Showing papers in "American Journal of Psychiatry in 2008"
TL;DR: The MATRICS Consensus Cognitive Battery is expected to be the standard tool for assessing cognitive change in clinical trials of cognition-enhancing drugs for schizophrenia and may also aid evaluation of cognitive remediation strategies.
Abstract: Objective: The lack of an accepted standard for measuring cognitive change in schizophrenia has been a major obstacle to regulatory approval of cognition-enhancing treatments. A primary mandate of the National Institute of Mental Health’s Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was to develop a consensus cognitive battery for clinical trials of cognition-enhancing treatments for schizophrenia through a broadly based scientific evaluation of measures. Method: The MATRICS Neurocognition Committee evaluated more than 90 tests in seven cognitive domains to identify the 36 most promising measures. A separate expert panel evaluated the degree to which each test met specific selection criteria. Twenty tests were selected as a beta battery. The beta battery was administered to 176 individuals with schizophrenia and readministered to 167 of them 4 weeks later so that the 20 tests could be compared directly. Results: The expert panel ratings are presented for th...
1,894 citations
TL;DR: It is suggested that comprehensive study of the psychological as well as biological correlates of depression can provide a new understanding of this debilitating disorder.
Abstract: Although the cognitive model of depression has evolved appreciably since its first formulation over 40 years ago, the potential interaction of genetic, neurochemical, and cognitive factors has only recently been demonstrated. Combining findings from behavioral genetics and cognitive neuroscience with the accumulated research on the cognitive model opens new opportunities for integrated research. Drawing on advances in cognitive, personality, and social psychology as well as clinical observations, expansions of the original cognitive model have incorporated in successive stages automatic thoughts, cognitive distortions, dysfunctional beliefs, and information-processing biases. The developmental model identified early traumatic experiences and the formation of dysfunctional beliefs as predisposing events and congruent stressors in later life as precipitating factors. It is now possible to sketch out possible genetic and neurochemical pathways that interact with or are parallel to cognitive variables. A hype...
1,212 citations
1,168 citations
TL;DR: Overall, controlled trial data suggest that psychosocial treatments provide benefits reflecting a moderate effect size according to Cohen's standards, and these effect sizes are comparable to those for other efficacious treatments in psychiatry.
Abstract: Objective: Despite significant advances in psychosocial treatments for substance use disorders, the relative success of these approaches has not been well documented. In this meta-analysis, the authors provide effect sizes for various types of psychosocial treatments, as well as abstinence and treatment-retention rates for cannabis, cocaine, opiate, and polysubstance abuse and dependence treatment trials. Method: With a comprehensive series of literature searches, the authors identified a total of 34 well-controlled treatment conditions—five for cannabis, nine for cocaine, seven for opiate, and 13 for polysubstance users—representing the treatment of 2,340 patients. Psychosocial treatments evaluated included contingency management, relapse prevention, general cognitive behavior therapy, and treatments combining cognitive behavior therapy and contingency management. Results: Overall, controlled trial data suggest that psychosocial treatments provide benefits reflecting a moderate effect size according to C...
1,096 citations
TL;DR: It is suggested that immigrants benefit from a protective context in their country of origin, possibly inoculating them against risk for substance disorders, particularly if they emigrated to the United States as adults.
Abstract: Objective: Although widely reported among Latino populations, contradictory evidence exists regarding the generalizability of the immigrant paradox, i.e., that foreign nativity protects against psychiatric disorders. The authors examined whether this paradox applies to all Latino groups by comparing estimates of lifetime psychiatric disorders among immigrant Latino subjects, U.S-born Latino subjects, and non-Latino white subjects. Method: The authors combined and examined data from the National Latino and Asian American Study and the National Comorbidity Survey Replication, two of the largest nationally representative samples of psychiatric information. Results: In the aggregate, risk of most psychiatric disorders was lower for Latino subjects than for non-Latino white subjects. Consistent with the immigrant paradox, U.S.-born Latino subjects reported higher rates for most psychiatric disorders than Latino immigrants. However, rates varied when data were stratified by nativity and disorder and adjusted fo...
