LD block disorder-specific pleiotropic roles of novel CRHR1 in type 2 diabetes and depression disorder comorbidity.

Major depressive disorder (MDD) and type 2 diabetes (T2D) are complex disorders whose comorbidity can be due to hypercortisolism and may be explained by dysfunction of the corticotropin-releasing hormone receptor 1 (CRHR1) and cortisol feedback within the hypothalamic-pituitary-adrenal axis (HPA axis). To investigate the role of the CRHR1 gene in familial T2D, MDD, and MDD-T2D comorbidity, we tested 152 CRHR1 single-nucleotide-polymorphisms (SNPs), via 2-point parametric linkage and linkage disequilibrium (LD; i.e., association) analyses using 4 models, in 212 peninsular families with T2D and MDD. We detected linkage/LD/association to/with MDD and T2D with 122 (116 novel) SNPs. MDD and T2D had 4 and 3 disorder-specific novel risk LD blocks, respectively, whose risk variants reciprocally confirm one another. Comorbidity was conferred by 3 novel independent SNPs. In silico analyses reported novel functional changes, including the binding site of glucocorticoid receptor-alpha [GR-α] on CRHR1 for transcription regulation. This is the first report of CRHR1 pleiotropic linkage/LD/association with peninsular familial MDD and T2D. CRHR1 contribution to MDD is stronger than to T2D and may antecede T2D onset. Our findings suggest a new molecular-based clinical entity of MDD-T2D and should be replicated in other ethnic groups.

Comorbidity of Novel CRHR2 Gene Variants in Type 2 Diabetes and Depression.

The corticotropin-releasing hormone receptor 2 (CRHR2) gene encodes CRHR2, contributing to the hypothalamic-pituitary-adrenal stress response and to hyperglycemia and insulin resistance. CRHR2-/- mice are hypersensitive to stress, and the CRHR2 locus has been linked to type 2 diabetes and depression. While CRHR2 variants confer risk for mood disorders, MDD, and type 2 diabetes, they have not been investigated in familial T2D and MDD. In 212 Italian families with type 2 diabetes and depression, we tested 17 CRHR2 single nucleotide polymorphisms (SNPs), using two-point parametric-linkage and linkage-disequilibrium (i.e., association) analysis (models: dominant-complete-penetrance-D1, dominant-incomplete-penetrance-D2, recessive-complete-penetrance-R1, recessive-incomplete-penetrance-R2). We detected novel linkage/linkage-disequilibrium/association to/with depression (3 SNPs/D1, 2 SNPs/D2, 3 SNPs/R1, 3 SNPs/R2) and type 2 diabetes (3 SNPs/D1, 2 SNPs/D2, 2 SNPs/R1, 1 SNP/R2). All detected risk variants are novel. Two depression-risk variants within one linkage-disequilibrium block replicate each other. Two independent novel SNPs were comorbid while the most significant conferred either depression- or type 2 diabetes-risk. Although the families were primarily ascertained for type 2 diabetes, depression-risk variants showed higher significance than type 2 diabetes-risk variants, implying CRHR2 has a stronger role in depression-risk than type 2 diabetes-risk. In silico analysis predicted variants' dysfunction. CRHR2 is for the first time linked to/in linkage-disequilibrium/association with depression-type 2 diabetes comorbidity and may underlie the shared genetic pathogenesis via pleiotropy.

The DSM-5 Clinical and Public Health Committee (CPHC): operations, mechanics, controversies and recommendations.

BACKGROUND: For DSM - 5, the American Psychiatric Association Board of Trustees established a robust vetting and review process that included two review committees that did not exist in the development of prior DSMs, the Scientific Review Committee (SRC) and the Clinical and Public Health Committee (CPHC). The CPHC was created as a body that could independently review the clinical and public health merits of various proposals that would fall outside of the strictly defined scientific process. METHODS: This article describes the principles and issues which led to the creation of the CPHC, the composition and vetting of the committee, and the processes developed by the committee - including the use of external reviewers. RESULTS: Outcomes of some of the more involved CPHC deliberations, specifically, decisions concerning elements of diagnoses for major depressive disorder, autism spectrum disorder, catatonia, and substance use disorders, are described. The Committee's extensive reviews and its recommendations regarding Personality Disorders are also discussed. CONCLUSIONS: On the basis of our experiences, the CPHC membership unanimously believes that external review processes to evaluate and respond to Work Group proposals is essential for future DSM efforts. The Committee also recommends that separate SRC and CPHC committees be appointed to assess proposals for scientific merit and for clinical and public health utility and impact.

