The 10 most-cited articles in American Journal of Psychiatry, 2016

OBJECTIVE: Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines. METHOD: A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus. RESULTS: Of 2,808 studies identified, 42 met inclusion criteria. Of these, 21 studies (50%) did not provide operationalized criteria. In the remaining studies, criteria varied considerably, particularly regarding symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies (5%) utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current…

Tremendous progress has been made in basic neuroscience in recent decades. One area that has been especially successful is research on how the brain detects and responds to threats. Such studies have demonstrated comparable patterns of brain-behavior relationships underlying threat processing across a range of mammalian species, including humans. This would seem to be an ideal body of information for advancing our understanding of disorders in which altered threat processing is a key factor, namely, fear and anxiety disorders. But research on threat processing has not led to significant improvements in clinical practice. The authors propose that in order to take advantage of this progress for clinical gain, a conceptual reframing is needed. Key to this conceptual change is recognition of a distinction between circuits underlying two classes of responses elicited by threats: 1) behavioral responses and accompanying physiological changes in the brain and body and 2) conscious feeling states reflected in self-reports of fear and anxiety. This distinction leads to a "two systems" view…

OBJECTIVE: Previous meta-analyses indicate that computerized cognitive training (CCT) is a safe and efficacious intervention for cognition in older adults. However, efficacy varies across populations and cognitive domains, and little is known about the efficacy of CCT in people with mild cognitive impairment or dementia. METHOD: The authors searched Medline, Embase, PsychINFO, CINAHL, and CENTRAL through July 1, 2016, for randomized controlled trials of CCT in older adults with mild cognitive impairment or dementia. Overall cognition, individual cognitive domains, psychosocial function, and activities of daily living were pooled separately for mild cognitive impairment and dementia trials. RESULTS: The overall effect on cognition in mild cognitive impairment across 17 trials was moderate (Hedges' g=0.35, 95% CI=0.20-0.51). There was no evidence of publication bias or difference between active- and passive-controlled trials. Small to moderate effects were found for global cognition, attention, working memory, learning, and memory, with the exception of nonverbal memory, and for…

OBJECTIVE: While suicide attempt history is considered to robustly predict completed suicide, previous studies have limited generalizability because of using convenience samples of specific methods/treatment settings, disregarding previous attempts, or overlooking first-attempt deaths. Eliminating these biases should more accurately estimate suicide prevalence in attempters. METHOD: This observational retrospective-prospective cohort study using the Rochester Epidemiology Project identified 1,490 (males, N=555; females, N=935) Olmsted County residents making index suicide attempts (first lifetime attempts reaching medical attention) between January 1, 1986, and December 31, 2007. The National Death Index identified suicides between enrollment and December 31, 2010 (follow-up 3-25 years). Medical records were queried for sex, age, method, and follow-up care for index attempt survivors. Coroner records yielded data on index attempt deaths. RESULTS: During the study period, 81/1,490 enrollees (5.4%) died by suicide. Of the 81, 48 (59.3%) perished on index attempt; 27 of the surviving…

The quality of fetal growth and development predicts the risk for a range of noncommunicable, chronic illnesses. These observations form the basis of the "developmental origins of health and disease" hypothesis, which suggests that the intrauterine signals that compromise fetal growth also act to "program" tissue differentiation in a manner that predisposes to later illness. Fetal growth also predicts the risk for later psychopathology. These findings parallel studies showing that antenatal maternal emotional well-being likewise predicts the risk for later psychopathology. Taken together, these findings form the basis for integrative models of fetal neurodevelopment, which propose that antenatal maternal adversity operates through the biological pathways associated with fetal growth to program neurodevelopment. The authors review the literature and find little support for such integrated models. Maternal anxiety, depression, and stress all influence neurodevelopment but show modest, weak, or no associations with known stress mediators (e.g., glucocorticoids) or with fetal growth.…

OBJECTIVE: Attitudes toward marijuana are changing, the prevalence of DSM-IV cannabis use disorder has increased, and DSM-5 modified the cannabis use disorder criteria. Therefore, updated information is needed on the prevalence, demographic characteristics, psychiatric comorbidity, disability, and treatment for DSM-5 cannabis use disorder. METHOD: In 2012-2013, 36,309 participants ≥18 years old were interviewed in the National Epidemiologic Survey on Alcohol and Related Conditions-III. Psychiatric and substance use disorders were assessed with the Alcohol Use Disorders and Associated Disabilities Interview Schedule-5. RESULTS: The prevalences of 12-month and lifetime cannabis use disorder were 2.5% and 6.3%. Among those with 12-month and lifetime diagnoses, the mean days of marijuana use per year were 225.3 (SE=5.7) and 274.2 (SE=3.8). The odds of 12-month and lifetime cannabis use disorder were higher for men, Native Americans, unmarried individuals, those with low incomes, and young adults (e.g., among those age 18-24 years versus ≥45: odds ratio for 12-month disorder, 7.2; 95%…

OBJECTIVE: Approximately 20%-35% of individuals 12-35 years old who meet criteria for a prodromal risk syndrome convert to psychosis within 2 years. However, this estimate ignores the fact that clinical high-risk cases vary considerably in risk. The authors sought to create a risk calculator, based on profiles of risk indicators, that can ascertain the probability of conversion to psychosis in individual patients. METHOD: The study subjects were 596 clinical high-risk participants from the second phase of the North American Prodrome Longitudinal Study who were followed up to the time of conversion to psychosis or last contact (up to 2 years). The predictors examined were limited to those that are supported by previous studies and are readily obtainable in general clinical settings. Time-to-event regression was used to build a multivariate model predicting conversion, with internal validation using 1,000 bootstrap resamples. RESULTS: The 2-year probability of conversion to psychosis was 16%. Higher levels of unusual thought content and suspiciousness, greater decline in social…

OBJECTIVE: Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression. METHOD: In a multicenter, double-blind study, adults (ages 18-64 years) with treatment-resistant depression were randomized to receive either intravenous ketamine (0.5 mg/kg of body weight) or intravenous placebo, administered over 40 minutes, either two or three times weekly, for up to 4 weeks. Patients who discontinued double-blind treatment after at least 2 weeks for lack of efficacy could enter an optional 2-week open-label phase to receive ketamine with the same frequency as in the double-blind phase. The primary outcome measure was change from baseline to day 15 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: In total, 67 (45 women) of 68 randomized patients received treatment.…

Author(s): Reus, Victor I; Fochtmann, Laura J; Eyler, A Evan; Hilty, Donald M; Horvitz-Lennon, Marcela; Jibson, Michael D; Lopez, Oscar L; Mahoney, Jane; Pasic, Jagoda; Tan, Zaldy S; Wills, Cheryl D; Rhoads, Richard; Yager, Joel

OBJECTIVE: There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted. METHOD: A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, a random-effects model analyzed the standard mean difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed. RESULTS: Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D, with positive isolated studies for creatine,…