Perspective: the evolution of hormones and person perception-a quantitative genetic framework.

Evolutionary biology provides a unifying theory for testing hypotheses about the relationship between hormones and person perception. Person perception usually receives attention from the perspective of sexual selection. However, because person perception is one trait in a suite regulated by hormones, univariate approaches are insufficient. In this Perspectives article, quantitative genetics is presented as an important but underutilized framework for testing evolutionary hypotheses within this literature. We note tacit assumptions within the current literature on psychiatric genetics, which imperil the interpretation of findings thus far. As regulators of a diverse manifold of traits, hormones mediate tradeoffs among an array of functions. Hormonal pleiotropy also provides the basis of correlational selection, a process whereby selection on one trait in a hormone-mediated suite generates selection on the others. This architecture provides the basis for conflicts between sexual and natural selection within hormone-mediated suites. Due to its role in person perception, psychiatric disorders, and reproductive physiology, the sex hormone estrogen is highlighted as an exemplar here. The implications of this framework for the evolution of person perception are discussed. Empirical quantification of selection on traits within hormone-mediated suites remains an important gap in this literature with great potential to illuminate the fundamental nature of psychiatric disorders.

Race, History of Abuse, and Homelessness Are Associated With Forced Medication Administration During Psychiatric Inpatient Care.

OBJECTIVE: Although previous research has suggested that racial disparities exist in the administration of forced medication (FM) in psychiatric inpatients, data remain scarce regarding other contributing variables. Therefore, this study examined sociodemographic and clinical variables associated with FM administration in psychiatric inpatients. METHODS: Electronic medical records from 57,615 patients admitted to an academic psychiatric hospital between 2010 and 2018 were reviewed to identify patients who received FM. These records indicated that FM petitions were requested and approved for ∼6200 patients. Patients were excluded from the analysis if they met the following exclusion criteria: under 18 years of age, presence of intellectual/developmental disability, dementia, or other neurological condition, or primary diagnosis of a nonpsychiatric medical condition or a substance-induced mood or psychotic disorder. After data on those patients were excluded, the final sample included records from 2569 patients (4.5% of the total records) in which the administration of FM was petitioned for and approved. The FM group was compared with a control group of 2569 patients matched in terms of age, sex, and admission date (no-forced medication group; NFM) via propensity scoring matching. Group comparisons (FM vs. NFM group) examined sociodemographic factors (race, age, sex, living situation), clinical features (diagnosis, substance abuse, history of abuse), and outcomes (length of stay, readmission rate). Regression analyses examined the association between FM and sociodemographic, clinical, and outcome variables. RESULTS: Compared with the NFM group, the FM group contained significantly more African Americans (P<0.001), homeless individuals (P<0.001), and individuals with histories of abuse (P<0.001). Having received FM was a significant predictor of a longer length of stay (P<0.001) and higher readmission rates (P<0.001). DISCUSSION: These results suggest that FM is more likely to be instituted in psychiatric inpatients who are of a minority race (African American), are in a homeless living situation, and/or have a history of abuse. Moreover, FM may be associated with poorer clinical outcomes at least as measured by the length of stay and higher readmission rates. We discuss possible reasons for these results and the importance of culturally competent and trauma-focused care.

Higher Prevalence of Metabolic Syndrome in Child-adolescent Patients with Bipolar Disorder.

OBJECTIVE: Previous studies have indicated a convergent and bidirectional relationship between metabolic syndrome (MetS) and bipolar disorder (BD). As most of these studies focused mainly on adults diagnosed with BD, our study aims to investigate and characterize metabolic disturbances in child-adolescents diagnosed with BD. METHODS: We retrospectively examined the medical records of psychiatric hospitalizations with admitting diagnosis of BD in child-adolescents (age ＜ 18 years). Body mass index (BMI), lipid profile, fasting blood glucose, and blood pressure were primary variables. National Cholesterol Education Program criteria were used to define MetS. Reference group data was obtained from the National Health and Nutrition Examination Survey study. Statistical analyses included t tests, chi-square tests, and Fisher's exact tests. RESULTS: We identified 140 child-adolescent patients with BD (mean age = 15.12 ± 1.70 years, 53% male). MetS was significantly more common in BD compared to the reference group: 14% (95% confidence interval [95% CI] 8-20) vs. 6.7% (95% CI 4.1-9.2), p = 0.001 with no significant difference by sex. MetS components were higher in the BD group, particularly BMI ≥ 95% (25% vs. 11.8%, p ＜ 0.001) and high blood pressure (17% vs. 8%, p = 0.05). Moreover, female patients had lower odds of high blood pressure (odds ratio = 0.24 [95% CI 0.08-0.69], p = 0.005). CONCLUSION: Compared with the general child-adolescent population, the prevalence of MetS was significantly higher in patients with BD of same age. This reiterates the notion of an increased risk of MetS in patients diagnosed with BD; and thus, further exploration is warranted.

