Dwight Dickinson

The 2009 Schizophrenia PORT Psychosocial Treatment Recommendations and Summary Statements

The Schizophrenia Patient Outcomes Research Team (PORT) psychosocial treatment recommendations provide a comprehensive summary of current evidence-based psychosocial treatment interventions for persons with schizophrenia. There have been 2 previous sets of psychosocial treatment recommendations (Lehman AF, Steinwachs DM. Translating research into practice: the Schizophrenia Patient Outcomes Research Team (PORT) treatment recommendations. Schizophr Bull. 1998;24:1-10 and Lehman AF, Kreyenbuhl J, Buchanan RW, et al. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2003. Schizophr Bull. 2004;30:193-217). This article reports the third set of PORT recommendations that includes updated reviews in 7 areas as well as adding 5 new areas of review. Members of the psychosocial Evidence Review Group conducted reviews of the literature in each intervention area and drafted the recommendation or summary statement with supporting discussion. A Psychosocial Advisory Committee was consulted in all aspects of the review, and an expert panel commented on draft recommendations and summary statements. Our review process produced 8 treatment recommendations in the following areas: assertive community treatment, supported employment, cognitive behavioral therapy, family-based services, token economy, skills training, psychosocial interventions for alcohol and substance use disorders, and psychosocial interventions for weight management. Reviews of treatments focused on medication adherence, cognitive remediation, psychosocial treatments for recent onset schizophrenia, and peer support and peer-delivered services indicated that none of these treatment areas yet have enough evidence to merit a treatment recommendation, though each is an emerging area of interest. This update of PORT psychosocial treatment recommendations underscores both the expansion of knowledge regarding psychosocial treatments for persons with schizophrenia at the same time as the limitations in their implementation in clinical practice settings.

The global cognitive impairment in schizophrenia: consistent over decades and around the world.

OBJECTIVE Schizophrenia results in cognitive impairments as well as positive, negative, and disorganized symptomatology. The present study examines the extent to which these cognitive deficits are generalized across domains, potential moderator variables, and whether the pattern of cognitive findings reported in schizophrenia has remained consistent over time and across cultural and geographic variation. METHOD Relevant publications from 2006 to 2011 were identified through keyword searches in PubMed and an examination of reference lists. Studies were included if they (1) compared the cognitive performance of adult schizophrenia patients and healthy controls, (2) based schizophrenia diagnoses on contemporary diagnostic criteria, (3) reported information sufficient to permit effect size calculation, (4) were reported in English, and (5) reported data for neuropsychological tests falling into at least 3 distinct cognitive domains. A set of 100 non-overlapping studies was identified, and effect sizes (Hedges g) were calculated for each cognitive variable. RESULTS Consistent with earlier analyses, patients with schizophrenia scored significantly lower than controls across all cognitive tests and domains (grand mean effect size, g=-1.03). Patients showed somewhat larger impairments in the domains of processing speed (g=-1.25) and episodic memory (g=-1.23). Our results also showed few inconsistencies when grouped by geographic region. CONCLUSIONS The present study extends findings from 1980 to 2006 of a substantial, generalized cognitive impairment in schizophrenia, demonstrating that this finding has remained robust over time despite changes in assessment instruments and alterations in diagnostic criteria, and that it manifests similarly in different regions of the world despite linguistic and cultural differences.

Meta-analysis of neuropsychological functioning in euthymic bipolar disorder: an update and investigation of moderator variables

Mann‐Wrobel MC, Carreno JT, Dickinson D. Meta‐analysis of neuropsychological functioning in euthymic bipolar disorder: an update and investigation of moderator variables.
Bipolar Disord 2011: 13: 334–342.

General and Specific Cognitive Deficits in Schizophrenia: Goliath Defeats David?

