Showing papers in "American Journal of Psychiatry in 2014"
1,147 citations
TL;DR: Three models are considered to explain the overlap between emotion dys regulation and ADHD: emotion dysregulation and ADHD are correlated but distinct dimensions; the combination constitutes a nosological entity distinct from both ADHD and emotion Dysregulation alone.
Abstract: Emotion dysregulation, a major contributor to impairment throughout life, is common in ADHD and may arise from deficits in orienting toward and processing emotional stimuli, implicating dysfunction within the prefrontal cortical network. Understanding the nature of the overlap between emotional dysregulation and ADHD can stimulate novel treatment approaches.
759 citations
TL;DR: Findings validate previous findings that this condition is one of the strongest risk factors for psychosis and highlight the need to monitor and reduce the long-term burden of psychopathology in 22q11.2 deletion syndrome.
Abstract: ObjectiveChromosome 22q11.2 deletion syndrome is a neurogenetic disorder associated with high rates of schizophrenia and other psychiatric conditions. The authors report what is to their knowledge the first large-scale collaborative study of rates and sex distributions of psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome. The associations among psychopathology, intellect, and functioning were examined in a subgroup of participants.MethodThe 1,402 participants with 22q11.2 deletion syndrome, ages 6–68 years, were assessed for psychiatric disorders with validated diagnostic instruments. Data on intelligence and adaptive functioning were available for 183 participants ages 6 to 24 years.ResultsAttention deficit hyperactivity disorder (ADHD) was the most frequent disorder in children (37.10%) and was overrepresented in males. Anxiety disorders were more prevalent than mood disorders at all ages, but especially in children and adolescents. Anxiety and unipolar mood disorders were o...
613 citations
TL;DR: Midlife outcomes of childhood bullying victimization was associated with a lack of social relationships, economic hardship, and poor perceived quality of life at age 50, and interventions need to reduce bullying exposure in childhood and minimize long-term effects on victims' well-being.
Abstract: A five decade-long nationwide study revealed that the impact of being bullied in childhood persists up to mid-life. The harmful effects extend beyond psychological distress to lower levels of education, physical and cognitive health problems, and poor social functioning.
581 citations
TL;DR: Findings from all major studies in bipolar disorder that used functional MRI, volumetric analysis, diffusion imaging, and resting-state techniques are examined, integrating findings to provide a better understanding of larger-scale neural circuitry abnormalities in bipolar Disorder.
Abstract: Neuroimaging findings support conceptualizing bipolar disorder as a result of neural circuitry abnormalities in emotion and reward processing and regulation. Future studies should adopt these four strategies to improve the prediction of future illness development, diagnosis, and personalized treatment for bipolar patients.
479 citations
TL;DR: A comprehensive meta-analysis of prospective studies of community as well as patient samples associating depression at baseline with excess mortality at follow-up could confirm the presence of a significant association between depression and excess mortality, although this association may have been overestimated because of publication bias and low study quality.
Abstract: Objective: Several hundred studies have shown that depression is associated with an elevated risk of dying at follow-up. It is not clear, however, whether the mechanisms for this association are disease specific, leading to higher mortality in specific patient groups, or generic, resulting in comparable mortality rates in all patient groups as well as in community samples. The authors conducted a comprehensive meta-analysis of prospective studies of community as well as patient samples associating depression at baseline with excess mortality at follow-up.
435 citations
TL;DR: The moderation of paternal PTSD effects by maternal PTSD suggests different mechanisms for the intergenerational transmission of trauma-related vulnerabilities.
Abstract: Important differences in the expression and effect of maternal and paternal PTSD were found when examining parental PTSD in the offspring of Holocaust survivors and methylation of the glucocorticoid receptor gene exon 1F.
390 citations
TL;DR: Schema therapy was superior to treatment as usual on recovery, other interview-based outcomes, and dropout, and exercise-based schema therapy training was inferior to lecture-based training.