Co-shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome.

Schizophrenia (SCZ) and major depressive disorder (MDD) in treatment-naive patients are associated with increased risk for type 2 diabetes (T2D) and metabolic syndrome (MetS). SCZ, MDD, T2D, and MetS are often comorbid and their comorbidity increases cardiovascular risk: Some risk genes are likely co-shared by them. For instance, transcription factor 7-like 2 (TCF7L2) and proteasome 26S subunit, non-ATPase 9 (PSMD9) are two genes independently reported as contributing to T2D and SCZ, and PSMD9 to MDD as well. However, there are scarce data on the shared genetic risk among SCZ, MDD, T2D, and/or MetS. Here, we briefly describe T2D, MetS, SCZ, and MDD and their genetic architecture. Next, we report separately about the comorbidity of SCZ and MDD with T2D and MetS, and their respective genetic overlap. We propose a novel hypothesis that genes of the prolactin (PRL)-pathway may be implicated in the comorbidity of these disorders. The inherited predisposition of patients with SCZ and MDD to psychoneuroendocrine dysfunction may confer increased risk of T2D and MetS. We illustrate a strategy to identify risk variants in each disorder and in their comorbid psychoneuroendocrine and mental-metabolic dysfunctions, advocating for studies of genetically homogeneous and phenotype-rich families. The results will guide future studies of the shared predisposition and molecular genetics of new homogeneous endophenotypes of SCZ, MDD, and metabolic impairment.

Underlying construct of empathy, optimism, and burnout in medical students.

OBJECTIVE: This study was designed to explore the underlying construct of measures of empathy, optimism, and burnout in medical students. METHODS: Three instruments for measuring empathy (Jefferson Scale of Empathy, JSE); Optimism (the Life Orientation Test-Revised, LOT-R); and burnout (the Maslach Burnout Inventory, MBI, which includes three scales of Emotional Exhaustion, Depersonalization, and Personal Accomplishment) were administered to 265 third-year students at Sidney Kimmel (formerly Jefferson) Medical College at Thomas Jefferson University. Data were subjected to factor analysis to examine relationships among measures of empathy, optimism, and burnout in a multivariate statistical model. RESULTS: Factor analysis (principal component with oblique rotation) resulted in two underlying constructs, each with an eigenvalue greater than one. The first factor involved "positive personality attributes" (factor coefficients greater than .58 for measures of empathy, optimism, and personal accomplishment). The second factor involved "negative personality attributes" (factor coefficients greater than .78 for measures of emotional exhaustion, and depersonalization). CONCLUSIONS: Results confirmed that an association exists between empathy in the context of patient care and personality characteristics that are conducive to relationship building, and considered to be "positive personality attributes," as opposed to personality characteristics that are considered as "negative personality attributes" that are detrimental to interpersonal relationships. Implications for the professional development of physicians-in-training and in-practice are discussed.

Who's your expert? Use of an expert opinion survey to inform development of American Psychiatric Association practice guidelines.

OBJECTIVE: For many clinical questions in psychiatry, high-quality evidence is lacking. Credible practice guidelines for such questions depend on transparent, reproducible, and valid methods for assessing expert opinion. The objective of this study was to develop and demonstrate the feasibility of a method for assessing expert opinion to aid in the development of practice guidelines by the American Psychiatric Association (APA). METHODS: A "snowball" process initially soliciting nominees from three sets of professional leaders was used to identify experts on a guideline topic (psychiatric evaluation). In a Web-based survey, the experts were asked to rate their level of agreement that specific assessments improve specific outcomes when they are included in an initial psychiatric evaluation. The experts were also asked about their own practice patterns with respect to the doing of the assessments. The main outcome measures are the following: number of nominated experts, number of experts who participated in the survey, and number and nature of quantitative and qualitative responses. RESULTS: The snowball process identified 1,738 experts, 784 (45 %) of whom participated in the opinion survey. Participants generally, but not always, agreed or strongly agreed that the assessments asked about would improve specified outcomes. Participants wrote 716 comments explaining why they might not typically include some assessments in an initial evaluation and 1,590 comments concerning other aspects of the topics under consideration. CONCLUSIONS: The snowball process based on initial solicitation of Psychiatry's leaders produced a large expert panel. The Web-based survey systematically assessed the opinions of these experts on the utility of specific psychiatric assessments, providing useful information to substantiate opinion-based practice guidelines on how to conduct a psychiatric evaluation. The considerable engagement of respondents shows promise for using this methodology in developing future APA practice guidelines.

