Factors Having an Impact on Relapse and Survival in Transplant Recipients With Alcohol-Induced Liver Disease.

OBJECTIVE: To assess the impact of standardized pretransplant alcohol abstinence and treatment guidelines on liver transplant outcomes. METHODS: This study assessed the posttransplant relapse and survival associated with a pretransplant guideline mandating alcohol abstinence, addiction treatment, and Alcoholics Anonymous (AA) attendance. This retrospective cohort study included liver recipients with alcohol-induced liver disease transplanted between January 1, 2000, and December 31, 2012, at a Midwest transplant center. Cox regression models tested for associations between pretransplant treatment, demographic and clinical characteristics, and outcome measures. RESULTS: Of 236 liver recipients (188 [79.7%] male; 210 [89%] white; mean follow-up, 88.6±55.0 months), 212 (90.2%) completed pretransplant treatment and 135 (57.2%) attended AA weekly. At 5 years, 16.3% and 8.2% had relapsed to any alcohol use and to high-dose drinking, respectively. Smoking during the 6 months before transplant was associated with any relapse (P=.0002) and high-dose relapse (P<.0001), and smoking at transplant was associated with death (P=.001). High-dose relapse was associated with death (hazard ratio, 3.5; P<.0001). CONCLUSION: A transplant center with a guideline requiring abstinence, treatment, and AA participation experienced lower posttransplant relapse rates from those previously reported in comparable large US transplant programs. Smoking cessation may further improve posttransplant outcomes.

Substance Use Disorders and Telehealth in the COVID-19 Pandemic Era: A New Outlook.

During the current coronavirus disease 2019 epidemic, many outpatient chemical dependency treatment programs and clinics are decreasing their number of in-person patient contacts. This has widened an already large gap between patients with substance use disorders (SUDs) who need treatment and those who have actually received treatment. For a disorder where group therapy has been the mainstay treatment option for decades, social distancing, shelter in place, and treatment discontinuation have created an urgent need for alternative approaches to addiction treatment. In an attempt to continue some care for patients in need, many medical institutions have transitioned to a virtual environment to promote safe social distancing. Although there is ample evidence to support telemedical interventions, these can be difficult to implement, especially in the SUD population. This article reviews current literature for the use of telehealth interventions in the treatment of SUDs and offers recommendations on safe and effective implementation strategies based on the current literature.

Cannabis abuse and dependence in kidney transplant candidates.

OBJECTIVE: Cannabis is the most commonly used non-alcohol intoxicant in the general population. There are no consistent guidelines on the implications of cannabis abuse and dependence (CAD) in kidney transplant candidates. The aims of this study were to characterize kidney transplant candidates with comorbid CAD and examine the implications of CAD on transplant candidacy. METHOD: This was a retrospective cohort study of kidney transplant candidates meeting diagnostic criteria for CAD at a tertiary center from 2012 to 2016. Candidates were reviewed for psychiatric and substance use disorders (SUDs), family history, and medical variables. The cohort was divided by severity of CAD and transplant listing status for comparisons. Statistical analysis included Kruskal-Wallis tests for continuous variables and Fisher's Exact Test for categorical variables. RESULTS: Sixty-one of 2067 (3%) kidney transplant candidates met criteria for CAD, and 13/61 (21%) underwent transplantation. Of 61, 58% smoked cannabis daily, 47% had alcohol dependence history, 31% had other illicit drug dependencies, 38% were smokers, 60% had a SUD family history, and 42% and 27% had depressive and anxiety disorders, respectively. Severity of CAD was inversely associated with transplant listing; those with cannabis abuse were more often listed than those with dependence (67% vs 33%, p = .02) by study end. Three case presentations illustrate cannabis-related issues. CONCLUSION: In this cohort, kidney transplant candidates with comorbid CAD have high prevalence of other substance use disorders, psychiatric comorbidities, and strong family histories of addictions that resemble other SUD populations. These findings have implications for pre-transplant screening and treatment and post-transplant monitoring.

Sex-specific association of depressive disorder and transient emotional states with alcohol consumption in male and female alcoholics.

