Michael Bodnar

Neurocognition: clinical and functional outcomes in schizophrenia.

Schizophrenia is characterized by significant heterogeneity in outcome. The last decades have witnessed a significant interest in identifying factors that can moderate or influence clinical and functional outcomes in people with schizophrenia. One factor of particular interest is neurocognition, as performance on various measures of cognitive abilities, such as memory, attention, and executive functions, have been consistently related to functional outcome and, to a lesser extent, clinical outcome. This review aims to provide an up-to-date description of recent studies examining the association between neurocognition and clinical and (or) functional outcomes. In the first section, studies examining neurocognitive performance in relation to clinical outcome are examined. When clinical outcome is defined dichotomously (for example, comparing remitted and nonremitted), verbal memory performance consistently exhibits a strong association with clinical status, with the poor outcome group showing the largest deficits. In the second section, studies exploring the relation between neurocognition and various dimensions of functional outcome are reviewed. These dimensions include independent living, social functioning, and vocational functioning, among others. Again, a strong link between neurocognitive deficits and impairments in several aspects of functioning clearly emerges from this review. Finally, several measurement issues are discussed that pertain to the need to standardize definitions of clinical and (or) functional outcomes, the importance of defining cognitive domains consistently across studies, and distinguishing between ones competence to perform tasks and what one actually does in everyday life. Addressing these measurement issues will be key to studies examining the development of effective interventions targeting neurocognitive functions and their impact on clinical and functional outcomes.

Duration of untreated psychosis is associated with orbital–frontal grey matter volume reductions in first episode psychosis

BACKGROUND Delay in treatment of psychosis is associated with poor clinical and social outcome and is measured as the duration of untreated psychosis (DUP) prior to treatment of the first episode. It has been suggested that this may be mediated through toxic effects of psychosis on the structure and function of the brain. Equivocal evidence exists regarding association between longer DUP and neuro-anatomical changes such as, reduced grey matter volume in specific regions in the brain and deficits in neurocognitive functions. OBJECTIVE To examine if duration of untreated psychosis (DUP) preceding treatment of a first episode of psychosis is associated with structural brain abnormalities and deficits in neurocognitive functions. METHOD We investigated the relationship between DUP and grey matter volume using voxel-based morphometry techniques and with multiple domains of cognition. Eighty patients with a first episode of psychosis were separated into two equal sized groups based on a median split (18 weeks) of their DUP. RESULTS Compared to the short-DUP group (mean DUP 7.9 weeks ± 5.6), the long-DUP group (mean 113.7 weeks ± 170 .4) showed significant grey matter volume reductions in orbital-frontal regions (bilateral medial frontal gyrus and bilateral rectal gyrus, BA 11) and parietal regions (postcentral gyrus and superior parietal lobule) as well as a significant reduction in whole brain grey matter volume (p<0.04). For schizophrenia spectrum cases only these findings were confined to left rectal gyrus. There were no differences in white matter or cerebral spinal fluid volumes or on cognitive functions. Results are controlled for antipsychotic medication exposure. LIMITATIONS The inherent difficulty in separating slow and insidious onset from long-DUP may limit the interpretation of our results and there may be an overlap between DUP and duration of illness (including the prodrome). CONCLUSION Patients with a longer delay in treatment of psychosis show a significant reduction in overall grey matter volume with specific reductions in the inferior-orbital region. These results provide some support to a possible neurotoxic effect of prolonged untreated psychosis.

Cognitive insight and verbal memory in first episode of psychosis.

Beck and collaborators have proposed a distinction between clinical insight and cognitive insight and have developed a tool for the assessment of the latter, namely the Beck Cognitive Insight Scale (BCIS). The present study explored in 51 patients with a first episode of psychosis the neurocognitive correlates of cognitive insight as assessed with the BCIS. Global measures for seven domains of cognition including verbal learning and memory, visual learning and memory, working memory, speed of processing, reasoning and problem solving, attention, and social cognition were examined. Secondly, we examined whether two clinical insight measures, the Scale to assess Unawareness of Mental Disorder (SUMD) and the insight item from the Positive and Negative Symptoms Scale (PANSS), could produce similar or different patterns of association with neurocognitive functions as those identified with the BCIS. Correlational analyses revealed significant associations between the BCIS Composite Index and the verbal learning and memory. No significant associations were observed between any of the neurocognitive domains and the PANSS or SUMD clinical insight measures, despite high inter-correlations among the three insight measures. These results suggest that cognitive insight, but not clinical insight, may rely on memory processes whereby current experiences are appraised based on previous ones.

