Psychosocial Risk Impacts Mortality in Women After Liver Transplantation.

BACKGROUND: Liver transplant candidates undergo psychosocial assessment as a component of their pretransplant evaluation. Global psychosocial assessment scales, including the Psychosocial Assessment of Candidates for Transplantation (PACT), capture and quantify these psychiatric and social variables. OBJECTIVE: Our primary aim was to assess for an association between global PACT score and survival in liver transplant recipients. METHODS: This retrospective cohort study examined records of all liver recipients at one U.S. Transplant Center from 2000 to 2012 with outcomes monitoring until 07/01/2016. We investigated for associations between the following variables and mortality: PACT score, age, gender, marital status, race, alcoholic liver disease (ALD), and body mass index (BMI). Statistical methods included Student's t-test, Wilcoxon rank sum test, chi-square, Fisher's exact test, Kaplan-Meier curve, and Cox proportional hazard models. RESULTS: Of 1040 liver recipients, 538 had a documented PACT score. Among these, PACT score was not associated with mortality. In women, a lower PACT score was associated with mortality (p = 0.003) even after adjustments for age, marital status, and BMI. Women with ALD had a 2-fold increased hazard of death (p = 0.012). Increasing age was associated with increased risk of death for the cohort as a whole (p = 0.019) and for men (p = 0.014). In men, being married and BMI were marginally protective (p = 0.10 and p = 0.13, respectively). CONCLUSIONS: Transplant psychosocial screening scales, specifically the PACT, identify psychosocial burden and may predict post-transplant outcomes in certain populations. In female liver recipients, lower PACT scores and ALD were associated with a greater risk of post-transplant mortality.

Impact of Sex and ADHD Status on Psychiatric Comorbidity in Treatment-Seeking Alcoholics.

Objective: To assess for intrasex and intersex differences in psychiatric comorbidity according to ADHD status in treatment-seeking adults with alcohol use disorders (AUDs). Method: This study was a secondary analysis of data utilizing descriptive statistics from 472 treatment-seeking alcoholics who completed the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). Results: The prevalence of ADHD in males and females was 6.0% and 6.4%, respectively. Males with ADHD and AUDs had higher rates of current and lifetime drug use disorders, current depressive disorders, and current and lifetime anxiety disorders than male alcoholics without ADHD. No intrasex differences in psychiatric comorbidities were identified in female alcoholics with respect to ADHD status. Males with ADHD and AUDs were more likely to have had opioid dependence than ADHD-positive females. No other intersex differences were found. Conclusion: Positive ADHD status was associated with increased psychiatric comorbidity among treatment-seeking alcoholic men.

Psychosocial Risk Predicts New Episode Depression After Heart Transplant.

BACKGROUND: Psychosocial assessment is an essential component of the pretransplant evaluation. Many individuals have significant psychosocial problems, and they are either denied for transplantation or deferred from listing and transplant until the psychosocial issues are addressed. OBJECTIVE: The primary aim of this study was to evaluate the outcomes of patients who initially had significant psychosocial problems, but who addressed them and received a heart transplant. METHODS: This retrospective study included heart transplant recipients from 1/1/2000 to 12/31/2012. Those with initial Psychosocial Assessment of Candidates for Transplantation (PACT) scale score <2 were compared with those whose initial score was ≥2 for the variables new onset depression and anxiety, length of stay, rejection, and survival using logistic and linear regression and Cox proportional hazards modeling. RESULTS: Of 164 heart recipients with pretransplant PACT scores, 46 (28%) were female, 154 (94%) were white, and the mean age was 52.7 years. Only 11 (7%) received an initial PACT score <2; these candidates underwent heart transplantation after their scores increased to ≥2. Initial PACT <2 increased the odds of new depression by 11-fold (p = 0.002), but was not associated with differences in survival, posttransplant length of stay, the occurrence of treated episodes of rejection or new anxiety (p ≥ 0.20 for all). CONCLUSION: Among heart recipients, initially high pretransplant psychosocial risk, as assessed by PACT, was associated with posttransplant new episode depression. However, after addressing the primary psychosocial issues before transplant, posttransplant length of stay, organ rejection, and survival were the same as those without prior psychosocial concerns.

