Showing papers in "American Journal of Psychiatry in 2018"
La Salle University1, Universidade Federal do Rio Grande do Sul2, University of Western Sydney3, University of New South Wales4, Karolinska Institutet5, Rio de Janeiro State University6, Federal University of Rio de Janeiro7, Centre for Addiction and Mental Health8, King's College London9, South London and Maudsley NHS Foundation Trust10
TL;DR: In this paper, the prospective relationship between physical activity and incident depression was examined and potential moderators explored, and a prospective cohort study evaluating incident depression and physical activity was conducted. But the results were limited.
Abstract: Objective:The authors examined the prospective relationship between physical activity and incident depression and explored potential moderators.Method:Prospective cohort studies evaluating incident...
758 citations
TL;DR: The authors summarize the history of the unidimensional idea, review modern research into p, demystify statistical models, articulate some implications of p for prevention and clinical practice, and outline a transdiagnostic research agenda.
Abstract: In both child and adult psychiatry, empirical evidence has now accrued to suggest that a single dimension is able to measure a person’s liability to mental disorder, comorbidity among disorders, persistence of disorders over time, and severity of symptoms. This single dimension of general psychopathology has been termed “p,” because it conceptually parallels a dimension already familiar to behavioral scientists and clinicians: the “g” factor of general intelligence. As the g dimension reflects low to high mental ability, the p dimension represents low to high psychopathology severity, with thought disorder at the extreme. The dimension of p unites all disorders. It influences present/absent status on hundreds of psychiatric symptoms, which modern nosological systems typically aggregate into dozens of distinct diagnoses, which in turn aggregate into three overarching domains, namely, the externalizing, internalizing, and psychotic experience domains, which finally aggregate into one dimension of psychopath...
542 citations
TL;DR: The emerging findings suggest that the authors are entering a phase of accelerated genetic discovery for multiple psychiatric disorders, and these findings are likely to elucidate the genetic portions of these truly complex traits.
Abstract: The Psychiatric Genomics Consortium (PGC) is the largest consortium in the history of psychiatry. This global effort is dedicated to rapid progress and open science, and in the past decade it has delivered an increasing flow of new knowledge about the fundamental basis of common psychiatric disorders. The PGC has recently commenced a program of research designed to deliver “actionable” findings—genomic results that 1) reveal fundamental biology, 2) inform clinical practice, and 3) deliver new therapeutic targets. The central idea of the PGC is to convert the family history risk factor into biologically, clinically, and therapeutically meaningful insights. The emerging findings suggest that we are entering a phase of accelerated genetic discovery for multiple psychiatric disorders. These findings are likely to elucidate the genetic portions of these truly complex traits, and this knowledge can then be mined for its relevance for improved therapeutics and its impact on psychiatric practice within a precisio...
453 citations
TL;DR: In longitudinal studies, reduced striatal activation in fMRI and blunted FRN in EEG were found to precede the onset of depression in adolescents and have important implications for development of new treatments.
Abstract: Objective:A role for aberrant reward processing in the pathogenesis of depression has long been proposed. However, no review has yet examined its role in depression by integrating conceptual and qu...
305 citations
TL;DR: Preliminary findings indicate that intranasal esketamine compared with placebo, given in addition to comprehensive standard-of-care treatment, may result in significantly rapid improvement in depressive symptoms, including some measures of suicidal ideation, among depressed patients at imminent risk for suicide.
Abstract: Objective:The authors compared the efficacy of standard-of-care treatment plus intranasal esketamine or placebo for rapid reduction of symptoms of major depression, including suicidality, among ind...
300 citations
TL;DR: The findings suggest that ketamine's acute antidepressant effect requires opioid system activation, and the dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects ofketamine in adults with treatment-resistant depression.
Abstract: Objective:In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior ...
290 citations
TL;DR: Regular leisure-time exercise of any intensity provides protection against future depression but not anxiety, and relatively modest changes in population levels of exercise may have important public mental health benefits and prevent a substantial number of new cases of depression.