An Unusual Case of Acute Psychosis With Obsessive-Compulsive Features Following Arsenic Poisoning.

Arsenic exposure, particularly the chronic type, can lead to poisoning with manifestations presenting in multiple organ systems. However, acute psychosis is not a commonly described manifestation of arsenic exposure. In this report, we present the case of a patient who developed acute psychosis with hallucinations, disorganized thinking, and obsessive-compulsive symptoms following chronic occupational arsenic exposure. The patient was treated with the combination of an antipsychotic and an antidepressant and he responded well with significant improvement in both the acute psychosis and obsessive-compulsive symptoms. The authors concluded that patients can develop atypical symptoms, including acute psychosis, following arsenic poisoning. In the case described in this report, the patient also presented with a new onset of obsessive-compulsive symptoms. Given this rare manifestation of arsenic poisoning for which there is no clearly defined treatment regimen, this case suggests that the use of a combination of an antipsychotic and an antidepressant may be considered in the rare event of psychosis with obsessive-compulsive features following arsenic poisoning.

Early-Life Trauma in Hospitalized Patients With Mood Disorders and Its Association With Clinical Outcomes.

BACKGROUND: The prevalence of childhood trauma and its impact on clinical outcomes in hospitalized patients with mood disorders is unknown. We studied the frequency of childhood trauma among inpatient adults with mood disorders and its association with clinical outcomes. METHODS: Patients admitted to our hospital with a primary diagnosis of mood disorders completed the short form of the Early Trauma Inventory-Self-Report (ETISR-SF), the Sheehan Disability Scale, and the Clinician-Rated Dimensions of Psychosis Symptom Severity scale. A regression model adjusted for multiple comparisons was used to examine the association between scores on the ETISR-SF and clinical outcomes. RESULTS: Subjects were 167 patients, all of whom reported ≥1 types of childhood trauma: 90% general trauma, 75% physical abuse, 71% emotional abuse, 50% sexual abuse, and 35% all 4 types of abuse. The subtypes of abuse did not differ by sex or race. Diagnoses in the sample were bipolar disorder 56%, major depressive disorder 24%, schizoaffective disorder 14%, and substance-induced mood disorder 5%. The mean age in the sample was 35±11.5 years, 53% were male, and 64% also had substance abuse disorders. Higher scores on the ETISR-SF were associated with longer hospital stays [odds ratio (OR)=1.13; 95% confidence interval (CI), 1.05-1.22], and greater disruption of work/school life (OR=1.12; 95% CI, 1.04-1.21). There was also a trend for higher ETISR-SF scores to be associated with more severe psychotic symptoms (OR=1.13; 95% CI, 1.01-1.27) and more disruption in social (OR=1.14; 95% CI, 1.06-1.22) and family life (OR=1.09; 95% CI, 1.02-1.17). CONCLUSION: Childhood trauma was reported by all of the 167 patients, with general trauma the most common and approximately half reporting sexual abuse. Childhood trauma was associated with poor clinical outcomes. Early recognition of trauma and trauma-related therapeutic interventions may improve outcomes.