The Clinical Utility of ASRS-v1.1 for Identifying ADHD in Alcoholics Using PRISM as the Reference Standard.

Objective: The objective was to assess the clinical utility of the Adult ADHD Self-Report Scale (ASRS-v1.1) in identifying ADHD in alcoholics using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) as the diagnostic "gold standard." Method: We performed a secondary analysis of data from 379 treatment-seeking alcoholics who completed the ASRS-v1.1 and the ADHD module of the PRISM. Data analysis included descriptive statistics. Results: The prevalence of ADHD was 7.7% (95% CI = [5.4, 10.8]). The positive predictive value (PPV) of the ASRS-v1.1 was 18.1% (95% CI = [12.4, 25.7]) and the negative predictive value (NPV) was 97.6% (95% CI = [94.9, 98.9]). The ASRS-v1.1 demonstrated a sensitivity of 79.3% (95% CI = [61.6, 90.2]) and a specificity of 70.3% (95% CI = [65.3, 74.8]). Conclusion: The ASRS-v1.1 demonstrated acceptable sensitivity and specificity in a sample of treatment-seeking alcoholics when compared with the PRISM as the reference standard for ADHD diagnosis.

Metabolomics biomarkers to predict acamprosate treatment response in alcohol-dependent subjects.

Precision medicine for alcohol use disorder (AUD) allows optimal treatment of the right patient with the right drug at the right time. Here, we generated multivariable models incorporating clinical information and serum metabolite levels to predict acamprosate treatment response. The sample of 120 patients was randomly split into a training set (n = 80) and test set (n = 40) five independent times. Treatment response was defined as complete abstinence (no alcohol consumption during 3 months of acamprosate treatment) while nonresponse was defined as any alcohol consumption during this period. In each of the five training sets, we built a predictive model using a least absolute shrinkage and section operator (LASSO) penalized selection method and then evaluated the predictive performance of each model in the corresponding test set. The models predicted acamprosate treatment response with a mean sensitivity and specificity in the test sets of 0.83 and 0.31, respectively, suggesting our model performed well at predicting responders, but not non-responders (i.e. many non-responders were predicted to respond). Studies with larger sample sizes and additional biomarkers will expand the clinical utility of predictive algorithms for pharmaceutical response in AUD.

Acute suicidal affective disturbance: Factorial structure and initial validation across psychiatric outpatient and inpatient samples.

BACKGROUND: A new clinical entity, Acute Suicidal Affective Disturbance (ASAD), was recently proposed to characterize rapid-onset, acute suicidality including the cardinal symptom of behavioral intent. This study examines the proposed ASAD criteria factor-analytically and in relation to correlates of suicidal behavior and existing psychiatric disorders in samples of psychiatric outpatients and inpatients. METHODS: Two samples of psychiatric outpatients (N=343, aged 18-71 years, 60.6% female, 74.9% White) and inpatients (N=7,698, aged 15-99 years, 57.2% female, 87.8% White) completed measures of their ASAD symptoms and psychological functioning. RESULTS: Across both samples, results of a confirmatory factor analysis supported the unidimensional nature of the ASAD construct. Additionally, results provided evidence for the convergent and discriminant validity of ASAD, demonstrating its relation to, yet distinction from, other psychiatric disorders and correlates of suicide in expected ways. Importantly, ASAD symptoms differentiated multiple attempters, single attempters, and non-attempters, as well as attempters, ideators, and non-suicidal patients, and was an indicator of past suicide attempts above and beyond symptoms of depression and other psychiatric disorders. LIMITATIONS: This study utilized cross-sectional data and did not use a standardized measure of ASAD. CONCLUSIONS: ASAD criteria formed a unidimensional construct that was associated with suicide-related variables and other psychiatric disorders in expected ways. If supported by future research, ASAD may fill a gap in the current diagnostic classification system (DSM-5) by characterizing and predicting acute suicide risk.

The Psychosocial Assessment of Candidates for Transplantation: A Cohort Study of its Association With Survival Among Lung Transplant Recipients.