BACKGROUND: We assessed the impact of comorbid depression and anxiety disorders as well as positive and negative emotional states on alcohol consumption in alcohol dependent men and women. METHODS: Per day alcohol consumption during 90 days before enrolment was assessed by the Time Line Follow Back (TLFB) in 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Propensity to drink in negative/positive emotional states was assessed using the Inventory of Drug Taking Situations (IDTS). Psychiatric comorbidities, including major depressive disorder (MDD), substance-induced depression (SID), anxiety disorders (AnxD), or substance-induced anxiety (SIA) were identified by Psychiatric Research Interview of Substance and Mood Disorders (PRISM). RESULTS: In the combined group, increased number of drinks per day and number of heavy drinking days correlated with increased IDTS scores (all p < 0.0001), while the lifetime history of MDD was associated with fewer drinking days (p = 0.045) but not average number of drinks per day. Male sex was associated with higher alcohol consumption per day (p < 0.0001), but not with the number of drinking days (p > 0.05). Lifetime MDD history was associated with less drinking days (p = 0.0084) and less heavy drinking days (p = 0.021) in alcohol dependent men, while current MDD was associated with higher alcohol use per day in alcohol dependent women (p = 0.044). CONCLUSIONS: Our findings suggest that emotional states and lifetime MDD history have sex-specific impact on alcohol use in alcohol dependent men and women. The mechanisms underlying these findings and their relevance to treatment outcomes need to be examined in future studies.

The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression.

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants for the treatment of major depressive disorder (MDD). However, treatment response during an initial therapeutic trial is often poor and is difficult to predict. Heterogeneity of response to SSRIs in depressed patients is partly driven by co-occurring somatic disorders such as coronary artery disease (CAD) and obesity. CAD and obesity may also be associated with metabolic side effects of SSRIs. In this study, we assessed the association of CAD and obesity with treatment response to SSRIs in patients with MDD using a polygenic score (PGS) approach. Additionally, we performed cross-trait meta-analyses to pinpoint genetic variants underpinnings the relationship of CAD and obesity with SSRIs treatment response. First, PGSs were calculated at different p value thresholds (PT) for obesity and CAD. Next, binary logistic regression was applied to evaluate the association of the PGSs to SSRIs treatment response in a discovery sample (ISPC, N = 865), and in a replication cohort (STAR*D, N = 1,878). Finally, a cross-trait GWAS meta-analysis was performed by combining summary statistics. We show that the PGSs for CAD and obesity were inversely associated with SSRIs treatment response. At the most significant thresholds, the PGS for CAD and body mass index accounted 1.3%, and 0.8% of the observed variability in treatment response to SSRIs, respectively. In the cross-trait meta-analyses, we identified (1) 14 genetic loci (including NEGR1, CADM2, PMAIP1, PARK2) that are associated with both obesity and SSRIs treatment response; (2) five genetic loci (LINC01412, PHACTR1, CDKN2B, ATXN2, KCNE2) with effects on CAD and SSRIs treatment response. Our findings implicate that the genetic variants of CAD and obesity are linked to SSRIs treatment response in MDD. A better SSRIs treatment response might be achieved through a stratified allocation of treatment for MDD patients with a genetic risk for obesity or CAD.

Pharmacokinetic-Pharmacodynamic interaction associated with venlafaxine-XR remission in patients with major depressive disorder with history of citalopram / escitalopram treatment failure.

BACKGROUND: The purpose of this study was to identify specific pharmacokinetic (PK) and pharmacodynamics (PD) factors that affect the likelihood of treatment remission with a serotonin norepinephrine reuptake inhibitor (SNRI) in depressed patients whose initial selective serotonin reuptake inhibitor (SSRI) failed. METHODS: Multiple logistic regression modeling of PK and PD variation hypothesized to contribute to SNRI (i.e. duloxetine or venlafaxine) treatment remission in prior SSRI (i.e. citalopram or escitalopram) failure was conducted on 139 subjects from the Pharmacogenomics Research Network (PGRN) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies. Depressive symptoms were assessed with the Quick Inventory of Depressive Symptomatology Clinician-rated (QIDS-C16). RESULTS: Venlafaxine-XR remission was associated with a significant interaction between CYP2D6 ultra-rapid metabolizer (URM) phenotype and SLC6A4 5-HTTLPR L/L genotype. A similar significant interaction effect was observed between CYP2D6 URM and SLC6A2 G1287A GA genotype. Stratifying by transporter genotypes, venlafaxine-XR remission was associated with CYP2D6 URM in patients with SLC6A4 L/L (p = 0.001) and SLC6A2 G1287A GA genotypes. LIMITATIONS: The primary limitation of this post hoc study was small sample size. CONCLUSION: Our results suggest that CYP2D6 ultra-rapid metabolizer status contributes to venlafaxine-XR treatment remission in MDD patients; in particular, there is a PK-PD interaction with treatment remission associated with CYP2D6 URM phenotype and SLC6A4 5-HTTLPR L/L or SLC6A2 G1287A G/A genotype, respectively. These preliminary data are encouraging and support larger pharmacogenomics studies differentiating treatment response to mechanistically different antidepressants in addition to further PK-PD interactive analyses.