Atomoxetine treatment of attention-deficit/hyperactivity disorder in young adults with assessment of functional outcomes: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with significant impairment in multiple functional domains. This trial evaluated efficacy in ADHD symptoms and functional outcomes in young adults treated with atomoxetine. METHODS: Young adults (18-30 years old) with ADHD were randomized to 12 weeks of double-blind treatment with atomoxetine (n = 220) or placebo (n = 225). The primary efficacy measure of ADHD symptom change was Conners' Adult ADHD Rating Scale (CAARS): Investigator-Rated: Screening Version Total ADHD Symptoms score with adult prompts. Secondary outcomes scales included the Adult ADHD Quality of Life-29, Clinical Global Impression-ADHD-Severity, Patient Global Impression-Improvement, CAARS Self-Report, Behavior Rating Inventory of Executive Function-Adult Version Self-Report, and assessments of depression, anxiety, sleepiness, driving behaviors, social adaptation, and substance use. RESULTS: Atomoxetine was superior to placebo on CAARS: Investigator-Rated: Screening Version (atomoxetine [least-squares mean ± SE, -13.6 ± 0.8] vs placebo [-9.3 ± 0.8], 95% confidence interval [-6.35 to -2.37], P < 0.001), Clinical Global Impression-ADHD-Severity (atomoxetine [-1.1 ± 0.1] vs placebo [-0.7 ± 0.1], 95% confidence interval [-0.63 to -0.24], P < 0.001), and CAARS Self-Report (atomoxetine [-11.9 ± 0.8] vs placebo [-7.8 ± 0.7], 95% confidence interval [-5.94 to -2.15], P < 0.001) but not on Patient Global Impression-Improvement. In addition, atomoxetine was superior to placebo on Adult ADHD Quality of Life-29 and Behavior Rating Inventory of Executive Function-Adult Version Self-Report. Additional assessments failed to detect significant differences (P ≥ 0.05) between atomoxetine and placebo. The adverse event profile was similar to that observed in other atomoxetine studies. Nausea, decreased appetite, insomnia, dry mouth, irritability, dizziness, and dyspepsia were reported significantly more often with atomoxetine than with placebo. CONCLUSIONS: Atomoxetine reduced ADHD symptoms and improved quality of life and executive functioning deficits in young adults compared with placebo. Atomoxetine was also generally well tolerated.

Duloxetine versus escitalopram and placebo: an 8-month, double-blind trial in patients with major depressive disorder.

BACKGROUND: Duloxetine and escitalopram were compared in an 8-month, randomized, double-blind, placebo-controlled trial in adult outpatients meeting DSM-IV criteria for major depressive disorder (MDD). The results regarding the primary objective of the study (onset of antidepressant action) have been previously published. The current paper focuses on the longer-term (8-month) comparisons of efficacy and safety between duloxetine and escitalopram. RESEARCH DESIGN AND METHODS: Upon completion of the 8-week, fixed-dose, placebo-controlled, acute-treatment phase (duloxetine 60 mg/day (n = 273), escitalopram 10 mg/day (n = 274), placebo (n = 137)), patients remaining in the duloxetine (n = 188) and escitalopram (n = 208) groups were eligible for double-blind dose increases (duloxetine to 120 mg/day, escitalopram to 20 mg/day), and placebo non-responders were eligible for double-blind rescue to active drug. MAIN OUTCOME MEASURES: Efficacy was primarily assessed using the HAMD(17). Safety/tolerability assessments included spontaneously reported adverse events (AEs), overall rates and reasons for discontinuation, laboratory analyses, and vital signs. RESULTS: Both drugs demonstrated similar remission rates over the course of the study, with the probability of remission reaching 70% (duloxetine) and 75% (escitalopram) at 8 months (p = 0.44). Similar improvement was observed for both duloxetine and escitalopram on efficacy measures with the exception of the sleep subscale of the HAMD(17), wherein escitalopram had a statistically significant advantage over duloxetine in improving sleep. Over the entire 8-month study, discontinuation rates differed significantly for duloxetine (62%) compared with escitalopram (55%; p = 0.02). Rates of discontinuation due to AEs did not differ significantly between duloxetine (12.8%), escitalopram (12.0%), and placebo (10.2%) (p > 0.05 all pairwise comparisons). AEs associated with duloxetine tended to emerge early in treatment (e.g., nausea, dry mouth), whereas AEs associated with escitalopram tended to emerge later in treatment (e.g., diarrhea, weight increase). The incidence of sustained hypertension was similar between drugs (1.5 vs. 1.1% patients for duloxetine and escitalopram, respectively). Statistically significant drug differences were identified in the mean changes from baseline to study endpoint for pulse (+3.05 beats per minute (bpm), duloxetine; -0.89 bpm, escitalopram; p < 0.001) and systolic blood pressure (+3.73 mmHg, duloxetine; +0.31 mmHg, escitalopram; p < 0.05), but not diastolic blood pressure (+0.81 mmHg, duloxetine; -0.24 mmHg, escitalopram; p = 0.27). At 8 months, mean change in weight was significantly higher for escitalopram compared with duloxetine (+0.61 kg, duloxetine; +1.83 kg, escitalopram; p < 0.05), however, the incidence of treatment-emergent abnormal weight gain (> or = 7% increase in weight from baseline) was similar between drugs and was significantly greater for both duloxetine and escitalopram compared with placebo. LIMITATIONS: Because so few patients on placebo (n = 15), in comparison to duloxetine (n = 104) or escitalopram (n = 123), completed the entire 8-month study, the power to detect a difference between the active treatments and placebo after 8 weeks was significantly decreased and very likely insufficient. CONCLUSION: Throughout the 8-month study, similar improvement was observed for both duloxetine and escitalopram on most efficacy measures with the exception of the sleep subscale of the HAMD(17). Drug differences were identified in safety/tolerability measures.

