Showing papers in "American Journal of Psychiatry in 2010"
5,173 citations
TL;DR: Research is reviewed about variation in the promoter region of the serotonin transporter gene (SLC6A4) and its contribution to stress sensitivity and the contribution of GxE research to the public understanding of genetic science.
Abstract: Evidence of marked variability in response among people exposed to the same environmental risk implies that individual differences in genetic susceptibility might be at work. The study of such Gene-by-Environment (GxE) interactions has gained momentum. In this article, the authors review research about one of the most extensive areas of inquiry: variation in the promoter region of the serotonin transporter gene (SLC6A4; also known as 5-HTT) and its contribution to stress sensitivity. Research in this area has both advanced basic science and generated broader lessons for studying complex diseases and traits. The authors evaluate four lines of evidence about the 5-HTT stress-sensitivity hypothesis: 1) observational studies about the serotonin transporter linked polymorphic region (5-HTTLPR), stress sensitivity, and depression in humans; 2) experimental neuroscience studies about the 5-HTTLPR and biological phenotypes relevant to the human stress response; 3) studies of 5-HTT variation and stress sen...
1,200 citations
TL;DR: The promise of this work for facilitating the identification of susceptibility loci in genetic studies of schizophrenia is illustrated by examples of interaction between in utero exposure to infection and genetic variants.
Abstract: An emerging literature from epidemiologic, clinical, and preclinical investigations has provided evidence that gestational exposure to infection contributes to the etiology of schizophrenia. In recent years, these studies have moved from ecologic designs, which ascertain infection based on epidemics in populations, to investigations that have capitalized on reliable biomarkers in individual pregnancies. These studies have documented specific candidate infections that appear to be associated with an elevated risk of schizophrenia. Animal models of maternal immune activation inspired by this work have revealed intriguing findings indicating behavioral, neurochemical, and neurophysiologic abnormalities consistent with observations in schizophrenia. In parallel studies in humans and animals, investigators are working to uncover the cellular and molecular mechanisms by which in utero exposure to infection contributes to schizophrenia risk. In this review, the authors discuss and critically evaluate the...
1,103 citations
TL;DR: In the absence of adequate prospective, randomized drug-drug comparisons, the present findings provide broad, international, expert consensus-based recommendations for most clinically employed antipsychotic drugs that can support clinical practice, trial design, and interpretation of comparative antipsychotics trials.
Abstract: ObjectivePotency equivalents for antipsychotic drugs are required to guide clinical dosing and for designing and interpreting research studies. Available dosing guidelines are limited by the methods and data from which they were generated. MethodWith a two-step Delphi method, the authors surveyed a diverse group of international clinical and research experts, seeking consensus regarding antipsychotic dosing. The authors determined median clinical dosing equivalents and recommended starting, target range, and maximum doses for 61 drugs, adjusted for selected clinical circumstances. ResultsParticipants (N=43) from 18 countries provided dosing recommendations regarding treatment of psychotic disorders for 37 oral agents and 14 short-acting and 10 long-acting parenteral agents. With olanzapine 20 mg/day as reference, estimated clinical equivalency ratios of oral agents ranged from 0.025 for sulpiride to 10.0 for trifluperidol. Seventeen patient and treatment characteristics, including age, hepatic and renal ...
1,071 citations
TL;DR: More of the public embraces a neurobiological understanding of mental illness, which translates into support for services but not into a decrease in stigma.
Abstract: Objective:Clinicians, advocates, and policy makers have presented mental illnesses as medical diseases in efforts to overcome low service use, poor adherence rates, and stigma. The authors examined the impact of this approach with a 10-year comparison of public endorsement of treatment and prejudice. Method:The authors analyzed responses to vignettes in the mental health modules of the 1996 and 2006 General Social Survey describing individuals meeting DSM-IV criteria for schizophrenia, major depression, and alcohol dependence to explore whether more of the public 1) embraces neurobiological understandings of mental illness; 2) endorses treatment from providers, including psychiatrists; and 3) reports community acceptance or rejection of people with these disorders. Multivariate analyses examined whether acceptance of neurobiological causes increased treatment support and lessened stigma. Results:In 2006, 67% of the public attributed major depression to neurobiological causes, compared with 54% in 1996. Hi...