Abstract: Schema therapy, an integrative psychotherapy that emphasizes processing negative experiences and using the therapeutic relationships as a way to fulfill unmet needs, was superior to treatment as usual and clarification-oriented psychotherapy in patients with personality disorders, adding to the growing evidence for this combination therapy.
367 citations
TL;DR: A six-session virtual reality treatment was associated with reduction in PTSD diagnoses and symptoms in Iraq and Afghanistan veterans, although there was no control condition for the virtual reality exposure.
Abstract: Six sessions of virtual reality exposure therapy reduced PTSD symptoms in Iraq and Afghanistan veterans, but the treatment was less effective when augmented with alprazolam, and only more effective with [d]-cycloserine when extinction learning was well achieved between sessions. Clinicians should be cautious in the use of benzodiazepines in patients with PTSD.
335 citations
TL;DR: An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice.
Abstract: OBJECTIVE: Major depressive disorder has been linked with inflammatory processes, but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial. The authors tested the hypothesis that C-reactive protein (CRP), a commonly available marker of systemic inflammation, predicts differential response to escitalopram (a serotonin reuptake inhibitor) and nortriptyline (a norepinephrine reuptake inhibitor). METHOD: The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, a multicenter open-label randomized clinical trial. CRP was measured with a high-sensitivity method in serum samples from 241 adult men and women with major depressive disorder randomly allocated to 12-week treatment with escitalopram (N=115) or nortriptyline (N=126). The primary outcome measure was the score on the Montgomery-Asberg Depression Rating Scale (MADRS), administered weekly. RESULTS: CRP level at baseline differentially predicted treatment outcome with the two antidepressants (CRP-drug interaction: β=3.27, 95% CI=1.65, 4.89). For patients with low levels of CRP (<1 mg/L), improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline. For patients with higher CRP levels, improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram. CRP and its interaction with medication explained more than 10% of individual-level variance in treatment outcome. CONCLUSIONS: An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice.
327 citations
TL;DR: There are small but reliable differences in efficacy between psychological interventions for psychosis, and they occur in a pattern consistent with the specific factors of particular interventions.
Abstract: After six psychological interventions for psychosis were compared across 48 outcome trials, some small but reliable differences in efficacy were found. Cognitive-behavioral therapy was more successful than befriending, cognitive remediation, psychoeducation, and supportive counseling in treating positive symptoms, but not as effective as social skills training for negative symptoms.
TL;DR: The findings demonstrate that the most consistent gray matter abnormalities in individuals exposed to childhood maltreatment are in relatively late-developing ventrolateral prefrontal-limbic-temporal regions that are known to mediate late-developmenting functions of affect and cognitive control, which are typically compromised in this population.
Abstract: ObjectiveChildhood maltreatment acts as a severe stressor that produces a cascade of physiological and neurobiological changes that lead to enduring alterations in brain structure. However, structural neuroimaging findings have been inconsistent. The authors conducted a meta-analysis of published whole-brain voxel-based morphometry studies in childhood maltreatment to elucidate the most robust volumetric gray matter abnormalities relative to comparison subjects to date.MethodTwelve data sets were included, comprising 331 individuals (56 children/adolescents and 275 adults) with a history of childhood maltreatment and 362 comparison subjects (56 children/adolescents and 306 adults). Anisotropic effect size-signed differential mapping, a voxel-based meta-analytic method, was used to examine regions of smaller and larger gray matter volumes in maltreated individuals relative to comparison subjects.ResultsRelative to comparison subjects, individuals exposed to childhood maltreatment exhibited significantly sm...
TL;DR: Monotherapy with lurasidone in the dosage range of 20-120 mg/day significantly reduced depressive symptoms in patients with bipolar I depression.
Abstract: In July 2013, the Food and Drug Administration approved lurasidone for the treatment of bipolar I depression. Two studies discussing its monotherapy and adjunctive use that were pivotal in obtaining this approval are featured in this issue.
TL;DR: For instance, this article found that personality and failures in interpersonal relationships played a stronger etiologic role in major depression for women than for men, while externalizing psychopathology, prior depression, and specific “instrumental” classes of acute stressors were more important for men.
