Shaun M. Eack

Neuroprotective Effects of Cognitive Enhancement Therapy Against Gray Matter Loss in Early Schizophrenia Results From a 2-Year Randomized Controlled Trial

CONTEXT Cognitive rehabilitation has shown efficacy in improving cognition in patients with schizophrenia but the underlying neurobiologic changes that occur during these treatments and support cognitive improvement are not well known. OBJECTIVE To examine differential changes in brain morphology in early course schizophrenia during cognitive rehabilitation vs supportive therapy. DESIGN Randomized controlled trial. SETTING An outpatient research clinic at a university-based medical center that provides comprehensive care services for patients with severe mental illness. PATIENTS A total of 53 symptomatically stable but cognitively disabled outpatients in the early course of schizophrenia or schizoaffective disorder. INTERVENTIONS A 2-year trial with annual structural magnetic resonance imaging and cognitive assessments. Cognitive enhancement therapy is an integrated approach to the remediation of cognitive impairment in schizophrenia that uses computer-assisted neurocognitive training and group-based social-cognitive exercises. Enriched supportive therapy is an illness management approach that provides psychoeducation and teaches applied coping strategies. MAIN OUTCOME MEASURES Broad areas of frontal and temporal gray matter change were analyzed with longitudinal, voxel-based morphometry methods using mixed-effects models followed by volumetric analyses of regions that demonstrated significant differential changes between treatment groups. RESULTS Patients who received cognitive enhancement therapy demonstrated significantly greater preservation of gray matter volume over 2 years in the left hippocampus, parahippocampal gyrus, and fusiform gyrus, and significantly greater gray matter increases in the left amygdala (all corrected P < .04) compared with those who received enriched supportive therapy. Less gray matter loss in the left parahippocampal and fusiform gyrus and greater gray matter increases in the left amygdala were significantly related to improved cognition and mediated the beneficial cognitive effects of cognitive enhancement therapy. CONCLUSION Cognitive enhancement therapy may offer neurobiologic protective and enhancing effects in early schizophrenia that are associated with improved long-term cognitive outcomes.

Social Cognition Deficits Among Individuals at Familial High Risk for Schizophrenia

Social cognition in young relatives of schizophrenia probands (N=70) and healthy controls (N=63) was assessed using the Penn Emotion Recognition Test-40 to examine the presence of social cognitive deficits in individuals at risk for the disorder. Measures of neurocognitive function and prodromal psychopathology were collected to assess the cognitive and clinical correlates of social cognitive impairments in at-risk relatives. Results indicated that when compared with healthy controls, individuals at familial high risk for schizophrenia were significantly more likely to overattribute emotions to neutral faces, with such individuals frequently misinterpreting neutral faces as negative. In addition, at-risk individuals had significantly greater reaction times when completing emotion recognition tasks, regardless of valence. Impairments in neurocognition were largely independent of social cognitive performance, and emotion recognition impairments persisted after adjusting for deficits in neurocognitive function. Further, social cognitive impairments in the interpretation of neutral faces were significantly associated with greater positive and general prodromal psychopathology, whereas neurocognitive impairments were only associated with disorganization. These results suggest that impairments in social cognition may be unique endophenotypes for schizophrenia.

A dimensional approach to the psychosis spectrum between bipolar disorder and schizophrenia: The Schizo-Bipolar Scale

BACKGROUND There is increasing evidence for phenomenological, biological and genetic overlap between schizophrenia and bipolar disorder, bringing into question the traditional dichotomy between them. Neurobiological models linked to dimensional clinical data may provide a better foundation to represent diagnostic variation in neuropsychiatric disorders. METHOD To capture the interaction between psychosis and affective symptoms dimensionally, we devised a brief descriptive scale based on the type and relative proportions of psychotic and affective symptoms over the illness course. The scale was administered to a series of 762 patients with psychotic disorders, including schizophrenia, schizoaffective and psychotic bipolar disorder assessed as part of the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) study. RESULTS The resulting Schizo-Bipolar Scale scores across these disorders showed neither a clear dichotomy nor a simple continuous distribution. While the majority of cases had ratings close to prototypic schizophrenia or bipolar disorder, a large group (45% of cases) fell on the continuum between these two prototypes. CONCLUSIONS Our data suggest a hybrid conceptualization model with a representation of cases with prototypic schizophrenia or bipolar disorder at the extremes, but a large group of patients on the continuum between them that traditionally would be considered schizoaffective. A dimensional approach, using the Schizo-Bipolar Scale, characterized patients across a spectrum of psychopathology. This scale may provide a valuable means to examine the relationships between schizophrenia and psychotic bipolar disorder.

