Michael M. Francis

Metacognition, social cognition, and symptoms in patients with first episode and prolonged psychoses.

While it has been documented that persons with prolonged schizophrenia have deficits in metacognition and social cognition, it is less clear whether these difficulties are already present during a first episode. To explore this issue we assessed and compared metacognition using the Metacognition Assessment Scale-Abbreviated (MAS-A) and social cognition using the Eyes, Hinting and Bell-Lysaker Emotional Recognition Tests (BLERT) in participants with first episode psychosis (FEP; n=26), participants with a prolonged psychosis (n=72), and a psychiatric control group consisting of persons with a substance use disorder and no history of psychosis (n=14). Analyses revealed that both psychosis cohorts scored lower than controls on the MAS-A total and all subscales except metacognitive mastery. Compared to the FEP group, the persons with prolonged psychosis demonstrated greater metacognitive capacities only in those MAS-A domains reflective of the ability to understand the mental state of others and to see that others may have motivations and desires separate from their own. Other domains of metacognition did not differ between psychosis groups. The Eyes, Hinting and BLERT scores of the two psychosis groups did not differ but were poorer than those produced by the control group. Exploratory correlations in the FEP group showed a pattern similar to that previously observed in prolonged psychosis. Taken together, these findings suggest that while certain domains of metacognition could improve with prolonged psychosis, difficulties with global metacognition and social cognition may be stable features of the disorder and perhaps unique to psychosis.

Deficits in metacognitive capacity distinguish patients with schizophrenia from those with prolonged medical adversity

Research has suggested that many with schizophrenia experience decrements in synthetic metacognition, or the abilities to form integrated representations of oneself and others and then utilize that knowledge to respond to problems. Although such deficits have been linked with functional impairments even after controlling for symptoms and neurocognition, it is unclear to what extent these deficits can distinguish persons with schizophrenia from others experiencing significant life adversity but without psychosis. To explore this issue we conducted logistic regression analysis to determine whether assessment of metacognition could distinguish between 166 participants with schizophrenia and 51 adults with HIV after controlling for social cognition and education. Metacognition was assessed with the Metacognitive Assessment Scale Abbreviated (MAS-A), and social cognition with the Bell Lysaker Emotion Recognition Test. We observed that the MAS-A total score was able to correctly classify 93.4% of the schizophrenia group, with higher levels of metacognition resulting in increased likelihood of accurate categorization. Additional exploratory analyses showed specific domains of metacognition measured by the MAS-A were equally able to predict membership in the schizophrenia group. Results support the assertion that deficits in the abilities to synthesize thoughts about oneself and others into larger representations are a unique feature of schizophrenia.

Capacities for theory of mind, metacognition, and neurocognitive function are independently related to emotional recognition in schizophrenia.

While many with schizophrenia spectrum disorders experience difficulties understanding the feelings of others, little is known about the psychological antecedents of these deficits. To explore these issues we examined whether deficits in mental state decoding, mental state reasoning and metacognitive capacity predict performance on an emotion recognition task. Participants were 115 adults with a schizophrenia spectrum disorder and 58 adults with substance use disorders but no history of a diagnosis of psychosis who completed the Eyes and Hinting Test. Metacognitive capacity was assessed using the Metacognitive Assessment Scale Abbreviated and emotion recognition was assessed using the Bell Lysaker Emotion Recognition Test. Results revealed that the schizophrenia patients performed more poorly than controls on tests of emotion recognition, mental state decoding, mental state reasoning and metacognition. Lesser capacities for mental state decoding, mental state reasoning and metacognition were all uniquely related emotion recognition within the schizophrenia group even after controlling for neurocognition and symptoms in a stepwise multiple regression. Results suggest that deficits in emotion recognition in schizophrenia may partly result from a combination of impairments in the ability to judge the cognitive and affective states of others and difficulties forming complex representations of self and others.

Metacognitive capacity as a predictor of insight in first-episode psychosis.