Abstract: Objective: The authors sought to clarify the nature of sex differences in the etiologic pathways to major depression. Method: Retrospective and prospective assessments of 20 developmentally organized risk factors and the occurrence of past-year major depression were conducted at twowaves of personalinterviews at least 12 months apart in 1,057 oppositesex dizygotic twin pairs from a populationbased register. Analyses were conducted by structural modeling, examining within-pair differences. Results: Sixty percent of all paths in the best-fit model exhibited sex differences. Eleven of the 20 risk factors differed across sexes in their impact on liability to major depression. Five had a greater impact in women: parental warmth, neuroticism, divorce, social support, and marital satisfaction. Six had a greater impact in men: childhood sexual abuse, conduct disorder, drug abuse, prior history of major depression, and distal anddependent proximal stressful life events. The life event categories responsible for the stronger effect in males were financial, occupational, and legal in nature. Conclusions: In a co-twin control design, which matches sisters and brothers on genetic and familial-environmental background, personality and failures in interpersonal relationships played a stronger etiologic role in major depression for women than for men. Externalizing psychopathology, prior depression, and specific “instrumental” classes of acute stressors were more important in the etiologic pathway to major depression for men. The results are consistent with previously proposed typologies of major depression that suggest two subtypes that differ in prevalence in women (deficiencies in caring relationships and interpersonal loss) and men (failures to achieve expected goals, with lowered self-worth). (Am J Psychiatry 2014; 171:426–435) Because women consistently have a higher rate of major depression than do men (1–5), sex differences in the etiologic pathways to major depression have often been explored (2, 3, 6–10). Most studies have examined single risk factors, such as marital status or quality (5, 11, 12), stressful life events (7), prior anxiety disorders (13), personality (6), and ruminative propensity (9). Given the important etiologic role of genetic and environmental familial factors in major depression (14–18), delineating risk factors that differentiate the sexes would be facilitated by a design controlling for these background variables. In this study, we examined sex differences in the etiologic pathway to major depression with a wide array of risk factors organized developmentally (19, 20), using a co-twin control design in opposite-sex dizygotic twin pairs—the optimal sample for studying sex differences.
TL;DR: The bereavement period is associated with elevated risk for the onset of multiple psychiatric disorders, consistently across the life course and coincident with the experience of the loved one's death.
Abstract: Unexpected death of a loved one was associated with heightened vulnerability for virtually all commonly occurring psychiatric disorders, including depression, PTSD, manic episodes, phobias, panic disorder, and substance use disorders in one of the first population-based studies to examine these relations across the lifespan.
TL;DR: An increased incidence of mild cognitive impairment was observed in community-dwelling elderly adults who had nonpsychotic psychiatric symptoms at baseline and these baseline psychiatric symptoms were of similar or greater magnitude as biomarkers in increasing the risk of incident mild Cognitive impairment.
Abstract: ObjectiveThe authors conducted a prospective cohort study to estimate the risk of incident mild cognitive impairment in cognitively normal elderly (aged ≥70 years) individuals with or without neuropsychiatric symptoms at baseline. The research was conducted in the setting of the population-based Mayo Clinic Study of Aging.MethodA classification of normal cognitive aging, mild cognitive impairment, and dementia was adjudicated by an expert consensus panel based on published criteria. Hazard ratios and 95% confidence intervals were computed using Cox proportional hazards model, with age as a time scale. Baseline Neuropsychiatric Inventory Questionnaire data were available for 1,587 cognitively normal persons who underwent at least one follow-up visit.ResultsThe cohort was followed to incident mild cognitive impairment (N=365) or censoring variables (N=179) for a median of 5 years. Agitation (hazard ratio=3.06, 95% CI=1.89–4.93), apathy (hazard ratio=2.26, 95% CI=1.49–3.41), anxiety (hazard ratio=1.87, 95% C...
TL;DR: Cognitive training offers considerable promise, especially given the limited efficacy of pharmacological interventions in ameliorating cognitive deficits, but more research is needed to understand the mechanisms underlying cognitive training, predictors of response, generalization and real-world applicability, and approaches to dissemination in practice settings.
