Context Although the prevalence of depression among medical interns substantially exceeds that of the general population, the specific factors responsible are not well understood. Recent reports of a moderating effect of a genetic polymorphism (5-HTTLPR) in the serotonin transporter protein gene on the likelihood that life stress will precipitate depression may help to understand the development of mood symptoms in medical interns. Objective To identify psychological, demographic and residency program factors that associate with depression among interns and use medical internship as a model to study the moderating effects of this polymorphism using a prospective, within-subject design that addresses the design limitations of earlier studies. Design Prospective cohort study Setting 13 United States hospitals Participants 740 interns entering participating residency programs Main outcome measures Subjects were assessed for depressive symptoms using the Patient Health Questionnaire (PHQ-9), a series of psychological traits and 5-HTTLPR genotype prior to internship and then assessed for depressive symptoms and potential stressors at 3-month intervals during internship. Results The PHQ-9 depression score increased from 2.4 prior to internship to a mean of 6.4 during internship (p<0.001). The proportion of participants who met PHQ-9 criteria for depression increased from 3.9% prior to internship to a mean of 25.7% during internship (p<0.001). A series of factors measured prior to internship (female sex, U.S. medical education, difficult early family environment, history of major depression, lower baseline depressive symptom score and higher neuroticism) and during internship (increased work hours, perceived medical errors and stressful life events) were associated with a greater increase in depressive symptoms during internship. In addition, subjects with at least one copy of a less transcribed 5-HTTLPR allele reported a greater increase in depressive symptoms under the stress of internship (p=0.002). Conclusions There is a marked increase in depressive symptoms during medical internship. Specific individual, internship and genetic factors are associated with the increase in depressive symptoms.

ehaviors related to self-regulation, such as substance use disorders or antisocial behaviors, have far-reaching consequences for affected individuals, their families, communities and society at large 1,2 . Collectively, this group of correlated traits are classified as externalizing 3 . Twin studies have demonstrated that externalizing liability is highly heritable (~80%) 4,5 . To date, however, no large-scale molecular genetic studies have utilized the extensive degree of genetic overlap among externalizing traits to aid gene discovery, as most studies have focused on individual disorders 6 . For many high-cost, high-risk behaviors with an externalizing component-opioid use disorder and suicide attempts 7 being salient examples-there are limited genotyped cases available for gene discovery 8,9 .A complementary strategy to the single-disease approach is to study the shared genetic architecture across traits in multivariate analyses, which boosts statistical power by pooling data across

We examined the prevalence and course of psychiatric and substance dependence (SD) disorders in subjects with SD and attention deficit hyperactivity disorder (ADHD).Method-We interviewed 1,761 adults with a lifetime diagnosis of cocaine and/or opioid dependence using the Semi-Structured Assessment for Drug Dependence and Alcoholism. Generalized linear regression with generalized estimating equation analysis was used to examine the associations between a lifetime diagnosis of ADHD and indicators of clinical course, and to identify unique correlates of ADHD.Results-Lifetime ADHD prevalence in the SD sample was 5.22% (vs. 0.85% in a group of individuals without SD). ADHD was associated with an earlier age of first substance use, more SD and psychiatric diagnoses, a greater likelihood of attempted suicide, and more hospitalizations. After controlling for conduct disorder and bipolar type I disorder, there were unique effects of ADHD on age of first substance use and number of SD diagnoses.Conclusion-In subjects with cocaine or opioid dependence, ADHD is associated with greater SD and psychiatric comorbidity and a more severe course of illness.

Aims Adverse childhood events (ACEs) are associated with negative health outcomes. We examined ACEs as risk factors for substance dependence (SD) and the mediating effects of mood and anxiety disorders on the relations between ACEs and SD risk. Design We compared early life experiences in 2,061 individuals with a lifetime diagnosis of alcohol, cocaine, or opioid dependence and 449 controls. Measurements Diagnostic and ACE data were obtained using the Semi-Structured Assessment for Drug Dependence and Alcoholism. Findings Childhood abuse or exposure to violent crime was positively related to the number of lifetime mood and anxiety disorders and to SD risk. Mood and anxiety disorders had their first onset a mean of nearly 3 years before the first SD diagnosis and mediated the effect of ACEs on SD risk. Conclusion ACEs appear to contribute additively to the risk of SD, with mood and anxiety disorders in the causal path for a portion of this risk. The identification and effective treatment of mood and anxiety disorders associated with ACEs could reduce the risk of developing SD.

The Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) yields reliable DSM-IV diagnoses for a variety of psychiatric disorders, including alcohol and drug dependence. This study examines the reliability of individual DSM-IV criteria for lifetime substance dependence diagnoses and the impact of those criteria on diagnostic reliability.Methods-Two hundred ninety-three subjects (52.2% women; 38.2% African American, 46.8% European American, 7.5% Hispanic) were interviewed twice over a two-week period to examine the inter-rater reliability (n = 173) or test-retest reliability (n = 120) of the SSADDA. Cohen's κ statistic and its confidence interval were used to assess the reliability of individual diagnostic criteria.Results-Overall, the inter-rater reliability estimates were excellent for individual DSM-IV criteria for nicotine and opioid dependence; good for alcohol and cocaine dependence, and fair for dependence on cannabis, sedatives and stimulants. The impact of any individual criterion on diagnostic reliability was minimal, consistent with the notion that the DSM-IV diagnosis of substance dependence measures an underlying construct that is relatively consistent across specific groups of substances.Conclusions-These results, combined with results from a study of the SSADDA's diagnostic reliability (Pierucci-Lagha et al., 2005), show that the instrument can be used reliably to assess substance dependence.

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The diagnosis of Graves' disease in pregnancy can be complex because of normal gravid physiologic changes in thyroid hormone metabolism. Mothers with active Graves' disease should be treated with antithyroid drugs, which impact both maternal and fetal thyroid function. Optimally, the lowest possible dose should be used to maintain maternal free thyroxine levels at or just above the upper limit of the normal nonpregnant reference range. Fetal thyroid function depends on the balance between the transplacental passage of thyroid-stimulating maternal antibodies and thyroid-inhibiting antithyroid drugs. Elevated levels of serum maternal anti-TSH-receptor antibodies early in the third trimester are a risk factor for fetal hyperthyroidism and should prompt evaluation of the fetal thyroid by ultrasound, even in women with previously ablated Graves' disease. Maternal antithyroid medication can be modulated to treat fetal hyperthyroidism. Serum TSH and either total or free thyroxine levels should be measured in fetal cord blood at delivery in women with active Graves' disease, and those with a history of (131)I-mediated thyroid ablation or thyroidectomy who have anti-TSH-receptor antibodies. Neonatal thyrotoxicosis can occur in the first few days of life after clearance of maternal antithyroid drug, and can last for several months, until maternal antibodies are also cleared.

Objective: A low level of response (LR) to alcohol as measured through alcohol challenges is an early-appearing, genetically influenced characteristic that predicts the risk of heavier drinking and alcohol problems. A less expensive and more easily used measure of LR, the retrospective Self-Rating of the Effects of Alcohol (SRE) questionnaire, also relates to alcohol intake and problems but has not been evaluated for its ability to predict alcohol-related problems 5 years later. Method: At Time 1, 95 18-to 35-year-old (mean age: 25.9 years) subjects who were offspring from families participating at the San Diego site of the Collaborative Study on the Genetics of Alcoholism (COGA) were administered the SRE and evaluated regarding alcohol, drug, and demographic characteristics using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview. Follow-up interviews (Time 2) using the SSAGA were completed an average (SD) of 5.4 (1.34) years later for approximately 80% of the original sample. Re-