Publications by authors named "Lisa T Eyler"

140 Publications

Long-term Associations of Cigarette Smoking in Early Midlife with Predicted Brain Aging from Midlife to Late Life.

Addiction 2021 Oct 4. Epub 2021 Oct 4.

Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.

Background And Aims: Smoking is associated with increased risk for brain aging/atrophy and dementia. Few studies have examined early associations with brain aging. This study aimed to measure whether adult men with a history of heavier smoking in early midlife would have older than predicted brain age 16 to 28 years later.

Design: Prospective cohort observational study, utilizing smoking pack years data from average age 40 (early midlife) predicting predicted brain age difference scores (PBAD) at average ages 56, 62 (later midlife) and 68 (early old age). Early midlife alcohol use was also evaluated.

Setting: Population-based United States sample.

Participants/cases: Participants were male twins of predominantly European ancestry who served in the United States military sometime between 1965 and 1975. Structural magnetic resonance imaging (MRI) began at average age 56. Subsequent study waves included most baseline participants; attrition replacement subjects were added at later waves.

Measurements: Self-reported smoking information was used to calculate pack years smoked at ages 40, 56, 62, and 68. MRIs were processed with the BARACUS program to create PBAD scores (chronological age - predicted brain age) acquired at average ages 56 (N=493; 2002-08), 62 (N=408; 2009-14), and 68 (N=499; 2016-19).

Findings: In structural equation modelling, age 40 pack years predicted more advanced age 56 PBAD (β = -0.144, p = 0.012, 95% confidence interval (CI) -0.257, -0.032). Age 40 pack years did not additionally predict PBAD at later ages. Age 40 alcohol consumption, but not a smoking-by-alcohol interaction, predicted more advanced PBAD at age 56 (β = -0.166, p=0.001, 95%CI -0.261,-0.070) with additional influences at age 62 (β = -0.115, p = 0.005, 95%CI -0.195,-0.036). Age 40 alcohol did not predict age 68 PBAD. Within-twin pair analyses suggested some genetic mechanism partially underlying effects of alcohol, but not smoking, on PBAD.

Conclusions: Heavier smoking and alcohol consumption by age 40 appears to predict advanced brain aging by age 56 in men.
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http://dx.doi.org/10.1111/add.15710DOI Listing
October 2021

Lifestyle and the aging brain: interactive effects of modifiable lifestyle behaviors and cognitive ability in men from midlife to old age.

Neurobiol Aging 2021 Aug 19;108:80-89. Epub 2021 Aug 19.

Department of Psychiatry, University of California San Diego, San Diego, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, San Diego, CA, USA.

We examined the influence of lifestyle on brain aging after nearly 30 years, and tested the hypothesis that young adult general cognitive ability (GCA) would moderate these effects. In the community-dwelling Vietnam Era Twin Study of Aging (VETSA), 431 largely non-Hispanic white men completed a test of GCA at mean age 20. We created a modifiable lifestyle behavior composite from data collected at mean age 40. During VETSA, MRI-based measures at mean age 68 included predicted brain age difference (PBAD), Alzheimer's disease (AD) brain signature, and abnormal white matter scores. There were significant main effects of young adult GCA and lifestyle on PBAD and the AD signature (ps ≤ 0.012), and a GCA-by-lifestyle interaction on both (ps ≤ 0.006). Regardless of GCA level, having more favorable lifestyle behaviors predicted less advanced brain age and less AD-like brain aging. Unfavorable lifestyles predicted advanced brain aging in those with lower age 20 GCA, but did not affect brain aging in those with higher age 20 GCA. Targeting early lifestyle modification may promote dementia risk reduction, especially among lower reserve individuals.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.08.007DOI Listing
August 2021

Relationships between daily mood states and real-time cognitive performance in individuals with bipolar disorder and healthy comparators: A remote ambulatory assessment study.

J Clin Exp Neuropsychol 2021 Sep 8:1-12. Epub 2021 Sep 8.

Department of Psychiatry, University of California San Diego, San Diego, CA, USA.