Abstract: ObjectiveThis article reviews the conceptual basis, definitions, and evolution of cognitive training approaches for the treatment of mental disorders.MethodThe authors review the current state of the knowledge on cognitive training in psychiatric illnesses, and its neural and behavioral targets, and summarize the factors that appear to relate to a successful response, including learner characteristics that influence clinical outcome. They also discuss methodological issues relevant to the development and testing of cognitive training approaches, with the goal of creating maximally efficient and effective approaches to training. Finally, they identify gaps in existing knowledge and outline key research directions for the future.ResultsWhile much of the early research has been conducted in schizophrenia, cognitive training has more recently been applied to a widening range of neuropsychiatric illnesses, including attention deficit hyperactivity disorder, mood disorders, and substance use disorders. Cognitiv...
VU University Amsterdam1, King's College London2, Stellenbosch University3, University of Cape Town4, Universidade Federal do ABC5, University of São Paulo6, University of Amsterdam7, Kyoto Prefectural University of Medicine8, Seoul National University9, University of Pittsburgh10, Pompeu Fabra University11
TL;DR: Findings partially support the prevailing fronto-striatal models of OCD and offer additional insights into the neuroanatomy of the disorder that were not apparent from previous smaller studies.
Abstract: The effect of persistent symptoms or compensatory processes related to cognitive dysfunction in obsessive-compulsive disorder may contribute to brain structure alterations in OCD, indicating that age is an important factor in evaluating changes in gray and white matter volumes.
Objective
Results from structural neuroimaging studies of obsessive-compulsive disorder (OCD) have been only partially consistent. The authors sought to assess regional gray and white matter volume differences between large samples of OCD patients and healthy comparison subjects and their relation with demographic and clinical variables.
Method
A multicenter voxel-based morphometry mega-analysis was performed on 1.5-T structural T1-weighted MRI scans derived from the International OCD Brain Imaging Consortium. Regional gray and white matter brain volumes were compared between 412 adult OCD patients and 368 healthy subjects.
Results
Relative to healthy comparison subjects, OCD patients had significantly smaller volumes of frontal gray and white matter bilaterally, including the dorsomedial prefrontal cortex, the anterior cingulate cortex, and the inferior frontal gyrus extending to the anterior insula. Patients also showed greater cerebellar gray matter volume bilaterally compared with healthy subjects. Group differences in frontal gray and white matter volume were significant after correction for multiple comparisons. Additionally, group-by-age interactions were observed in the putamen, insula, and orbitofrontal cortex (indicating relative preservation of volume in patients compared with healthy subjects with increasing age) and in the temporal cortex bilaterally (indicating a relative loss of volume in patients compared with healthy subjects with increasing age).
Conclusions
These findings partially support the prevailing fronto-striatal models of OCD and offer additional insights into the neuroanatomy of the disorder that were not apparent from previous smaller studies. The group-by-age interaction effects in orbitofrontal-striatal and (para)limbic brain regions may be the result of altered neuroplasticity associated with chronic compulsive behaviors, anxiety, or compensatory processes related to cognitive dysfunction.
TL;DR: The most compelling biomarkers for suicide are linked to altered stress responses and their downstream effects, and to abnormalities in the serotonergic system.
Abstract: Objective:Suicide, a major cause of death worldwide, has distinct biological underpinnings. The authors review and synthesize the research literature on biomarkers of suicide, with the aim of using the findings of these studies to develop a coherent model for the biological diathesis for suicide.Method:The authors examined studies covering a large range of neurobiological systems implicated in suicide. They provide succinct descriptions of each system to provide a context for interpreting the meaning of findings in suicide.Results:Several lines of evidence implicate dysregulation in stress response systems, especially the hypothalamic-pituitary-adrenal axis, as a diathesis for suicide. Additional findings related to neuroinflammatory indices, glutamatergic function, and neuronal plasticity at the cellular and circuitry level may reflect downstream effects of such dysregulation. Whether serotonergic abnormalities observed in individuals who have died by suicide are independent of stress response abnormalit...