Medial temporal lobe structures and hippocampal subfields in psychotic disorders: findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study.

IMPORTANCE Structural alterations in the hippocampus and other medial temporal lobe regions have been observed in schizophrenia. How these alterations and hippocampal subfields might differ across the psychosis spectrum remains unclear. OBJECTIVES To characterize medial temporal lobe structures, including hippocampal subfields, using magnetic resonance imaging and to examine their relation to psychosis and cognitive function across the psychosis spectrum. DESIGN, SETTING, AND PARTICIPANTS Case-control, cross-sectional neuroimaging study in a large series of probands with psychotic disorders and healthy volunteers as part of the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). Patients with psychotic disorders (schizophrenia, n = 219; schizoaffective disorder, n = 142; and psychotic bipolar disorder, n = 188) and healthy controls (n = 337) were recruited across ambulatory clinics at university health centers in the B-SNIP consortium. MAIN OUTCOMES AND MEASURES Medial temporal lobe and hippocampal subfields were quantified with an automated parcellation approach using FreeSurfer software. Memory and other cognitive parameters were assessed using standardized neuropsychological tests. RESULTS Hippocampal volume reductions were seen in all 3 diagnostic groups when compared with healthy controls; alterations in the entorhinal cortex and parahippocampal regions were limited to schizophrenia and schizoaffective disorders (P < .001). Smaller volumes across the hippocampal subfields were seen in all 3 psychotic disorders, with the most prominent differences being in cornu ammonis 2/3 (P < .001). Hippocampal volumes were positively correlated with psychosis severity, declarative memory, and overall cognitive performance (P < .05). CONCLUSIONS AND RELEVANCE Alterations in the hippocampus were evident across psychotic disorders. Hippocampal subfields that participate in memory-related processes supporting pattern separation and pattern completion might be abnormal and may underlie the pathophysiology of psychosis.

One-year durability of the effects of cognitive enhancement therapy on functional outcome in early schizophrenia

Cognitive rehabilitation is an effective intervention for addressing cognitive impairments in patients with schizophrenia. Previous research has shown that the early application of Cognitive Enhancement Therapy (CET) can improve neurocognitive and social-cognitive deficits in the early course of the disorder, and ultimately reduce the substantial functional disability that these patients experience. However, the lasting effects of CET on functional outcome in early course schizophrenia patients remain unknown. In this study, 58 patients in the early course of schizophrenia or schizoaffective disorder treated with 2 years of either CET or an Enriched Supportive Therapy (EST) control were followed-up 1 year after the completion of treatment to examine the durability of CET effects on functional outcome. At one-year post-treatment, a high (72%) retention rate was observed in both treatments. Results from intent-to-treat analyses employing linear mixed-effects models indicated that CET effects on functional outcome were broadly maintained one-year post-treatment, and that patients receiving CET continued to demonstrate highly significant differential functional benefits compared to patients treated with EST. These findings support the durability of CET effects on functional outcome in the early course of schizophrenia, and point to the potential of cognitive rehabilitation to have a lasting impact on the early trajectory of the disorder.

Commonalities in social and non-social cognitive impairments in adults with autism spectrum disorder and schizophrenia.

Autism spectrum disorder (ASD) and schizophrenia are both conditions that are characterized by impairments in social and non-social cognition, yet commonalities in the magnitude and domains of cognitive deficits across these two conditions remain unclear. This study examined neurocognitive and social-cognitive functioning in 47 outpatients with schizophrenia, 43 verbal adults with ASD, and 24 healthy volunteers. A comprehensive neuropsychological battery assessing processing speed, attention, memory, and problem-solving domains was administered along with a social-cognitive battery of emotion processing. Results demonstrated large and significant impairments in emotion processing and neurocognition relative to healthy individuals in participants with autism (d=-.97 and -1.71, respectively) and schizophrenia (d=-.65 and -1.48, respectively). No significant differences were observed between those with ASD and schizophrenia on any cognitive domain assessed, and the areas of greatest impairment were identical across both disorders and included slowness in speed of processing and an inability to understand emotions. These findings indicate a high degree of similarity in the cognitive challenges experienced by verbal adults with autism and schizophrenia, and the potential need for trans-diagnostic remediation approaches to enhance cognition in these conditions.

Violent behavior in borderline personality.