Objective: Neuropsychological impairments are observed in individuals with Bipolar Disorder (BD), yet knowledge of how cognitive deficits unfold in real-time remains limited. Given intraindividual variability in mood observed in people with BD, and the potential for mood and cognition to be mutually influential, we employed ambulatory assessment technologies to examine potential contemporaneous (same survey) and lagged (next survey) relationships of congition and mood.

Methods: Outpatients with BD (n = 46) or no psychiatric disorders (heathy volunteers [HV]; n = 20) completed in-laboratory neurobehavioral assessments and 14 days of smartphone-administered mobile cognitive tests and ratings of affective variables. Linear mixed-effects models were used to analyze real-time relationships between mobile cognitive test performance and mood.

Results: On in-laboratory tests, participants with BD showed worse cognitive performance than HVs as well as mild depression severity; mood and cognitive performance were unrelated. On mobile cognitive tests and surveys, participants with BD showed somewhat worse cognitive performance and ratings of lower energy and greater sadness relative to HV participants. Among those with BD, mania and sadness earlier in the day related to worse processing speed and better working memory performance, respectively, on the next survey. In contrast, same survey ratings of greater stress related to better working memory, and greater happiness related to better processing speed.

Conclusions: Real-time assessments of mood and cognition provide incremental information beyond what can be gleaned from laboratory assessments. Understanding how these affect-related changes in processing speed emerge and play out in daily life may provide clinically useful information for treatment planning.
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http://dx.doi.org/10.1080/13803395.2021.1975656DOI Listing
September 2021

12-year prediction of mild cognitive impairment aided by Alzheimer's brain signatures at mean age 56.

Brain Commun 2021 23;3(3):fcab167. Epub 2021 Jul 23.

Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA 92093, USA.

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 (s = 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%;  = 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.
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http://dx.doi.org/10.1093/braincomms/fcab167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361427PMC
July 2021

Correlates of poor sleep based upon wrist actigraphy data in bipolar disorder.

J Psychiatr Res 2021 09 21;141:385-389. Epub 2021 Jun 21.

Department of Psychiatry, University of California San Diego School of Medicine, La Jolla, CA, USA; Stein Institute for Research on Aging, University of California San Diego School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA.

Background: Wrist-worn actigraphy can objectively measure sleep, and has advantages over self-report, particularly for people with Bipolar Disorder (BD) for whom self-reports might be influenced by affect. Clinically useful data reduction approaches are needed to explore these complex data.

Methods: We created a composite score of sleep metrics in BD based on 51 BD and 80 healthy comparison (HC) participants. Subjects wore an actigraph for up to 14 consecutive 24-h periods, and we assessed total sleep time (TST), wake after sleep onset (WASO), percent sleep (PS), and number of awakenings (NA). We focused on participants who had at least 5 nights of actigraphy data. We computed z-scores for within-person means of sleep measures for BD subjects versus HCs, which were averaged to create a composite measure. We correlated this composite with participant characteristics, and used LASSO regression to identify sleep measures best explaining variability in identified correlates.

Results: Sleep measures and the composite did not differ between BDs and HCs; however, there was considerable variability in z-scores among those with BD. In BDs, the composite score was higher in women (t = 2.28, p = 0.027) and those who were employed (t = 2.34, p = 0.025), and positively correlated with medication load (r = 0.41, p = 0.003) while negatively correlated with Young Mania Rating Scale (YMRS; r = -0.35, p = 0.030). In LASSO regression, TST and NA best explained medication load while PS best explained employment and YMRS.

Conclusion: While a composite score of sleep metrics may provide useful information about sleep quality globally, our findings suggest that selection of theory-driven sleep measures may be more clinically meaningful.
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http://dx.doi.org/10.1016/j.jpsychires.2021.06.038DOI Listing
September 2021

Bipolar symptoms, somatic burden, and functioning in older-age bipolar disorder: Analyses from the Global Aging & Geriatric Experiments in Bipolar Disorder Database project.

Bipolar Disord 2021 Jul 27. Epub 2021 Jul 27.