Mapping depression rating scale phenotypes onto research domain criteria (RDoC) to inform biological research in mood disorders.

BACKGROUND: Substantial research progress can be achieved if available clinical datasets can be mapped to the National Institute of Mental Health Research-Domain-Criteria (RDoC) constructs. This mapping would allow investigators to both explore more narrowly defined clinical phenotypes and the relationship of these phenotypes to biological markers and clinical outcomes approximating RDoC criteria. METHODS: Using expert review and consensus, we defined four major depression phenotypes based on specific RDoC constructs. Having matched these constructs to individual items from the Hamilton Depression Rating Scale and Quick Inventory of Depressive Symptomatology, we identified subjects meeting criteria for each of these phenotypes from two large clinical trials of patients treated for major depression. In a post hoc analysis, we evaluated the overall treatment response based on the phenotypes: Core Depression (CD), Anxiety (ANX), and Neurovegetative Symptoms of Melancholia (NVSM) and Atypical Depression (NVSAD). RESULTS: The phenotypes were prevalent (range 10.5-52.4%, 50% reduction range 51.9-82.9%) and tracked with overall treatment response. Although the CD phenotype was associated with lower rates of remission in both cohorts, this was mainly driven by baseline symptom severity. However, when controlling for baseline severity, patients with the ANX phenotype had a significantly lower rate of remission. LIMITATIONS: The lack of replication between the studies of the phenotypes' treatment prediction value reflects important variability across studies that may limit generalizability. CONCLUSION: Further work evaluating biological markers associated with these phenotypes is needed for further RDoC concept development.

Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder.

Studies reported a strong genetic correlation between the Big Five personality traits and major depressive disorder (MDD). Moreover, personality traits are thought to be associated with response to antidepressants treatment that might partly be mediated by genetic factors. In this study, we examined whether polygenic scores (PGSs) derived from the Big Five personality traits predict treatment response and remission in patients with MDD who were prescribed selective serotonin reuptake inhibitors (SSRIs). In addition, we performed meta-analyses of genome-wide association studies (GWASs) on these traits to identify genetic variants underpinning the cross-trait polygenic association. The PGS analysis was performed using data from two cohorts: the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS, n = 529) and the International SSRI Pharmacogenomics Consortium (ISPC, n = 865). The cross-trait GWAS meta-analyses were conducted by combining GWAS summary statistics on SSRIs treatment outcome and on the personality traits. The results showed that the PGS for openness and neuroticism were associated with SSRIs treatment outcomes at p < 0.05 across PT thresholds in both cohorts. A significant association was also found between the PGS for conscientiousness and SSRIs treatment response in the PGRN-AMPS sample. In the cross-trait GWAS meta-analyses, we identified eight loci associated with (a) SSRIs response and conscientiousness near YEATS4 gene and (b) SSRI remission and neuroticism eight loci near PRAG1, MSRA, XKR6, ELAVL2, PLXNC1, PLEKHM1, and BRUNOL4 genes. An assessment of a polygenic load for personality traits may assist in conjunction with clinical data to predict whether MDD patients might respond favorably to SSRIs.

Beta-defensin 1, aryl hydrocarbon receptor and plasma kynurenine in major depressive disorder: metabolomics-informed genomics.