Abstract: Objective:The purpose of the present study was to address 1) whether exercise provides protection against new-onset depression and anxiety and 2) if so, the intensity and amount of exercise required to gain protection and, lastly, 3) the mechanisms that underlie any association.Method:A “healthy” cohort of 33,908 adults, selected on the basis of having no symptoms of common mental disorder or limiting physical health conditions, was prospectively followed for 11 years. Validated measures of exercise, depression, anxiety, and a range of potential confounding and mediating factors were collected.Results:Undertaking regular leisure-time exercise was associated with reduced incidence of future depression but not anxiety. The majority of this protective effect occurred at low levels of exercise and was observed regardless of intensity. After adjustment for confounders, the population attributable fraction suggests that, assuming the relationship is causal, 12% of future cases of depression could have been prev...
265 citations
TL;DR: A systematic and evidence-based study of the prevalence and distribution of dissociation, as assessed by the Dissociative Experiences Scale, within different categories of mental disorders, and it updates an earlier meta-analysis.
Abstract: Objective:Dissociation is a complex, ubiquitous construct in psychopathology. Symptoms of dissociation are present in a variety of mental disorders and have been connected to higher burden of illness and poorer treatment response, and not only in disorders with high levels of dissociation. This meta-analysis offers a systematic and evidence-based study of the prevalence and distribution of dissociation, as assessed by the Dissociative Experiences Scale, within different categories of mental disorders, and it updates an earlier meta-analysis.Method:More than 1,900 original publications were screened, and 216 were included in the meta-analysis, comprising 15,219 individuals in 19 diagnostic categories.Results:The largest mean dissociation scores were found in dissociative disorders (mean scores >35), followed by posttraumatic stress disorder, borderline personality disorder, and conversion disorder (mean scores >25). Somatic symptom disorder, substance-related and addictive disorders, feeding and eating dis...
235 citations
TL;DR: In this article, the authors developed and validated models using electronic health records to predict suicide attempt and suicide death following an outpatient visit, using logistic regression models predicting suicide attempts and death.
Abstract: Objective:The authors sought to develop and validate models using electronic health records to predict suicide attempt and suicide death following an outpatient visit.Method:Across seven health systems, 2,960,929 patients age 13 or older (mean age, 46 years; 62% female) made 10,275,853 specialty mental health visits and 9,685,206 primary care visits with mental health diagnoses between Jan. 1, 2009, and June 30, 2015. Health system records and state death certificate data identified suicide attempts (N=24,133) and suicide deaths (N=1,240) over 90 days following each visit. Potential predictors included 313 demographic and clinical characteristics extracted from records for up to 5 years before each visit: prior suicide attempts, mental health and substance use diagnoses, medical diagnoses, psychiatric medications dispensed, inpatient or emergency department care, and routinely administered depression questionnaires. Logistic regression models predicting suicide attempt and death were developed using penal...
233 citations
TL;DR: Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention.
Abstract: Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and "tantalizing beyond reach." (Am J Psychiatry 1925: 81: 643-662 ).
191 citations
TL;DR: Victor I. Reus, M.D., Laura J. Fochtmann,M.P.H., Jane Mahoney, Ph.D, and Seung-Hee Hong (Systematic Review) are the authors of this systematic review of the determinants of hippocampal dissection in mice.
Abstract: Victor I. Reus, M.D., Laura J. Fochtmann, M.D., M.B.I., Oscar Bukstein, M.D., M.P.H., A. Evan Eyler, M.D., M.P.H., Donald M. Hilty, M.D., Marcela Horvitz-Lennon, M.D., M.P.H., Jane Mahoney, Ph.D., R.N., PMHCNS-B.C., Jagoda Pasic, M.D., Ph.D., Michael Weaver, M.D., Cheryl D. Wills, M.D., Jack McIntyre, M.D. (Consultant), Jeremy Kidd, M.D. (Consultant), Joel Yager, M.D. (Systematic Review), Seung-Hee Hong (Systematic Review)
TL;DR: The authors propose a complementary approach that includes deconstructing neuropsychiatric outcomes of maternal immune activation into key pathophysiologically defined phenotypes that are identifiable in humans and animals and that evaluate the interspecies concordance regarding interactions between maternal immuneactivation and genetic and epigenetic factors, including processes involving intergenerational disease transmission.
