature of ASD that also explains why the disorder has deviant early language and social development. Given that these atypical connectivity patterns are also present in older individuals with ASD, we conclude these atypical connectivity patterns persist across age and may explain why successful interventions targeting language and social skills at all ages in ASD are so difficult to achieve. [ABSTRACT FROM AUTHOR]

Objectives: The distinction between bipolar I disorder (BD‐I) and bipolar II disorder (BD‐II) has been a topic of long‐lasting debate. This study examined differences between BD‐I and BD‐II in a large, global sample of OABD, focusing on general functioning, cognition and somatic burden as these domains are often affected in OABD. Methods: Cross‐sectional analyses were conducted with data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE‐BD) database. The sample included 963 participants aged ≥50 years (714 BD‐I, 249 BD‐II). Sociodemographic and clinical factors were compared between BD subtypes including adjustment for study cohort. Multivariable analyses were conducted with generalized linear mixed models (GLMMs) and estimated associations between BD subtype and (1) general functioning (GAF), (2) cognitive performance (g‐score) and (3) somatic burden, with study cohort as random intercept. Results: After adjustment for study cohort, BD‐II patients more often had a late onset ≥50 years (p = 0.008) and more current severe depression (p = 0.041). BD‐I patients were more likely to have a history of psychiatric hospitalization (p < 0.001) and current use of anti‐psychotics (p = 0.003). Multivariable analyses showed that BD subtype was not related to GAF, cognitive g‐score or somatic burden. Conclusion: BD‐I and BD‐II patients did not differ in terms of general functioning, cognitive impairment or somatic burden. Some clinical differences were observed between the groups, which could be the consequence of diagnostic definitions. The distinction between BD‐I and BD‐II is not the best way to subtype OABD patients. Future research should investigate other disease specifiers in this population. [ABSTRACT FROM AUTHOR]

Objective Sleep disturbances are prevalent, persistent, and impairing features of bipolar disorder. However, the near-term and cumulative impact of the severity and variability of sleep disturbances on symptoms and functioning remains unclear. We examined self-reported daily sleep duration and variability in relation to mood symptoms, medication adherence, cognitive functioning, and concurrent daily affect. Methods Forty-one outpatients diagnosed with bipolar disorder were asked to provide daily reports of sleep duration and affect collected via ecological momentary assessment with smartphones over eleven weeks. Measures of depressive and manic symptoms, medication adherence, and cognitive function were collected at baseline and concurrent assessment of affect were collected daily. Analyses examined whether sleep duration or variability were associated with baseline measures and changes in same-day or next-day affect. Results Greater sleep duration variability (but not average sleep duration) was associated with greater depressive and manic symptom severity, and lower medication adherence at baseline, and with lower and more variable ratings of positive affect and higher ratings of negative affect. Sleep durations shorter than 7–8 h were associated with lower same-day ratings of positive and higher same-day ratings of negative affect, however this did not extend to next-day affect. Conclusions Greater cumulative day-to-day sleep duration variability, but not average sleep duration, was related to more severe mood symptoms, lower self-reported medication adherence and higher levels of negative affect. Bouts of short- or long-duration sleep had transient impact on affect. Day-to-day sleep variability may be important to incorporate into clinical assessment of sleep disturbances in bipolar disorder. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does mindfulness training, exercise, or the combination of these interventions improve cognitive function in older adults with subjective cognitive concerns? Findings: In this randomized clinical trial that included 585 participants, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function composite scores at 6 months. Meaning: The findings do not support the use of mindfulness training, exercise, or a combination of both for significantly improving cognitive function in older adults with subjective cognitive concerns. Importance: Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. Objective: To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. Design, Setting, and Participants: This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020). Interventions: Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice. Main Outcomes and Measures: The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns. Results: Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, –0.04 points [95% CI, –0.15 to 0.07]; P =.50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, –0.04 to 0.17]; P =.23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, –0.02 to 0.19]; P =.12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, –0.03 to 0.18]; P =.17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P =.93 for memory and P =.29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention. Conclusions and Relevance: Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns. Trial Registration: ClinicalTrials.gov Identifier: NCT02665481 This randomized clinical trial examines whether mindfulness-based stress reduction, exercise, or a combination of both interventions improves cognitive function in older adults with subjective cognitive concerns. [ABSTRACT FROM AUTHOR]

Objectives: Late-onset bipolar disorder (LOBD) represents a significant subgroup of bipolar disorder (BD). However, knowledge for this group is mostly extrapolated from small studies in subjects with early/mixed age of illness onset. In this global sample of older adults with BD (OABD: ≥50 years old) we aim to characterize the sociodemographic and clinical presentation of LOBD (≥40 years at BD onset) compared to early-onset BD (EOBD: <40 years at BD onset).Methods: The Global Aging and Geriatric Experiments in Bipolar Disorder consortium provided international data on 437 older age bipolar disorder participants. We compared LOBD versus EOBD on depression, mania, functionality, and physical comorbidities. Exploratory analyses were performed on participants with BD onset ≥50 years old.Results: LOBD (n = 105) did not differ from EOBD (n = 332) on depression, mania, global functioning, nor employment status (p > 0.05). Late-onset bipolar disorder was associated with higher endocrine comorbidities (odds ratio = 1.48, [95%CI = 1.0,12.1], p = 0.03). This difference did not remain significant when subjects with BD onset ≥50 years old were analyzed.Limitations: This study is limited by the retrospective nature of the variable age of onset and the differences in evaluation methods across studies (partially overcame by harmonization processes).Conclusion: The present analysis is in favor of the hypothesis that LOBD might represent a similar clinical phenotype as classic EOBD with respect to core BD symptomatology, functionality, and comorbid physical conditions. Large-scale global collaboration to improve our understanding of BD across the lifespan is needed. [ABSTRACT FROM AUTHOR]