TL;DR: Cognitive therapy for PTSD delivered intensively over little more than a week was as effective as cognitive therapy delivered over 3 months and both had specific effects and were superior to supportive therapy.
Abstract: ObjectivePsychological treatments for posttraumatic stress disorder (PTSD) are usually delivered once or twice a week over several months. It is unclear whether they can be successfully delivered over a shorter period of time. This clinical trial had two goals: to investigate the acceptability and efficacy of a 7-day intensive version of cognitive therapy for PTSD and to investigate whether cognitive therapy has specific treatment effects by comparing intensive and standard weekly cognitive therapy with an equally credible alternative treatment.MethodPatients with chronic PTSD (N=121) were randomly allocated to 7-day intensive cognitive therapy for PTSD, 3 months of standard weekly cognitive therapy, 3 months of weekly emotion-focused supportive therapy, or a 14-week waiting list condition. The primary outcomes were change in PTSD symptoms and diagnosis as measured by independent assessor ratings and self-report. The secondary outcomes were change in disability, anxiety, depression, and quality of life. E...
TL;DR: Treatment with lurasidone adjunctive to lithium or valproate significantly improved depressive symptoms and was generally well tolerated in patients with bipolar I depression.
Abstract: ObjectiveFew studies have been reported that support the efficacy of adjunctive therapy for patients with bipolar I depression who have had an insufficient response to monotherapy with mood-stabilizing agents. The authors investigated the efficacy of lurasidone, a novel antipsychotic agent, as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression.MethodPatients were randomly assigned to receive 6 weeks of double-blind adjunctive treatment with lurasidone (N=183) or placebo (N=165), added to therapeutic levels of either lithium or valproate. Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Asberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP), respectively.ResultsLurasidone treatment significantly reduced mean MADRS total score at week 6 compared with the placebo group (−17.1 versus −13.5; effect size=0.34). Similarly, lurasidone treatment res...
TL;DR: There is substantial neuropsychological decline in schizophrenia from the premorbid to the postonset period, but the extent and developmental progression of decline varies across mental functions, suggesting that different pathophysiological mechanisms may underlie deficits in different mental functions.
Abstract: ObjectiveDespite the widespread belief that neuropsychological decline is a cardinal feature of the progression from the premorbid stage to the chronic form of schizophrenia, few longitudinal studies have examined change in neuropsychological functioning from before to after illness onset. The authors examined whether neuropsychological decline is unique to schizophrenia, whether it is generalized or confined to particular mental functions, and whether individuals with schizophrenia also have cognitive problems in everyday life.MethodParticipants were members of a representative cohort of 1,037 individuals born in Dunedin, New Zealand, in 1972 and 1973 and followed prospectively to age 38, with 95% retention. Assessment of IQ and specific neuropsychological functions was conducted at ages 7, 9, 11, and 13, and again at age 38. Informants also reported on any cognitive problems at age 38.ResultsIndividuals with schizophrenia exhibited declines in IQ and in a range of mental functions, particularly those ta...
TL;DR: Internet-delivered interventions such as TES have the potential to expand access and improve addiction treatment outcomes and additional research is needed to assess effectiveness in non-specialty clinical settings.
Abstract: The Therapeutic Education System, which combines skills-oriented counseling and contingency management in an Internet-delivered behavioral intervention, produced high rates of abstinence from drugs and heavy drinking among patients with a good prognosis (those who entered the study with positive urine drug or breath alcohol screen) but doubled the likelihood of abstinence among patients with an otherwise poor prognosis.
TL;DR: CBT was more effective in relieving binging and purging than psychoanalytic psychotherapy and was generally faster in alleviating eating disorder features and general psychopathology.
Abstract: Two years of psychoanalytic psychotherapy and 5 months of CBT with follow up visits for bulimia nervosa were compared. The proportions of patients who had stopped binging and purging at 2 years were 15% for psychoanalytic psychotherapy and 44% for CBT. Both treatments improve other eating disorder features and general psychopathology, but CBT does so faster, and therapists can learn CBT through videoconferencing.
