Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia?

Growing interest in gut and digestive processes and their potential link to brain and peripheral based inflammation or biobehavioral phenotypes has led to an increasing number of basic and translational scientific reports focused on the role of gut microbiota within the context of neuropsychiatric disorders. However, the effect of dietary modification on specific gut metabolites, in association with immune, metabolic, and psychopathological functioning in schizophrenia spectrum disorders has not been well characterized. The short chain fatty acids (SCFA) acetate, butyrate, and propionate, major metabolites derived from fermentation of dietary fibers by gut microbes, interact with multiple immune and metabolic pathways. The specific pathways that SCFA are thought to target, are dysregulated in cardiovascular disease, type II diabetes, and systemic inflammation. Most notably, these disorders are consistently linked to an attenuated lifespan in schizophrenia. Although, unhealthy dietary intake patterns and increased prevalence of immune and metabolic dysfunction has been observed in people with schizophrenia; dietary interventions have not been well utilized to target immune or metabolic illness. Prior schizophrenia patient trials primarily focused on the effects of gluten free diets. Findings from these studies indicate that a diet avoiding gluten benefits a limited subset of patients, individuals with celiac disease or non-celiac gluten sensitivity. Therefore, alternative dietary and nutritional modifications such as high-fiber, Mediterranean style, diets that enrich the production of SCFA, while being associated with a minimal likelihood of adverse events, may improve immune and cardiovascular outcomes linked to premature mortality in schizophrenia. With a growing literature demonstrating that SCFA can cross the blood brain barrier and target key inflammatory and metabolic pathways, this article highlights enriching dietary intake for SCFA as a potential adjunctive therapy for people with schizophrenia

Not All Distraction Is Bad: Working Memory Vulnerability to Implicit Socioemotional Distraction Correlates with Negative Symptoms and Functional Impairment in Psychosis

This study investigated implicit socioemotional modulation of working memory (WM) in the context of symptom severity and functional status in individuals with psychosis (N = 21). A delayed match-to-sample task was modified wherein task-irrelevant facial distracters were presented early and briefly during the rehearsal of pseudoword memoranda that varied incrementally in load size (1, 2, or 3 syllables). Facial distracters displayed happy, sad, or emotionally neutral expressions. Implicit socioemotional modulation of WM was indexed by subtracting task accuracy on nonfacial geometrical distraction trials from facial distraction trials. Results indicated that the amount of implicit socioemotional modulation of high WM load accuracy was significantly associated with negative symptoms (r = 0.63, P < 0.01), role functioning (r = −0.50, P < 0.05), social functioning (r = −0.55, P < 0.01), and global assessment of functioning (r = −0.53, P < 0.05). Specifically, greater attentional distraction of high WM load was associated with less severe symptoms and functional impairment. This study demonstrates the importance of the WM-socioemotional interface in influencing clinical and psychosocial functional status in psychosis

Association of Neurocognition With Transition to Psychosis: Baseline Functioning in the Second Phase of the North American Prodrome Longitudinal Study

Neurocognition is a central characteristic of schizophrenia and other psychotic disorders. Identifying the pattern and severity of neurocognitive functioning during the “near-psychotic”, prodromal, clinical high-risk (CHR) state is necessary to develop accurate predictors of psychosis and more effective and potentially preventative treatments

O2.8. TRAJECTORIES OF NEUROCOGNITIVE FUNCTIONING OVER TIME IN YOUTH AT CLINICAL HIGH RISK WHO DO AND DO NOT TRANSITION TO PSYCHOSIS

