Gerhard Hellemann

Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: A meta-analysis

BACKGROUND Neurocognitive functioning in schizophrenia has received considerable attention because of its robust prediction of functional outcome. Psychiatric symptoms, in particular negative symptoms, have also been shown to predict functional outcome, but have garnered much less attention. The high degree of intercorrelation among all of these variables leaves unclear whether neurocognition has a direct effect on functional outcome or whether that relationship to functional outcome is partially mediated by symptoms. METHODS A meta-analysis of 73 published English language studies (total n=6519) was conducted to determine the magnitude of the relationship between neurocognition and symptoms, and between symptoms and functional outcome. A model was tested in which symptoms mediate the relationship between neurocognition and functional outcome. Functional outcome involved measures of social relationships, school and work functioning, and laboratory assessments of social skill. RESULTS Although negative symptoms were found to be significantly related to neurocognitive functioning (p<.01) positive symptoms were not (p=.97). The relationship was moderate for negative symptoms (r=-.24, n=4757, 53 studies), but positive symptoms were not at all related to neurocogniton (r=.00, n=1297, 25 studies). Negative symptoms were significantly correlated with functional outcome (r=-.42, p<.01), and again the correlation was higher than for positive symptoms (r=-.03, p=.55). Furthermore, our findings support a model in which negative symptoms significantly mediate the relationship between neurocognition and functional outcome (Sobel test p<.01). CONCLUSIONS Although neurocognition and negative symptoms are both predictors of functional outcome, negative symptoms might at least partially mediate the relationship between neurocognition and outcome.

Social Cognition in Schizophrenia, Part 1: Performance Across Phase of Illness

Social cognitive impairments are consistently reported in schizophrenia and are associated with functional outcome. We currently know very little about whether these impairments are stable over the course of illness. In the current study, 3 different aspects of social cognition were assessed (emotion processing, Theory of Mind [ToM], and social relationship perception) at 3 distinct developmental phases of illness: prodromal, first episode, and chronic. In this cross-sectional study, participants included 50 individuals with the prodromal risk syndrome for psychosis and 34 demographically comparable controls, 81 first-episode schizophrenia patients and 46 demographically comparable controls, and 53 chronic schizophrenia patients and 47 demographically comparable controls. Outcome measures included total and subtest scores on 3 specialized measures of social cognition: (1) emotion processing assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test, (2) ToM assessed with The Awareness of Social Inference Test, and (3) social relationship perception assessed the Relationships Across Domains Test. Social cognitive performance was impaired across all domains of social cognition and in all clinical samples. Group differences in performance were comparable across phase of illness, with no evidence of progression or improvement. Age had no significant effect on performance for either the clinical or the comparison groups. The findings suggest that social cognition in these 3 domains fits a stable pattern that has outcome and treatment implications. An accompanying article prospectively examines the longitudinal stability of social cognition and prediction of functional outcome in the first-episode sample.

From Perception to Functional Outcome in Schizophrenia: Modeling the Role of Ability and Motivation

CONTEXT Schizophrenia remains a highly disabling disorder, but the specific determinants and pathways that lead to functional impairment are not well understood. It is not known whether these key determinants of outcome lie on 1 or multiple pathways. OBJECTIVE To evaluate theoretically based models of pathways to functional outcome starting with early visual perception. The intervening variables were previously established determinants of outcome drawn from 2 general categories: ability (ie, social cognition and functional capacity) and beliefs/motivation (ie, defeatist beliefs, expressive and experiential negative symptoms). We evaluated an integrative model in which these intervening variables formed a single pathway to poor outcome. DESIGN This was a cross-sectional study that applied structural equation modeling to evaluate the relationships among determinants of functional outcome in schizophrenia. SETTING Assessments were conducted at a Veterans Administration Medical Center. PARTICIPANTS One hundred ninety-one clinically stable outpatients with schizophrenia or schizoaffective disorder were recruited from the community. RESULTS A measurement model showed that the latent variables of perception, social cognition, and functional outcome were well reflected by their indicators. An initial untrimmed structural model with functional capacity, defeatist beliefs, and expressive and experiential negative symptoms had good model fit. A final trimmed model was a single path running from perception to ability to motivational variables to outcome. It was more parsimonious and had better fit indices than the untrimmed model. Further, it could not be improved by adding or dropping connections that would change the single path to multiple paths. The indirect effect from perception to outcome was significant. CONCLUSIONS The final structural model was a single pathway running from perception to ability to beliefs/motivation to outcome. Hence, both ability and motivation appear to be needed for community functioning and can be modeled effectively on the same pathway.