Are medical students being taught invasive skills using simulation?

INTRODUCTION: Basic invasive procedural skills are traditionally taught during clerkships. Using simulation to teach invasive skills provides students the opportunity to practice in a structured environment without risking patient safety. We surveyed incoming interns at Thomas Jefferson University Hospital to assess the prevalence of simulation training for invasive and semi-invasive procedural skills during medical school. METHODS: From 2008 to 2010, we surveyed 357 incoming interns at Thomas Jefferson University Hospital. The questionnaire asked incoming interns if they received formal instruction or procedural training with or without a simulation component for 34 procedures during medical school. Interns indicated their number of attempts and successes for each procedure in clinical care. RESULTS: All 357 incoming interns completed the survey. Experience in 28 procedures is reported in this article. For all but three basic procedures, more than 75% of interns received formal didactic instruction. Only 3 advanced procedures were formally taught to most interns. The prevalence of simulation training for the basic and advanced procedures was 46% and 23%, respectively. For the basic procedures, the average number of attempts and successes was 6.5 (range, 0-13.9) and 6.2 (range, 0-13.4), respectively. For the advanced procedures, the average number of attempts and successes was 1.5 (range, 0-4.8) and 1.3 (range, 0-4.7), respectively. CONCLUSIONS: Although most medical students receive formal instruction in basic procedures, fewer receive formal instruction in advanced procedures. The use of simulation to complement this training occurs less often. Simulation training should be increased in undergraduate medical education and integrated into graduate medical education.

Psychometrics of the scale of attitudes toward physician-pharmacist collaboration: a study with medical students.

BACKGROUND: Despite the emphasis placed on interdisciplinary education and interprofessional collaboration between physicians and pharmacologists, no psychometrically sound instrument is available to measure attitudes toward collaborative relationships. AIM: This study was designed to examine psychometrics of an instrument for measuring attitudes toward physician-pharmacist collaborative relationships for administration to students in medical and pharmacy schools and to physicians and pharmacists. METHODS: The Scale of Attitudes Toward Physician-Pharmacist Collaboration was completed by 210 students at Jefferson Medical College. Factor analysis and correlational methods were used to examine psychometrics of the instrument. RESULTS: Consistent with the conceptual framework of interprofessional collaboration, three underlying constructs, namely "responsibility and accountability;" "shared authority;" and "interdisciplinary education" emerged from the factor analysis of the instrument providing support for its construct validity. The reliability coefficient alpha for the instrument was 0.90. The instrument's criterion-related validity coefficient with scores of a validated instrument (Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration) was 0.70. CONCLUSIONS: Findings provide support for the validity and reliability of the instrument for medical students. The instrument has the potential to be used for the evaluation of interdisciplinary education in medical and pharmacy schools, and for the evaluation of patient outcomes resulting from collaborative physician-pharmacist relationships.

The devil is in the third year: a longitudinal study of erosion of empathy in medical school.