1,054 citations
TL;DR: The neural manifestations of the dissociative subtype in PTSD are compared to those underlying the reexperiencing/hyperaroused subtype and have important implications for treatment of PTSD, including the need to assess patients with PTSD for Dissociative symptoms and to incorporate the treatment of dissociatives symptoms into stage-oriented trauma treatment.
Abstract: In this article, the authors present evidence regarding a dissociative subtype of PTSD, with clinical and neurobiological features that can be distinguished from nondissociative PTSD. The dissociative subtype is characterized by overmodulation of affect, while the more common undermodulated type involves the predominance of reexperiencing and hyperarousal symptoms. This article focuses on the neural manifestations of the dissociative subtype in PTSD and compares it to those underlying the reexperiencing/hyperaroused subtype. A model that includes these two types of emotion dysregulation in PTSD is described. In this model, reexperiencing/hyperarousal reactivity is viewed as a form of emotion dysregulation that involves emotional undermodulation, mediated by failure of prefrontal inhibition of limbic regions. In contrast, the dissociative subtype of PTSD is described as a form of emotion dysregulation that involves emotional overmodulation mediated by midline prefrontal inhibition of the same limbic regions. Both types of modulation are involved in a dynamic interplay and lead to alternating symptom profiles in PTSD. These findings have important implications for treatment of PTSD, including the need to assess patients with PTSD for dissociative symptoms and to incorporate the treatment of dissociative symptoms into stage-oriented trauma treatment.
862 citations
TL;DR: The identification and treatment of a range of psychiatric disorders are important for optimal adaptation after traumatic injury and the influence of mild TBI on psychiatric status is determined.
Abstract: ObjectiveTraumatic injury affects millions of people each year. There is little understanding of the extent of psychiatric illness that develops after traumatic injury or of the impact of mild traumatic brain injury (TBI) on psychiatric illness. The authors sought to determine the range of new psychiatric disorders occurring after traumatic injury and the influence of mild TBI on psychiatric status. MethodIn this prospective cohort study, patients were drawn from recent admissions to four major trauma hospitals across Australia. A total of 1,084 traumatically injured patients were initially assessed during hospital admission and followed up 3 months (N=932, 86%) and 12 months (N=817, 75%) after injury. Lifetime psychiatric diagnoses were assessed in hospital. The prevalence of psychiatric disorders, levels of quality of life, and mental health service use were assessed at the follow-ups. The main outcome measures were 3- and 12-month prevalence of axis I psychiatric disorders, levels of quality of life, a...
670 citations
TL;DR: An association between habitual diet quality and the high-prevalence mental disorders is demonstrated, although reverse causality and confounding cannot be ruled out as explanations.
Abstract: ObjectiveKey biological factors that influence the development of depression are modified by diet. This study examined the extent to which the high-prevalence mental disorders are related to habitual diet in 1,046 women ages 20–93 years randomly selected from the population. MethodA diet quality score was derived from answers to a food frequency questionnaire, and a factor analysis identified habitual dietary patterns. The 12-item General Health Questionnaire (GHQ-12) was used to measure psychological symptoms, and a structured clinical interview was used to assess current depressive and anxiety disorders. ResultsAfter adjustments for age, socioeconomic status, education, and health behaviors, a "traditional" dietary pattern characterized by vegetables, fruit, meat, fish, and whole grains was associated with lower odds for major depression or dysthymia and for anxiety disorders. A "western" diet of processed or fried foods, refined grains, sugary products, and beer was associated with a higher GHQ-12 scor...
605 citations
TL;DR: Different neuropsychiatric disorders seem to have a common genetic etiology, suggesting caution in the use of diagnostic entities and proband status in efforts to uncover genes predisposing to autism spectrum disorders.
