Dataset Information

Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters.

ABSTRACT: Previous studies in late-life depression (LLD) have found that patients have altered intrinsic functional connectivity in the dorsal default mode network (DMN) and executive control network (ECN). We aimed to detect connectivity differences across a treatment trial among LLD patients as a function of remission status. LLD patients (N=37) were enrolled into a 12-week trial of venlafaxine and underwent five functional magnetic resonance imaging resting state scans during treatment. Patients had no history of drug abuse, psychosis, dementia/neurodegenerative diseases or medical conditions with known effects on mood. We investigated whether there were differences in three networks: DMN, ECN and anterior salience network connectivity, as well as a whole brain centrality measure (eigenvector centrality). We found that remitters showed increases in ECN connectivity in the right precentral gyrus and decreases in DMN connectivity in the right inferior frontal gyrus and supramarginal gyrus. The ECN and DMN had regions (middle temporal gyrus and bilateral middle/inferior temporal/fusiform gyrus, respectively) that showed reversed effects (decreased ECN and increased DMN, respectively). Early changes in functional connectivity can occur after initial medication exposure. This study offers new data, indicating that functional connectivity changes differ depending on treatment response and can occur shortly after exposure to antidepressant medication.

SUBMITTER: Karim HT

PROVIDER: S-EPMC5322273 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters.

Karim H T HT Andreescu C C Tudorascu D D Smagula S F SF Butters M A MA Karp J F JF Reynolds C C Aizenstein H J HJ

Molecular psychiatry 20160419 3

Previous studies in late-life depression (LLD) have found that patients have altered intrinsic functional connectivity in the dorsal default mode network (DMN) and executive control network (ECN). We aimed to detect connectivity differences across a treatment trial among LLD patients as a function of remission status. LLD patients (N=37) were enrolled into a 12-week trial of venlafaxine and underwent five functional magnetic resonance imaging resting state scans during treatment. Patients had no ...[more]

PMID: 27090303

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Project description:Pharmacological treatment of major depressive disorder (MDD) typically involves a lengthy trial and error process to identify an effective intervention. This lengthy period prolongs suffering and worsens all-cause mortality, including from suicide, and is typically longer in late-life depression (LLD). Our group has recently demonstrated that during an open-label venlafaxine (serotonin-norepinephrine reuptake inhibitor) trial, significant changes in functional resting state connectivity occurred following a single dose of treatment, which persisted until the end of the trial. In this work, we propose an analysis framework to translate these perturbations in functional networks into predictors of clinical remission. Participants with LLD (N?=?49) completed 12-weeks of treatment with venlafaxine and underwent functional magnetic resonance imaging (fMRI) at baseline and a day following a single dose of venlafaxine. Data was collected at rest as well as during an emotion reactivity task and an emotion regulation task. Remission was defined as a Montgomery-Asberg Depression Rating Scale (MADRS) ?10 for two weeks. We computed eigenvector centrality (whole brain connectivity) and activation during the emotion regulation and emotion reactivity tasks. We employed principal components analysis, Tikhonov-regularized logistic classification, and least angle regression feature selection to predict remission by the end of the 12-week trial. We utilized ten-fold cross-validation and Receiver Operator Curves (ROC) curve analysis. To determine task-region pairs that significantly contributed to the algorithm's ability to predict remission, we used permutation testing. Using the fMRI data at both baseline and after the first dose of treatment yielded a sensitivity of 72% and a specificity of 68% (AUC?=?0.77), a 15% increase in accuracy over baseline MADRS. In general, the accuracy at baseline was further improved by using the change in activation following a single dose. Activation of the frontal cortex, hippocampus, parahippocampus, caudate, thalamus, medial temporal cortex, middle cingulate, and visual cortex predicted treatment remission. Acute, dynamic trajectories of functional imaging metrics in response to a pharmacological intervention are a valuable tool for predicting treatment response in late-life depression and elucidating the mechanism of pharmacological therapies in the context of the brain's functional architecture.