PURPOSE: This longitudinal study was designed to examine changes in medical students' empathy during medical school and to determine when the most significant changes occur. METHOD: Four hundred fifty-six students who entered Jefferson Medical College in 2002 (n = 227) and 2004 (n = 229) completed the Jefferson Scale of Physician Empathy at five different times: at entry into medical school on orientation day and subsequently at the end of each academic year. Statistical analyses were performed for the entire cohort, as well as for the "matched" cohort (participants who identified themselves at all five test administrations) and the "unmatched" cohort (participants who did not identify themselves in all five test administrations). RESULTS: Statistical analyses showed that empathy scores did not change significantly during the first two years of medical school. However, a significant decline in empathy scores was observed at the end of the third year which persisted until graduation. Findings were similar for the matched cohort (n = 121) and for the rest of the sample (unmatched cohort, n = 335). Patterns of decline in empathy scores were similar for men and women and across specialties. CONCLUSIONS: It is concluded that a significant decline in empathy occurs during the third year of medical school. It is ironic that the erosion of empathy occurs during a time when the curriculum is shifting toward patient-care activities; this is when empathy is most essential. Implications for retaining and enhancing empathy are discussed.

Barriers to recovery and recommendations for change: the Pennsylvania Consensus Conference on psychiatry's role.

OBJECTIVE: Recovery has emerged over the past decade as a dominant theme in public mental health care. METHODS: The 2006 Pennsylvania Consensus Conference brought together 24 community psychiatrists to explore the barriers they experienced in promoting recovery and their recommendations for change. RESULTS: Twelve barriers were identified and classified into one of three categories: psychiatry knowledge, roles, and training; the need to transform public mental health systems and services; and environmental barriers to opportunity. Participants made 22 recommendations to address these barriers through changes in policies, programs, and psychiatric knowledge and practice. CONCLUSIONS: The recommendations identify areas for change that can be accomplished through individual psychiatrist action and organized group efforts.

The tipping point from private practice to publicly funded settings for early- and mid-career psychiatrists.

OBJECTIVE: Practice settings for American psychiatrists were examined for recent trends. METHODS: Surveys were conducted in 1996 (N=970) and 2002 (N=917) among members of the American Psychiatric Association. RESULTS: Between 1996 and 2002 the percentage of direct patient care hours in publicly funded settings increased from 40 to 50 percent for early-career psychiatrists and from 29 to 44 percent for mid-career psychiatrists. By 2002 the percentage of direct patient care hours was higher in publicly funded settings than in solo office practices for early-career psychiatrists (50 percent versus 17 percent) and mid-career psychiatrists (44 percent versus 29 percent). CONCLUSIONS: The popular image of the psychiatrist sitting in a private office does not conform with current survey data, which show that psychiatric practice is increasingly taking place in publicly funded settings. Because it extends to mid-career psychiatrists, the shift from private office practice to publicly funded settings is not just a manifestation of early-career psychiatrists' earning a salary while building up their private practices but is a more enduring change in the landscape of psychiatric practice. The authors discuss the implications of these findings with regard to professional identity and training of psychiatrists.

Medical symptoms associated with tobacco smoking with and without marijuana abuse among crack cocaine-dependent patients.

Despite the widespread use of tobacco and marijuana by cocaine abusers, it remains unclear whether combined tobacco and marijuana smoking is more harmful than tobacco smoking alone in cocaine abusers. We investigated the differences in medical symptoms reported among 34 crack cocaine abusers who did not smoke tobacco or marijuana (C), 86 crack cocaine abusers who also smoked tobacco (C + T), and 48 crack abusers who smoked both tobacco and marijuana (C + T + M). Medical symptoms were recorded using a 134-item self-report instrument (MILCOM), and drug use was assessed using the Addiction Severity Index (ASI). After controlling for clinical and demographic differences, the C + T + M group reported significantly more total symptoms on the MILCOM as well as on the respiratory, digestive, general, and nose/throat subscales than the C + T or C groups. The C + T group reported higher total and respiratory and nose/throat symptoms than the C group. HOwever, the C group had the highest number of mood symptoms among the three groups. The C + T and C + T + M groups were comparable in number of cigarettes smoked and ASI scores. Although tobacco smoking is associated with higher reports of medical problems in crack abusers, smoking both marijuana and tobacco seems to be associated with greater medical problems than smoking tobacco alone. Tobacco smoking was not related to changes in cocaine use. Also, marijuana smoking does not appear to be associated with a reduction in tobacco or cocaine use.

Differences in peripheral noradrenergic function among actively drinking and abstinent alcohol-dependent individuals.