Fronto-temporal disconnectivity and clinical short-term outcome in first episode psychosis: A DTI-tractography study

Determining reliable markers of clinical outcome for psychosis is essential to adjust intervention efforts. White matter alterations exist prior to psychosis onset but its association with clinical outcome in the very early phase of psychosis is currently unknown. In the present study, white matter was assessed by diffusion tensor imaging (DTI) in patients with first episode psychosis (FEP) and healthy controls. Forty-four FEP patients and 30 matched healthy controls completed a DTI scan. The patient group was split in poor (n = 24) and good (n = 20) outcome subgroups based on 6-month clinical data. DTI tractography was used to estimate fractional anisotropy (FA) in the three main tracts connecting frontal and temporal regions (i.e. the cingulum, the superior longitudinal fasciculus and the uncinate fasciculus). The analyses showed selective FA reductions in both the uncinate and the superior longitudinal fasciculi, but not in the cingulum, when comparing FEP patients to healthy controls. FEP subgroup analyses revealed greater white matter changes in these tracts in patients with poor outcome as compared to patients with good outcome. These findings confirm that abnormal fronto-temporal connectivity contributes to the physiopathology of FEP and constitutes an early marker of clinical short-term outcome.

Cognitive markers of short-term clinical outcome in first-episode psychosis

BACKGROUND Outcome from psychotic disorders is heterogeneous with poorer outcomes frequently identified too late to be influenced. Symptomatic ratings at 1 or more years following initiation of treatment have been related to cognition in first-episode psychosis. However, the relationship between cognition and early outcome remains unclear. AIMS To determine whether specific cognitive domains could identify poor short-term outcome among individuals with first-episode psychosis. METHOD One hundred and fifty-one individuals with first-episode psychosis were divided into two groups based on 6-month clinical data after the initiation of treatment. Six cognitive domains were compared among 78 participants with poor outcomes, 73 with good outcomes and 31 healthy controls. RESULTS Lower performance on verbal memory (z-scores: poor outcome=-1.3 (s.d.=1.1); good outcome=-0.8 (s.d.=0.9); P=0.001) and working memory (poor outcome=-1.0 (s.d.=1.2); good outcome=-0.4 (s.d.=0.9); P=0.003) identified individuals with first-episode psychosis with a poor outcome after 6 months of treatment. CONCLUSIONS The early identification of those individuals with first-episode psychosis with a poor clinical outcome may encourage clinicians to pay special attention to them in the form of alternative pharmacological and psychological treatments for a more favourable outcome in the long term.

Identifying persistent negative symptoms in first episode psychosis

BackgroundAlthough persistent negative symptoms (PNS) are known to contribute significantly to poor functional outcome, they remain poorly understood. We examined the heuristic value of various PNS definitions and their respective prevalence in patients with first episode psychosis (FEP). We also contrasted those definitions to the Proxy for the Deficit Syndrome (PDS) to identify deficit syndrome (DS) in the same FEP cohort.MethodsOne hundred and fifty-eight FEP patients were separated into PNS and non-PNS groups based on ratings from the Scale for Assessment of Negative Symptoms (SANS). PNS was defined in the following ways: 1) having a score of 3 or greater on at least 1 global subscale of the SANS (PNS_1); 2) having a score of 3 or more on at least 2 global subscales of the SANS (PNS_2); and 3) having a score of 3 or more on a combination of specific SANS subscales and items (PNS_H). For all three definitions, symptoms had to be present for a minimum of six consecutive months. Negative symptoms were measured upon entry to the program and subsequently at 1,2,3,6,9 and 12 months. Functional outcome was quantified at first assessment and month 12.ResultsPNS prevalence: PNS_1 (27%); PNS_2 (13.2%); PNS_H (13.2%). The prevalence of DS was found to be 3% when applying the PDS. Regardless of the definition being applied, when compared to non-PNS, patients in the PNS group were shown to have significantly worse functioning at month 12. All three PNS definitions showed similar associations with functional outcome at month 12.ConclusionPersistent negative symptoms are present in about 27% of FEP patients with both affective and non-affective psychosis. Although there has previously been doubt as to whether PNS represents a separate subdomain of negative symptoms, the current study suggests that PNS may be more applicable to FEP when compared to DS. Although all three PNS definitions were comparable in predicting functional outcome, we suggest that the PNS definition employed is dependent on the clinical or research objective at hand.