Objectives: There is limited information on the characteristics of older adults with bipolar disorder (OABD) treated with lithium, along with safety concerns about its use by older adults. The aim of the present study is to describe the demographic and clinical characteristics of OABD receiving lithium therapy, using data from the Global Ageing & Geriatric Experiments in Bipolar Disorder (GAGE‐BD). Experimental Procedures: Cross‐sectional analysis of the GAGE‐BD dataset to determine differences and similarities between lithium users and non‐users. We analysed data from 986 participants aged 50 years or older (mean age 63.5 years; 57.5% females) from 12 study sites. Two subgroups ('Lithium'; 'Non‐lithium') were defined according to the current prescription of lithium. We compared several outcomes between these groups, controlling for age, gender, and study site. Results: OABD treated with lithium had lower scores on depression rating scales and were less likely to be categorised as with moderate or severe depression. There was a lower proportion of lithium users than non‐users among those with evidence of rapid cycling and non‐bipolar psychiatric diagnoses. Assessment of global cognitive state and functionality indicated better performance among lithium users. The current use of antipsychotics was less frequent among lithium users, who also reported fewer cardiovascular comorbidities than non‐users. Conclusion: We found several potentially relevant differences in the clinical profile of OABD treated with lithium compared with those treated with other mood stabilisers. However, the interpretation of the present results must take into account the methodological limitations inherent to the cross‐sectional approach and data harmonisation. [ABSTRACT FROM AUTHOR]

Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well‐characterized samples of individuals with BD. Methods: Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors. Results: We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. Conclusions: The bipolar clinical research community is poised to work together to characterize the multi‐dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large‐scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness. [ABSTRACT FROM AUTHOR]

Background: Impulsivity is a prominent feature of bipolar disorder associated with various negative sequelae; moreover, it may be a precursor to shifts in affect or mood, but little is known about its association with affect on a day-to-day timescale. Ecological momentary assessments (a method that captures moment-to-moment ratings of psychological states by repeatedly sampling the same individual) of impulsivity and affect using mobile surveys allow for more nuanced examination of mechanisms of mood and behavior dysregulation. However, few existing studies have validated an ecological momentary assessment of impulsivity in bipolar disorder and examined its time-lagged associations with positive and negative affect. 70 participants with bipolar disorder and 102 healthy comparisons participated in an intensive longitudinal study: they underwent 14 days of ecological momentary assessment data collection annually for 1–4 years. Multiple measures of impulsivity and affect were collected using self-report, behavioral, and ecological momentary assessment modalities; these measures were compared, and levels of impulsivity were compared between bipolar disorder and healthy comparison groups. Time-lagged analyses using daily means explored the next-day predictive relationship of impulsivity on positive/negative affect, and vice versa. Results: The ecological momentary measure of impulsivity was moderately correlated with the self-report but not behavioral impulsivity measure. Bipolar disorder participants evinced higher self-report, behavioral, and daily impulsivity than healthy comparison participants. Time-lagged analyses revealed a bi-directional association between high impulsivity and high next-day negative (but not positive) affect. Post hoc analyses showed that impulsivity specifically predicted next-day anger and anxiety. Conclusions: Our multimodal assessment of impulsivity allowed for an examination of the day-to-day course of impulsivity and affect, crucial steps toward understanding the mechanisms of mood symptom and episode onset in bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: Clarifying 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. Methods: The 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)]. Results: Total 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). Conclusions: A 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. [ABSTRACT FROM AUTHOR]

Objective: Harmonizing different depression severity scales often requires creation of categorical variables that may decrease the sensitivity of the measure. Our aim was to compare the associations between categorical and continuous and harmonized measures of depression and global functioning in a large dataset of older age patients with bipolar disorder (OABD).Method: In the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) the 17-item Hamilton Depression scale (HAM-D), Montgomery Asberg Depression Rating Scale (MADRS) or the Center for Epidemiological Studies Depression scales (CES-D) was used to assess current depressive symptoms, while the Global Assessment of Functioning (GAF) assessed functional status. Data were harmonized from 8 OABD studies (n = 582). In each subsample, the relationship of depression severity as a continuous and categorical measure was compared to GAF. In the total sample, harmonized ordinal depression categories were compared to GAF.Results: Effect size and variance explained by the model for the categorical measure in the total sample was higher than both the categorical and continuous measure in the CES-D subsample, higher than the categorical but lower than the continuous measure in the HAM-D subsample, and lower than both the categorical and continuous measures in the MADRS subsample.Limitations: All included studies have different inclusion and exclusion criteria, study designs, and differ in aspects of sociodemographic variables.Conclusions: Associations were only slightly larger for the continuous vs categorical measures of depression scales. Harmonizing different depression scales into ordinal categories for analyses is feasible without losing statistical power. [ABSTRACT FROM AUTHOR]

The article presents a study on regional white matter abnormalities in patients with first-episode schizophrenia (FES) and their healthy siblings (HS) in the Chinese Han population. It discusses the use of optimized Voxel-based morphometry (VBM), comparison of the demographic and clinical traits of FES patients, HS and healthy comparisons (HC) and the difference in white matter abnormalities in brain regions such as left inferior frontal gyrus (IFG), left hippocampus and right internal capsule.