We examined whether excessive alcohol consumption was related to changes in plasma levels of noradrenaline (NA) and whether these changes recover following abstinence. We also explored whether there were differences in NA levels between Type I and Type II alcoholics and controls during active drinking and abstinence. Plasma concentrations of NA were determined in (1) 27 Caucasian men with alcohol dependence who were regularly drinking (active drinkers) within 24 hours of hospitalization, (2) 29 Caucasian alcohol-dependent men who were in remission (abstinent for a minimum of three months), and (3) 28 race- and gender-matched healthy controls. NA concentrations were significantly higher in actively drinking alcohol-dependent subjects compared to those in remission and controls. While Type I and Type II alcoholic individuals differed across clinical measures, NA levels were similar in the two subtypes. Both subtypes showed an elevation in NA levels during active drinking compared to controls, but NA levels did not differ between the two subtypes and controls during remission. The findings indicate that chronic exposure to alcohol may lead to disturbances in NA activity that may manifest in early abstinence. However, the changes in NA activity appears to normalize after a longer period of abstinence. Alterations in NA activity do not seem to be specific for Type I or Type II subtypes of alcoholism.

Academic performance of psychiatrists compared to other specialists before, during, and after medical school.

OBJECTIVE: This study was designed to compare psychiatrists with other physicians on measures of academic performance before, during, and after medical school. METHOD: More than three decades of data for graduates of Jefferson Medical College (N=5,701) were analyzed. Those who pursued psychiatry were compared to physicians in seven other specialties on 18 performance measures. Analysis of covariance was used to control for gender effect. RESULTS: Compared to other physicians, psychiatrists scored higher on measures of verbal ability and general information before medical school and on evaluations of knowledge and skills in behavioral sciences during medical school, but they scored lower on United States Medical Licensing Examinations step 3. CONCLUSIONS: The results generally confirmed the authors' expectations about psychiatrists' academic performance. More attention should be paid to the general medical education of psychiatrists.

Pre-treatment measures of impulsivity, aggression and sensation seeking are associated with treatment outcome for African-American cocaine-dependent patients.

We investigated whether measures of impulsivity, aggression and sensation seeking differed between cocaine-dependent subjects and controls, and whether these measures were related to treatment-outcome for cocaine patients. Pre-treatment assessments of impulsivity (Barratt Impulsivity Scale [BIS]), aggression (Buss-Durkee Hostility Inventory [BDHI]) and sensation seeking (Zuckerman Sensation Seeking Scale [SSS]) were obtained for 141 African-American cocaine-dependent patients entering a 12-week, intensive outpatient treatment program and 60 controls. The outcome measures were number of negative urine drug screens, days in treatment, dropout rates and number of treatment sessions. Cocaine patients reported significantly higher scores on the SSS, the BIS and the BDHI than controls. Furthermore, the SSS scores showed a significantly negative correlation with days in treatment and negative urines, and a significant positive correlation with the dropout rate. The BIS and the BDHI scores were significantly associated with days in treatment and dropout rates respectively. A combination of the three variables contributed significantly toward predicting retention and abstinence. Higher levels of pretreatment impulsivity and aggression and sensation seeking seem to associated with poor treatment outcome for cocaine dependent patients receiving intensive outpatient treatment. Combining these behavioral measures with other clinical predictors may help in early identification of 'poor responders' who may benefit from additional or alternative treatment approaches.

Comparison of pretreatment characteristics and treatment outcomes for alcohol-, cocaine-, and multisubstance-dependent patients.

We investigated whether pretreatment characteristics and measures of outcome differed for alcohol-, cocaine-, and multisubstance-dependent patients receiving outpatient substance abuse treatment. One hundred and forty substance dependent individuals (32 alcohol, 76 cocaine, and 32 multisubstance) enrolled in a 12-week outpatient treatment program were compared across measures of addiction severity, personality, and treatment-readiness at admission. In-treatment, end-of-treatment and 9-month follow-up assessments of treatment outcome were then compared across the three groups. Outcome measures included reduction in problem severity, abstinence, retention, number of sessions attended, dropout, and counselor and patient ratings of treatment benefit. At admission, the multisubstance group had a higher proportion of positive urines, reported more severe drug, alcohol and psychiatric problems, and displayed higher impulsivity and anxiety scores than one or both of the other groups. However, multisubstance patients were more treatment ready in terms of adopting a total abstinence orientation than alcohol or cocaine patients. While a significant reduction in symptoms occurred for the total sample during treatment as well as at follow-up, comparisons of outcomes did not consistently favor any particular group. The three groups had equivalent improvements in eleven of fourteen during-treatment and five of seven follow-up measures. Despite pretreatment differences, in severity and treatment-readiness, outcomes were more similar than different for alcohol-, cocaine-, and multisubstance-dependent patients. Clinicians should be cautious about forecasting treatment-outcomes for addicted patients based on their primary substances of abuse.