Cortical thickness is associated with poor insight in first-episode psychosis

Through conceptualizing poor insight in psychotic disorders as a form of anosognosia (neurological deficit), frontal lobe dysfunction is often ascribed a vital role in its pathogenesis. Whether non-frontal brain regions are important for insight remains to be investigated. We used a multi-method approach to examine the neural morphometry of all cortical regions for insight in first-episode psychosis. Insight was rated in 79 people with a first-episode psychosis with the awareness of illness and awareness of treatment need and efficacy items of the Scale for assessment of Unawareness of Mental Disorder. Participants were assessed with magnetic resonance imaging. Cortical thickness analysis and voxel-based morphometry were utilized to identify the possible neuroanatomical basis of insight. Cortical thickness technique revealed that poorer awareness of illness was associated with regional thinning in left middle frontal and inferior temporal gyri. Poorer awareness of treatment need and efficacy was associated with cortical thinning in left medial frontal gyrus, precuneus and temporal gyri. No significant associations emerged between any insight measure and gray matter density using voxel-based morphometry. The results confirm predictions derived from the anosognosia/neuropsychology account and assert that regional thickness in frontal cortex is associated with awareness of illness in the early phase of psychosis. The fact that prominent thickness reductions emerged in non-frontal regions of the brain in parietal and temporal cortices for both awareness of illness and awareness of treatment need and efficacy suggests that the neural signature of insight involves a network of brain structures, and not only the frontal lobes as previously suggested.

Neural markers of remission in first-episode schizophrenia: A volumetric neuroimaging study of the hippocampus and amygdala

OBJECTIVE The temporolimbic region has been implicated in the pathophysiology in schizophrenia. More specifically, significantly smaller hippocampal volumes but not amygdala volumes have been identified at onset in first-episode schizophrenia (FES) patients. However, volumetric differences (namely, in the hippocampus) exhibit an ambiguous relationship with long-term outcome. So, we examined the relationship between hippocampus and amygdala volumes and early remission status. METHODS We compared hippocampus and amygdala volumes between 40 non-remitted and 17 remitted FES patients and 57 healthy controls. Amygdala and hippocampus were manually traced with the hippocampus additionally segmented into three parts: body, head, and tail. Remission was defined as mild or less on both positive and negative symptoms over a period of 6 consecutive months as per the 2005 Remission in Schizophrenia Working Group criteria. RESULTS A significant [group x structure x side] interaction revealed outcome groups differed in hippocampus tail volumes; significantly on the left (non-remitted=694+/-175 mm(3); remitted=855+/-133 mm(3); p=0.001) with a trend difference on the right (non-remitted=723+/-162 mm(3); remitted=833+/-126 mm(3); p=0.023). Groups did not differ in body, head, or amygdala volumes bi-laterally. CONCLUSIONS A smaller hippocampal tail volume may represent a neural marker in FES patients who do not achieve early remission after the first 6 months of treatment. The early identification of patients with poor outcome with respect to the hippocampus tail may encourage the search for new, more target-specific, medications in hope of improving outcome and moving us towards a better understanding of the pathophysiology of schizophrenia.

A 12-month outcome study of insight and symptom change in first-episode psychosis

Aim: We first aimed to evaluate the progression of insight and psychopathology over the first year of treatment for a psychosis. We hypothesized that improvement in insight would associate with improvement in positive and negative symptoms, and depressive and anxious symptom exacerbation. Secondly, in an exploratory analysis, we aimed to identify quantitatively distinct insight trajectory groups, and to describe the impact of psychopathology over time on the different trajectory groups.

The structural neural substrates of persistent negative symptoms in first-episode of non-affective psychosis: a voxel-based morphometry study

Objectives: An important subset of patients with schizophrenia present clinically significant persistent negative symptoms (PNS). Identifying the neural substrates of PNS could help improve our understanding and treatment of these symptoms. Methods: This study included 64 non-affective first-episode of psychosis (FEP) patients and 60 healthy controls; 16 patients displayed PNS (i.e., at least one primary negative symptom at moderate or worse severity sustained for at least six consecutive months). Using voxel-based morphometry (VBM), we explored for gray matter differences between PNS and non-PNS patients; patient groups were also compared to controls. All comparisons were performed at p < 0.05, corrected for multiple comparisons. Results: PNS patients had smaller gray matter in the right frontal medial–orbital gyrus (extending into the inferior frontal gyrus) and right parahippocampal gyrus (extending into the fusiform gyrus) compared to non-PNS patients. Compared to controls, PNS patients had smaller gray matter in the right parahippocampal gyrus (extending into the fusiform gyrus and superior temporal gyrus); non-PNS patients showed no significant differences to controls. Conclusion: Neural substrates of PNS are evident in FEP patients. A better understanding of the neural etiology of PNS may encourage the search for new medications and/or alternative treatments to better help those affected.