Editor's Note: Over the next weeks, we will be bringing you reports from the International Congress on Schizophrenia Research (ICOSR), 29 March to 1 April 2009, and the satellite Mt. Sinai Conference on Cognition in Schizophrenia, 27-28 March, in San Diego, California. In the case of the ICOSR, we are very grateful to organizers Carol Tamminga and Chuck Schulz, who helped us recruit some roving reporters from among the Young Investigator awardees. A special thanks also to Laura Rowland and Scott Sponheim, who directed the Young Investigator program. Our first news story is from Amy Pinkham of the University of Pennsylvania.
1 April 2009. On 30 March 2009, Kristin Cadenhead of the University of California, San Diego, chaired a morning session featuring informative presentations from several members of the North American Prodrome Longitudinal Study (NAPLS) consortium, which is under the direction of Robert Heinssen at NIMH. Cadenhead and the other speakers—Jean Addington (University of Toronto), Barbara Cornblatt (Zucker Hillside Hospital), and Elaine Walker (Emory University)—emphasized three primary conclusions:
1. Impairments in social functioning are prominent in individuals who are at risk of developing schizophrenia and are even more pronounced in those individuals who do convert to psychosis.
2. These impairments are stable over time and do not worsen after formal illness onset.
3. The identification of these impairments highlights the necessity of targeted interventions that specifically focus on social and role functioning and that can be implemented in high-risk groups during the prodromal phase.
Jean Addington presented first and began by explaining the concept of the prodromal period in the development of schizophrenia, which is marked by functional decline and in some cases the appearance of attenuated or brief psychotic symptoms. With proper identification of individuals who are at risk of developing schizophrenia, this period allows a valuable opportunity for early intervention and ameliorative change. Addington reported results from three different investigations focusing on social functioning during the prodromal period. The first investigation utilized data from the NAPLS consortium and cluster analyses to identify four patterns of social functioning in individuals who were identified as being at risk based on clinical presentation. Identified patterns included stable-good, stable-intermediate, deteriorating, and poor-deteriorating. Addington noted that individuals in the deteriorating and poor-deteriorating groups were more likely to have a more severe clinical presentation but that membership in either of these groups was not associated with an increased rate of conversion to psychosis. In the second investigation, Addington used data from the PREDICT (Prodromal Research for Early Detection in a Collaborative Team) study to compare social functioning in individuals at clinical high risk (CHR), individuals with a first episode of psychosis, individuals with chronic psychosis, and non-clinical controls. All three clinical groups showed significantly lower levels of social functioning than controls, and more strikingly, CHR individuals showed comparable levels of functioning relative to first episode and chronic individuals. The last investigation highlighted the potential role of cognitive and environmental factors in social impairment by demonstrating that CHR individuals show increased levels of social defeat and negative self schema. Addington summarized by noting that impaired social functioning is the most devastating feature of the prodromal period, that social functioning impairments are prominent in CHR regardless of eventual conversion, and that understanding social functioning impairments will be useful for investigating the underlying pathophysiology of psychosis and for developing effective interventions.
Barbara Cornblatt presented next and first discussed the neurodevelopmental model upon which prodromal work is based. This model postulates that genetic vulnerabilities and in utero insults are reflected in every stage of development and that social functioning abnormalities are the downstream results of abnormal neural development. Cornblatt then presented findings from a subset of the NAPLS consortium data in which social and role functioning were assessed in individuals who met criteria for risk based on the presence of attenuated positive symptoms and who had follow-up data over a two and a half year period. In this study, individuals who converted to psychosis at any point during the follow-up period were identified and then matched to at-risk individuals who did not convert to psychosis during the follow-up period. A total of 50 converter-non-converter pairs was identified, and social and role functioning at baseline was compared between these groups. For social functioning, converters showed lower levels of functioning than non-converters at baseline and all follow-up time points. Notably, in both groups, social functioning ability was stable over time, and for converters, did not decline further after conversion occurred. Results were similar for role functioning, indicating that converters showed impaired role functioning relative to non-converters and that these impairments were stable and not impacted by conversion. In her closing remarks, Cornblatt emphasized the finding that both social and role functioning appear to be independent from the onset of psychosis and that these impairments therefore require early and specific intervention.
Kristin Cadenhead then reviewed previous work demonstrating that in addition to social functioning impairments, CHR individuals show impairments in neurocognition relative to healthy individuals. Directly following from these findings, she sought to determine whether baseline neurocognitive abilities, symptomatology, and social functioning were predictive of social functioning outcome at one-year follow-up. Participants were individuals from the Cognitive Assessment and Risk Evaluation (CARE) program at UCSD. Consistent with data from other presenters, CHR individuals failed to show a significant improvement in social functioning from baseline to follow-up, and no changes in social functioning were associated with conversion to psychosis. Multiple regression analyses also demonstrated that baseline executive functioning abilities and symptoms of disorganization were significant predictors of social functioning ability at follow-up. Cadenhead concluded that these associations between baseline neurocognitive abilities and disorganized symptoms and later functional outcome provide some insight into potential targets for early interventions that may positively alter the course of illness.
Elaine Walker concluded the symposium by presenting data from an investigation of the relationship between cortisol levels and role functioning in CHR individuals. Participants were individuals from the Emory Prodrome Project, and social and role functioning as well as cortisol levels were assessed at baseline, 7-10-month follow-up, and one-year follow-up. Of the 43 participants, 13 converted to psychosis after the follow-up period, and as reported in the other presentations, role functioning at baseline and one-year follow-up was worse for the individuals who would convert and stable over time in both converters and non-converters. Changes in cortisol levels were assessed by calculating area under the curve (AUC) indices, which allowed for comparisons of absolute levels of cortisol as well as increases in cortisol levels relative to baseline. Analyses of these indices identified higher levels of cortisol in individuals who would convert relative to non-converters at both 7-10-month and one-year follow-up. Additionally, increases in cortisol levels from baseline were significantly and positively correlated to role function deficits at baseline and one-year follow-up. Finally, Walker also presented an additional analysis that investigated whether increased cortisol levels were related to conversion. This analysis revealed that cortisol levels mediated the relationship between role functioning and conversion, suggesting that stress-induced increases in HPA activity may be superimposed on normative developmental increases and may hasten or trigger conversion to psychosis.—Amy Pinkham.