904 citations
TL;DR: Pharmacological interventions such as mood stabilizers, which dampen limbic irritability, or selective serotonin reuptake inhibitors (SSRIs), which may enhance "top-down" control, as well as psychosocial interventions to develop alternative coping skills and reinforce reflective delays may be therapeutic.
Abstract: Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are grounded in an underlying neurobiological susceptibility that is just beginning to be understood. The failure of “top-down” control systems in the prefrontal cortex to modulate aggressive acts that are triggered by anger provoking stimuli appears to play an important role. An imbalance between prefrontal regulatory influences and hyper-responsivity of the amygdala and other limbic regions involved in affective evaluation are implicated. Insufficient serotonergic facilitation of “top-down” control, excessive catecholaminergic stimulation, and subcortical imbalances of glutamatergic/gabaminergic systems as well as pathology in neuropeptide systems involved in the regulation of affiliative behavior may contribute to abnormalities in this circuitry. Thus, pharmacol...
781 citations
TL;DR: These findings support the contention that callous and unemotional personality traits are associated with reduced amygdala response to distress-based social cues.
Abstract: Objective: Extensive work implicates abnormal amygdala activation in emotional facial expression processing in adults with callous-unemotional traits. However, no research has examined amygdala response to emotional facial expressions in adolescents with disruptive behavior and callous-unemotional traits. Moreover, despite high comorbidity of callous-unemotional traits and attention deficit hyperactivity disorder (ADHD), no research has attempted to distinguish neural correlates of pediatric callous-unemotional traits and ADHD. Method: Participants were 36 children and adolescents (ages 10–17 years); 12 had callous-unemotional traits and either conduct disorder or oppositional defiant disorder, 12 had ADHD, and 12 were healthy comparison subjects. Functional MRI was used to assess amygdala activation patterns during processing of fearful facial expressions. Patterns in the callous-unemotional traits group were compared with those in the ADHD and comparison groups. Results: In youths with callous-unemotion...
750 citations
TL;DR: Remission was significantly less likely and took longer to occur in these patients than in those with nonanxious depression, and ratings of side effect frequency, intensity, and burden, as well as the number of serious adverse events, were significantly greater in the anxious depression group.
Abstract: Objective: About half of outpatients with major depressive disorder also have clinically meaningful levels of anxiety. The authors conducted a secondary data analysis to compare antidepressant treatment outcomes for patients with anxious and nonanxious major depression in Levels 1 and 2 of the STAR*D study. Method: A total of 2,876 adult outpatients with major depressive disorder, enrolled from 18 primary and 23 psychiatric care sites, received citalopram in Level 1 of STAR*D. In Level 2, a total of 1,292 patients who did not remit with or tolerate citalopram were randomly assigned either to switch to sustained-release bupropion (N=239), sertraline (N=238), or extended-release venlafaxine (N=250) or to continue taking citalopram and receive augmentation with sustained-release bupropion (N=279) or buspirone (N=286). Treatment could last up to 14 weeks in each level. Patients were designated as having anxious depression if their anxiety/somatization factor score from the 17-item Hamilton Depression Rating S...
729 citations
TL;DR: Patients with 18 months of mentalization-based treatment by partial hospitalization followed by 18 years of maintenance mentalizing group therapy remain better than those receiving treatment as usual, but their general social function remains impaired.
Abstract: Objective: This study evaluated the effect of mentalization-based treatment by partial hospitalization compared to treatment as usual for borderline personality disorder 8 years after entry into a randomized, controlled trial and 5 years after all mentalization-based treatment was complete. Method: Interviewing was by research psychologists blind to original group allocation and structured review of medical notes of 41 patients from the original trial. Multivariate analysis of variance, chi-square, univariate analysis of variance, and nonparametric Mann-Whitney statistics were used to contrast the two groups depending on the distribution of the data. Results: Five years after discharge from mentalization-based treatment, the mentalization-based treatment by partial hospitalization group continued to show clinical and statistical superiority to treatment as usual on suicidality (23% versus 74%), diagnostic status (13% versus 87%), service use (2 years versus 3.5 years of psychiatric outpatient treatment), ...
702 citations
TL;DR: The consensus cognitive battery developed by the National Institute of Mental Health's (NIMH) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative includes 10 independently developed tests that are recommended as the standard battery for clinical trials of cognitionenhancing interventions for schizophrenia as mentioned in this paper.