Abstract: Objective: Autism spectrum disorders are considered to be among the most heritable mental disorders, a notion based on surprisingly sparse data from small clinical studies. Population-based studies of the heritability of other neuro-psychiatric disorders and comorbidities among them have also been sparse. The authors sought to address both of these issues. Method: Parents of all Swedish 9- and 12-year-old twin pairs born between 1992 and 2000 (N=10,895) were interviewed regarding autism spectrum disorders and associated conditions (response rate, 80%). Concordance rates and structural equation modeling were used for evaluating causes for familial aggregation and overlap between conditions. Results: Monozygotic twins had higher concordance rates than dizygotic twins for autism spectrum disorders, attention defcit hyperactivity disorder (ADHD), developmental coordination disorder, and tic disorder. Genetic effects accounted for 80% (95% CI=29-91) of the variation in liability for autism spectrum disorders, 79% (95% CI=61-88) for ADHD, 70% (95% CI=35-83) for developmental coordination disorder, and 56% (95% CI=37-68) for tic disorder. Among monozygotic co-twins of children with autism spectrum disorders, the probability of having a diagnosis of ADHD was 44%, compared with 15% for dizygotic co-twins. Differences in cross-disorder effects between monozygotic and dizygotic twins were observed for most other comorbidities, and substantial proportions of the genetic variance for autism spectrum disorders was shared with each of the other disorders. Conclusions: Different neuropsychiatric disorders seem to have a common genetic etiology, suggesting caution in the use of diagnostic entities and proband status in efforts to uncover genes predisposing to autism spectrum disorders.
598 citations
TL;DR: In this paper, a review summarizes the current knowledge of the neurobiology of depression by combining insights from human clinical studies and molecular explanations from animal models, with a focus on translating today's discoveries into improved diagnostic tests and treatments.
Abstract: Major depressive disorder is a heritable psychiatric syndrome that appears to be associated with subtle cellular and molecular alterations in a complex neural network. The affected brain regions display dynamic neuroplastic adaptations to endocrine and immunologic stimuli arising from within and outside the CNS. Depression's clinical and etiological heterogeneity adds a third level of complexity, implicating different pathophysiological mechanisms in different patients with the same DSM diagnosis. Current pharmacological antidepressant treatments improve depressive symptoms through complex mechanisms that are themselves incompletely understood. This review summarizes the current knowledge of the neurobiology of depression by combining insights from human clinical studies and molecular explanations from animal models. The authors provide recommendations for future research, with a focus on translating today's discoveries into improved diagnostic tests and treatments.
533 citations
TL;DR: For a PTSD population with chronic and early-life trauma, a phase-based skills-to-exposure treatment was associated with greater benefits and fewer adverse effects than treatments that excluded either skills training or exposure.
Abstract: ObjectivePosttraumatic stress disorder (PTSD) related to childhood abuse is associated with features of affect regulation and interpersonal disturbances that substantially contribute to impairment. Existing treatments do not address these problems or the difficulties they may pose in the exploration of trauma memories, an efficacious and frequently recommended approach to resolving PTSD. The authors evaluated the benefits and risks of a treatment combining an initial preparatory phase of skills training in affect and interpersonal regulation (STAIR) followed by exposure by comparing it against two control conditions: Supportive Counseling followed by Exposure (Support/Exposure) and skills training followed by Supportive Counseling (STAIR/Support). MethodParticipants were women with PTSD related to childhood abuse (N=104) who were randomly assigned to the STAIR/Exposure condition, Support/Exposure condition (exposure comparator), or STAIR/Support condition (skills comparator) and assessed at posttreatment,...
TL;DR: A postmortem molecular changes suggest a selective reduction in glutamate transmission in the dentate gyrus and in its efferent fibers, the mossy fiber pathway, which could result in a resulting increase in "runaway" CA3-mediated pattern completion, generating psychotic associations and resulting in memories with psychotic content.
Abstract: The hippocampal formation is one of the most extensively studied regions of the brain, with well-described anatomy and basic physiology; moreover, aspects of human memory mediated by the hippocampus are well characterized. In schizophrenia, alterations in hippocampal anatomy, perfusion, and activation are consistently reported; impairments in declarative memory function, especially in the flexible use of event memories (e.g., in the service of memory-based inference), are common. Postmortem molecular changes suggest a selective reduction in glutamate transmission in the dentate gyrus and in its efferent fibers, the mossy fiber pathway. A reduction in dentate gyrus glutamatergic output and in its information processing functions could generate two co-occurring outcomes in the hippocampus: 1) a change in homeostatic plasticity processes in cornu ammonis 3 (CA3), accompanied by increased activity due to reduced afferent stimulation from the dentate gyrus onto CA3 neurons, a process that could increase the pa...
