Objectives:Patient-reported outcomes such as health-related quality of life (HRQOL) are impaired in cirrhosis due to under-treated mood and sleep disorders, which can adversely impact their caregivers. Mindfulness-based stress reduction (MBSR) can improve patient-reported outcomes (PRO) in non-cirrhotic patients but their impact in cirrhosis is unclear. To evaluate the effect of MBSR and supportive group therapy on mood, sleep and HRQOL in cirrhotic patients and their caregivers.Methods:Cirrhotic outpatients with mild depression (Beck Depression Inventory (BDI)>14) on screening with an adult caregiver were enrolled. At baseline, BDI, sleep (Pittsburgh sleep quality index PSQI, Epworth Sleepiness Scale, ESS), anxiety (Beck Anxiety inventory) and HRQOL (Sickness Impact Profile, SIP) for both patients/caregivers and caregiver burden (Zarit Burden Interview Short-form, ZBI-SF and perceived caregiver burden, PCB) and patient covert HE(CHE) status were measured. Patients who had BDI>14 at baseline, along with their caregivers then underwent a structured MBSR program with four weekly hour-long group sessions interspersed with home practice using CDs. After the last group, all questionnaires were repeated.Results:20 patient/caregiver dyads were included. All patients were men (60±8 years MELD 12.9±5.7, 14 prior hepatic encephalopathy (HE)) while most caregivers (n=15) were women (55±12 years, 23±14 years of relationship, 65% spouses). There was no change in patient BDI between screening and baseline (20.1±11.2 vs. 19.0±10.6, P=0.81). All dyads were able to complete the four MBSR+supportive group therapy sessions. There was a significant improvement in BDI (19.0±10.6 vs.15.6±8.2 P=0.01), PSQI (7.2±3.7 vs. 5.5±3.7, P<0.001) and overall HRQOL (25.0±13.2 vs. 17.7±14.0,P=0.01) but not in anxiety or CHE rates in patients. Similarly caregiver burden (ZBI-SF13.0±9.0 vs. 9.8±6.9,P=0.04, Perceived burden 72.1±29.9 vs. 63.0±14.5,P=0.05) and depression reduced (BDI 9.1±7.8 vs. 5.9±6.0,P=0.03) while caregiver sleep quality (7.2±3.7 vs. 5.5±3.7,P<0.001) improved. Prior HE did not affect PRO change after MBSR+supportive groups but the ZBI-SF of caregivers taking care of HE patients improved to a greater extent (delta −1.1±6.5 vs. 7.4±5.3 HE, P=0.04).Conclusion:A short program of mindfulness and supportive group therapy significantly improves PRO and caregiver burden in cirrhotic patients with depression. This non-pharmacological method could be a promising approach to alleviate psychosocial stress in patients with end-stage liver disease and their caregivers.

Drug-related attentional bias may have significant implications for the treatment of cocaine use disorder (CocUD). However, the neurobiology of attentional bias is not completely understood. This study employed dynamic causal modeling (DCM) to conduct an analysis of effective (directional) connectivity involved in drug-related attentional bias in treatment-seeking CocUD subjects. The DCM analysis was conducted based on functional magnetic resonance imaging (fMRI) data acquired from fifteen CocUD subjects while performing a cocaine-word Stroop task, during which blocks of Cocaine Words (CW) and Neutral Words (NW) alternated. There was no significant attentional bias at group level. Although no significant brain activation was found, the DCM analysis found that, relative to the NW, the CW caused a significant increase in the strength of the right (R) anterior cingulate cortex (ACC) to R hippocampus effective connectivity. Greater increase of this connectivity was associated with greater CW reaction time (relative to NW reaction time). The increased strength of R ACC to R hippocampus connectivity may reflect ACC activation of hippocampal memories related to drug use, which was triggered by the drug cues. This circuit could be a potential target for therapeutics in CocUD patients. No significant change was found in the other modeled connectivities.

ABSTRACT. Objective: This study examined the residual effects of young adult diagnostic drinking on health outcomes four decades later in late life. Results were differentiated by drinking status during midlife. Method: A subsample of Vietnam Era Twin Registry members, all of whom had a lifetime diagnosis of alcohol dependence, was grouped according to life span drinking patterns as assessed by the Lifetime Drinking History interview in 2001. Those drinking at diagnostic levels (endorsing three or more alcohol dependence symptoms) before age 30 were then grouped based on their midlife drinking status (i.e., drinking at diagnostic levels vs. at minimal [nonsymptomatic] levels throughout midlife). Linear (or logistic) regression models were used to examine the association between life span drinking patterns and health outcomes in late life (about age 64). Results: Those who drank at diagnostic levels in young adulthood and in midlife exhibited significant health liabilities on every late-life health measure; those who drank at diagnostic levels for 5 or more years in young adulthood but drank only at minimal levels or not at all in midlife still exhibited similar liabilities on most late-life health measures. Only those individuals who drank diagnostically for less than 5 years in young adulthood displayed normal levels of late-life health. Conclusions: This study identified residual effects resulting from persistent young adult diagnostic drinking (5 or more years) that resulted in negative health outcomes in late life even after decades of remission. There is a distal but surprisingly strong association between persistent early life diagnostic drinking and late-life morbidity. (J. Stud. Alcohol Drugs, 77, 859-867, 2016)

ABSTRACT. Objective: Prior research on predictors of problem drinking has been limited because of an inability to attribute an unambiguous environmental explanation to observed fi ndings. Using a prospective co-twin control design, we examined the extent to which a history of psychiatric symptoms exerts an environmental infl uence on problem drinking in midlife that is unconfounded by genetic underpinnings. Method: Participants were 367 complete male twin pairs (208 monozygotic, 159 dizygotic) from the Vietnam Era Twin Registry who were assessed in midlife as part of the Family Twin Study (M age = 51.4 years, SD = 2.8). Twin pairs who were concordant for a lifetime diagnosis of an alcohol use disorder (AUD) in 1992 were selected for participation and were reinterviewed in 2001 to measure symptoms of AUD (i.e., problem drinking) since the prior assessment (past 10 years). Results: Within-pair differences in lifetime symptom counts of several psychiatric disorders measured in 1992 (i.e., major depression, dysthymia, generalized anxiety disorder, panic disorder, antisocial personality, mania, and posttraumatic stress disorder) were signifi cantly associated with within-pair differences in AUD symptoms in the subsequent 10 years. Conclusions: A history of psychiatric problems, particularly one marked by internalizing symptoms, appears to be linked to problem drinking in midlife above and beyond the confounding infl uence of genetic effects and underscores the potential value of integrated interventions for comorbidity to address problem drinking among individuals during this period of the life course. (J. Stud. Alcohol Drugs, 74, 136-140, 2013)