Abstract Impaired insight is common in the first episode of psychosis (FEP). Although considerable research has examined the factors that are associated with impaired insight in chronic psychosis, less is known about the factors that underlie and sustain poor insight in FEP. Impaired metacognition, or the ability to form integrated representations of self and others, is a promising potential contributor to poor insight in FEP. To explore this possibility, the authors assessed insight and metacognition in 40 individuals with FEP and then examined the relationship between these areas and social cognition domains, neurocognitive domains, and psychotic symptoms. Correlation analyses revealed that improved insight was associated with higher metacognition, better vocabulary and Theory of Mind scores, and fewer symptoms. The domain of metacognitive mastery also predicted clinical insight. Results support the need to develop an integrative therapeutic approach focused on improving metacognition, hence addressing poor insight in FEP.

Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis

Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n = 35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness.

Developmental Resting State Functional Connectivity for Clinicians

Resting state functional magnetic imaging (fMRI) is a novel means to examine functional brain networks. It allows investigators to identify functional networks defined by distinct, spontaneous signal fluctuations. Resting state functional connectivity (RSFC) studies examining child and adolescent psychiatric disorders are being published with increasing frequency, despite concerns about the impact of motion on findings. Here we review important RSFC findings on typical brain development and recent publications on child and adolescent psychiatric disorders. We close with a summary of the major findings and current strengths and limitations of RSFC studies.

Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates

Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis.

Metacognitive Reflection and Insight Therapy for Early Psychosis: A preliminary study of a novel integrative psychotherapy

Poor insight impedes treatment in early phase psychosis (EPP). This manuscript outlines preliminary findings of an investigation of the novel metacognitively oriented integrative psychotherapy, Metacognitive Reflection and Insight Therapy, for individuals with early phase psychosis (MERIT-EP). Twenty adults with EPP and poor insight were randomized to either six months of MERIT-EP or treatment as usual (TAU). Therapists were trained and therapy was successfully delivered under routine, outpatient conditions. Insight, assessed before and after treatment, revealed significant improvement for the MERIT-EP, but not TAU, group. These results suggest MERIT-EP is feasible to deliver, accepted by patients, and leads to clinically significant improvements in insight.

Effects of 12-month, double-blind N-acetyl cysteine on symptoms, cognition and brain morphology in early phase schizophrenia spectrum disorders

BACKGROUND Currently approved medications for schizophrenia are relatively ineffective for negative symptoms and cognitive impairment. N-Acetyl Cysteine (NAC) is a neuroprotective agent that improved general symptoms, cognitive impairment and negative symptoms in some but not all studies, but failed to improve positive symptoms in patients with schizophrenia. Progressive brain mass loss (PBML) has been consistently observed in early phase schizophrenia. NAC mitigates the deleterious effects oxidative stress, inflammation and glutamatergic excitotoxicity and these three pathological processes are hypothesized to contribute to PBML. METHODS In this study, we assessed the effects NAC (3600mg/day) in a 52-week, double-blind, placebo controlled trial on symptoms, and cognition in early phase schizophrenia spectrum disorders (N=60). In the context of the clinical trial, we explored the effects of NAC on brain morphology. RESULTS NAC significantly improved (time×group) PANSS total (F=14.7, p<0.001), negative (F=5.1, p=0.024) and disorganized thought (F=13.7, p<0.001) symptom scores. NAC failed to improve PANSS positive symptoms and BACS cognitive scores. In preliminary analyses, baseline right (r=-0.48, p=0.041) and left (r=-0.45, p=0.018) total cortical thickness, and thickness in other cortical regions, were associated with NAC related improvement in PANSS total scores, but NAC, as compared to placebo, did not significantly impact brain morphology over the study treatment period. CONCLUSIONS These results replicate some but not all previous findings of NAC efficacy. Preliminary results suggest that NACs symptom effects may be related to structural integrity, but NAC failed to demonstrate treatment effects on longitudinal measures of brain morphology. ClinicalTrials.gov Identifier: NCT01339858.

Characterization of white matter abnormalities in early-stage schizophrenia.

White matter abnormalities have been reported in schizophrenia and may indicate altered cortical network integrity and structural connectivity, which have been hypothesized as key pathophysiological components of this illness. In this study, we aimed to further characterize the nature and progression of white matter alterations during the early stages of the disorder.