TL;DR: The findings suggest that the origins of schizophrenia include two interrelated developmental processes evident from childhood to early adolescence (ages 7-13 years).
Abstract: ObjectivePremorbid cognitive deficits in schizophrenia are well documented and have been interpreted as supporting a neurodevelopmental etiological model. The authors investigated the following three unresolved questions about premorbid cognitive deficits: What is their developmental course? Do all premorbid cognitive deficits follow the same course? Are premorbid cognitive deficits specific to schizophrenia or shared by other psychiatric disorders? MethodParticipants were members of a representative cohort of 1,037 males and females born between 1972 and 1973 in Dunedin, New Zealand. Cohort members underwent follow-up evaluations at specific intervals from age 3 to 32 years, with a 96% retention rate. Cognitive development was analyzed and compared in children who later developed schizophrenia or recurrent depression as well as in healthy comparison subjects. ResultsChildren who developed adult schizophrenia exhibited developmental deficits (i.e., static cognitive impairments that emerge early and remain...
TL;DR: Patients with generalized anxiety disorder show significant deficits in the noninstructed and spontaneous regulation of emotional processing, which may open up avenues for novel treatments, such as by targeting the medial prefrontal cortex.
Abstract: Objective: Clinical data suggest that abnormalities in the regulation of emotional processing contribute to the pathophysiology of generalized anxiety disorder, yet these abnormalities remain poorly understood at the neurobiological level. The authors recently reported that in healthy volunteers the pregenual anterior cingulate regulates emotional conflict on a trial-by-trial basis by dampening activity in the amygdala. The authors also showed that this process is specific to the regulation of emotional, compared to nonemotional, conflict. Here the authors examined whether this form of noninstructed emotion regulation is perturbed in generalized anxiety disorder. Method: Seventeen patients w ith generalized anxiety disorder and 24 healthy comparison subjects underwent functional M RI while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect label words. Behavioral and neural measures were used to compare trial-by-trial changes in conflict regulation. Results: Comparison subjects effectively regulated emotional conflict from trial to trial, even though they were unaware of having done so. By contrast, patients w ith generalized anxiety disorder were completely unable to regulate emotional conflict and failed to engage the pregen ual anterior cingulate in ways that would dampen amygdalar activity. M oreover, performance and brain activation were correlated w ith symptoms and could be used to accurately classify the two groups. Conclusions: These data demonstrate that patients w ith generalized anxiety disorder show significant deficits in the noninstructed and spontaneous regulation of emotional processing. Conceptualization of anxiety as importantly involving abnormalities in emotion regulation, particularly a type occurring outside of awareness, may open up avenues for novel treatments, such as by targeting the medial prefrontal cortex.
TL;DR: A laboratory-based assessment of this potential correlate of panic disorder by testing the degree to which panic patients and healthy subjects manifest generalization of conditioned fear demonstrates a marked proclivity toward fear overgeneralization in panic disorder.
Abstract: ObjectiveClassical conditioning features prominently in many etiological accounts of panic disorder. According to such accounts, neutral conditioned stimuli present during panic attacks acquire panicogenic properties. Conditioned stimuli triggering panic symptoms are not limited to the original conditioned stimuli but are thought to generalize to stimuli resembling those co-occurring with panic, resulting in the proliferation of panic cues. The authors conducted a laboratory-based assessment of this potential correlate of panic disorder by testing the degree to which panic patients and healthy subjects manifest generalization of conditioned fear. MethodNineteen patients with a DSM-IV-TR diagnosis of panic disorder and 19 healthy comparison subjects were recruited for the study. The fear-generalization paradigm consisted of 10 rings of graded size presented on a computer monitor; one extreme size was a conditioned danger cue, the other extreme a conditioned safety cue, and the eight rings of intermediary s...