BACKGROUND Our earlier work suggested that the cognitive performance impairment in individuals with schizophrenia relative to healthy control subjects was generalized, cutting across narrower cognitive ability dimensions. Current analyses sought to extend these findings. METHODS Seventeen neuropsychological variables, available for 148 schizophrenia subjects and 157 control subjects, were subjected to structural equation modeling. Analyses incorporated a hierarchical model, grouping the variables into six familiar cognitive domains and linking these to a higher-order, general cognitive ability factor. We added diagnosis to the model as a grouping factor and estimated loadings from diagnosis to the general cognitive factor and, separately, to the domain factors. RESULTS The fit of the final model was good (e.g., Non-Normed Fit Index [NNFI] = .988). Approximately 63.6% of the diagnosis-related variance in cognitive performance was mediated through the general factor, with smaller direct effects on verbal memory (13.8%) and processing speed (9.1%). CONCLUSIONS The schizophrenia cognitive deficit is largely generalized across performance domains, with small, direct effects of diagnostic group confined to selected domains. This generalized deficit sometimes has been seen as a function of the psychometric limitations of traditional cognitive test batteries. Alternatively, it may be a fundamental manifestation of schizophrenia, with similarly general neurobiological underpinnings.

Genes, cognition and brain through a COMT lens.

Various genes are known to modulate the delicate balance of dopamine in prefrontal cortex and influence cortical information processing. Catechol-O-methyltransferase (COMT) on chromosome 22q11 is the most widely studied of these genes. Val158Met, a common, functional variant in the coding sequence that increases or decreases the enzymatic activity of the gene has been shown to impact the efficiency of prefrontally-mediated cognition, specifically executive functioning, working memory, fluid intelligence and attentional control. We review the rapidly evolving literature exploring the association between COMT genotype and cognitive performance, and illustrate how this polymorphism has served a pivotal role in characterizing various interacting dimensions of complexity in the relationship between genes and cognition. We review how Val158Met has been used to help develop and validate behavioral and neurophysiological phenotypes, as a critical tool in dissecting overlapping neural functional systems and exploring interactions within and between genes, and in exploring how gene effects on cognition are modulated by environmental, demographic and developmental factors. Despite the impressive range of findings, the COMT story is also a bracing reminder of how much work remains to translate this knowledge into practical clinical applications.

A Randomized, Controlled Trial of Computer-Assisted Cognitive Remediation for Schizophrenia

OBJECTIVE There is considerable interest in cognitive remediation for schizophrenia, but its essential components are still unclear. The goal of the current study was to develop a broadly targeted computer-assisted cognitive remediation program and conduct a rigorous clinical trial in a large group of schizophrenia patients. METHOD Sixty-nine people with schizophrenia or schizoaffective disorder were randomly assigned to 36 sessions of computer-assisted cognitive remediation or an active control condition. Remediation broadly targeted cognitive and everyday performance by providing supportive, graduated training and practice in selecting, executing, and monitoring cognitive operations. It used engaging computer-based cognitive exercises and one-on-one training. A total of 61 individuals (34 in remediation group, 27 in control group) engaged in treatment, completed posttreatment assessments, and were included in intent-to-treat analyses. Primary outcomes were remediation exercise metrics, neuropsychological composites (episodic memory, working memory, attention, executive functioning, and processing speed), and proxy measures of community functioning. RESULTS Regression modeling indicated that performance on eight of 10 exercise metrics improved significantly more in the remediation condition than in the control condition. The mean effect size, favoring the remediation condition, was 0.53 across all 10 metrics. However, there were no significant benefits of cognitive remediation on any neuropsychological or functional outcome measure, either immediately after treatment or at the 3-month follow-up. CONCLUSIONS Cognitive remediation for people with schizophrenia was effective in improving performance on computer exercises, but the benefits of training did not generalize to broader neuropsychological or functional outcome measures. The evidence for this treatment approach remains mixed.