Relationship between serotonin transporter gene polymorphisms and platelet serotonin transporter sites among African-American cocaine-dependent individuals and healthy volunteers.

Alterations in the serotonin transporter (5-HTT) have been implicated in a variety of psychiatric disorders including cocaine dependence. A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) appears to influence the expression of 5-HTT in human cell lines. We investigated whether 5-HTTLPR variants were related to differences in measures of platelet 5-HTT sites in cocaine-dependent patients and healthy volunteers (controls). Polymerase chain reaction-based genotyping of a 44 base pair insertion/deletion polymorphism in 5-HTTLPR was performed in 138 cocaine-dependent African-American subjects and 60 African-American controls. This yielded a short (S) and a long (L) allele. Platelet 5-HTT sites were measured using the tritiated paroxetine binding assay. Relationships of 5-HTTLPR genotypes with Bmax (density of serotonin transporter) and Kd (affinity constant) were examined. Bmax values were significantly lower in cocaine-dependent patients (640 +/- 233) than controls (906 +/- 225) (P < 0.001); however, 5-HTTLPR genotype distributions or allele frequencies did not differ between the two groups. There were no significant differences in Bmax between the three genotypes among cocaine-dependent patients (LL = 690 +/- 246, LS = 620 +/- 235, SS = 587 +/- 183; P = 0.14) or controls (LL = 909 +/- 233, LS = 938 +/- 279, SS = 866 +/- 143; P = 0.65). All three genotypes in cocaine-dependent patients showed comparable reductions in Bmax from the corresponding genotypes in controls. Demographic variables, severity of substance use or depression were unrelated to Bmax or 5-HTTLPR genotypes. Although platelet 5-HTT densities are reduced in patients with cocaine dependence compared with healthy volunteers, these genotypic variations in the serotonin transporter do not seem to influence levels of platelet 5-HTT in cocaine-dependent patients or healthy volunteers.

Relationship of serum prolactin with severity of drug use and treatment outcome in cocaine dependence.

RATIONALE: Alteration in serum prolactin (PRL) levels may reflect changes in central dopamine activity, which modulates the behavioral effects of cocaine. Therefore, serum PRL may have a potential role as a biological marker of drug severity and treatment outcome in cocaine dependence. OBJECTIVE: We investigated whether serum PRL levels differed between cocaine-dependent (CD) subjects and controls, and whether PRL levels were associated with severity of drug use and treatment outcome in CD subjects. METHODS: Basal PRL concentrations were assayed in 141 African-American (AA) CD patients attending an outpatient treatment program and 60 AA controls. Severity of drug use was assessed using the Addiction Severity Index (ASI). Measures of abstinence and retention during 12 weeks of treatment and at 6-month follow-up were employed as outcome variables. RESULTS: The basal PRL (ng/ml) in CD patients (9.28+/-4.13) was significantly higher than controls (7.33+/-2.94) (t=3.77, P<0.01). At baseline, PRL was positively correlated with ASI-drug (r=0.38, P<0.01), ASI-alcohol (r=0.19, P<0.05), and ASI-psychological (r=0.25, P<0.01) composite scores, and with the quantity of cocaine use (r=0.18, P<0.05). However, PRL levels were not significantly associated with number of negative urine screens, days in treatment, number of sessions attended, dropout rate or changes in ASI scores during treatment and at follow-up. Also, basal PRL did not significantly contribute toward the variance in predicting any of the outcome measures. CONCLUSION: Although cocaine use seems to influence PRL levels, it does not appear that PRL is a predictor of treatment outcome in cocaine dependence.