Social Cognition in Schizophrenia, Part 2: 12-Month Stability and Prediction of Functional Outcome in First-Episode Patients

This study evaluated the longitudinal stability and functional correlates of social cognition during the early course of schizophrenia. Fifty-five first-episode schizophrenia patients completed baseline and 12-month follow-up assessments of 3 key domains of social cognition (emotional processing, theory of mind, and social/relationship perception), as well as clinical ratings of real-world functioning and symptoms. Scores on all 3 social cognitive tests demonstrated good longitudinal stability with test-retest correlations exceeding .70. Higher baseline and 12-month social cognition scores were both robustly associated with significantly better work functioning, independent living, and social functioning at the 12-month follow-up assessment. Furthermore, cross-lagged panel analyses were consistent with a causal model in which baseline social cognition drove later functional outcome in the domain of work, above and beyond the contribution of symptoms. Social cognitive impairments are relatively stable, functionally relevant features of early schizophrenia. These results extend findings from a companion study, which showed stable impairments across patients in prodromal, first-episode, and chronic phases of illness on the same measures. Social cognitive impairments may serve as useful vulnerability indicators and early clinical intervention targets.

Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study

IntroductionCurcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimers disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD.MethodsWe performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex® with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimers Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimers Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured.ResultsMean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex® was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between treatment groups in clinical or biomarker efficacy measures. The levels of native curcumin measured in plasma were low (7.32 ng/mL).ConclusionsCurcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms. We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound.Trial registrationClinicalTrials.gov Identifier: NCT00099710.

Longitudinal follow-up of children with autism receiving targeted interventions on joint attention and play.

OBJECTIVE This study examines the cognitive and language outcomes of children with an autism spectrum disorder (ASD) over a 5-year period after receiving targeted early interventions that focused on joint attention and play skills. METHOD Forty children from the original study (n = 58) had complete data at the 5-year follow-up. RESULTS In all, 80% of children had achieved functional use of spoken language with baseline play level predicting spoken language at the 5-year follow-up. Of children who were using spoken language at age 8 years, several baseline behaviors predicted their later ability, including earlier age of entry into the study, initiating joint attention skill, play level, and assignment to either the joint attention or symbolic play intervention group. Only baseline play diversity predicted cognitive scores at age 8 years. CONCLUSIONS This study is one of the only long-term follow-up studies of children who participated in preschool early interventions aimed at targeting core developmental difficulties. The study findings suggest that focusing on joint attention and play skills in comprehensive treatment models is important for long-term spoken language outcomes.

Examining predictive models of HRQOL in a population-based, multiethnic sample of women with breast carcinoma

BackgroundThis study examined health related quality of life (HRQOL) and its predictors among African-, Asian-, Latina-, and European American breast cancer survivors (BCS) using a socio-ecologically and culturally contextual theoretical model of HRQOL.MethodsWe employed a case–control, cross sectional design with a population-based sample from the California Cancer Registry. Descriptive, bivariate, and multivariate regression analyses were conducted.ResultsThe sample included 703 BCS: 135 (19%) African-, 206 (29%) Asian-, 183 (26%) Latina-, and 179 (26%) European Americans. Latinas reported the lowest HRQOL (p < 0.0001). The final regression model explained 70% of variance in HRQOL. Years since diagnosis, number of comorbidities, role limitation, emotional wellbeing, quality of doctor–patient relationship, social support, and life stress are significant HRQOL determinants. Exploratory regression analyses indicate ethnic differences in significant predictors for HRQOL.ConclusionsHRQOL among this multiethnic sample ranged from fair to good. Bivariate analysis suggests that ethnic differences in HRQOL exist. However, regression analyses demonstrated that socio-ecological factors in conjunction with medical characteristics are more salient to HRQOL outcomes, and that ethnic group membership may be a proxy for socio-ecological context. Furthermore, the influence of ethnicity, culture, and social-ecology are complex; research with large, population-based samples are necessary to disentangle the impact of contextual factors on HRQOL.

