Jason K. Johannesen

Metacognition amidst narratives of self and illness in schizophrenia : associations with neurocognition, symptoms, insight and quality of life

Objective:  Impairments in laboratory tasks of metacognition appear to be associated with symptoms, functioning, and neurocognition in schizophrenia. We sought to replicate these results in a study of metacognition within personal narratives of self and illness.

Social Cognitive Impairments and Negative Symptoms in Schizophrenia: Are There Subtypes With Distinct Functional Correlates?

Social cognitive impairments and negative symptoms are core features of schizophrenia closely associated with impaired community functioning. However, little is known about whether these are independent dimensions of illness and if so, whether individuals with schizophrenia can be meaningfully classified based on these dimensions (SANS) and potentially differentially treated. Five social cognitive measures plus Scale for the Assessment of Negative Symptoms (SANS) and Positive and Negative Syndrome Scale (PANSS) scores in a sample of 77 outpatients produced 2 distinct factors--a social cognitive factor and a negative symptom factor. Factor scores were used in a cluster analysis, which yielded 3 well-defined groupings--a high negative symptom group (HN) and 2 low negative symptom groups, 1 with higher social cognition (HSC) and 1 with low social cognition (LSC). To make these findings more practicable for research and clinical settings, a rule of thumb for categorizing using only the Mayer-Salovey-Caruso Emotional Intelligence Test and PANSS negative component was created and produced 84.4% agreement with the original cluster groups. An additional 63 subjects were added to cross validate the rule of thumb. When samples were combined (N = 140), the HSC group had significantly better quality of life and Global Assessment of Functioning (GAF) scores, higher rates of marriage and more hospitalizations. The LSC group had worse criminal and substance abuse histories. With 2 common assessment instruments, people with schizophrenia can be classified into 3 subgroups that have different barriers to community integration and could potentially benefit from different treatments.

Perceptual Anomalies in Schizophrenia Co-Occur With Selective Impairments in the Gamma Frequency Component of Midlatency Auditory ERPs

This study aimed to establish concordance between phenomenological and psychophysiological indices of sensory gating disturbance in schizophrenia. Perceptually normal and deviant subgroups of schizophrenia (SZ) and healthy comparison (HC) participants were empirically determined on the basis of self-rated Sensory Gating Inventory scores. Contrasts by diagnosis and subgroup classification were conducted on event-related brain potential (ERP) response attenuation to paired auditory stimuli, measured in time (P50 ERP) and frequency (low frequency, 1-20 Hz; gamma band, 20-50 Hz) domains. The SZ sample evidenced significantly less low-frequency response attenuation than did HC but comparable P50 and gamma responses. The low-frequency response, however, appeared insensitive to variation in perceptual experience between SZ subgroups. Conversely, smaller P50 amplitude and weaker gamma response attenuation distinguished deviant SZ (n=17) from normal SZ (n=9) and normal HC (n=29) subgroups. Perceptually normal SZ and normal HC subgroups were statistically equivalent across all comparisons. These findings support hypotheses relating perceptual disturbance in schizophrenia to an early sensory input dysfunction, which is thought to involve gamma-mediated thalamocortical integration of sensory stimuli.

Hope, awareness of illness, and coping in schizophrenia spectrum disorders: evidence of an interaction.

Controversy exists regarding whether awareness of schizophrenia is linked with healthier or poorer psychosocial function. This study examined whether hope might interact with insight to affect function at the level of active versus avoidant coping preferences among 96 persons with schizophrenia spectrum disorders. Factorial multivariate analysis of variance comparing groups classified on the basis of hope and insight scores revealed a significant interaction between hope and insight (Wilks λ = 2.7; p< 0.05). Post hoc analyses indicated that persons with high insight and high hope demonstrated the most adaptive coping preferences, whereas those with high insight and lower hope demonstrated the least.