Little is known about the nature and prevalence of interpersonal violence among individuals with borderline personality disorder (BPD). Employing a longitudinal, multi-site sample, this study examined the degree to which BPD constitutes a risk marker for future violent behavior, and describes the characteristics of violent individuals with BPD and the nature of their violence. Findings showed that 73% of BPD subjects engaged in violence during the one-year study period, and frequently exhibited co-morbid antisocial personality disorder (ASPD) and psychopathic characteristics. Reported violence was mostly characterized by disputes with acquaintances or significant others. Results also suggest that the shared variance among ASPD, psychopathy, and BPD served to diminish the independent predictive effect of BPD on violence. These findings point to violence as a serious and prevalent problem among individuals with BPD, for whom targeted violence reduction strategies that take into account ASPD and psychopathic co-morbidity must be developed.

Mechanisms of functional improvement in a 2-year trial of cognitive enhancement therapy for early schizophrenia.

BACKGROUND Cognitive rehabilitation has emerged as an effective treatment for addressing cognitive impairments and functional disability in schizophrenia; however, the degree to which changes in various social and non-social cognitive processes translate into improved functioning during treatment remains unclear. This research sought to identify the neurocognitive and social-cognitive mechanisms of functional improvement during a 2-year trial of cognitive enhancement therapy (CET) for early-course schizophrenia. METHOD Patients in the early course of schizophrenia were randomly assigned to CET (n=31) or an enriched supportive therapy control (n=27) and treated for up to 2 years. A comprehensive neurocognitive assessment battery and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) were completed annually, along with measures of functioning. Mediator analyses using mixed-effects growth models were conducted to examine the effects of neurocognitive and social-cognitive improvement on functional change. RESULTS Improvements over 2 years in neurocognition and the emotion management branch of the MSCEIT were found to be significantly related to improved functional outcome in early-course schizophrenia patients. Neurocognitive improvement, primarily in executive functioning, and social-cognitive change in emotion management also mediated the robust effects of CET on functioning. CONCLUSIONS Improvements in neurocognition and social cognition that result from cognitive rehabilitation are both significant mediators of functional improvement in early-course schizophrenia. Cognitive rehabilitation programs for schizophrenia may need to target deficits in both social and non-social cognition to achieve an optimal functional response.

ASD, a Psychiatric Disorder, or Both? Psychiatric Diagnoses in Adolescents with High-Functioning ASD

Varied presentations of emotion dysregulation in autism complicate diagnostic decision making and may lead to inaccurate psychiatric diagnoses or delayed autism diagnosis for high-functioning children. This pilot study aimed to determine the concordance between prior psychiatric diagnoses and the results of an autism-specific psychiatric interview in adolescents with high-functioning autism. Participants included 35 predominantly Caucasian and male verbal 10- to 17-year-olds with a confirmed autism spectrum disorder and without intellectual disability. The average age of autism spectrum diagnosis was 11 years old. Lifetime psychiatric diagnoses were established via the Autism Comorbidity Interview, developed to identify comorbid conditions within the context of autism. Autism Comorbidity Interview results were compared to parent report of prior community psychiatric diagnoses. Approximately 60% of prior psychiatric diagnoses were not supported on the Autism Comorbidity Interview; the lowest diagnostic concordance was for prior bipolar disorder and obsessive-compulsive disorder diagnoses. Although 51% of children met Autism Comorbidity Interview criteria for at least one psychiatric disorder, rates of prior diagnoses were much higher, with 77% having at least one prior psychiatric diagnosis and 60% having two or more. Although many participants met criteria for comorbid psychiatric disorders, the majority of previous psychiatric diagnoses were not supported when autism-related manifestations were systematically taken into account. These findings require replication and may not generalize to lower functioning and earlier diagnosed children with autism spectrum disorder. Results emphasize the importance of increasing awareness of the manifestations of high-functioning autism in order to improve accuracy of diagnosis and appropriateness of interventions.

Quality of Life for Persons Living with Schizophrenia: More Than Just Symptoms.

Quality of life is an important outcome for persons living with schizophrenia and for the treatment of schizophrenia. However, studies of quality of life among persons living with schizophrenia have focused primarily on the symptoms experienced by the individual. This study sought to determine the influence of unmet need and social support on the quality of life of individuals with schizophrenia. Thirty-two persons living in the community with schizophrenia or schizoaffective disorder were assessed on quality of life, psychopathology, unmet need and social support. Hierarchical regression analyses indicated that unmet need and social support are important contributors to the quality of life of a person with schizophrenia, even after controlling for symptoms. Implications for schizophrenia treatment are discussed.