Symptom Domains and Neurocognitive Functioning Can Help Differentiate Social Cognitive Processes in Schizophrenia: A Meta-Analysis

BACKGROUND The existence of deficits in several social cognitive domains has been established in schizophrenia, and those impairments are known to be a significant determinant of functional outcome. Both symptoms and neurocognition have been linked to social cognitive deficits, but the nature and the relative strength of these relationships have not been established. METHODS A meta-analysis of 154 studies (combined N = 7175) was conducted to determine the magnitude of the relationships between 3 symptom domains (reality distortion, disorganization, and negative symptoms) and 6 Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains of neurocognition with 4 domains of social cognition. Analyses were conducted to determine whether the strength of these relationships differed depending on the symptom type or neurocognitive domain under investigation. RESULTS The correlations between reality distortion and the domains of social cognition ranged from near zero to moderate (rs range from -.07 to -.22), as compared with the moderate association for disorganization (rs range from -.22 to -.32) and negative symptoms (rs range from -.20 to -.26). For each of the neurocognitive domains, the relationships to social cognitive domains were mostly moderate (rs range from .17 to .37), with no one neurocognitive domain being prominent. CONCLUSIONS The effect sizes of the correlations between disorganization and negative symptoms with social cognition were relatively larger and more consistent than reality distortion. The relationship between social cognition and 6 MATRICS domains of neurocognition were mostly moderate and relatively consistent. When considering disorganization and negative symptoms, the relationship to social cognitive processes was relatively as strong as for neurocognition.

Efficacy and specificity of social cognitive skills training for outpatients with psychotic disorders.

Psychosocial interventions that target social cognition show promise for enhancing the functional outcomes of people with psychotic disorders. This randomized controlled trial evaluated the efficacy and treatment-outcome specificity of a 24-session Social Cognitive Skills Training (SCST) that targets emotional processing, social perception, attributional bias, and mentalizing (or Theory of Mind). Sixty-eight stable outpatients with primary psychotic disorders were randomly assigned to one of four time- and group format-matched treatment conditions: (1) SCST, (2) computerized neurocognitive remediation, (3) standard illness management skills training, or (4) a Hybrid treatment that combined elements of SCST and neurocognitive remediation. The SCST group demonstrated greater improvements over time than comparison groups in the social cognitive domain of emotional processing, including improvement on measures of facial affect perception and emotion management. There were no differential benefits among treatment conditions on neurocognitive or clinical symptom changes over time. Results indicate that a targeted social cognitive intervention led to improvements in social cognition among outpatients with psychosis. Findings provide guidance for continued efforts to maximize the benefits of social cognitive interventions.

Prevalence and correlates of eating disorders in 875 patients with bipolar disorder

OBJECTIVE Relatively little is known about the co-occurrence of bipolar and eating disorders. We therefore assessed the prevalence and clinical correlates of eating disorders in 875 patients with bipolar disorder. METHOD 875 outpatients with DSM-IV bipolar I or II disorder were evaluated with structured diagnostic interviews and clinician- and self-administered questionnaires to determine bipolar and eating disorder diagnoses, other comorbid Axis I disorder diagnoses, and demographic and historical illness characteristics. RESULTS 125 (14.3%) patients met DSM-IV criteria for at least one comorbid lifetime Axis I eating disorder, with binge eating disorder (N=77) being more common than bulimia nervosa (n=42) and anorexia nervosa (N=27). There were no significant eating disorder comorbidity differences between bipolar I and bipolar II patients. Presence of a lifetime comorbid eating disorder was associated with female gender, younger age, earlier age of onset of mood symptoms and of bipolar disorder, presentation in a mixed episode, greater number of prior mood episodes, history of rapid cycling and suicide attempts, greater mean BMI, obesity and severe obesity, and family history of depression, bipolar disorder, alcoholism, and drug abuse. When the three eating disorder groups were compared, lifetime anorexia nervosa was associated with normal weight and a lifetime anxiety disorder, lifetime bulimia nervosa was associated with overweight, and lifetime binge eating disorder was associated with obesity and severe obesity. CONCLUSIONS Patients with bipolar disorder, especially women, not infrequently have comorbid eating disorders, and this comorbidity is associated with an earlier age of onset and more severe course of bipolar illness.