Abstract: Objective: The consensus cognitive battery developed by the National Institute of Mental Health’s (NIMH’s) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative includes 10 independently developed tests that are recommended as the standard battery for clinical trials of cognition-enhancing interventions for schizophrenia. To facilitate interpretation of results from the MATRICS Consensus Cognitive Battery using a common scaling across tests, normative data were obtained from a single representative U.S. community sample with the battery administered as a unit. Method: The MATRICS Consensus Cognitive Battery was administered to 300 individuals from the general community at five sites in differing geographic regions. For each site, recruitment was stratified by age, gender, and education. A scientific survey sampling method was used to help avoid sampling bias. The battery was administered in a standard order to each participant in a single session lasting approximate...
615 citations
TL;DR: This study confirms that at least two independent variants in this nicotinic receptor gene cluster contribute to the development of habitual smoking in some populations, and it underscores the importance of multiple genetic variants contributing to theDevelopment of common diseases in various populations.
Abstract: Objective: A recent study provisionally identified numerous genetic variants as risk factors for the transition from smoking to the development of nicotine dependence, including an amino acid change in the α5 nicotinic cholinergic receptor ( CHRNA5 ). The purpose of this study was to replicate these findings in an independent data set and more thoroughly investigate the role of genetic variation in the cluster of physically linked nicotinic receptors, CHRNA5-CHRNA3-CHRNB4 , and the risk of smoking. Method: Individuals from 219 European American families (N=2,284) were genotyped across this gene cluster to test the genetic association with smoking. The frequency of the amino acid variant (rs16969968) was studied in 995 individuals from diverse ethnic populations. In vitro studies were performed to directly test whether the amino acid variant in the CHRNA5 influences receptor function. Results: A genetic variant marking an amino acid change showed association with the smoking phenotype (p=0.007). This varia...
TL;DR: Comparing first-episode schizophrenia and chronic schizophrenia, the authors did not find evidence for the temporolimbic progression of pathology from hippocampus to amygdala, but there was evidence for progression of cortical changes.
Abstract: Objective: The authors sought to map gray matter changes in first-episode schizophrenia and to compare these with the changes in chronic schizophrenia. They postulated that the data would show a progression of changes from hippocampal deficits in first-episode schizophrenia to include volume reductions in the amygdala and cortical gray matter in chronic schizophrenia. Method: A systematic search was conducted for voxel-based structural MRI studies of patients with first-episode schizophrenia and chronic schizophrenia in relation to comparison groups. Meta-analyses of the coordinates of gray matter differences were carried out using anatomical likelihood estimation. Maps of gray matter changes were constructed, and subtraction meta-analysis was used to compare them. Results: A total of 27 articles were identified for inclusion in the meta-analyses. A marked correspondence was observed in regions affected by both first-episode schizophrenia and chronic schizophrenia, including gray matter decreases in the t...
TL;DR: Overall, schizophrenia samples demonstrated a reliable, medium-sized impairment in premorbid IQ, and all studies with pre- and post-onset testing within the same sample suggested that a significant decline in the IQ of individuals with schizophrenia, relative to comparison subjects, was associated with the onset of frank psychosis.
Abstract: Objective: Over the past three decades, there have been significant changes in the diagnostic criteria for schizophrenia as well as changes in measurement of IQ. The last quantitative review of the literature on premorbid IQ in schizophrenia was published more than two decades ago. Since that time, there have been many published studies of data sets pertaining to this issue. The purpose of the present review was to provide an updated meta-analysis of premorbid IQ in individuals who later develop schizophrenia. Method: The authors performed a systematic literature search, which yielded 18 studies that met criteria for the meta-analysis. Inclusion criteria were 1) premorbid psychometric measures of IQ in subjects who were later diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder, 2) similar comparison data, and 3) sufficient data for calculation of an effect size. The analogue to the analysis of variance method was used to model between-study variance due to key study-design...
TL;DR: A four-factor structure explained a large proportion of the heterogeneity in the clinical symptoms of OCD and further item-level factor analyses are needed to determine the appropriate placement of miscellaneous somatic and checking OCD symptoms.