Abstract Background: In spite of evidence for the premorbid and prodromal onset of cognitive deficits in schizophrenia and related psychotic disorders, there is some limited evidence to suggest that deficits may progress with psychosis onset. Cognitive remediation in youth at risk for psychosis is being touted as an opportunity not only to remediate deficits but to potentially prevent this progression. Yet trajectories of cognitive functioning over time remain poorly understood in youth at risk, including the degree to which age at assessment or illness onset, sociodemographic factors, or symptom progression influence these trajectories. Methods: The North American Prodrome Longitudinal Study (NAPLS) -2 collected data on an extensive battery of neuropsychological (NP) tests at baseline, one year, two years, and post-conversion in a sample of clinical high risk (CHR) youth and healthy comparison (HC) subjects ages 12–35 (N= 960, 92% of the full sample) followed clinically for up to 2 years. NP data were available for 694 at CHR and 265 HC. Linear mixed effects analyses were used to test the effects of group, age, gender, age of onset, maternal education, and clinical outcome on cognitive trajectories. Results: Those who transitioned to a psychotic disorder over the course of follow-up performed significantly below those who did not and well below healthy comparisons. Tasks reliant on attention, visual and auditory working memory, visuospatial and verbal memory, and processing speed best differentiated those who transitioned from those who did not at one year (Cohen’s d from -0.33 to -0.54). Discrepancies from normal functioning on these tests were generally large (Cohen’s d from -0.67 to -1.02) consistent with findings for first episode samples. Although clinical outcome was not associated with a significantly different trajectory over time on any cognitive domain, these are likely due to high rates of conversion in this sample within the first year. Predictors of different trajectories will be presented. Discussion These data from one of the largest CHR studies to date suggest that much of the neuropsychological dysfunction in major psychotic disorders is present early in the course of illness and prior to its full expression. However, trajectories are highly heterogeneous. More frequent assessment prior to and during the onset of illness are needed to fully understand the cognitive correlates of psychosis onset and the implications for early intervention

Healthy adolescent performance on the MATRICS Consensus Cognitive Battery (MCCB): Developmental data from two samples of volunteers

The MATRICS Consensus Cognitive Battery (MCCB) fills a significant need for a standardized battery of cognitive tests to use in clinical trials for schizophrenia in adults aged 20-59. A need remains, however, to develop norms for younger individuals, who also show elevated risks for schizophrenia. Toward this end, we assessed performance in healthy adolescents. Baseline MCCB, reading and IQ data were obtained from healthy controls (ages 12-19) participating in two concurrent NIMH-funded studies: North American Prodromal Longitudinal Study phase 2 (NAPLS-2; n=126) and Boston Center for Intervention Development and Applied Research (CIDAR; n=13). All MCCB tests were administered except the Managing Emotions subtest from the Mayer-Salovey-Caruso Emotional Intelligence Test. Data were collected from 8 sites across North America. MCCB scores were presented in four 2-year age cohorts as T-scores for each test and cognitive domain, and analyzed for effects of age and sex. Due to IQ differences between age-grouped subsamples, IQ served as a covariate in analyses. Overall and sex-based raw scores for individual MCCB tests are presented for each age-based cohort. Adolescents generally showed improvement with age in most MCCB cognitive domains, with the clearest linear trends in Speed of Processing, Attention/Vigilance, and Working Memory. These control data show that healthy adolescence is a dynamic period for cognitive development that is marked by substantial improvement in MCCB performance through the 12-19 age range. They also provide healthy comparison raw scores to facilitate clinical evaluations of adolescents, including those at risk for developing psychiatric disorders such as schizophrenia-related conditions

Reliability of an fMRI paradigm for emotional processing in a multisite longitudinal study

Multisite neuroimaging studies can facilitate the investigation of brain-related changes in many contexts, including patient groups that are relatively rare in the general population. Though multisite studies have characterized the reliability of brain activation during working memory and motor functional magnetic resonance imaging tasks, emotion processing tasks, pertinent to many clinical populations, remain less explored. A traveling participants study was conducted with eight healthy volunteers scanned twice on consecutive days at each of the eight North American Longitudinal Prodrome Study sites. Tests derived from generalizability theory showed excellent reliability in the amygdala ( Eρ2 = 0.82), inferior frontal gyrus (IFG; Eρ2 = 0.83), anterior cingulate cortex (ACC; Eρ2 = 0.76), insula ( Eρ2 = 0.85), and fusiform gyrus ( Eρ2 = 0.91) for maximum activation and fair to excellent reliability in the amygdala ( Eρ2 = 0.44), IFG ( Eρ2 = 0.48), ACC ( Eρ2 = 0.55), insula ( Eρ2 = 0.42), and fusiform gyrus ( Eρ2 = 0.83) for mean activation across sites and test days. For the amygdala, habituation ( Eρ2 = 0.71) was more stable than mean activation. In a second investigation, data from 111 healthy individuals across sites were aggregated in a voxelwise, quantitative meta-analysis. When compared with a mixed effects model controlling for site, both approaches identified robust activation in regions consistent with expected results based on prior single-site research. Overall, regions central to emotion processing showed strong reliability in the traveling participants study and robust activation in the aggregation study. These results support the reliability of blood oxygen level-dependent signal in emotion processing areas across different sites and scanners and may inform future efforts to increase efficiency and enhance knowledge of rare conditions in the population through multisite neuroimaging paradigms

Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk

Severe neuropsychiatric conditions, such as schizophrenia, affect distributed neural computations. One candidate system profoundly altered in chronic schizophrenia involves the thalamocortical networks. It is widely acknowledged that schizophrenia is a neurodevelopmental disorder that likely affects the brain before onset of clinical symptoms. However, no investigation has tested whether thalamocortical connectivity is altered in individuals at risk for psychosis or whether this pattern is more severe in individuals who later develop full-blown illness

Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia?