Eyeblink conditioning anomalies in bipolar disorder suggest cerebellar dysfunction

OBJECTIVES Accumulating research implicates the cerebellum in non-motor psychological processes and psychiatric diseases, including bipolar disorder (BD). Despite recent evidence that cerebellar lesions have been documented to trigger bipolar-like symptoms, few studies have directly examined the functional integrity of the cerebellum in those afflicted with BD. METHODS Using a single-cue delay eyeblink conditioning procedure, the functional integrity of the cerebellum was examined in 28 individuals with BD (9 manic, 8 mixed, and 11 euthymic) and 28 age-matched healthy controls. RESULTS Analysis of the bipolar group as a whole indicated a conditioned response acquisition and timing deficit compared to controls. However, when the bipolar group was categorized according to mood state (mixed, manic, euthymic), individuals tested during mixed episodes were strikingly impaired, performing significantly worse than all other groups on both the acquisition and timing of conditioned responses. CONCLUSIONS These findings extend prior research implicating cerebellar functional abnormalities in BD and suggest that cerebellar dysfunction may be associated with mood state and course of illness.

Diagnostic Specificity of Neurophysiological Endophenotypes in Schizophrenia and Bipolar Disorder

BACKGROUND The utility of an endophenotype depends on its ability to reduce complex disorders into stable, genetically linked phenotypes. P50 and P300 event-related potential (ERP) measures are endophenotype candidates for schizophrenia; however, their abnormalities are broadly observed across neuropsychiatric disorders. This study examined the diagnostic efficiency of P50 and P300 in schizophrenia as compared with healthy and bipolar disorder samples. Supplemental ERP measures and a multivariate classification approach were evaluated as methods to improve specificity. METHODS Diagnostic classification was first modeled in schizophrenia (SZ = 50) and healthy normal (HN = 50) samples using hierarchical logistic regression with predictors blocked by 4 levels of analysis: (1) P50 suppression, P300 amplitude, and P300 latency; (2) N100 amplitude; (3) evoked spectral power; and (4) P50 and P300 hemispheric asymmetry. The optimal model was cross-validated in a holdout sample (SZ = 34, HN = 31) and tested against a bipolar (BP = 50) sample. RESULTS P50 and P300 endophenotypes classified SZ from HN with 71% accuracy (sensitivity = .70, specificity = .72) but did not differentiate SZ from BP above chance level. N100 and spectral power measures improved classification accuracy of SZ vs HN to 79% (sensitivity = .78, specificity = .80) and SZ vs BP to 72% (sensitivity = .74, specificity = .70). Cross validation analyses supported the stability of these models. CONCLUSIONS Although traditional P50 and P300 measures failed to differentiate schizophrenia from bipolar participants, N100 and evoked spectral power measures added unique variance to classification models and improved accuracy to nearly the same level achieved in comparison of schizophrenia to healthy individuals.

Functional significance of preserved affect recognition in schizophrenia

Affect recognition (AR) is a core component of social information processing; thus, it may be critical to understanding social behavior and functioning in broader aspects of daily living. Deficits in AR are well documented in schizophrenia, but there is also evidence that many individuals with schizophrenia perform AR tasks at near-normal levels. In the current study, we sought to evaluate the functional significance of AR deficits in schizophrenia by comparing subgroups with normal-range and impaired AR performance on proxy and interviewer-rated measures of real-world functioning. Schizophrenia outpatients were classified as normal-range (N=17) and impaired (N=31) based on a logistic cut point in the sample distribution of Bell-Lysaker Emotion Recognition Task (BLERT) scores, referenced to a normative sample of healthy control subjects (N=56). The derived schizophrenia subgroups were then compared on proxy [University of California San Diego Performance-Based Skill Assessment (UPSA), Social Skills Performance Assessment (SSPA), Medication Management Ability Assessment (MMAA)] and interviewer-rated [Quality of Life Scale (QLS), Independent Living Skills Survey (ILSS)] measures of functioning, as well as a battery of neurocognitive tests. Initial analyses indicated superior MMAA and QLS performance in the near-normal AR subgroup. Covariate analyses indicated that group differences in neurocognition fully mediated the observed associations between AR and MMAA, and attenuated the observed relationships between AR classification and QLS. These results support three main conclusions. First, AR, like many other domains of psychopathology studied in schizophrenia, is preserved in select subgroups. Second, there is a positive relationship between AR performance and functional outcome measures. Third, neurocognition appears to mediate the relationship between AR and measures of functioning.