Abstract: Objective: OCD is a clinically heterogeneous condition. This heterogeneity has the potential to reduce power in genetic, neuroimaging, and clinical trials. Despite a mounting number of studies, there remains debate regarding the exact factor structure of OCD symptoms. The authors conducted a meta-analysis to determine the factor structure of the Yale-Brown Obsessive Compulsive Scale Symptom Checklist. Method: Studies were included if they involved subjects with OCD and included an exploratory factor analysis of the 13 Yale-Brown Obsessive Compulsive Scale Symptom Checklist categories or the items therein. A varimax-rotation was conducted in SAS 9.1 using the PROC FACTOR CORR to extract factors from sample-size weighted co-occurrence matrices. Stratified meta-analysis was conducted to determine the factor structure of OCD in studies involving children and adults separately. Results: Twenty-one studies involving 5,124 participants were included. The four factors generated were 1) symmetry: symmetry obsessio...
TL;DR: The author presents a model that recognizes a role for genetic vulnerability and suggests that there is a bidirectional relationship between daytime affect regulation and nighttime sleep such that an escalating vicious circle of disturbance in affect regulation during the day interferes with nighttime sleep/circadian functioning.
Abstract: Despite advances in the treatment of bipolar disorder, a significant proportion of patients experience disabling symptoms between episodes, and relapse rates are high. These circumstances suggest that there is a critical need to achieve a mechanistic understanding of triggers of relapse and to target them with specific, empirically derived treatments. Sleep disturbances are among the most prominent correlates of mood episodes and inadequate recovery, yet sleep has been minimally studied in ways that integrate mechanistic understanding and treatment. In this article, the author seeks to define the limits of current knowledge and to specify preliminary clinical implications. Sleep disturbance is important because it impairs quality of life, contributes to relapse, and has adverse consequences for affective functioning. While sleep disturbance and circadian dysregulation are critical pathophysiological elements in bipolar disorder, many questions about the mechanisms that underpin the association remain. The author presents a model that recognizes a role for genetic vulnerability and suggests that there is a bidirectional relationship between daytime affect regulation and nighttime sleep such that an escalating vicious circle of disturbance in affect regulation during the day interferes with nighttime sleep/circadian functioning, and the effects of sleep deprivation contribute to difficulty in affect regulation the following day.
TL;DR: Although the concept of mentalization is a useful heuristic that enables clinicians to adopt a coherent treatment approach, it may be too broad and multifaceted to be operationalized as a marker for specific forms of psychopathology such as borderline personality disorder.
Abstract: This article aims to review the development of the concept of mentalization, its applications in the understanding and treatment of borderline personality disorder, and the issue of its assessment While conceptually derivative of theory of mind, Fonagy's concept of mentalization concerns more affectively and interpersonally complex understandings of oneself and others, reflecting abilities that enable an individual not only to navigate the social world effectively but also to develop an enriched, stable sense of self The components of mentalization can be organized around self-/other-oriented, implicit/explicit, and cognitive/affective dimensions Concepts of mindfulness, psychological mindedness, empathy, and affect consciousness are shown to partially overlap with mentalization within these three dimensions Mentalization is assessed by the measure of reflective function, a scale to be used adjunctively on semistructured narrative interviews such as the Adult Attachment Interview Its validity has not been fully tested, and its usage has been hampered by the time and expense it requires Although the concept of mentalization is a useful heuristic that enables clinicians to adopt a coherent treatment approach, it may be too broad and multifaceted to be operationalized as a marker for specific forms of psychopathology such as borderline personality disorder Research elucidating the relationship between reflective function, overlapping concepts, and features of borderline psychopathology is needed
TL;DR: In this paper, the authors conducted a meta-analysis of 19 randomized controlled studies in which the incidence of depressive disorders (based on diagnostic criteria) in an experimental group could be compared with that of a control group.