Abstract: Epidemiologic studies, including prospective birth cohort investigations, have implicated maternal immune activation in the etiology of neuropsychiatric disorders. Maternal infectious pathogens and inflammation are plausible risk factors for these outcomes and have been associated with schizophrenia, autism spectrum disorder, and bipolar disorder. Concurrent with epidemiologic research are animal models of prenatal immune activation, which have documented behavioral, neurochemical, neuroanatomic, and neurophysiologic disruptions that mirror phenotypes observed in these neuropsychiatric disorders. Epidemiologic studies of maternal immune activation offer the advantage of directly evaluating human populations but are limited in their ability to uncover pathogenic mechanisms. Animal models, on the other hand, are limited in their generalizability to psychiatric disorders but have made significant strides toward discovering causal relationships and biological pathways between maternal immune activation and neuropsychiatric phenotypes. Incorporating these risk factors in reverse translational animal models of maternal immune activation has yielded a wealth of data supporting the predictive potential of epidemiologic studies. To further enhance the translatability between epidemiology and basic science, the authors propose a complementary approach that includes deconstructing neuropsychiatric outcomes of maternal immune activation into key pathophysiologically defined phenotypes that are identifiable in humans and animals and that evaluate the interspecies concordance regarding interactions between maternal immune activation and genetic and epigenetic factors, including processes involving intergenerational disease transmission. [AJP AT 175: Remembering Our Past As We Envision Our Future October 1857: The Pathology of Insanity J.C. Bucknill: "In the brain the state of inflammation itself either very quickly ceases or very soon causes death; but when it does cease it leaves behind it consequences which are frequently the causes of insanity, and the conditions of cerebral atrophy." (Am J Psychiatry 1857; 14:172-193 )].
TL;DR: Pre-reactivation propranolol, a treatment protocol suggested by reconsolidation theory, appears to be a novel and efficacious treatment for PTSD.
Abstract: Objective:The authors assessed the efficacy of trauma memory reactivation performed under the influence of propranolol, a noradrenergic beta-receptor blocker, as a putative reconsolidation blocker,...
TL;DR: Cannabis use appears to increase rather than decrease the risk of developing nonmedical prescription opioid use and opioid use disorder.
Abstract: Objective:The authors sought to determine whether cannabis use is associated with a change in the risk of incident nonmedical prescription opioid use and opioid use disorder at 3-year follow-up.Method:The authors used logistic regression models to assess prospective associations between cannabis use at wave 1 (2001–2002) and nonmedical prescription opioid use and prescription opioid use disorder at wave 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Corresponding analyses were performed among adults with moderate or more severe pain and with nonmedical opioid use at wave 1. Cannabis and prescription opioid use were measured with a structured interview (the Alcohol Use Disorder and Associated Disabilities Interview Schedule–DSM-IV version). Other covariates included age, sex, race/ethnicity, anxiety or mood disorders, family history of drug, alcohol, and behavioral problems, and, in opioid use disorder analyses, nonmedical opioid use.Results:In logistic regression mod...
TL;DR: Patients with major depression exhibited higher epigenetic aging in blood and brain tissue, suggesting that they are biologically older than their corresponding chronological age.
Abstract: Objective:Major depressive disorder is associated with an increased risk of mortality and aging-related diseases. The authors examined whether major depression is associated with higher epigenetic ...
TL;DR: The results suggest a direct or indirect association of elevated amyloid beta levels with worsening anxious-depressive symptoms and support the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer's disease.
Abstract: Objective:To understand the role of depressive symptoms in preclinical Alzheimer’s disease, it is essential to define their temporal relationship to Alzheimer’s proteinopathies in cognitively norma...
