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

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.

Long-term associations of cigarette smoking in early mid-life with predicted brain aging from mid- to late life.

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 mid-life would have older than predicted brain age 16-28 years later. DESIGN: Prospective cohort observational study, utilizing smoking pack years data from average age 40 (early mid-life) predicting predicted brain age difference scores (PBAD) at average ages 56, 62 (later mid-life) and 68 years (early old age). Early mid-life 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 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 Brain-Age Regression Analysis and Computation Utility software (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 modeling, age 40 pack years predicted more advanced age 56 PBAD [ß = -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 × alcohol interaction, predicted more advanced PBAD at age 56 (ß = -0.166, P = 0.001, 95% CI = -0.261, -0.070) with additional influences at age 62 (ß = -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.

Medical Correlates of Chronic Multisymptom Illness in Gulf War Veterans.

BACKGROUND: Chronic multisymptom illness (CMI) is more prevalent among deployed than nondeployed veterans from the first Gulf War. Objective physiologic markers of CMI are lacking. The purpose of this study is to determine whether measurable abnormalities in the autonomic nervous system or hypothalamic-pituitary adrenal axis would distinguish CMI cases (CMI+) from controls (CMI-) among deployed veterans of the 1990-1991 Gulf War. METHODS: This is a cross-sectional case-control cohort study that examined deployed veterans who participated in the Phase III study: National Health Survey of Gulf War Veterans and Their Families. Autonomic nervous system and hypothalamic-pituitary adrenal axis function-related measures included: 24-hour heart-rate variability, urinary catecholamines and cortisol, hypertension, insulin sensitivity, dyslipidemia, body fat, bone mineral density, and ultrasensitive C-reactive protein. RESULTS: Veterans of the first Gulf War with CMI (n = 73) and without the condition (n = 111) were studied. Sociodemographic characteristics were similar. Veterans with CMI reported poorer mental and physical functioning, greater use of prescription medications, and more nonroutine clinic visits. These veterans were also more likely to have fibromyalgia syndrome, irritable bowel syndrome, metabolic syndrome, and among males, a larger waist-to-hip ratio. Lower values for a nonlinear heart-rate-variability parameter-the short-term fractal scaling exponent (DFA1), reflecting an increased randomness of beat-to-beat changes in heart rate-were observed in veterans with CMI than those veterans without it (1.28±0.16vs 1.35±0.15; p=0.005). Hypothalamic-pituitary-adrenal axis function measures were similar between the two groups. CONCLUSION: In this cohort of deployed veterans from the first Gulf War, we identified abnormal heart-rate variability in veterans with CMI compared to veterans without the condition, which suggests abnormal functioning of the autonomic nervous system and possible long-term cardiovascular effects.

The role of cerebellar impairment in emotion processing: a case study.

BACKGROUND: Though the cerebellum's role in visuospatial and fine motor functioning has been well-established over the last several years, the role of the cerebellum in emotion has more recently been a focus of scientific inquiry. Cerebellar impairment has been associated with deficits in emotional processing and is linked to a wide range of clinical behaviors including social withdrawal, blunted emotional expression, and impulsivity. In addition, cerebellar impairments have been associated with the onset of psychiatric disorders including major depressive disorder and, more recently, obsessive-compulsive disorder. CASE PRESENTATION: We describe a 32-year-old patient who presented to our clinic for a neuropsychological evaluation with a childhood history of a cerebellar brain tumor and detail-oriented, perfectionistic tendencies. Neuropsychological assessment data revealed impairments in visuospatial processing and in fine motor skills, likely stemming from the cerebellar tumor. Clinical assessment led to a diagnosis of obsessive-compulsive personality disorder and also suggested impairments in socio-emotional processing. CONCLUSIONS: Our findings lend support to recent data which has suggested the impact of cerebellar impairment on emotional processing and related domains. Unlike many previous studies, however, our report focuses on an individual who, despite having marked impairments in certain domains, demonstrates a high level of functioning. We believe that this report holds important clinical relevance for proper diagnosis of cerebellar-related impairment and for the necessity of early intervention.

Individual differences in cognitive ability at age 20 predict pulmonary function 35†years later.

BACKGROUND: Poor pulmonary function is associated with mortality and age-related diseases, and can affect cognitive performance. However, extant longitudinal studies indicate that early cognitive ability also affects later pulmonary function. Despite the multifaceted nature of pulmonary function, most longitudinal studies were limited to a single index of pulmonary function: forced expiratory volume in 1 s (FEV1). In this study, we examined whether early adult cognitive ability predicted five different indices of pulmonary function in mid-life. METHODS: Mixed modelling tested the association between young adult general cognitive ability (mean age=20), measured by the Armed Forces Qualification Test (AFQT), and mid-life pulmonary function (mean age=55), in 1019 men from the Vietnam Era Twin Study of Aging. Pulmonary function was indexed by per cent predicted values for forced vital capacity (FVC%p), FEV1%p, maximum forced expiratory flow (FEFmax%p), and maximal voluntary ventilation (MVV%p), and by the ratio of FEV1 to FVC (FEV1/FVC), an index of lung obstruction. RESULTS: After adjusting for smoking, pulmonary disease, occupation, income and education, age 20 AFQT was significantly (p<0.05) associated with mid-life FVC%p (ß=0.10), FEV1%p (ß=0.13), FEFmax%p (ß=0.13), and MVV%p (ß=0.13), but was not significantly associated with FEV1/FVC (ß=0.03, p=0.34). CONCLUSIONS: Early adult cognitive ability is a predictor of multiple indices of aging-related pulmonary function 35 years later, including lung volume, airflow and ventilator capacity. Cognitive deficits associated with impaired aging-related lung function may, thus, be partly pre-existing. However, results also highlight that early life risk factors may be differentially related to different metrics of later-life pulmonary health.