Abstract: Objective: A growing number of studies have tested the efficacy of preventive interventions in reducing the incidence of depressive disorders. Until now, no meta-analysis has integrated the results of these studies. Method: The authors conducted a meta-analysis. After a comprehensive literature search, 19 studies were identified that met inclusion criteria. The studies had to be randomized controlled studies in which the incidence of depressive disorders (based on diagnostic criteria) in an experimental group could be compared with that of a control group. Results: The mean incidence rate ratio was 0.78, indicating a reduction of the incidence of depressive disorders by 22% in experimental compared with control groups. Heterogeneity was low to moderate (I 2 =33%). The number needed to treat to prevent one case of depressive disorder was 22. Moderator analyses revealed no systematic differences between target populations or types of prevention (universal, selective, or indicated). The data included indicat...
TL;DR: These results add to a growing body of evidence that mental disorders are associated with substantial societal-level impairments that should be taken into consideration when making decisions about the allocation of treatment and research resources.
Abstract: Objective: The purpose of this report was to update previous estimates of the association between mental disorders and earnings. Current estimates for 2002 are based on data from the National Comorbidity Survey Replication (NCS-R). Method: The NCS-R is a nationally representative survey of the U.S. household population that was administered from 2001 to 2003. Following the same basic approach as prior studies, with some modifications to improve model fitting, the authors predicted personal earnings in the 12 months before interview from information about 12-month and lifetime DSM-IV mental disorders among respondents ages 18–64, controlling for sociodemographic variables and substance use disorders. The authors used conventional demographic rate standardization methods to distinguish predictive effects of mental disorders on amount earned by persons with earnings from predictive effects on probability of having any earnings. Results: A DSM-IV serious mental illness in the preceding 12 months significantly...
TL;DR: Results support further investigation of xanomeline as a novel approach to treating schizophrenia and show improvements most robustly in measures of verbal learning and short-term memory function.
Abstract: Objective: There are significant unmet needs in the treatment of schizophrenia, especially for the treatment of cognitive impairment, negative syndrome, and cognitive function. Preclinical data suggest that agonists with selective affinity for acetylcholine muscarinic receptors provide a potentially new mechanism to treat schizophrenia. The authors studied xanomeline, a relatively selective muscarinic type 1 and type 4 (M 1 and M 4 ) receptor agonist, to determine if this agent is effective in the treatment of schizophrenia. Method: In this pilot study, the authors examined the efficacy of xanomeline on clinical outcomes in subjects with schizophrenia (N=20) utilizing a double-blind, placebo-controlled, 4-week treatment design. Outcome measures included the Positive and Negative Syndrome Scale (PANSS) for schizophrenia, the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) scale, and a test battery designed to measure cognitive function in patients with schizophrenia. Results: Su...
TL;DR: Findings support the longitudinal distinction of anorexia nervosa and bulimia nervosa but do not support the anoremia nervosa subtyping schema.
Abstract: Objective: The Diagnostic and Statistical Manual of Mental Disorders (DSM) is designed primarily as a clinical tool. Yet high rates of diagnostic “crossover” among the anorexia nervosa subtypes and bulimia nervosa may reflect problems with the validity of the current diagnostic schema, thereby limiting its clinical utility. This study was designed to examine diagnostic crossover longitudinally in anorexia nervosa and bulimia nervosa to inform the validity of the DSM-IV-TR eating disorders classification system. Method: A total of 216 women with a diagnosis of anorexia nervosa or bulimia nervosa were followed for 7 years; weekly eating disorder symptom data collected using the Eating Disorder Longitudinal Interval Follow-Up Examination allowed for diagnoses to be made throughout the follow-up period. Results: Over 7 years, the majority of women with anorexia nervosa experienced diagnostic crossover: more than half crossed between the restricting and binge eating/purging anorexia nervosa subtypes over time;...
TL;DR: DMXB-A, a nicotinic agonist that activates alpha(7)-nicotinic receptors, improved clinical ratings of negative symptoms that are generally resistant to treatment with dopamine antagonist antipsychotic drugs.