Major depressive disorder (MDD) is a heterogeneous disease. Efforts to identify biomarkers for sub-classifying MDD and antidepressant therapy by genome-wide association studies (GWAS) alone have generally yielded disappointing results. We applied a metabolomics-informed genomic research strategy to study the contribution of genetic variation to MDD pathophysiology by assaying 31 metabolites, including compounds from the tryptophan, tyrosine, and purine pathways, in plasma samples from 290 MDD patients. Associations of metabolite concentrations with depressive symptoms were determined, followed by GWAS for selected metabolites and functional validation studies of the genes identified. Kynurenine (KYN), the baseline plasma metabolite that was most highly associated with depressive symptoms, was negatively correlated with severity of those symptoms. GWAS for baseline plasma KYN concentrations identified SNPs across the beta-defensin 1 (DEFB1) and aryl hydrocarbon receptor (AHR) genes that were cis-expression quantitative trait loci (eQTLs) for DEFB1 and AHR mRNA expression, respectively. Furthermore, the DEFB1 locus was associated with severity of MDD symptoms in a larger cohort of 803 MDD patients. Functional studies demonstrated that DEFB1 could neutralize lipopolysaccharide-stimulated expression of KYN-biosynthesizing enzymes in monocytic cells, resulting in altered KYN concentrations in the culture media. In addition, we demonstrated that AHR was involved in regulating the expression of enzymes in the KYN pathway and altered KYN biosynthesis in cell lines of hepatocyte and astrocyte origin. In conclusion, these studies identified SNPs that were cis-eQTLs for DEFB1 and AHR and, which were associated with variation in plasma KYN concentrations that were related to severity of MDD symptoms.

Gender-specific effects of comorbid depression and anxiety on the propensity to drink in negative emotional states.

BACKGROUND AND AIMS: Depression and anxiety are often comorbid with alcoholism and contribute to craving and relapse. We aimed to estimate the prevalence of life-time diagnoses of major depressive disorder (MDD), substance-induced depression (SID), anxiety disorder (AnxD) and substance-induced anxiety (SIA), the effects of these comorbidities on the propensity to drink in negative emotional states (negative craving), and test whether these effects differ by sex. DESIGN: Secondary analyses of baseline data collected in a single-arm study of pharmacogenetic predictors of acamprosate response. SETTING: Academic medical center and affiliated community-based treatment programs in the American upper mid-west. PARTICIPANTS: A total of 287 males and 156 females aged 18-80 years, meeting DSM-IV criteria for alcohol dependence. MEASUREMENTS: The primary outcome measure was 'propensity to drink in negative emotional situations' (determined by the Inventory of Drug Taking Situations) and the key predictors/covariates were sex and psychiatric comorbidities, including MDD, SID, AnxD and SIA (determined by Psychiatric Research Interview of Substance and Mood Disorders). FINDINGS: The prevalence of the MDD, SID and AnxD was higher in females compared with males (33.1 versus 18.4%, 44.8 versus 26.4% and 42.2 versus 27.4%, respectively; P < 0.01, each), while SIA was rare (3.3%) and did not differ by sex. Increased propensity to drink in negative emotional situations was associated with comorbid MDD (ß = 6.6, P = 0.013) and AnxD (ß = 4.8, P = 0.042) as well as a SID × sex interaction effect (P = 0.003), indicating that the association of SID with propensity to drink in negative emotional situations differs by sex and is stronger in males (ß = 7.9, P = 0.009) compared with females (ß = -6.6, P = 0.091). CONCLUSIONS: There appears to be a higher prevalence of comorbid depression and anxiety disorders as well as propensity to drink in negative emotional situations in female compared with male alcoholics. Substance-induced depression appears to have a sex-specific effect on the increased risk for drinking in negative emotional situations in males.

Validation of the 17-item Hamilton Depression Rating Scale definition of response for adults with major depressive disorder using equipercentile linking to Clinical Global Impression scale ratings: analysis of Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) data.