Growing interest in gut and digestive processes and their potential link to brain and peripheral based inflammation or biobehavioral phenotypes has led to an increasing number of basic and translational scientific reports focused on the role of gut microbiota within the context of neuropsychiatric disorders. However, the effect of dietary modification on specific gut metabolites, in association with immune, metabolic, and psychopathological functioning in schizophrenia spectrum disorders has not been well characterized. The short chain fatty acids (SCFA) acetate, butyrate, and propionate, major metabolites derived from fermentation of dietary fibers by gut microbes, interact with multiple immune and metabolic pathways. The specific pathways that SCFA are thought to target, are dysregulated in cardiovascular disease, type II diabetes, and systemic inflammation. Most notably, these disorders are consistently linked to an attenuated lifespan in schizophrenia. Although, unhealthy dietary intake patterns and increased prevalence of immune and metabolic dysfunction has been observed in people with schizophrenia; dietary interventions have not been well utilized to target immune or metabolic illness. Prior schizophrenia patient trials primarily focused on the effects of gluten free diets. Findings from these studies indicate that a diet avoiding gluten benefits a limited subset of patients, individuals with celiac disease or non-celiac gluten sensitivity. Therefore, alternative dietary and nutritional modifications such as high-fiber, Mediterranean style, diets that enrich the production of SCFA, while being associated with a minimal likelihood of adverse events, may improve immune and cardiovascular outcomes linked to premature mortality in schizophrenia. With a growing literature demonstrating that SCFA can cross the blood brain barrier and target key inflammatory and metabolic pathways, this article highlights enriching dietary intake for SCFA as a potential adjunctive therapy for people with schizophrenia

Not all distraction is bad: working memory vulnerability to implicit socioemotional distraction correlates with negative symptoms and functional impairment in psychosis.

This study investigated implicit socioemotional modulation of working memory (WM) in the context of symptom severity and functional status in individuals with psychosis (N = 21). A delayed match-to-sample task was modified wherein task-irrelevant facial distracters were presented early and briefly during the rehearsal of pseudoword memoranda that varied incrementally in load size (1, 2, or 3 syllables). Facial distracters displayed happy, sad, or emotionally neutral expressions. Implicit socioemotional modulation of WM was indexed by subtracting task accuracy on nonfacial geometrical distraction trials from facial distraction trials. Results indicated that the amount of implicit socioemotional modulation of high WM load accuracy was significantly associated with negative symptoms (r = 0.63, P &lt; 0.01), role functioning (r = -0.50, P &lt; 0.05), social functioning (r = -0.55, P &lt; 0.01), and global assessment of functioning (r = -0.53, P &lt; 0.05). Specifically, greater attentional distraction of high WM load was associated with less severe symptoms and functional impairment. This study demonstrates the importance of the WM-socioemotional interface in influencing clinical and psychosocial functional status in psychosis

Not all distraction is bad: working memory vulnerability to implicit socioemotional distraction correlates with negative symptoms and functional impairment in psychosis.

This study investigated implicit socioemotional modulation of working memory (WM) in the context of symptom severity and functional status in individuals with psychosis (N = 21). A delayed match-to-sample task was modified wherein task-irrelevant facial distracters were presented early and briefly during the rehearsal of pseudoword memoranda that varied incrementally in load size (1, 2, or 3 syllables). Facial distracters displayed happy, sad, or emotionally neutral expressions. Implicit socioemotional modulation of WM was indexed by subtracting task accuracy on nonfacial geometrical distraction trials from facial distraction trials. Results indicated that the amount of implicit socioemotional modulation of high WM load accuracy was significantly associated with negative symptoms (r = 0.63, P &lt; 0.01), role functioning (r = -0.50, P &lt; 0.05), social functioning (r = -0.55, P &lt; 0.01), and global assessment of functioning (r = -0.53, P &lt; 0.05). Specifically, greater attentional distraction of high WM load was associated with less severe symptoms and functional impairment. This study demonstrates the importance of the WM-socioemotional interface in influencing clinical and psychosocial functional status in psychosis