Department of Psychiatry, University of California San Diego, San Diego, CA, USA.

Objective: Literature on older-age bipolar disorder (OABD) is limited. This first-ever analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated associations among age, BD symptoms, comorbidity, and functioning.

Methods: This analysis used harmonized, baseline, cross-sectional data from 19 international studies (N = 1377). Standardized measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Global Assessment of Functioning (GAF).

Results: Mean sample age was 60.8 years (standard deviation [SD] 12.2 years), 55% female, 72% BD I. Mood symptom severity was low: mean total YMRS score of 4.3 (SD 5.4) and moderate-to-severe depression in only 22%. Controlled for sample effects, both manic and depressive symptom severity appeared lower among older individuals (p's < 0.0001). The negative relationship between older age and symptom severity was similar across sexes, but was stronger among those with lower education levels. GAF was mildly impaired (mean =62.0, SD = 13.3) and somatic burden was high (mean =2.42, SD = 1.97). Comorbidity burden was not associated with GAF. However, higher depressive (p < 0.0001) and manic (p < 0.0001) symptoms were associated with lower GAF, most strongly among older individuals.

Conclusions: Findings suggest an attenuation of BD symptoms in OABD, despite extensive somatic burden. Depressive symptom severity was strongly associated with worse functioning in older individuals, underscoring the need for effective treatments of BD depression in older people. This international collaboration lays a path for the development of a better understanding of aging in BD.
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http://dx.doi.org/10.1111/bdi.13119DOI Listing
July 2021

Periventricular and deep abnormal white matter differ in associations with cognitive performance at midlife.

Neuropsychology 2021 Mar;35(3):252-264

Center for Behavior Genetics of Aging, University of California.

Abnormal white matter (AWM) on magnetic resonance imaging is associated with cognitive performance in older adults. We explored cognitive associations with AWM during late-midlife. Participants were community-dwelling men ( = 242; = 61.90 years; range = 56-66). Linear-mixed effects regression models examined associations of total, periventricular, and deep AWM with cognitive performance, controlling for multiple comparisons. Models considering specific cognitive domains controlled for current general cognitive ability (GCA). We hypothesized that total AWM would be associated with worse processing speed, executive function, and current GCA; deep AWM would correlate with GCA and periventricular AWM would relate to specific cognitive abilities. We also assessed the potential influence of cognitive reserve by examining a moderation effect of early life (mean age of 20) cognition. Greater total and deep AWM were associated with poorer current GCA. Periventricular AWM was associated with worse executive function, working memory, and episodic memory. When periventricular and deep AWM were modeled simultaneously, both retained their respective significant associations with cognitive performance. Cognitive reserve did not moderate associations. Our findings suggest that AWM contributes to poorer cognitive function in late-midlife. Examining only total AWM may obscure the potential differential impact of regional AWM. Separating total AWM into subtypes while controlling for current GCA revealed a dissociation in relationships with cognitive performance; deep AWM was associated with nonspecific cognitive ability whereas periventricular AWM was associated with specific frontal-related abilities and memory. Management of vascular or other risk factors that may increase the risk of AWM should begin during or before early late-midlife. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500190PMC
March 2021

Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.

Mol Psychiatry 2021 Apr 16. Epub 2021 Apr 16.

Unit for Psychosomatics / CL Outpatient Clinic for Adults, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles  and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
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http://dx.doi.org/10.1038/s41380-021-01098-xDOI Listing
April 2021

Chemokine MCP1 is associated with cognitive flexibility in schizophrenia: A preliminary analysis.

J Psychiatr Res 2021 06 3;138:139-145. Epub 2021 Apr 3.

Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, Mental Illness Research, Education, and Clinical Center (MIRECC), La Jolla, CA, USA; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA, USA. Electronic address:

Background: Peripheral levels of pro-inflammatory biomarkers have been shown to be altered in schizophrenia (SZ) and associated with cognitive impairments, but their relevance to specific cognitive domains remains unclear.