The MCCB impairment profile for schizophrenia outpatients: Results from the MATRICS psychometric and standardization study

The MATRICS Psychometric and Standardization Study was conducted as a final stage in the development of the MATRICS Consensus Cognitive Battery (MCCB). The study included 176 persons with schizophrenia or schizoaffective disorder and 300 community residents. Data were analyzed to examine the cognitive profile of clinically stable schizophrenia patients on the MCCB. Secondarily, the data were analyzed to identify which combination of cognitive domains and corresponding cut-off scores best discriminated patients from community residents, and patients competitively employed vs. those not. Raw scores on the ten MCCB tests were entered into the MCCB scoring program which provided age- and gender-corrected T-scores on seven cognitive domains. To test for between-group differences, we conducted a 2 (group)×7 (cognitive domain) MANOVA with follow-up independent t-tests on the individual domains. Classification and regression trees (CART) were used for the discrimination analyses. Examination of patient T-scores across the seven cognitive domains revealed a relatively compact profile with T-scores ranging from 33.4 for speed of processing to 39.3 for reasoning and problem-solving. Speed of processing and social cognition best distinguished individuals with schizophrenia from community residents; speed of processing along with visual learning and attention/vigilance optimally distinguished patients competitively employed from those who were not. The cognitive profile findings provide a standard to which future studies can compare results from other schizophrenia samples and related disorders; the classification results point to specific areas and levels of cognitive impairment that may advance work rehabilitation efforts.

Systemic Hypotheses for Generalized Cognitive Deficits in Schizophrenia: A New Take on An Old Problem

The schizophrenia research community, including government, industry, and academia, has made development of procognitive treatment strategies a priority. Much current research is directed at dividing broad impairments in cognition into more delineated components that might correspond to relatively specific neural systems and serve as targets for intervention. Sometimes overlooked in this ambitious agenda is the substantial neuropsychological literature that signals a more broadly generalized dysfunction in higher order cognitive functions in this illness. In this article, we argue that a generalized cognitive deficit is at the core of the disorder, is not a methodological artifact, and deserves more focused consideration from cognitive specialists in the field. Further, we weigh evidence that this broad deficit may have systemic biological underpinnings. At the level of the central nervous system, examples of findings that might help to account for broad cognitive impairment include gray and white matter irregularities, poor signal integration by neurons and neural networks, and abnormalities in glutamate and gamma-aminobutyric acid neurotransmission. Other, more speculative hypotheses focus on even broader somatic systems, including energy metabolism and inflammatory processes. Treatment implications of systemic conceptualizations of schizophrenia are also considered.

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

The purpose of this study was to examine measures of anatomical connectivity between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to assess their functional implications. We measured thalamocortical connectivity with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients with schizophrenia and 22 age- and sex-matched controls. The relationship between thalamocortical connectivity and prefrontal cortical blood-oxygenation-level-dependent (BOLD) functional activity as well as behavioral performance during working memory was examined in a subsample of 9 patients and 18 controls. Compared with controls, schizophrenia patients showed reduced total connectivity of the thalamus to only one of six cortical regions, the LPFC. The size of the thalamic region with at least 25% of model fibers reaching the LPFC was also reduced in patients compared with controls. The total thalamocortical connectivity to the LPFC predicted working memory task performance and also correlated with LPFC BOLD activation. Notably, the correlation with BOLD activation was accentuated in patients as compared with controls in the ventral LPFC. These results suggest that thalamocortical connectivity to the LPFC is altered in schizophrenia with functional consequences on working memory processing in LPFC.

A comparison of cognitive structure in schizophrenia patients and healthy controls using confirmatory factor analysis

There is evidence that cognitive task performance breaks down into the same broad domains in schizophrenia as in healthy populations. However, this does not mean that the domains are independent of one another or that the interrelationships among domains are the same between groups. We used confirmatory factor analysis (CFA) to compare the latent structure of a broad neuropsychological battery in schizophrenia patients (n = 148) and healthy controls (n = 157). Main analyses examined the fit of a hierarchical six-factor model, in which associations among the factors were assumed to reflect their strong shared relationship to a general cognitive ability factor. The model incorporated the factors of verbal comprehension, perceptual organization, verbal memory, spatial memory, processing speed, and executive/working memory. The hierarchical model provided a good overall fit to data from both groups. However multiple groups CFA revealed significant differences in factor loadings between groups, reflecting a more generalized latent structure of cognitive ability in schizophrenia. This was also evident in higher bivariate correlations among cognitive domain composite scores calculated from the observed test data. Cognitive ability, as reflected in test performance, appears to be more unitary in schizophrenia than in healthy subjects. This finding may have measurement and treatment implications.