Abstract: Objective: Nicotinic acetylcholine receptors are possible therapeutic targets for schizophrenia, as shown by neurobiological and molecular evidence for deficiencies in expression of α 7 -nicotinic receptors. Patients’ heavy smoking suggests attempted self-medication through this mechanism. The agent 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A) is a partial α 7 -nicotinic agonist and can be taken orally. A phase 1 trial showed evidence for cognitive enhancement in schizophrenia. Method: Thirty-one subjects with schizophrenia received DMXB-A at two different doses and placebo for periods of 4 weeks in a three-arm, two-site, double-blind, crossover phase 2 trial. The MATRICS Consensus Cognitive Battery assessed cognitive effects, and the Scale for the Assessment of Negative Symptoms (SANS) and Brief Psychiatric Rating Scale (BPRS) assessed clinical effects. Subjects continued their current antipsychotic drug during the trial and were nonsmokers. Results: There were no significant differences in the MATRI...
TL;DR: The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia and schizoaffective disorder and the safety findings related to weight gain and metabolic problems raise important public health concerns.
Abstract: Objective: Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. Method: This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5–20 mg/day), risperidone (0.5–6 mg/day), or molindone (10–140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and ≥20% reduction in Positive and Negative Syndrome Scale (PANS...
TL;DR: Findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.
Abstract: Objective: Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory, and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, the authors sought to determine whether this pattern of altered gene expression is restricted to the dorsolateral prefrontal cortex or could also contribute to the dysfunction of other cortical areas in subjects with schizophrenia. Method: Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (dorsolateral prefrontal cortex, anterior cingulate cortex, and primary motor and primary visual cortices) of subjects (N=12) with schizophrenia and matched normal comparison subjects. Results: Expression levels of seven transcripts were lower in subjects with schizophrenia, with the magnitude of reduction for each transcript comparable across the four areas. The largest reductions were detected for mRNA encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67-kilodalton isoform of glutamic acid decarboxylase, the GABA membrane transporter GAT-1, and the α1 and δ subunits of GABAA receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas. Conclusions: Because the areas examined represent the major functional domains (e.g., association, limbic, motor, and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.
TL;DR: It is unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects cannot be ruled out.
Abstract: Objective: The authors carried out a genetic association study of 14 schizophrenia candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT, and ARVCF). This study tested the hypothesis of association of schizophrenia with common single nucleotide polymorphisms (SNPs) in these genes using the largest sample to date that has been collected with uniform clinical methods and the most comprehensive set of SNPs in each gene. Method: The sample included 1,870 cases (schizophrenia and schizoaffective disorder) and 2,002 screened comparison subjects (i.e. controls), all of European ancestry, with ancestral outliers excluded based on analysis of ancestry-informative markers. The authors genotyped 789 SNPs, including tags for most common SNPs in each gene, SNPs previously reported as associated, and SNPs located in functional domains of genes such as promoters, coding exons (including nonsynonymous SNPs), 3′ untranslated regions, and conserved noncoding sequences. After extensive data cleaning, 648 SNPs were analyzed for association of single SNPs and of haplotypes. Results: Neither experiment-wide nor gene-wide statistical significance was observed in the primary single-SNP analyses or in secondary analyses of haplotypes or of imputed genotypes for additional common HapMap SNPs. Results in SNPs previously reported as associated with schizophrenia were consistent with chance expectation, and four functional polymorphisms in COMT, DRD2, and HTR2A did not produce nominally significant evidence to support previous evidence for association. Conclusions: It is unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects cannot be ruled out.
TL;DR: Data provide support for the use of D-cycloserine as an augmentation of behavior therapy for OCD and extend findings in animals and other human disorders suggesting that behavior therapy acts by way of long-term potentiation of glutamatergic pathways and that the effects of behavior Therapy are potentiated by an NMDA agonist.
Abstract: Objective: This study examined whether d -cycloserine, a partial agonist at the N -methyl- d -aspartate (NMDA) glutamatergic receptor, enhances the efficacy of behavior therapy for obsessive-compulsive disorder (OCD). Method: A randomized, double-blind, placebo-controlled trial investigating d -cycloserine versus placebo augmentation of behavior therapy was conducted in 23 OCD patients. Patients first underwent a diagnostic interview and pretreatment evaluation, followed by a psychoeducational/treatment planning session. Then they received 10 behavior therapy sessions. Treatment sessions were conducted twice per week. One hour before each of the behavior therapy sessions, the participants received either d -cycloserine, 100 mg, or a placebo. Results: Relative to the placebo group, the d -cycloserine group’s OCD symptoms were significantly more improved at mid-treatment, and the d -cycloserine group’s depressive symptoms were significantly more improved at posttreatment. Conclusions: These data provide sup...