Methods: Plasma levels of cytokines, chemokines, and vascular biomarkers were quantified and compared between SZ and healthy comparison (HC) groups. Cognition was assessed using the Delis-Kaplan Executive Function System Trail Making (TM) and Color Word Interference (CWI) tests. Linear regression analyses examined differential relationships of inflammatory biomarkers with executive function between groups.

Results: Plasma levels of TNFα, ICAM1, and MCP1 were higher in individuals with SZ compared to HCs. Higher level of MCP1 was associated with increased CWI Inhibition Switching Errors in SZ but not HCs.

Conclusion: Like other studies, we found evidence for increased peripheral inflammation in SZ. We also showed that SZ with particularly high MCP1 levels had poor cognitive flexibility. Interventions to reduce chemokine elevations might prove beneficial for cognitive performance.
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http://dx.doi.org/10.1016/j.jpsychires.2021.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192469PMC
June 2021

MRI-assessed locus coeruleus integrity is heritable and associated with multiple cognitive domains, mild cognitive impairment, and daytime dysfunction.

Alzheimers Dement 2021 06 13;17(6):1017-1025. Epub 2021 Feb 13.

Department of Psychiatry, University of California San Diego, La Jolla, California, USA.

Introduction: The 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.

Methods: Participants 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 (LC ). We examined LC , cognition, amnestic mild cognitive impairment (aMCI), and daytime dysfunction.

Results: Heritability of LC was .48. Participants with aMCI showed greater daytime dysfunction. Lower LC 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.

Discussion: Reduced 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.
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http://dx.doi.org/10.1002/alz.12261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248066PMC
June 2021

Associations between depression and cardiometabolic health: A 27-year longitudinal study.

Psychol Med 2021 Jan 12:1-11. Epub 2021 Jan 12.

Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.

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.
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http://dx.doi.org/10.1017/S003329172000505XDOI Listing
January 2021

Links between objective sleep and sleep variability measures and inflammatory markers in adults with bipolar disorder.

J Psychiatr Res 2021 02 13;134:8-14. Epub 2020 Dec 13.

Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA, USA; Desert-Pacific Mental Illness Research Education and Clinical Center, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. Electronic address:

Premature mortality and increased physical comorbidity associated with bipolar disorder (BD) may be related to accelerated biological aging. Sleep disturbances and inflammation may be key mechanisms underlying accelerated aging in adults with BD. To our knowledge, these relationships have not been examined rigorously. This cross-sectional study included 50 adults with BD and 73 age- and sex-comparable non-psychiatric comparison (NC) subjects, age 26-65 years. Participants were assessed with wrist-worn actigraphy for total sleep time (TST), percent sleep (PS), and bed/wake times for 7 consecutive nights as well as completing scales for subjective sleep quality. Within-individual variability in sleep measures included intra-individual standard deviation (iSD) and atypicality of one evening's sleep. Blood-based inflammatory biomarkers included interleukin (IL)-6, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). Linear regression analyses tested relationships of mean and iSD sleep variables with inflammatory marker levels; time-lagged analyses tested the influence of the previous evening's sleep on inflammation. BD participants had worse subjective sleep quality, as well as greater TST iSD and wake time iSD compared to the NC group. In all participants, higher TST iSD and lower mean PS were associated with higher IL-6 levels (p = 0.04, η = 0.042; p = 0.05, η = 0.039, respectively). Lower mean PS was associated with higher CRP levels (p = 0.05, η = 0.039). Atypicality of the previous night's TST predicted next day IL-6 levels (p = 0.05, η = 0.04). All of these relationships were present in both BD and NC groups and remained significant even after controlling for sleep medications. Overall, sleep measures and their variability may influence inflammatory markers in all adults. Thus, sleep may be linked to the inflammatory processes believed to underlie accelerated aging in BD.
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http://dx.doi.org/10.1016/j.jpsychires.2020.12.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899704PMC
February 2021

What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group.

Hum Brain Mapp 2020 Jul 29. Epub 2020 Jul 29.

Division of Mental Health and Addicition, Oslo University Hospital, Oslo, Norway.