TL;DR: The data suggest that, depending on how it is defined, sibling recurrence in autism spectrum disorder may exceed previously published estimates and varies as a function of family type.
Abstract: Objective:Although the symptoms of autism exhibit quantitative distributions in nature, estimates of recurrence risk in families have never previously considered or incorporated quantitative characterization of the autistic phenotype among siblings. Method:The authors report the results of quantitative characterization of 2,920 children from 1,235 families participating in a national volunteer register, with at least one child clinically affected by an autism spectrum disorder and at least one full biological sibling. Results:A traditionally defined autism spectrum disorder in an additional child occurred in 10.9% of the families. An additional 20% of nonautism-affected siblings had a history of language delay, one-half of whom exhibited autistic qualities of speech. Quantitative characterization using the Social Responsiveness Scale supported previously reported aggregation of a wide range of subclinical (quantitative) autistic traits among otherwise unaffected children in multiple-incidence families and...
TL;DR: The results support the shared role of neurocognition in bipolar disorder and schizophrenia in producing disability, with predictive differences between disorders in domain-specific effects of symptoms and social and adaptive competence.
Abstract: Objective:Schizophrenia and bipolar disorder are associated with multidimensional disability. This study examined differential predictors of functional deficits in the two disorders. Method:Community-dwelling individuals with schizophrenia (N=161) or bipolar disorder (N=130) were assessed with neuropsychological tests, symptom measures, and performance-based social and adaptive (i.e., everyday living skills) functional competence measures as well as three domains of real-world functioning: community and household activities; work skills; and interpersonal relationships. The authors used confirmatory path analysis to find the best-fitting models to examine the direct and indirect (as mediated by competence) prediction of the three domains of real-world functioning. Results:In all models for both groups, neurocognition's relationship with outcomes was largely mediated by competence. Symptoms were negatively associated with outcomes but unassociated with competence, with the exception of depression, which wa...
TL;DR: This review focuses on translational methods that have been used to examine fear conditioning and inhibition of fear in PTSD and summarizes genetic and neurobiological factors related to fear inhibition.
Abstract: Exposure to traumatic events that produce extreme fear and horror is all too common in both military and civilian populations, but not all individuals develop posttraumatic stress disorder (PTSD) as a result of the exposure. What mediates risk and resilience in the development of PTSD and other stress-related psychopathology is of paramount importance to our further understanding of trauma-related psychopathology as well as the development of new treatment approaches. Biological factors, such as genotype and neurobiology, interact with environmental factors, such as childhood background and trauma load, to affect vulnerability and resilience in the aftermath of trauma exposure. One of the core symptoms of PTSD is the inability to control fear, which has led some investigators and clinicians to conceptualize PTSD as a disorder of fear or, more importantly, its inhibition. This review focuses on translational methods that have been used to examine fear conditioning and inhibition of fear in PTSD and...
TL;DR: Findings suggest that care management is a promising approach for improving medical care for patients treated in community mental health settings.
Abstract: Objective: Poor quality of healthcare contributes to impaired health and excess mortality in individuals with severe mental disorders. The authors tested a population-based medical care management intervention designed to improve primary medical care in community mental health settings. Method: A total of 407 subjects with severe mental illness at an urban community mental health center were randomly assigned to either the medical care management intervention or usual care. For individuals in the intervention group, care managers provided communication and advocacy with medical providers, health education, and support in overcoming system-level fragmentation and barriers to primary medical care. Results: At a 12-month follow-up evaluation, the intervention group received an average of 58.7% of recommended preventive services compared with a rate of 21.8% in the usual care group. They also received a significantly higher proportion of evidence-based services for cardiometabolic conditions (34.9% versus 27.7%) and were more likely to have a primary care provider (71.2% versus 51.9%). The intervention group showed significant improvement on the SF-36 mental component summary (8.0% [versus a 1.1% decline in the usual care group]) and a nonsignificant improvement on the SF36 physical component summary. Among subjects with available laboratory data, scores on the Framingham Cardiovascular Risk Index were significantly better in the intervention group (6.9%) than the usual care group (9.8%). Conclusions: M edical care management was associated with significant improve ments in the quality and outcomes of primary care. These findings suggest that care management is a promising approach for improving medical care for patients treated in community mental health settings.