TL;DR: Findings suggest that alterations in the developmental trajectories of limbic and striatal regions during adolescence may represent a neurobiological manifestation of a risk factor for the development of depression during this critical period and thus may provide clues as to etiological mechanisms of this disorder.
Abstract: Brain imaging in both early and mid adolescence revealed that adolescents who developed depression during the intervening period had less growth of the hippocampus and less reduction in putamen volume than nondepressed adolescents.
TL;DR: The use of topiramate at a daily dose of 200 mg to reduce heavy drinking in problem drinkers is supported and the moderator effect of rs2832407, if validated, would facilitate the identification of heavy drinkers who are likely to respond well toTopiramate treatment and provide an important personalized treatment option.
Abstract: Heavy drinkers trying to cut back but not completely eliminate their alcohol intake were treated with topiramate as an adjunct to counseling and reduced their drinking more rapidly than patients given placebo. The effect of topiramate was significant only in patients with a specific gene variation, the CC genotype of the GRIK1 polymorphism, offering a way to identify heavy drinkers who are likely to respond well to this treatment.
TL;DR: Although an infrequent event, DILI from antidepressant drugs may be irreversible, and clinicians should be aware of it, and prompt discontinuation of the drug responsible is essential.
Abstract: There are no strategies yet for preventing antidepressant-induced adverse hepatic events, but early detection by aminotransferase surveillance is essential, as drug-induced liver injury from antide...
TL;DR: The results show that mechanisms related to stress recovery can be modified in healthy individuals prior to stress exposure, with important implications for evidence-based mental health research and treatment.
Abstract: Objective: Military deployment can have profound effects on physical and mental health. Few studies have examined whether interventions prior to deployment can improve mechanisms underlying resilience. Mindfulness-based techniques have been shown to aid recovery from stress and may affect brain-behavior relationships prior to deployment. The authors examined the effect of mindfulness training on resilience mechanisms in active-duty Marines preparing for deployment. Method: Eight Marine infantry platoons (N=281) were randomly selected. Four platoons were assigned to receive mindfulness training (N=147) and four were assigned to a training-as-usual control condition (N=134). Platoons were assessed at baseline,8weeks afterbaseline,and during andafter astressfulcombattrainingsession approximately 9 weeks after baseline. The mindfulness training condition was delivered in the form of 8 weeks of MindfulnessBased Mind Fitness Training (MMFT), a
TL;DR: In this national registry study, antidepressant monotherapy was associated with an increased risk of mania, however, no risk ofMania was seen in patients receiving an antidepressant while treated with a mood stabilizer, highlighting the importance of avoiding antidepressants monotherapy in the treatment of bipolar disorder.
Abstract: The risk of a manic switch was increased in depressed patients with bipolar disorder who were on antidepressant monotherapy but not in depressed bipolar patients who were treated with an antidepressant and concurrent mood stabilizer.
TL;DR: The increased risk of subsequent autoimmune diseases in individuals with schizophrenia may involve neuropsychiatric manifestations from the undiagnosed autoimmune disease, medical treatment or lifestyle associated with schizophrenia, or common etiological mechanisms, such as infections and shared genetic factors.
Abstract: ObjectivePrevious research has found an increased risk of schizophrenia in individuals with autoimmune diseases and smaller but significant associations with a family history of autoimmune diseases. This study investigates, for the first time, the association between schizophrenia and subsequent autoimmune diseases (the reverse temporality) and also considers the effect of infections, a possible risk factor for both schizophrenia and autoimmune diseases.MethodDanish nationwide registers were linked to establish a cohort of 3.83 million people, identifying 39,364 individuals with schizophrenia-like psychosis and 142,328 individuals with autoimmune disease. Data were analyzed using survival analysis and adjusted for calendar year, age, and sex.ResultsIndividuals with schizophrenia had an elevated risk of subsequent autoimmune diseases, with an incidence rate ratio of 1.53 (95% CI=1.46–1.62). Among persons without hospital contacts for infections, the effect of having schizophrenia was smaller, with an incre...