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
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http://dx.doi.org/10.1002/hbm.25098DOI Listing
July 2020

Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group.

Mol Psychiatry 2020 May 18. Epub 2020 May 18.

Department of Psychiatry, University of Münster, Münster, Germany.

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.
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http://dx.doi.org/10.1038/s41380-020-0754-0DOI Listing
May 2020

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

Transl Psychiatry 2020 03 20;10(1):100. Epub 2020 Mar 20.

Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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http://dx.doi.org/10.1038/s41398-020-0705-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083923PMC
March 2020

The Independent and Interactive Associations of Bilingualism and Sex on Cognitive Performance in Hispanics/Latinos of the Hispanic Community Health Study/Study of Latinos.

J Alzheimers Dis 2019 ;71(4):1271-1283

Department of Neuroscience, Shiley-Marcos Alzheimer's Disease Research Center, University of California San Diego, San Diego, CA, USA.

Sixty percent of Hispanics/Latinos are bilingual which research suggests may confer certain cognitive advantages. Female sex confers cognitive advantages in verbal learning and memory compared to male sex, regardless of race or ethnicity. Understanding the independent and interactive associations of bilingualism and sex with cognition may aid in predicting cognitive aging in Hispanics/Latinos. We examined baseline (2008-2011) data from the Hispanic Community Health Study/Study of Latinos, a multicenter, prospective community-based study. Our analyses included 6,110 males and females ≥45 years old who self-reported birth and parents' origin outside of the continental US, Spanish as their first language, and were evaluated in Spanish. Bilingualism was assessed along a Likert scale (1 = only Spanish to 4 = English>Spanish) for language proficiency (reading/spoken) and patterns of use (thinking/socializing). Cognitive testing included verbal learning, memory, fluency, and Digit Symbol Substitution (DSS). Linear regression models adjusted for relevant confounders, the complex survey design, and sampling weights. Participants' self-reported language proficiency was Spanish better than English, while patterns of use suggested more Spanish than English. Higher language proficiency was associated with higher performance on all cognitive indices while higher patterns of use associated with higher fluency and DSS scores (p-values < 0.01). Female sex was associated with higher performance on all cognitive indices (p-values < 0.05). There were no significant interactions with bilingualism (regardless of metric) by sex on cognition. For Hispanics/Latinos residing in the continental US and reporting birth and parents' origin elsewhere, bilingualism and female sex have independent cognitive benefits that are important to consider when evaluating cognitive performance.
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http://dx.doi.org/10.3233/JAD-190019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050701PMC
November 2020

Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals.

Neuropsychopharmacology 2019 12 21;44(13):2285-2293. Epub 2019 Aug 21.

Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, UK.

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R = 0.041, P < 0.001) and cingulum (right: R = 0.041, left: R = 0.040, P < 0.001). Lithium medication, later onset and short disease duration were related to higher FA along multiple ROIs. Results of the meta-analysis showed similar effects. We demonstrated widespread WM abnormalities in BD and highlighted that altered WM connectivity within the corpus callosum and the cingulum are strongly associated with BD. These brain abnormalities could represent a biomarker for use in the diagnosis of BD. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
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http://dx.doi.org/10.1038/s41386-019-0485-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898371PMC
December 2019

Short-lived mixed affective states in bipolar disorder.

Psychiatry Res 2020 02 27;284:112496. Epub 2019 Jul 27.

Department of Psychiatry, University of California San Diego (UCSD). San Diego, California. USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.

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http://dx.doi.org/10.1016/j.psychres.2019.112496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983330PMC
February 2020

A novel biomarker of cardiometabolic pathology in schizophrenia?

J Psychiatr Res 2019 10 18;117:31-37. Epub 2019 Jun 18.

Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA, USA; Center for Healthy Aging, University of California San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. Electronic address:

Background: Persons with schizophrenia and schizoaffective disorder (PwS) have high rates of cardiometabolic pathology that contributes to premature mortality. Adiponectin is a metabolic hormone affecting insulin sensitivity and inflammation, and is active in the brain. High-molecular weight (HMW) adiponectin is considered a more sensitive marker of metabolic dysfunction than total adiponectin, but has been poorly studied in schizophrenia.