TL;DR: The results suggest that efficacy of antidepressants may be predicted by genetic markers other than traditional candidates, and genome-wide studies, if properly replicated, may be important steps in the elucidation of the genetic basis of pharmacological response.
Abstract: ObjectiveThe purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment. The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs. MethodHigh-quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram (N=394) or nortriptyline (N=312) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, a partially randomized open-label pharmacogenetic trial. ResultsSingle nucleotide polymorphisms in two intergenic regions containing copy number variants on chromosomes 1 and 10 were associated with the outcome of treatment with escitalopram or nortriptyline at suggestive levels of significance and with a high posterior likelihood of true association. Drug-specific analyses revealed a genome-wide significant association between...
TL;DR: It appears that a heterogeneous population of interneurons is implicated in schizophrenia, and the γ-aminobutyric acid (GABA) inhibitory system shows protracted development, and GABA-ergic deficits are widely replicated in postmortem schizophrenia studies.
Abstract: Objective:The onset of schizophrenia symptoms in late adolescence implies a neurodevelopmental trajectory for the disease. Indeed, the γ-aminobutyric acid (GABA) inhibitory system shows protracted development, and GABA-ergic deficits are widely replicated in postmortem schizophrenia studies. The authors examined expression of several interneuron markers across postnatal human development and in schizophrenia to assess whether protracted development of certain interneuron subpopulations may be associated with a particular vulnerability in schizophrenia. Method:RNA was extracted postmortem from dorsolateral prefrontal cortex of individuals from age 6 weeks to 49 years (N=68) and from a cohort of normal comparison subjects and schizophrenia patients (N=74, 37 pairs). Expression levels of parvalbumin, cholecystokinin, somatostatin, neuropeptide Y, calretinin, calbindin, and vasoactive intestinal peptide were measured by quantitative reverse transcription-polymerase chain reaction. Changes in calretinin protei...
TL;DR: Findings support the efficacy of meta-cognitive therapy as a viable psychosocial intervention in adults with attention deficit hyperactivity disorder (ADHD).
Abstract: ObjectiveThe authors investigated the efficacy of a 12-week manualized meta-cognitive therapy group intervention designed to enhance time management, organization, and planning in adults with attention deficit hyperactivity disorder (ADHD). MethodEighty-eight clinically referred adults who met DSM-IV criteria for ADHD according to clinical and structured diagnostic interviews and standardized questionnaires were stratified by ADHD medication use and otherwise randomly assigned to receive meta-cognitive therapy or supportive psychotherapy in a group modality. Meta-cognitive therapy uses cognitive-behavioral principles and methods to impart skills and strategies in time management, organization, and planning and to target depressogenic and anxiogenic cognitions that undermine effective self-management. The supportive therapy condition controlled for nonspecific aspects of treatment by providing support while avoiding discussion of cognitive-behavioral strategies. Therapeutic response was assessed by an inde...
TL;DR: Findings support the role of unique neural correlates in face-emotion processing among youths with bipolar disorder, ADHD, and severe mood dysregulation.
Abstract: ObjectiveTo understand disorder-unique and common pathophysiology, studies in multiple patient groups with overlapping symptoms are needed. Deficits in emotion processing and hyperarousal symptoms are prominent features of bipolar disorder, attention deficit hyperactivity disorder (ADHD), and severe mood dysregulation. The authors compared amygdala response during emotional and nonemotional ratings of neutral faces in youths with these disorders as well as a group of healthy comparison youths. MethodBlood-oxygen-level-dependent (BOLD) signal in the amygdala was examined in children with bipolar disorder (N=43), ADHD (N=18), and severe mood dysregulation (N=29) and healthy comparison subjects (N=37). During functional magnetic resonance imaging (fMRI), participants attended to emotional and nonemotional aspects of neutral faces. ResultsWhile rating subjective fear of neutral faces, youths with ADHD demonstrated left amygdala hyperactivity relative to the other three groups, whereas youths with severe mood ...