OBJECTIVE: The study aimed to define thresholds of clinically significant change in 17-item Hamilton Depression Rating Scale (HDRS-17) scores using the Clinical Global Impression-Improvement (CGI-I) Scale as a gold standard. METHODS: We conducted a secondary analysis of individual patient data from the Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study, an 8-week, single-arm clinical trial of citalopram or escitalopram treatment of adults with major depression. We used equipercentile linking to identify levels of absolute and percent change in HDRS-17 scores that equated with scores on the CGI-I at 4 and 8 weeks. Additional analyses equated changes in the HDRS-7 and Bech-6 scale scores with CGI-I scores. RESULTS: A CGI-I score of 2 (much improved) corresponded to an absolute decrease (improvement) in HDRS-17 total score of 11 points and a percent decrease of 50-57%, from baseline values. Similar results were observed for percent change in HDRS-7 and Bech-6 scores. Larger absolute (but not percent) decreases in HDRS-17 scores equated with CGI-I scores of 2 in persons with higher baseline depression severity. CONCLUSIONS: Our results support the consensus definition of response based on HDRS-17 scores (>50% decrease from baseline). A similar definition of response may apply to the HDRS-7 and Bech-6. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Change in consumption patterns for treatment-seeking patients with alcohol use disorder post-bariatric surgery.

OBJECTIVE: The aim of this study is to describe the clinical phenotype of alcohol use disorder (AUD) treatment-seeking patients with Roux-en-Y Gastric Bypass Surgery (RYGB) history; and to compare it to AUD obese non-RYGB controls. METHODS: Retrospective study of electronic medical records for all patients 30-60years treated at the Mayo Clinic Addiction Treatment Program, between June, 2004 and July, 2012. Comparisons were performed with consumption patterns pre-RYGB and at time of treatment; excluding patients with AUD treatments pre-RYGB. RESULTS: Forty-one out of 823 patients had a RYGB history (4.9%); 122 controls were selected. Compared to controls, the RYGB group had significantly more females [n=29 (70.7%) vs. n=35 (28.7%) p<0.0001]; and met AUD criteria at a significantly earlier age (19.1±0.4 vs. 25.0±1years old, p=0.002). On average, RYGB patients reported resuming alcohol consumption 1.4±0.2years post-surgery, meeting criteria for AUD at 3.1±0.5years and seeking treatment at 5.4±0.3years postoperatively. Pre-surgical drinks per day were significantly fewer compared to post-surgical consumption [2.5±0.4 vs. 8.1±1.3, p=0.009]. Prior to admission, RYGB patients reported fewer drinking days per week vs. controls (4.7±0.3 vs. 5.5±1.8days, p=0.02). Neither RYGB, gender, age nor BMI was associated with differential drinking patterns. CONCLUSION: The results of this study suggest that some patients develop progressive AUD several years following RYGB. This observation has important clinical implications, calling for AUD-preventive measures following RYGB. Further large-scale longitudinal studies are needed to clarify the association between RYGB and AUD onset.

Treatment outcomes of depression: the pharmacogenomic research network antidepressant medication pharmacogenomic study.

BACKGROUND: The effectiveness of selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder (MDD) is controversial. AIMS: The clinical outcomes of subjects with nonpsychotic MDD were reported and compared with the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study outcomes to provide guidance on the effectiveness of SSRIs. METHODS: Subjects were treated with citalopram/escitalopram for up to 8 weeks. Depression was measured using the Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) and the 17-item Hamilton Depression Rating Scale. RESULTS: The group of subjects with at least 1 follow-up visit had a remission (QIDS-C16 ≤ 5) rate of 45.8% as well as a response (50% reduction in QIDS-C16) rate of 64.8%, and 79.9% achieved an improvement of 5 points or higher in QIDS-C16 score. The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study subjects were more likely to achieve a response than STAR*D study subjects. After adjustment for demographic factors, the response rates were not significantly different. When reporting the adverse effect burden, 60.5% of the subjects reported no impairment, 31.7% reported a minimal-to-mild impairment, and 7.8% reported a moderate-to-severe burden at the 4-week visit. CONCLUSIONS: Patients contemplating initiating an SSRI to treat their MDD can anticipate a high probability of symptom improvement (79.9%) with a low probability that their symptoms will become worse. Patients with lower baseline severity have a higher probability of achieving remission. The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study replicates many findings of the first phase of the STAR*D study after controlling for the differences between the studies.

Association of GATA4 sequence variation with alcohol dependence.