Methods: This was a cross-sectional study of 100 PwS, age range 26-68 years (46 women), and 93 age- and sex-comparable non-psychiatric comparison (NC) subjects. Assessments included measures of psychopathology, physical health, cognitive function, and circulating biomarkers of metabolic dysfunction (HMW adiponectin, lipids, insulin resistance) and inflammation (high-sensitivity C-reactive protein or hs-CRP, Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-10).

Results: HMW adiponectin levels were lower in PwS compared to NCs. Lower HMW adiponectin levels were associated with higher body mass index (BMI), higher Framingham risk for coronary heart disease, higher number of metabolic syndrome criteria, greater insulin resistance, lower HDL cholesterol, and higher hs-CRP in both groups. Only in PwS, lower HMW adiponectin correlated with younger age. In the best-fit regression models of HMW adiponectin, lower levels were associated with lower HDL cholesterol and minority race/ethnicity in both groups; but with younger age, non-smoking, higher insulin resistance, and a diagnosis of schizoaffective disorder only among PwS, and with male sex, better cognitive functioning, and higher hs-CRP levels in NCs only.

Discussion: HMW adiponectin may be a promising biomarker of cardiometabolic health, especially among PwS. Adiponectin is a potential target for lifestyle and pharmacological interventions. Research on the possible role of HMW adiponectin in modifying cardiometabolic pathology in schizophrenia is needed.
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http://dx.doi.org/10.1016/j.jpsychires.2019.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707833PMC
October 2019

Resting State Abnormalities of the Default Mode Network in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

J Alzheimers Dis 2019 ;70(1):107-120

Department of Psychiatry, University of California San Diego, San Diego, CA, USA.

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.
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http://dx.doi.org/10.3233/JAD-180847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697380PMC
September 2020

Understanding Aging in Bipolar Disorder by Integrating Archival Clinical Research Datasets.

Am J Geriatr Psychiatry 2019 10 18;27(10):1122-1134. Epub 2019 Apr 18.

Department of Psychiatry (MEA, MS), Case Western Reserve University School of Medicine, Cleveland; Department of Neurology (CT, MS), Case Western Reserve University School of Medicine, Cleveland; Neurological and Behavioral Outcomes Center (CT, MS), Case Western Reserve University School of Medicine, Cleveland. Electronic address:

Objective: Although 25% of people with bipolar disorder (BD) are over age 60, there is a dearth of research on older age bipolar disorder (OABD). This report describes an initial effort to create an integrated OABD database using the U.S. National Institute of Mental Health Data Archive (NDA). Goals were to: 1) combine data from three BD studies in the United States that included overlapping data elements; 2) investigate research questions related to aims of the original studies; and 3) take an important first step toward combining existing datasets relevant to aging and BD.

Methods: Data were prepared and uploaded to the NDA, with a focus on data elements common to all studies. As appropriate, data were harmonized to select or collapse categories suitable for cross-walk analysis. Associations between age, BD symptoms, functioning, medication load, medication adherence, and medical comorbidities were assessed. The total sample comprised 451 individuals, mean age 57.7 (standard deviation: 13.1) years.

Results: Medical comorbidity was not significantly associated with either age or functioning and there did not appear to be an association between medication load, comorbidity, age, and adherence. Men and African-Americans were significantly more likely to have poor adherence. Both BD mania and depression symptoms were associated with functioning, but this differed across studies.

Conclusion: Despite limitations including heterogeneity in study design and samples and cross-sectional methodology, integrated datasets represent an opportunity to better understand how aging may impact the presentation and evolution of chronic mental health disorders across the lifespan.
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http://dx.doi.org/10.1016/j.jagp.2019.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739177PMC
October 2019

The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project: Understanding older-age bipolar disorder by combining multiple datasets.

Bipolar Disord 2019 11 30;21(7):642-649. Epub 2019 May 30.

GGZ inGeest, Amsterdam UMC, location VU Medical Center, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.