TL;DR: A conceptual model for identifying and evaluating evidence relevant to personalizing treatment for depression is described, finding that the inability to match patients with treatments implies that systematic follow-up assessment and adjustment of treatment are more important than initial treatment selection.
Abstract: Objective:Response to specific depression treatments varies widely among individuals. Understanding and predicting that variation could have great benefits for people living with depression. Method:The authors describe a conceptual model for identifying and evaluating evidence relevant to personalizing treatment for depression. They review evidence related to three specific treatment decisions: choice between antidepressant medication and psychotherapy, selection of a specific antidepressant medication, and selection of a specific psychotherapy. They then discuss potential explanations for negative findings as well as implications for research and clinical practice. Results:Many previous studies have examined general predictors of outcome, but few have examined true moderators (predictors of differential response to alternative treatments). The limited evidence indicates that some specific clinical characteristics may inform the choice between antidepressant medication and psychotherapy and the choice of ...
TL;DR: Findings demonstrate heterogeneity in major depressive disorder and support the validity of inclusion of subthreshold mania in the diagnostic classification and the broadening of criteria for bipolar disorder.
Abstract: Objective:There is growing clinical and epidemiologic evidence that major mood disorders form a spectrum from major depressive disorder to pure mania. The authors examined the prevalence and clinical correlates of major depressive disorder with subthreshold bipolarity compared with pure major depressive disorder in the National Comorbidity Survey Replication (NCS-R). Method:The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February 2001, and April 2003. Lifetime history of mood disorders, symptoms, and clinical indicators of severity were collected using version 3.0 of the World Health Organization's Composite International Diagnostic Interview. Results:Nearly 40% of study participants with a history of major depressive disorder had a history of subthreshold hypo-mania. This subgroup had a younger age at onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania and lower levels of clinical sev...
TL;DR: During the decade from 1998 to 2007, the percentage of the general population who used psychotherapy remained stable, however, psychotherapy assumed a less prominent role in outpatient mental health care as a large and increasing proportion of mental health outpatients received psychotropic medication without psychotherapy.
Abstract: Objective:The authors investigated recent trends in the use of outpatient psychotherapy in the United States. Method:Service use data from two representative surveys of the U.S. general population, the 1998 (N=22,953) and 2007 (N=29,370) Medical Expenditure Panel Surveys, were analyzed, focusing on individuals who made more than one outpatient psychotherapy visit during that calendar year. The authors computed rates of any psychotherapy use; percentages of persons treated for mental health conditions with only psychotherapy, only psychotropic medication, or their combination; the mean number of psychotherapy visits of persons receiving psychotherapy; and psychotherapy expenditures. Results:The percentage of persons using outpatient psychotherapy was 3.37% in 1998 and 3.18% in 2007 (adjusted odds ratio=0.95, 95% CI=0.82−1.09). Among individuals receiving outpatient mental health care, use of only psychotherapy (15.9% and 10.5% in 1998 and 2007, respectively; adjusted odds ratio=0.66, 95% CI=0.48−0.90) as w...
TL;DR: PTSD severity reductions were more likely to be associated with substance use improvement, with minimal evidence of substance use symptom reduction improving PTSD symptoms, which support the self-medication model of coping with PTSD symptoms and an empirical basis for integrated interventions for improved substance use outcomes in patients with severe symptoms.
Abstract: Objective: The purpose of the analysis was to examine the temporal course of improvement in symptoms of posttraumatic stress disorder (PTSD) and substance use disorder among women in outpatient substance abuse treatment. Method: Participants were 353 women randomly assigned to 12 sessions of either trauma-focused or health education group treatment. PTSD and substance use assessments were conducted during treatment and posttreatment at 1 week and after 3, 6, and 12 months. A continuous M arkov model was fit on four defined response categories (non response, substance use response, PTSD response, or global response [improvement in both PTSD and substance use]) to investigate the temporal association between improvement in PTSD and substance use symptom severity during the study’s treatment phase. A generalized linear model was applied to test this relationship over the follow-up period. Results: Subjects exhibiting nonresponse, substance use response, or global response tended to maintain original classification; subjects exhibiting PTSD response were significantly more likely to transition to global response over time, indicating maintained PTSD improvement was associated with subsequent substance use improvement. Traumafocused treatment was significantly more effective than health education in achieving substance use improvement, but only among those who were heavy substance users at baseline and had achieved significant PTSD reductions. Conclusions: PTSD severity reductions were more likely to be associated with substance use improvement, with minimal evidence of substance use symptom reduction improving PTSD symptoms. Results support the self-medication model of coping with PTSD symptoms and an empirical basis for integrated interventions for improved substance use outcomes in patients with severe symptoms.