Project description:Background and aimsAlcohol consumption changes markedly over the life course, with important implications for health and social development. Assessment of these patterns often relies on cross-sectional data, which cannot fully capture how individuals' drinking changes as they age. This study used data from 18 waves of a general population panel survey to measure drinking trajectories over the life course in Australia.Design and settingLongitudinal survey data from the Household, Income and Labour Dynamics in Australia (HILDA) survey between 2001 and 2018.ParticipantsA total of 20 593 individuals ages 15 or above in two samples assessing quantity-frequency (n = 20 569, 52.0% female) and risky single occasion drinking (RSOD), respectively, (n = 17 340, 52.5% female), interviewed as part of HILDA.MeasurementsUsual quantity of alcohol consumed per drinking occasion; frequency of drinking occasions per week; average daily consumption, calculated by combining reported usual quantity and frequency; and average reported frequency of RSOD per week.FindingsMultilevel, mixed effects models run with fractional polynomial terms found similar male and female alcohol consumption trajectories for quantity-frequency and RSOD measures. Usual quantity of alcohol consumed per drinking occasion (5.4 drinks for men, 3.8 for women) and RSOD frequency (0.56 occasions/week for men, 0.38 for women) peaked in young adulthood, whereas frequency of drinking occasions (2.5 occasions/week for men, 1.7 for women) peaked in middle age. Middle-age drinkers had the highest average daily consumption of alcohol (1.4 drinks/day for 54-year-old men, 0.6 drinks for 57-year-old women) and engaged in RSOD slightly less than young adults.ConclusionsAlcohol consumption in Australia appears to vary substantially over the life course, with usual quantity per drinking occasion and frequency of risky single occasion drinking peaking during early adulthood and average daily consumption and frequency of consumption peaking in middle age.

Project description:ImportanceIf we assume that women and men exhibit variations of the same fundamental vascular physiology, then conventional analyses of subclinical measures would suggest that women catch up to men by midlife in the extent of potentially important vascular disease. Alternatively, under the assumption that vascular physiology may fundamentally differ between women and men, a sex-specific analysis of existing data could offer new insights and augment our understanding of sex differences in cardiovascular diseases.ObjectiveTo evaluate whether longitudinal patterns of blood pressure (BP) elevation differ between women and men during the life course when considering baseline BP levels as the reference.Design, setting, and participantsWe conducted sex-specific analyses of longitudinal BP measures (144 599 observations) collected for a period of 43 years (1971 to 2014) in 4 community-based US cohort studies. The combined total included 32 833 participants (54% female) spanning ages 5 to 98 years. Data were analyzed between May 4, 2019, and August 5, 2019.ExposuresAge and serially assessed longitudinal BP measures: systolic BP, diastolic BP, mean arterial pressure (MAP), and pulse pressure (PP).Main outcomes and measuresSex-specific change in each primary BP measure compared with baseline BP levels, derived from multilevel longitudinal models fitted over the age span, and new-onset cardiovascular disease events.ResultsOf the 32 833 participants, 17 733 were women (54%). Women compared with men exhibited a steeper increase in BP that began as early as in the third decade and continued through the life course (likelihood ratio test χ2 = 531 for systolic BP; χ2 = 123 for diastolic BP; χ2 = 325 for MAP; and χ2 = 572 for PP; P for all <.001). After adjustment for multiple cardiovascular disease risk factors, these between-sex differences in all BP trajectories persisted (likelihood ratio test χ2 = 314 for systolic BP; χ2 = 31 for diastolic BP; χ2 = 129 for MAP; and χ2 = 485 for PP; P for all <.001).Conclusions and relevanceIn contrast with the notion that important vascular disease processes in women lag behind men by 10 to 20 years, sex-specific analyses indicate that BP measures actually progress more rapidly in women than in men, beginning early in life. This early-onset sexual dimorphism may set the stage for later-life cardiovascular diseases that tend to present differently, not simply later, in women compared with men.

Dataset Information

Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters.

Publications

Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters.

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