BACKGROUND: The United Network for Organ Sharing mandates a psychosocial assessment of transplant candidates before listing. A quantified measure for determining transplant candidacy is the Psychosocial Assessment of Candidates for Transplant (PACT) scale. This instrument's predictive value for survival has not been rigorously evaluated among lung transplantation recipients. METHODS: We reviewed medical records of all patients who underwent lung transplantation at Mayo Clinic, Rochester from 2000-2012. A transplant psychiatrist had assessed lung transplant candidates for psychosocial risk with the PACT scale. Recipients were divided into high- and low psychosocial risk cohorts using a PACT score cutoff of 2. The main outcome variable was posttransplant survival. Mortality was analyzed using the Kaplan-Meier estimator and Cox proportional hazard models. RESULTS: This study included 110 lung recipients: 57 (51.8%) were females, 101 (91.8%) Whites, mean age: 56.4 years. Further, 7 (6.4%) recipients received an initial PACT score <2 (poor or borderline candidates) and later achieved a higher score, allowing transplant listing; 103 (93.6%) received initial scores ≥2 (acceptable, good or great candidates). An initial PACT score < 2 was modestly associated with higher mortality (adjusted hazard ratio = 2.73, p = 0.04). CONCLUSIONS: Lung transplant recipients who initially received a low score on the PACT scale, reflecting poor or borderline psychosocial candidacy, experienced greater likelihood of mortality. This primary finding suggests that the psychosocial assessment, as measured by the PACT scale, may provide additional mortality risk stratification for lung transplant candidates.

How does active substance use at psychiatric admission impact suicide risk and hospital length-of-stay?

Despite their high prevalence, little is known about the effects of substance use disorders and active substance use on the suicide risk or length-of-stay of psychiatric inpatients. This study examines the relationship between active substance use at the time of psychiatric hospitalization and changes in suicide risk measures and length-of-stay. Admission and discharge ratings on the Suicide Status Form-II-R, diagnoses, and toxicology data from 2,333 unique psychiatric inpatients were examined. Data for patients using alcohol, tetrahydrocannabinol, methamphetamines, cocaine, benzodiazepines, opiates, barbiturates, phencyclidine, and multiple substances on admission were compared with data from 1,426 admissions without substance use. Patients with substance use by toxicology on admission had a 0.9 day shorter length-of-stay compared to toxicology-negative patients. During initial nurse evaluation on the inpatient unit, these patients reported lower suicide measures (i.e., suicidal ideation frequency, overall suicide risk, and wish-to-die). No significant between-group differences were seen at discharge. Patients admitted with a substance use disorder diagnosis had a 1.0 day shorter length-of-stay than those without, while those with a substance use disorder diagnosis and positive toxicology reported the lowest measures of suicidality on admission. These results remained independent of psychiatric diagnosis. For acute psychiatric inpatients, suicide risk is higher and length-of-stay is longer in patients with substance use disorders who are NOT acutely intoxicated compared with patients without a substance use disorder. Toxicology-positive patients are less suicidal on admission and improve faster than their toxicology-negative counterparts. This study gives support to the clinical observation that acutely intoxicated patients may stabilize quickly with regard to suicidal urges and need for inpatient care.

Antipsychotic-like effects of a neurotensin receptor type 1 agonist.

Although neurotensin (NT) analogs are known to produce antipsychotic-like effects, the therapeutic possibility of a brain penetrant NTS1 agonist in treating psychiatric disorders has not been well studied. Here, we examined whether PD149163, a brain-penetrant NTS1-specific agonist, displays antipsychotic-like effects in C57BL/6J mice by investigating the effect of PD149163 on amphetamine-mediated hyperactivity and amphetamine-induced disruption of prepulse inhibition. In addition, we assessed the effect of PD149163 on glycogen synthase kinase-3 (GSK-3) activity, a downstream molecular target of antipsychotics and mood stabilizers, using phospho-specific antibodies. PD149163 (0.1 and 0.5mg/kg) inhibited amphetamine-induced hyperactivity in mice, indicating that NTS1 activation inhibits psychomotor agitation. PD149163 (0.5mg/kg) also increased prepulse inhibition, suggesting that NTS1 activation reduces prepulse inhibition deficits which often co-occur with psychosis in humans. Interestingly, PD149163 increased the inhibitory serine phosphorylation on both GSK-3α and GSK-3ß in a dose- and time-dependent manner in the nucleus accumbens and medial prefrontal cortex of the mice. Moreover, PD149163 inhibited GSK-3 activity in the nucleus accumbens and medial prefrontal cortex in the presence of amphetamine. Thus, like most current antipsychotics and mood stabilizers, PD149163 inhibited GSK-3 activity in cortico-striatal circuitry. Together, our findings indicate that PD149163 may be a novel antipsychotic.

