Some antidepressant agents generate differential benefit based on gender. Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined. This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration. A total of 52 male and female outpatients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind, randomized, placebo-controlled, crossover clinical trial involving seven i.v. infusions of placebo or scopolamine (4 mg/kg). Following a single-blind placebo lead-in, participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence. Each block included three sessions. Clinical ratings were acquired before each infusion and included the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). A treatment group  block interaction (F ¼ 21.0, po0.001) was observed in MADRS scores across gender, and the reduction was significant by the evaluation following the first scopolamine administration (F ¼ 8.4, p ¼ 0.006). The treatment group  block interaction was also significant in males (F ¼ 3.8, p ¼ 0.043) and females (F ¼ 35.6, po0.001) separately. A block  gender interaction (F ¼ 7.4, p ¼ 0.009) indicated that the response magnitude was larger in women. The treatment  block interaction was significant for the HAM-A across gender (F ¼ 12.0, po0.001), and was significant for females (F ¼ 24.9, po0.001) but not for males (F ¼ 1.3, p ¼ 0.30). When comparing the baseline block to study end, the block  gender interaction (F ¼ 12.6, p ¼ 0.001) showed that the antianxiety response was greater in women. Men and women show a rapid antidepressant response following scopolamine, but the magnitude of response is larger in women than in men.

The need for improved treatment options for patients with major depressive disorder (MDD) is critical. Faster-acting antidepressants and biomarkers that predict clinical response will facilitate treatment. Scopolamine produces rapid antidepressant effects and thus offers the opportunity to characterize potential biomarkers of treatment response within short periods.Objective: To determine if baseline brain activity when processing emotional information can predict treatment response to scopolamine in MDD.Design: A double-blind, placebo-controlled, crossover study together with repeated functional magnetic resonance imaging, acquired as participants performed faceidentity and face-emotion working memory tasks.

Adults with substance use disorders (SUDs) report a high prevalence of childhood abuse. Research in the general population suggests specific types of abuse lead to particular negative outcomes; it is not known whether this pattern holds for adults with SUDs. We hypothesized that specific types of abuse would be associated with particular behavioral and emotional outcomes among substance users. That is, childhood sexual abuse would be associated with risky sex behaviors, childhood physical abuse with aggression, and childhood emotional abuse with emotion dysregulation. 280 inpatients (M age = 43.3; 69.7% male; 88.4% African American) in substance use treatment completed the Childhood Trauma Questionnaire (CTQ), HIV Risk-Taking Behavior Scale, Addiction Severity Index, Difficulties with Emotion Regulation Scale (DERS), Distress Tolerance Scale (DTS), and Affect Intensity and Dimensions of Affiliation Motivation (AIM). Consistent with our hypotheses, the CTQ Sexual Abuse subscale uniquely predicted exchanging sex for cocaine and heroin, number of arrests for prostitution, engaging in unprotected sex with a casual partner during the prior year, and experiencing low sexual arousal when sober. The Physical Abuse subscale uniquely predicted number of arrests for assault and weapons offenses. The Emotional Abuse subscale uniquely predicted the DERS total score, AIM score, and DTS score. Among substance users, different types of abuse are uniquely associated with specific negative effects. Assessment of specific abuse types among substances users may be informative in treatment planning and relapse prevention.

Background Adults with substance use disorders (SUDs) report higher rates of child abuse than adults without SUDs. Prior work suggests this abuse is associated with higher rates of psychosis, posttraumatic stress disorder, physical health problems, alcohol dependence, and cannabis dependence among substance users. Little is known about other problems associated with child abuse experienced by substance users. We hypothesized among adults with SUDs, child abuse would be associated with elevated rates of all Diagnostic and Statistical Manual (DSM-IV-TR) psychiatric disorders, substance dependencies, and comorbidities assessed. Method We assessed 280 inpatients in substance use treatment with the Structured Clinical Interview for the DSM-IV-TR, the Diagnostic Instrument for Personality Disorders, and Childhood Trauma Questionnaire (CTQ). We used chi-square and regression analyses to establish whether rates of psychiatric disorders, substance dependencies, and comorbidities differed as a function of child abuse. Results Consistent with our hypotheses, higher scores on the CTQ were associated with elevated rates of psychiatric disorders (mood disorders, anxiety disorders, psychotic symptoms, and personality disorders) and substance dependencies (alcohol dependence and cocaine dependence). Moreover, higher rates of all comorbidity patterns (e.g. comorbid alcohol dependence and anxiety) were observed among individuals who reported experiencing child abuse. Across all substance dependencies examined, individuals who had been abused had significantly higher rates of all psychiatric disorders assessed. Conclusions Individuals with substance use disorders who have been abused have particularly elevated rates of psychiatric and substance use disorders as a function of their abuse experiences. These findings have important treatment implications for individuals in residential substance use treatment settings.

Identifying predictors of antidepressant response will facilitate the successful treatment of patients suffering from depression. Scopolamine produces robust antidepressant responses in unipolar and bipolar depression. Here we evaluate the potential for baseline self-ratings to predict treatment response to scopolamine. Fifty-one unipolar and bipolar patients participated in a double-blind, placebo-controlled crossover trial. Following a single-blind placebo session, participants randomly received P/S or S/P (P=3 placebo; S=3 scopolamine (4ug/kg) sessions). Mood-state self-ratings (POMS and VAS) and depression severity (MADRS) were obtained before each infusion. Day 1 (baseline/placebo) self-ratings were used in a discriminant function analysis to identify linear combinations of individual items that predict response. The discriminant analysis separated responders from non-responders in both the unipolar (Chi-square=22.6, p=0.002) and bipolar (Chi-square=11.2, p=0.025) diagnostic subgroups. The discriminant functions accurately classified over 85% of patients as responders/non-responders. The POMS depression subscale correlated with clinical response (r=-.47; p<0.001), as did the VAS restlessness (r=-.49; p<0.001), sad (r=-.49, p<0.0001) and irritated (r=-.40, p=0.004) scales. These results indicate that self-report mood-ratings obtained prior to treatment can predict response outcome to scopolamine, and suggest that a constellation of mood-state features may be related to clinical response.