An integrative model of the impairments in insight in schizophrenia: emerging research on causal factors and treatments

Introduction: Poor insight, or unawareness of some major aspect of mental illness, is a major barrier to wellness when it interferes with persons seeking out treatment or forming their own understanding of the challenges they face. One barrier to addressing impaired insight is the absence of a comprehensive model of how poor insight develops. Areas covered: To explore this issue we review how poor insight is the result of multiple phenomena which interfere with the construction of narrative accounts of psychiatric challenges, rather than a single social or biological cause. Expert commentary: We propose an integrative model of poor insight in schizophrenia which involves the interaction of symptoms, deficits in neurocognition, social cognition, metacognition, and stigma. Emerging treatments for poor insight including therapies which focus on the development of metacognition are discussed

Metacognitive function and fragmentation in schizophrenia: Relationship to cognition, self-experience and developing treatments

Bleuler suggested that fragmentation of thought, emotion and volition were the unifying feature of the disorders he termed schizophrenia. In this paper we review research seeking to measure some of the aspects of fragmentation related to the experience of the self and others described by Bleuler. We focus on work which uses the concept of metacognition to characterize and quantify alterations or decrements in the processes by which fragments or pieces of information are integrated into a coherent sense of self and others. We describe the rationale and support for one method for quantifying metacognition and its potential to study the fragmentation of a person\u27s sense of themselves, others and the relative place of themselves and others in the larger human community. We summarize research using that method which suggests that deficits in metacognition commonly occur in schizophrenia and are related to basic neurobiological indices of brain functioning. We also present findings indicating that the capacity for metacognition in schizophrenia is positively related to a broad range of aspects of psychological and social functioning when measured concurrently and prospectively. Finally, we discuss the evolution and study of one therapy that targets metacognitive capacity, Metacognitive Reflection and Insight Therapy (MERIT) and its potential to treat fragmentation and promote recovery

The auditory steady-state response (ASSR): a translational biomarker for schizophrenia

Electrophysiological methods have demonstrated disturbances of neural synchrony and oscillations in schizophrenia which affect a broad range of sensory and cognitive processes. These disturbances may account for a loss of neural integration and effective connectivity in the disorder. The mechanisms responsible for alterations in synchrony are not well delineated, but may reflect disturbed interactions within GABAergic and glutamatergic circuits, particularly in the gamma range. Auditory steady-state responses (ASSRs) provide a non-invasive technique used to assess neural synchrony in schizophrenia and in animal models at specific response frequencies. ASSRs are electrophysiological responses entrained to the frequency and phase of a periodic auditory stimulus generated by auditory pathway and auditory cortex activity. Patients with schizophrenia show reduced ASSR power and phase locking to gamma range stimulation. We review alterations of ASSRs in schizophrenia, schizotypal personality disorder, and first-degree relatives of patients with schizophrenia. In vitro and in vivo approaches have been used to test cellular mechanisms for this pattern of findings. This translational, cross-species approach provides support for the role of N-methyl-D-aspartate and GABAergic dysregulation in the genesis of perturbed ASSRs in schizophrenia and persons at risk

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

Phencyclidine Disrupts the Auditory Steady State Response in Rats

The Auditory Steady-State Response (ASSR) in the electroencephalogram (EEG) is usually reduced in schizophrenia (SZ), particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR) hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP), produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP) and Phase Locking Factor (PLF). In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg) on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg), following two weeks of subchronic, continuous administration (5 mg/kg/day), and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz) ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule

Conceptual Disorganization Weakens Links in Cognitive Pathways: Disentangling Neurocognition, Social Cognition, and Metacognition in Schizophrenia

Disentangling links between neurocognition, social cognition, and metacognition offers the potential to improve interventions for these cognitive processes. Disorganized symptoms have shown promise for explaining the limiting relationship that neurocognition holds with both social cognition and metacognition. In this study, primary aims included: 1) testing whether conceptual disorganization, a specific disorganized symptom, moderated relationships between cognitive processes, and 2) examining the level of conceptual disorganization necessary for links between cognitive processes to break down. To accomplish these aims, comprehensive assessments of conceptual disorganization, neurocognition, social cognition, and metacognition were administered to 67 people with schizophrenia-spectrum disorders. We found that conceptual disorganization significantly moderated the relationship between neurocognition and metacognition, with links between cognitive processes weakening when conceptual disorganization is present even at minimal levels of severity. There was no evidence that conceptual disorganization—or any other specific disorganized symptom—drove the limiting relationship of neurocognition on social cognition. Based on our findings, conceptual disorganization appears to be a critical piece of the puzzle when disentangling the relationship between neurocognition and metacognition. Roles of specific disorganized symptoms in the neurocognition – social cognition relationship were less clear. Findings from this study suggest that disorganized symptoms are an important treatment consideration when aiming to improve cognitive impairments

Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats

BACKGROUND/AIMS: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. METHODS: Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. RESULTS: Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. CONCLUSIONS: Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders

Contrasting Metacognitive, Social Cognitive and Alexithymia Profiles in Adults with Borderline Personality Disorder, Schizophrenia and Substance Use Disorder

Deficits in the ability to recognize and think about mental states are broadly understood to be a root cause of dysfunction in Borderline Personality Disorder (PD). This study compared the magnitude of those deficits relative to other forms of serious mental illness or psychiatric conditions. Assessments were performed using the metacognition assessment scale-abbreviated (MAS-A), emotion recognition using the Bell Lysaker Emotion Recognition Test and alexithymia using the Toronto Alexithymia Scale among adults with schizophrenia (n = 65), Borderline PD (n = 34) and Substance Use disorder without psychosis or significant Borderline traits (n = 32). ANCOVA controlling for age revealed the Borderline PD group had significantly greater levels of metacognitive capacity on the MAS-A than the schizophrenia group and significantly lower levels of metacognitive capacity than the Substance Use group. Multiple comparisons revealed the Borderline PD group had significantly higher self-reflectivity and awareness of the other's mind than the schizophrenia group but lesser mastery and decentration on the MAS-A than substance use group, after controlling for self-report of psychopathology and overall number of PD traits. The Borderline PD and Schizophrenia group had significantly higher levels of alexithymia than the substance use group. No differences were found for emotion recognition. Results suggest metacognitive functioning is differentially affected in different mental disorders

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

A Recovery-Oriented Approach: Application of Metacognitive Reflection and Insight Therapy (MERIT) for Youth with Clinical High Risk (CHR) for Psychosis

Clinical High Risk for psychosis (CHR) refers to a phase of heightened risk for developing overt psychosis. CHR often emerges during adolescence or early adulthood. CHR has been identified as a group to target for intervention, with the hope that early intervention can both stave off prolonged suffering and intervene before mental health challenges become part of an individual’s identity. However, there are few treatment modalities that can address some of the specific needs of CHR. Metacognitive Reflection and Insight Therapy (MERIT) is an integrative psychotherapy that can be applied to the CHR population. MERIT offers unique advantages to working with the CHR population as it aims to improve self-direction and recovery through stimulation of metacognitive capacity, a phenomenon that has been associated with recovery. This paper explores unique aspects of the CHR population and how MERIT can address barriers to recovery for individuals experiencing psychosis-like symptoms. Several case examples and a clinical vignette using MERIT to support patients with CHR are offered to exemplify this approach. MERIT offers a way to assist persons with CHR to address barriers to their personal recovery and to develop nuanced understandings of ways to master challenges