Gulf War veterans' health: medical evaluation of a U.S. cohort.

BACKGROUND: United States military personnel reported various symptoms after deployment to the Persian Gulf during the 1991 Gulf War. However, the symptoms' long-term prevalence and association with deployment remain controversial. OBJECTIVE: To assess and compare the prevalence of selected medical conditions in a national cohort of deployed and nondeployed Gulf War veterans who were evaluated by direct medical and teledermatologic examinations. DESIGN: A cross-sectional prevalence study performed 10 years after the 1991 Gulf War. SETTING: Veterans were examined at 1 of 16 Veterans Affairs medical centers. PARTICIPANTS: Deployed (n = 1061) and nondeployed (n = 1128) veterans of the 1991 Gulf War. MEASUREMENTS: Primary outcome measures included fibromyalgia, the chronic fatigue syndrome, dermatologic conditions, dyspepsia, physical health-related quality of life (Short Form-36 [SF-36]), hypertension, obstructive lung disease, arthralgias, and peripheral neuropathy. RESULTS: Of 12 conditions, only 4 conditions were more prevalent among deployed than nondeployed veterans: fibromyalgia (deployed, 2.0%; nondeployed, 1.2%; odds ratio, 2.32 [95% CI, 1.02 to 5.27]); the chronic fatigue syndrome (deployed, 1.6%; nondeployed 0.1%; odds ratio, 40.6 [CI, 10.2 to 161]); dermatologic conditions (deployed, 34.6%; nondeployed, 26.8%; odds ratio, 1.38 [CI, 1.06 to 1.80]), and dyspepsia (deployed, 9.1%; nondeployed, 6.0%; odds ratio, 1.87 [CI, 1.16 to 2.99]). The mean physical component summary score of the SF-36 for deployed and nondeployed veterans was 49.3 and 50.8, respectively. LIMITATIONS: Relatively low participation rates introduce potential participation bias, and deployment-related illnesses that resolved before the research examination could not, by design, be detected. CONCLUSIONS: Ten years after the Gulf War, the physical health of deployed and nondeployed veterans is similar. However, Gulf War deployment is associated with an increased risk for fibromyalgia, the chronic fatigue syndrome, skin conditions, dyspepsia, and a clinically insignificant decrease in the SF-36 physical component score.

Co-twin control study of relationships among combat exposure, combat-related PTSD, and other mental disorders.

The well-documented association between combat-related PTSD (C-PTSD) and other mental disorders may be an artifact of shared familial vulnerability. This study uses a co-twin control design to examine whether the association between C-PTSD and other mental disorders persists after adjusting for shared familial vulnerability. Data were from male monozygotic twin pairs in the Vietnam Era Twin Registry. Logistic regression analyses demonstrated that combat exposure, adjusted for C-PTSD, was significantly associated with increased risk for alcohol and cannabis dependence and that C-PTSD mediated the association between combat exposure and both major depression and tobacco dependence. We conclude C-PTSD comorbidity persists after controlling for shared vulnerability. Combat exposure is directly and indirectly, through C-PTSD, associated with increased risk for other mental disorders.

Nicotine and familial vulnerability to schizophrenia: a discordant twin study.

Tobacco use is significantly associated with schizophrenia. However, it is not clear if smoking is associated with the illness itself, treatment, or underlying vulnerability to the disease. Smoking was studied in a sample of schizophrenic probands (n = 24), their unaffected co-twins (n = 24), and controls (n = 3,347). Unaffected co-twins had higher rates of daily smoking than controls. Probands and co-twins were more frequently unsuccessful in attempts to quit than controls. Probands reported shaky hands and depression following smoking cessation more often than controls, whereas unaffected co-twins reported difficulty concentrating, drowsiness, nervousness, and headache following smoking cessation more often than controls. Results are consistent with the hypothesis that nicotine use is influenced by familial vulnerability to schizophrenia, not just clinical schizophrenia per se.

Does marijuana use have residual adverse effects on self-reported health measures, socio-demographics and quality of life? A monozygotic co-twin control study in men.

AIMS: To assess the effects of former heavy marijuana use on selected aspects of health. DESIGN: A monozygotic co-twin control design was used to compare the health of former heavy marijuana using male monozygotic twins to that of their co-twins who never used marijuana significantly. SETTING: In-person survey and questionnaires. PARTICIPANTS: Fifty-six marijuana use discordant monozygotic twin pair members of the Vietnam Era Twin (VET) Registry. MEASUREMENTS: Current socio-demographic characteristics; current nicotine and alcohol use; life-time nicotine and alcohol abuse/dependence; past 5-year physical and mental health services utilization; and health-related quality of life. FINDINGS: The mean number of days on which the marijuana user twin used marijuana in his life-time was 1085, while the non-marijuana user used marijuana a maximum of 5 days. Marijuana was last used a mean of 20 years previously. No significant differences were found between the former marijuana user twins and their siblings for current socio-demographic characteristics; current nicotine or alcohol use; life-time nicotine or alcohol abuse/dependence; past 5-year out-patient or emergency room visits, hospitalizations or medication use for medical problems; past 5-year mental health out-patient use or hospitalizations; or health-related quality of life. CONCLUSIONS: Previous heavy marijuana use a mean of 20 years earlier by a group of men who reported no other significant illicit drug use does not appear to be associated with adverse socio-demographic, physical or mental health adverse effects. The conclusions of the study are limited by possible participation and recall biases, relatively small sample size and the absence of a physical health examination.