TL;DR: Advances in understanding of brain development and of the role of genes and environment on brain structure and function have built a foundation on which to develop more effective tools to prevent and treat substance use disorder.
Abstract: Addiction, the most severe form of substance use disorder, is a chronic brain disorder molded by strong biosocial factors that has devastating consequences to individuals and to society. Our understanding of substance use disorder has advanced significantly over the last 3 decades in part due to major progress in genetics and neuroscience research and to the development of new technologies, including tools to interrogate molecular changes in specific neuronal populations in animal models of substance use disorder, as well as brain imaging devices to assess brain function and neurochemistry in humans. These advances have illuminated the neurobiological processes through which biological and sociocultural factors contribute to resilience against or vulnerability for drug use and addiction. The delineation of the neurocircuitry disrupted in addiction, which includes circuits that mediate reward and motivation, executive control, and emotional processing, has given us an understanding of the aberrant behavior...
TL;DR: Findings from this epidemiological analysis of the epigenetic effects of early-life stress do not support the hypothesis of robust changes in DNA methylation in victimized young people, suggesting that epigenetic epidemiology is not yet well matched to experimental, nonhuman models in uncovering the biological embedding of stress.
Abstract: Objective:DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become “embedded” in the genome and alter transcriptional processes to compromise health. The ...
TL;DR: The author conducted a systematic review that explored the association between maternal depressive symptoms and child neurodevelopmental outcomes, including in neuroimaging studies, suggesting that maternal depression may appropriately be considered an issue of population health.
Abstract: The importance of maternal depression for child outcomes is well established, and impairments in psychosocial function and parenting are as severe in women with high subsyndromal levels of depressi...
TL;DR: Compared with region-of-interest data from patients with major depressive disorder, those with PTSD had reduced total brain volume and both disorders were associated with reduced hippocampal volume.
Abstract: Objective:The authors conducted a comprehensive meta-analysis of MRI region-of-interest and voxel-based morphometry (VBM) studies in posttraumatic stress disorder (PTSD). Because patients have high...
TL;DR: The CYP2C19 genotype had a substantial impact on exposure and therapeutic failure of escitalopram, as measured by switching of antidepressant therapy, and the results support the potential clinical utility of CYP1C19-genotyping for individualization of escITALopram therapy.
Abstract: Objective:The antidepressant escitalopram is predominantly metabolized by the polymorphic CYP2C19 enzyme. The authors investigated the effect of CYP2C19 genotype on exposure and therapeutic failure of escitalopram in a large patient population.Method:A total of 4,228 escitalopram serum concentration measurements from 2,087 CYP2C19-genotyped patients 10–30 hours after drug intake were collected retrospectively from the drug monitoring database at Diakonhjemmet Hospital in Oslo. The patients were divided into subgroups based on CYP2C19 genotype: those carrying inactive (CYP2C19Null) and gain-of-function (CYP2C19*17) variant alleles. The between-subgroup differences in escitalopram exposure (endpoint: dose-harmonized serum concentration) and therapeutic failure (endpoint: switching to another antidepressant within 1 year after the last escitalopram measurement) were evaluated by multivariate mixed model and chi-square analysis, respectively.Results:Compared with the CYP2C19*1/*1 group, escitalopram serum con...
TL;DR: Cognitive enhancement was the most commonly reported reason for misusing prescription stimulants, and patients who are using their medication for cognitive enhancement or diverting their medication to others present a high risk of substance use problems.
Abstract: Objective:The authors sought to simultaneously examine the prevalence and correlates of prescription stimulant use, misuse, use disorders, and motivations for misuse in the U.S. adult population.Me...
TL;DR: There are insufficient data to support the widespread use of combinatorial pharmacogenetic testing in clinical practice, although there are clinical situations in which the technology may be informative, particularly in predicting side effects.
Abstract: The accrual and analysis of genomic sequencing data have identified specific genetic variants that are associated with major depressive disorder. Moreover, substantial investigations have been devo...