Aripiprazole for the prevention of relapse in stabilized patients with chronic schizophrenia: a placebo-controlled 26-week study.

BACKGROUND: Aripiprazole is a novel antipsychotic for the management of schizophrenia. This study investigated the efficacy, safety, and tolerability of aripiprazole in preventing relapse in adult chronic schizophrenia patients experiencing ongoing stable symptomatology. METHOD: In this 26-week, randomized, double-blind, placebo-controlled, parallel-group, multi-center study, 310 patients with DSM-IV schizophrenia (mean Positive and Negative Syndrome Scale [PANSS] total score = 82) were randomly assigned to receive a once-daily fixed dose of aripiprazole, 15 mg, or placebo. The primary outcome measure was time to relapse following randomization. Secondary objectives were to assess the efficacy, safety, and tolerability of aripiprazole, 15 mg, compared with placebo, in the study population. The study was conducted between Dec. 21, 2000, and Aug. 20, 2001. RESULTS: The time to relapse following randomization was significantly (p < .001) longer for aripiprazole compared with placebo. More patients relapsed with placebo (N = 85; 57%) than aripiprazole (N = 50; 34%); the relative risk of relapse for the aripiprazole group was 0.59 (p < .001). Aripiprazole was significantly superior to placebo from baseline to endpoint in PANSS total, PANSS positive, PANSS-derived Brief Psychiatric Rating Scale, and Clinical Global Impressions-Severity of Illness scale (CGI-S) scores and demonstrated significantly better mean Clinical Global Impressions-Global Improvement scale scores (p < or = .01 for all comparisons except CGI-S: .01 < p < or = .05). Aripiprazole was well tolerated, with no evidence of marked sedation and no evidence of hyperprolactinemia or prolonged heart rate-corrected QT interval (QTc). Extrapyramidal symptoms were comparable in the aripiprazole and placebo groups. Modest mean weight loss at endpoint was evident in both groups. CONCLUSION: Aripiprazole, 15 mg once daily, is an effective, well-tolerated treatment for prevention of relapse in patients with chronic, stable schizophrenia.

Anxiety disorders in women.

Women have higher overall prevalence rates for anxiety disorders than men. Women are also much more likely than men to meet lifetime criteria for each of the specific anxiety disorders: generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), simple phobia, panic disorder, and agoraphobia. Considerable evidence suggests that anxiety disorders remain underrecognized and undertreated despite their association with increased morbidity and severe functional impairment. Increasing evidence suggests that the onset, presentation, clinical course, and treatment response of anxiety disorders in women are often distinct from that associated with men. In addition, female reproductive hormone cycle events appear to have a significant influence on anxiety disorder onset, course, and risk of comorbid conditions throughout a woman's life. Further investigations concerning the unique features present in women with anxiety disorders are needed and may represent the best strategy to increase identification and optimize treatment interventions for women afflicted with these long-neglected psychiatric disorders.