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.
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http://dx.doi.org/10.1111/bdi.12795DOI Listing
November 2019

Convergent neural substrates of inattention in bipolar disorder patients and dopamine transporter-deficient mice using the 5-choice CPT.

Bipolar Disord 2020 02 28;22(1):46-58. Epub 2019 May 28.

Department of Psychiatry, University of California San Diego, California.

Objectives: Bipolar disorder (BD) is a debilitating psychiatric illness affecting 2%-5% of the population. Although mania is the cardinal feature of BD, inattention and related cognitive dysfunction are observed across all stages. Since cognitive dysfunction confers poor functional outcome in patients, understanding the relevant neural mechanisms remains key to developing novel-targeted therapeutics.

Methods: The 5-choice continuous performance test (5C-CPT) is a mouse and fMRI-compatible human attentional task, requiring responding to target stimuli while inhibiting responding to nontarget stimuli, as in clinical CPTs. This task was used to delineate systems-level neural deficits in BD contributing to inattentive performance in human subjects with BD as well as mouse models with either parietal cortex (PC) lesions or reduced dopamine transporter (DAT) expression.

Results: Mania BD participants exhibited severe 5C-CPT impairment. Euthymic BD patients exhibited modestly impaired 5C-CPT. High impulsivity BD subjects exhibited reduced PC activation during target and nontarget responding compared with healthy participants. In mice, bilateral PC lesions impaired both target and nontarget responding. In the DAT knockdown mouse model of BD mania, knockdown mice exhibited severely impaired 5C-CPT performance versus wildtype littermates.

Conclusions: These data support the role of the PC in inattention in BD-specifically regarding identifying the appropriate response to target vs nontarget stimuli. Moreover, the findings indicate that severely reduced DAT function/hyperdopaminergia recreates the attentional deficits observed in BD mania patients. Determining the contribution of DAT in the PC to attention may provide a future target for treatment development.
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http://dx.doi.org/10.1111/bdi.12786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815232PMC
February 2020

Inaccuracy between subjective reports and objective measures of sleep duration and clinical correlates in bipolar disorder.

J Affect Disord 2019 05 5;250:226-230. Epub 2019 Mar 5.

Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.

Background: Sleep disturbances are common in bipolar disorder (BD) and are often assessed by self-report at clinic visits over the course of BD treatment. Self-report may be subject to recall bias based upon current mood/affect states. This study sought to identify the degree of inaccuracy between subjective and objective measures of sleep duration in those with and without BD, and to assess the demographic and clinical correlates of this inaccuracy.

Methods: Thirty-one individuals with BD and 54 healthy control (HC) participants reported on the number of hours slept a night over the past month and subsequently completed up to 14 days/nights of wrist actigraphy which provided an objective measure of sleep duration. We compared the subjective rating to the average of all nights of objective sleep duration, and correlated the magnitude of inaccuracy with demographic and clinical characteristics in the BD and HC groups.

Results: On average, both BD and HC groups overestimated their sleep, and there were no differences in inaccuracy between groups. In the BD group, greater inaccuracy was associated with lower functioning, even after controlling individually for objective and subjective sleep measures.

Limitations: Cross-sectional study, only focus on sleep duration, and less severe bipolar symptoms of sample.

Conclusions: Inaccuracy in reports of sleep duration was associated with lower functioning among BD patients. Better identifying discrepancies in reports of sleep duration in clinical practice could help in more efficient monitoring and management of BD symptoms.
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http://dx.doi.org/10.1016/j.jad.2019.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662606PMC
May 2019

Hidden in plain sight: Making a case for heterosexual Black college women being identified as a high-risk population for HIV infection.

Cultur Divers Ethnic Minor Psychol 2019 Jan;25(1):104-112

Department of Psychiatry, University of California, San Diego.

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).
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http://dx.doi.org/10.1037/cdp0000225DOI Listing
January 2019

Brain connections and social connections in autism spectrum disorders.

Authors:
Lisa T Eyler

Brain 2018 12;141(12):3287-3289

Department of Psychiatry, University of California San Diego, USA.