TL;DR: Evidence is provided that, contrary to general belief, the risk of treatment failure or relapse after discontinuation of antipsychotic use does not decrease as a function of time during the first 8 years of illness, and that long-term antipsychotics treatment is associated with increased survival.
Abstract: Objective:It is generally believed that after the first episode of schizophrenia, the risk of relapse decreases with time in patients who are stabilized. Many treatment guidelines recommend that af...
TL;DR: This first trial of computerized CBT as a virtual stand-alone intervention delivered in a clinical setting to a diverse sample of patients with current substance use disorders indicated that it was safe, effective, and durable relative to standard treatment approaches and was well-liked by participants.
Abstract: Objective:Previous trials have demonstrated the efficacy and durability of computer-based cognitive-behavioral therapy (CBT4CBT) as an add-on to standard outpatient care in a range of treatment-see...
TL;DR: It is suggested that future neuroimaging studies showing effects that are pathogenic in nature should additionally explore the possibility of the downstream effects of psychopathology on the brain to delineate the longitudinal relationship between childhood psychiatric problems and brain development.
Abstract: Objective:Psychiatric symptomatology during childhood predicts persistent mental illness later in life. While neuroimaging methodologies are routinely applied cross-sectionally to the study of child and adolescent psychopathology, the nature of the relationship between childhood symptoms and the underlying neurodevelopmental processes remains unclear. The authors used a prospective population-based cohort to delineate the longitudinal relationship between childhood psychiatric problems and brain development.Method:A total of 845 children participated in the study. Psychiatric symptoms were measured with the parent-rated Child Behavior Checklist at ages 6 and 10. MRI data were collected at ages 8 and 10. Cross-lagged panel models and linear mixed-effects models were used to determine the associations between psychiatric symptom ratings and quantitative anatomic and white matter microstructural measures over time.Results:Higher ratings for externalizing and internalizing symptoms at baseline predicted small...
TL;DR: The findings from this randomized controlled trial of a parent-child psychotherapy for early childhood depression suggest that earlier identification and intervention in this chronic and relapsing disorder represents a key new pathway for more effective treatment.
Abstract: Objective:Clinical depression in children as young as age 3 has been validated, and prevalence rates are similar to the school-age disorder. Homotypic continuity between early and later childhood d...
TL;DR: The ASAP intervention program shows promise in reducing the incidence of postdischarge suicide attempts among adolescents hospitalized for suicidality and merits further study.
Abstract: Objective:The authors report on a pilot study of an inpatient intervention for suicidal adolescents, As Safe as Possible (ASAP), supported by a smartphone app (BRITE) to reduce suicide attempts fol...
TL;DR: The data in this study provide mechanistic insights into the dysregulation of the TNF-α gene in the brains of individuals who died by suicide, which could potentially be involved in suicidal behavior.
Abstract: Objective:Proinflammatory cytokines have recently received considerable attention for their role in suicidal behavior; however, how the expression of cytokine genes is regulated is not clearly known. The authors examined underlying mechanisms of critical cytokine gene tumor necrosis factor–alpha (TNF-α) dysregulation in the brains of individuals who died by suicide.Method:TNF-α expression was examined in the dorsolateral prefrontal cortex of the postmortem brains of persons with and without major depressive disorder who died by suicide and of persons with major depressive disorder who died of causes other than suicide. The role of putative microRNAs targeting TNF-α and RNA-binding protein Hu antigen R (HuR) was tested with in vitro and in vivo approaches and by examining expression of transactivation response RNA binding protein (TRBP). Genetic influence on TNF-α expression was determined by expression quantitative trait loci analysis and by genotyping three single-nucleotide polymorphisms in the promoter...
TL;DR: The findings support the importance of insight for psychotherapy outcome and suggest that insight may be a relevant mechanism of change across different treatment modalities.
Abstract: Objective:An increased understanding of repetitive dysfunctional patterns and their relationship to an individual’s life history is regarded as a key mechanism of change in insight-oriented therapi...