TL;DR: Results indicate that spindle deficits can be reliably established in schizophrenia, are stable across the night, are unlikely to be due to antipsychotic medications, and point to deficits in the thalamic reticular nucleus and thalamo-reticular circuits.
Abstract: Objective:Slow waves and sleep spindles are the two main oscillations occurring during non-REM sleep. While slow oscillations are primarily generated and modulated by the cortex, sleep spindles are initiated by the thalamic reticular nucleus and regulated by thalamo-reticular and thalamo-cortical circuits. In a recent high-density EEG study, the authors found that 18 medicated schizophrenia patients had reduced sleep spindles, compared with healthy and depressed subjects, during the first non-REM episode. In the present study, the authors investigated whether spindle deficits were present in a larger sample of schizophrenia patients, were consistent across the night, were related to antipsychotic medications, and were suggestive of impairments in specific neuronal circuits. Method:Whole-night high-density EEG recordings were performed in 49 schizophrenia patients, 20 nonschizophrenia patients receiving antipsychotic medication, and 44 healthy subjects. In addition to sleep spindles, several parameters of ...
TL;DR: It is suggested that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication.
Abstract: Objective: Various classes of antidepressant medications generally induce remission of major depressive disorder in only about one-third of patients. In a previous study using mirtazapine or paroxetine alone or in combination from treatment initiation, the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone. In this double-blind study, the authors sought to produce evidence for the superiority of different combinations of antidepressant drugs from treatment initiation. Method: Patients (N=105) meeting DSMIV criteria for major depressive disorder were randomly assigned to receive, from treatment initiation, either fluoxetine monotherapy (20 mg/day) or mirtazapine (30 mg/day) in combination with fluox etine (20 mg/day), venlafaxine (225 mg/ day titrated in 14 days), or bupropion (150 mg/day) for 6 weeks. The primary outcome measure was the Hamilton Depression Rating Scale (HAM-D) score. Results: The overall dropout rate was 15% , without notable differences among the four groups. Compared with fluox etine monotherapy, all three combination groups had significantly greater improve ments on the HAM-D. Remission rates (defined as a HAM-D score of 7 or less) were 25% for fluoxetine, 52% for mirtazapine plus fluoxetine, 58% for mirtazapine plus venlafaxine, and 46% for mirtazapine plus bupropion. Among patients who had a marked response, double-blind discontinuation of one agent produced a relapse in about 40% of cases. Conclusions: The combination treatments were as well tolerated as fluox etine monotherapy and more clinically effective. The study results, which add to a growing body of evidence, suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication.
TL;DR: Evidence that Akt/GSK-3 and Wnt-related pathways are involved in the pathogenesis of schizophrenia as well as details of intracellular events related to these molecules mediated by both typical and atypical antipsychotic medications are reviewed.
Abstract: Dopamine D2 receptor antagonism is a unifying property of all antipsychotic drugs in clinical use. Remarkably, the effector molecules through which these medications exert their actions remain poorly characterized. Increasing attention is being focused on Akt/glycogen synthase kinase-3 (GSK-3) and wingless (Wnt) signaling pathways, which have been associated with schizophrenia in a number of genetic and postmortem studies. Antipsychotic medications may treat symptoms of psychosis, at least in part, through modulation of levels and activity of Akt, GSK-3, and Wnt-related intracellular signaling. The authors review evidence that Akt/GSK-3 and Wnt-related pathways are involved in the pathogenesis of schizophrenia as well as details of intracellular events related to these molecules mediated by both typical and atypical antipsychotic medications. Further study of Akt/GSK-3 and Wnt signaling may ultimately lead to alternative therapeutics of schizophrenia-related disorders.