CRAFFT as a Substance Use Screening Instrument for Adolescent Psychiatry Admissions.

BACKGROUND: Adolescent use of alcohol and illicit substances is quite common among pediatric psychiatry inpatients; however, little data exist on substance use screening instruments that can be used to augment thorough psychiatric diagnostic interviews. CRAFFT is a screening tool for adolescent substance use that has been validated in outpatient general medical settings. This is the first study to examine its use in adolescent psychiatric inpatients. METHODS: We performed a chart review of records from adolescents admitted to our inpatient psychiatric unit who completed a CRAFFT screen on admission. We compared CRAFFT scores with other measures of substance use, including urine drug screens and the diagnosis of a substance use disorder at discharge. We also examined measures of depression and suicidality in individuals with elevated CRAFFT scores (≥2 positive answers out of 6) and compared them with measures in those with normal CRAFFT scores. RESULTS: Elevated CRAFFT scores were correlated with other measures of alcohol and substance use, including the diagnosis of a substance use disorder at discharge (P<0.0001), and laboratory screening for alcohol (P=0.0048) and marijuana (P<0.0001) on admission. Previous suicide attempts (P=0.005) and "psychiatric trauma" (P=0.0027) were also positively associated with elevated CRAFFT scores. CONCLUSIONS: CRAFFT scores in adolescent inpatients were correlated with other measures of substance use, supporting its efficacy as a screening tool in this population. CRAFFT scores were also positively correlated with a history of psychiatric trauma and past suicide attempts, which is consistent with the results of previous studies associating pediatric substance use and traumatic life events with an increased risk of suicide.

Female smokers have the highest alcohol craving in a residential alcoholism treatment cohort.

BACKGROUND: Cigarette smoking among female and male alcoholics has not been extensively studied as a factor related to intensity of alcohol craving during residential treatment and corresponding sobriety length. METHODS: This retrospective cohort study assessed self-reported sobriety outcomes in patients with alcohol dependence at 3-month intervals over 12 months after completion of a 30-day residential treatment program. Demographic and clinical variables were collected including smoking status, alcohol craving utilizing the Penn Alcohol Craving Scale (PACS), and alcohol relapse. Statistical analyses included Chi-square, ANOVA, Tukey's test, Kaplan-Meier plots and Cox proportional hazards models as appropriate. RESULTS: Of the 761 alcohol-dependent study subjects, 355 (47%) were current smokers. Alcohol craving intensity was higher in smoking females compared to nonsmoking females (p=0.0096), smoking males (p<0.0001), and nonsmoking males (p<0.0001). Smoking status-by-sex interaction was not associated with post-treatment relapse. After controlling for other variables, higher PACS scores at admission were associated with higher probability of relapse (p=0.0003). CONCLUSIONS: In this study, female alcoholic smokers experienced the highest level of alcohol craving in an alcohol treatment setting. Interestingly, this did not translate into higher rates of post-treatment relapse. Further research is warranted to explore the neurobiological basis for sex differences in this highly prevalent comorbidity.

Gender differences in the association of agitation and suicide attempts among psychiatric inpatients.

OBJECTIVE: To determine if the relationship of agitation with suicide ideation and suicide attempts differed between men and women. METHOD: Self-reported severity of agitation and other suicide risk factors was obtained from 7698 consecutive patients during admission for inpatient psychiatric treatment during a 5-year period. RESULTS: Agitation was highest among men with a history of suicide attempts. Agitation was significantly associated with frequency of suicide ideation and history of suicide attempt, but the gender-by-suicide interaction was only significant as a predictor of suicide attempt history. For men, agitation was associated with significantly increased risk for suicide attempt, but for women, agitation was not associated with risk for suicide attempt history. Results were unchanged when analyses were repeated among the subgroup of patients with suicide ideation. CONCLUSIONS: Agitation is associated with history of suicide attempt among male but not female psychiatric inpatients. Agitation differentiates between those men who have only thought about suicide and those who have made suicide attempts.