TL;DR: Neuroimaging studies of bipolar disorder ideally should recruit both unmedicated and medicated individuals, and individuals who are unable to tolerate medication withdrawal likely have more severe illness and are especially informative for research examining biomarkers of illness and treatment response.
Abstract: Objective: Neuroimaging studies are promising components for a new diagnostic framework for bipolar disorder, but a major issue is the potential confound of psychotropic medication upon experimental measures. Withdrawing all individuals from medication and examining only unmedicated individuals may be clinically unfeasible, and examining only unmedicated individuals may render findings less generalizable. Method: The authors review structural and functional neuroimaging studies of medicated and unmedicated patients with bipolar disorder to discern the possible confounding effect of medication. Results: Findings from studies identified on MEDLINE that included medicated individuals with bipolar disorder indicated either no significant effect or ameliorative effects of psychotropic medications on abnormal structural and functional neuroimaging measures relevant to pathophysiologic mechanisms of the disorder. Different strategies for assessing medication effects are compared. Conclusions: Neuroimaging studie...
TL;DR: STEPPS, an adjunctive group treatment, can deliver clinically meaningful improvements in borderline personality disorder-related symptoms and behaviors, enhance global functioning, and relieve depression.
Abstract: Objective: Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a 20-week manual-based group treatment program for outpatients with borderline personality disorder that combines cognitive behavioral elements and skills training with a systems component. The authors compared STEPPS plus treatment as usual with treatment as usual alone in a randomized controlled trial. Method: Subjects with borderline personality disorder were randomly assigned to STEPPS plus treatment as usual or treatment as usual alone. Total score on the Zanarini Rating Scale for Borderline Personality Disorder was the primary outcome measure. Secondary outcomes included measures of global functioning, depression, impulsivity, and social functioning; suicide attempts and self-harm acts; and crisis utilization. Subjects were followed 1 year posttreatment. A linear mixed-effects model was used in the analysis. Results: Data pertaining to 124 subjects (STEPPS plus treatment as usual [N=65]; treatment as usual alone...
TL;DR: The data suggest that CBT4CBT is an effective adjunct to standard outpatient treatment for substance dependence and may provide an important means of making CBT, an empirically validated treatment, more broadly available.
Abstract: Objectives: This study evaluated the efficacy of a computer-based version of cognitive-behavioral therapy (CBT) for substance dependence. Method: This was a randomized clinical trial in which 77 individuals seeking treatment for substance dependence at an outpatient community setting were randomly assigned to standard treatment or standard treatment with biweekly access to computer-based training in CBT (CBT4CBT) skills. Results: Treatment retention and data availability were comparable across the treatment conditions. Participants assigned to the CBT4CBT condition submitted significantly more urine specimens that were negative for any type of drugs and tended to have longer continuous periods of abstinence during treatment. The CBT4CBT program was positively evaluated by participants. In the CBT4CBT condition, outcome was more strongly associated with treatment engagement than in treatment as usual; furthermore, completion of homework assignments in CBT4CBT was significantly correlated with outcome and a...
TL;DR: Amygdala and nucleus accumbens responses to affective stimuli may reflect vulnerability for major depression, and constraining attention may normalize emotion-related neural function possibly by engagement of the medial prefrontal cortex.
Abstract: Objective: Offspring of parents with major depressive disorder face a threefold higher risk for major depression than offspring without such family histories. Although major depression is a significant cause of morbidity and mortality, neural correlates of risk for major depression remain poorly understood. This study compares amygdala and nucleus accumbens activation in children and adolescents at high and low risk for major depression under varying attentional and emotional conditions. Method: Thirty-nine juveniles, 17 offspring of parents with major depression (high-risk group) and 22 offspring of parents without histories of major depression, anxiety, or psychotic disorders (low-risk group) completed a functional magnetic resonance imaging study. During imaging, subjects viewed faces that varied in intensity of emotional expressions across blocks of trials while attention was unconstrained (passive viewing) and constrained (rate nose width on face, rate subjective fear while viewing face). Results: Wh...