To further explore reports of association of alcohol dependence and response to acamprosate treatment with the GATA4 rs13273672 single nucleotide polymorphism (SNP), we genotyped this and 10 other GATA4 SNPs in 816 alcohol-dependent cases and 1248 controls. We tested for association of alcohol dependence with the 11 SNPs individually and performed a global test for association using a principle components analysis. Our analyses demonstrate significant association between GATA4 and alcohol dependence at the gene level (P = 0.009) but no association with rs13273672. Further studies are needed to identify potential causal GATA4 variation(s) and the functional mechanism(s) contributing to this association.

Detecting Associations between Major Depressive Disorder Treatment and Essential Hypertension using Electronic Health Records.

In this observational study, we investigate the correlation between depression and hypertension on a cohort of patients treated for major depressive disorder using Selective Serotonin Reuptake Inhibitors (SSRIs) and assess the effect of depression treatment on the diagnoses and treatment for essential hypertension. Our results indicate that the positive effect of successful depression treatment can be discovered and estimated from electronic health record (EHR) data even for a small sample size. We have also successfully detected differences in the effect of depression treatment in hypertensive patients between the two phenotypes representing successful treatment outcomes-response and remission- concluding that achieving remission has a longer lasting effect than response.

Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting.

OBJECTIVE: The objective was to evaluate the potential benefit of an integrated, five-gene pharmacogenomic test and interpretive report (GeneSight) for the management of psychotropic medications used to treat major depression in an outpatient psychiatric practice. METHODS: The open-label study was divided into two groups. In the first (unguided) group (n = 113), pharmacogenomic information was not shared until all participants completed the study. In the second (guided) group (n = 114), the pharmacogenomic report was provided to physicians for clinical use. Three depression ratings, the 17-item Hamilton Rating Scale for Depression (HAMD-17), the Quick Inventory of Depressive Symptomatology - Clinician Rated (QIDS-C16), and the Patient Health Questionnaire (PHQ-9), were collected at baseline, and at 2, 4, and 8 weeks. RESULTS: The guided group experienced greater percent improvement in depression scores from baseline on all three depression instruments (HAMD-17, P < 0.0001; QIDS-C16, P < 0.0001; PHQ-9, P < 0.0001) compared with the unguided group. Eight-week response rates were higher in the guided group than in the unguided group on all three measurements (HAMD-17, P = 0.03; QIDS-C16, P = 0.005; PHQ-9, P = 0.01). Eight-week QIDS-C16 remission rates were higher in the guided group (P = 0.03). Participants in the unguided group who at baseline were prescribed a medication that was most discordant with their genotype experienced the least improvement compared with other unguided participants (HAMD-17, P = 0.007). Participants in the guided group and on a baseline medication most discordant with their genotype showed the greatest improvement compared with the unguided cohort participants (HAMD-17, P = 0.01). CONCLUSION: These findings replicate previous studies and demonstrate significantly improved depression outcomes with use of GeneSight, an integrated, multigenetic pharmacogenomic testing platform.

A retrospective study of gender differences in depressive symptoms and risk of relapse in patients with alcohol dependence.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate potential gender differences in situations associated with heavy alcohol drinking. METHODS: Data from 395 alcohol dependent patients participating in the Mayo Clinic Intensive Addiction Program were evaluated. Each participant completed the inventory of drug taking situations (IDTS), Penn alcohol craving scale (PACS), patient health questionnaire (PHQ-9), and/or Beck depression inventory (BDI). Gender differences in IDTS scores representing three domains (negative, positive, and temptation) of situations associated with heavy alcohol use were examined. RESULTS: Women with alcohol dependence report a higher frequency of heavy drinking in unpleasant emotional (IDTS negative scores mean ± SD women vs. men: 52.3 ± 22.1 vs. 43.8 ± 21.8; p = .0006), and as a result of temptation (IDTS temptation scores mean ± SD women vs. men: 40.4 ± 23.0 vs. 35.3 ± 20.8; p = .035). Upon admission, women also scored significantly higher on depressive symptoms as measured by the BDI (23.4 ± 11.4 vs. 18.2 ± 9.8, p < .001). After controlling for depressive symptom severity as a covariate, the IDTS gender differences were no longer significant. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Our results suggest that unpleasant or temptation based emotional situations are a vulnerability risk factor for heavy drinking particularly in females. This risk appears to be at least partially driven by depressive symptom burden. Future research is needed to further investigate this finding.