Social cognitive deficits in schizophrenia and their relationship to clinical and functional status

While research on social cognitive impairments in schizophrenia is quickly growing, relatively little is still known about the severity and correlates of these impairments. The few studies that have examined this issue suggest that social cognitive impairments may be positively related to psychiatric symptoms and negatively related to functioning. In the current analyses of 119 stable outpatients with schizophrenia spectrum diagnoses, we sought to further characterize the nature of social cognitive impairments in schizophrenia. Specifically, we examined (1) social cognitive impairments on four different social cognitive tasks including measures of emotional processing and Theory of Mind and (2) the demographic, symptom and functional correlates of these impairments. For three of the four social cognitive tasks examined, the majority of participants performed 1 or more S.D. worse than healthy controls, with variability in the degree of impairment across tasks. Contrary to expectation, correlations between social cognitive performance on each of the four tasks and clinical and functional features were few and weak, and for the most part did not replicate the previously reported relationship of social cognition to severity of symptoms or current functional status.

Secretin Effects on Cerebellar-Dependent Motor Learning in Schizophrenia

OBJECTIVE Pervasive cognitive deficits in schizophrenia are a major cause of disability among individuals with the disorder. One such deficit is the loss of effective associative learning, which is readily assessed via eye-blink conditioning procedures. The authors examined the efficacy of secretin, a hormonal agonist for the prototype group B G-protein-coupled receptors, in ameliorating eye-blink conditioning deficits in schizophrenia patients. METHOD Immediately following a pretreatment delay eye-blink conditioning recording session, 25 individuals with schizophrenia received either secretin (RG1068; 20 microg/kg [N=15]) or a saline placebo (20 microg/kg [N=10]) subcutaneously in a double-blind fashion. Comparison groups were formed by yoking pairs of subjects on the basis of performance during the pretreatment baseline eye-blink conditioning recording session, and thus 20 subjects underwent further analysis. Secretin was selected because eye-blink conditioning depends on the release of Purkinje cell inhibition on deep nuclei of the cerebellum and recent findings indicate that secretin is endogenously released in the cerebellum, where it acts as a retrograde messenger and neuromodulator on basket and Purkinje cells. RESULTS Eye-blink conditioning was significantly improved at 2 and 24 hours after secretin administration but not after treatment with placebo. These results are consistent with evidence of intracellular signaling abnormalities in the pathophysiology of schizophrenia and indicate a possible role for secretin in modulating cerebellar-mediated classically conditioned learning. CONCLUSION If cerebellar abnormalities in individuals with schizophrenia are associated with fundamental mechanisms and symptoms of the disorder, as suggested by the cognitive dysmetria model, then cerebellar-targeted treatments may provide a novel approach to treatment for schizophrenia.

Comparison of computational methods for the evaluation of learning potential in schizophrenia.

Learning potential (LP) refers to the ability to improve cognitive performance as a result of training. It is typically assessed by test-train-test administrations of a task, wherein changes in pre-post performance are an index of LP. In schizophrenia research, LP has been suggested as a mediator of the relationship between static neurocognition and functional outcome. While a number of studies do indicate that LP assessment improves prediction of functioning beyond standard administrations of the same task, multiple approaches of computing LP indices have been used in this work. Multiple psychometric issues have been raised with respect to computation of change scores, but have not been widely recognized in LP assessment. To address this issue, the current study aimed to evaluate the test-retest reliability, interrelatedness, construct, and criterion validity of several conventional indices of LP, obtained from a test-train-test version of a list-learning task administered to 43 individuals with chronic schizophrenia. Overall, test-retest and intercorrelation coefficients indicated variable reliability and convergence across methods. While LP indices generally correlated more highly with independent measures of neurocognition and community functioning than pretraining list learning scores, coefficients were comparably small. Recommendations and measurement issues inherent to the LP construct are discussed.