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http://dx.doi.org/10.1093/brain/awy293DOI Listing
December 2018

Sleep Disturbances and Inflammatory Biomarkers in Schizophrenia: Focus on Sex Differences.

Am J Geriatr Psychiatry 2019 01 11;27(1):21-31. Epub 2018 Oct 11.

Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA, United States; Department of Neurosciences, University of California, San Diego, CA, United States. Electronic address:

Objectives: Persons with schizophrenia, and women in particular, are at high risk for sleep disturbances and inflammatory activation. The sleep-inflammation link has been reported to be stronger in women within the general population. This study sought to examine the sleep-inflammation link in persons with schizophrenia and its relationship with demographic, clinical and cognitive variables.

Design: Cross-sectional case-control study.

Participants: Community-dwelling outpatients with schizophrenia (N=144, 46% women) and non-psychiatric comparison (NC) participants (N=134, 52% women), age 26-65 years.

Measurements: Reported sleep disturbances (sleep quality and duration), and mental and physical health were assessed. Cognitive assessments included executive functioning (Delis-Kaplan Executive Function System) and global cognitive functioning (Telephone Interview for Cognitive Status - modified.) Inflammatory biomarkers included pro-inflammatory cytokines [high sensitivity C-Reactive Protein (hs-CRP), Interleukin (IL)-6, Tumor Necrosis Factor-α (TNF-α)] and an anti-inflammatory cytokine (IL-10).

Results: The schizophrenia group had longer sleep duration, worse sleep quality, and increased levels of hs-CRP, IL-6, and TNF-α compared to NCs. Women with schizophrenia were less likely to have good sleep quality and had elevated levels of hs-CRP and IL-6 compared to men with schizophrenia. In the schizophrenia group, worse sleep quality and global cognitive functioning were associated with higher hs-CRP and IL-6 levels. Female sex and younger age were also associated with higher hs-CRP levels.

Conclusions: Sleep disturbances and increased inflammation, which were common in schizophrenia, were associated in persons with schizophrenia. Moreover, women with schizophrenia had worse sleep quality and inflammation than men. Further examination of the sleep-inflammation links, their contribution to clinical outcomes, and sex-specific factors is warranted.
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http://dx.doi.org/10.1016/j.jagp.2018.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489497PMC
January 2019

Genetic architecture of hippocampal subfields on standard resolution MRI: How the parts relate to the whole.

Hum Brain Mapp 2019 04 15;40(5):1528-1540. Epub 2018 Nov 15.

Department of Psychiatry, University of California San Diego, San Diego, California.

The human hippocampus can be subdivided into subfields with unique functional properties and differential vulnerability to disease or neuropsychiatric conditions. Identifying genes that confer susceptibility to such processes is an important goal in developing treatments. Recent advances in automatic subfield segmentation from magnetic resonance images make it possible to use these measures as phenotypes in large-scale genome-wide association studies. Such analyses are likely to rely largely on standard resolution (~1 mm isotropic) T -weighted images acquired on 3.0T scanners. Determining whether the genetic architecture of subfields can be detected from such images is therefore an important step. We used Freesurfer v6.0 to segment hippocampal subfields in two large twin studies, the Vietnam Era Twin Study of Aging and the Human Connectome Project. We estimated heritability of subfields and the genetic overlap with total hippocampal volume. Heritability was similar across samples, but little genetic variance remained after accounting for genetic influences on total hippocampal volume. Importantly, we examined genetic relationships between subfields to determine whether subfields can be grouped based on a smaller number of underlying, genetically independent factors. We identified three genetic factors in both samples, but the high degree of cross loadings precluded formation of genetically distinct groupings of subfields. These results confirm the reliability of Freesurfer v6.0 generated subfields across samples for phenotypic analyses. However, the current results suggest that it will be difficult for large-scale genetic analyses to identify subfield-specific genes that are distinct from both total hippocampal volume and other subfields using segmentations generated from standard resolution T -weighted images.
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http://dx.doi.org/10.1002/hbm.24464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397064PMC
April 2019
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