Cognitive-Affective Risk & Protection in Psychosis (CARPP) Study

Transcription

1 Cognitive-Affective Risk & Protection in Psychosis (CARPP) Study Tony J. Simon Ph.D. MIND Institute University of California, Davis MIND INSTITUTE

2 Core Working Hypothesis Cognitive impairments limit competence in numerous domains but vary widely among children and across ages Despite cognitive limitations some children outperform predictions from testing while others fall very short copers show lower anxiety, higher real world functioning and often achieve in academics far beyond what cognitive testing would predict strugglers show the reverse pattern - more anxiety poorer adaptive functioning and worse academics Q: does coper/struggler status affect psychosis risk?

3 Matching Abilities to Requirements Fear, Hyperarousal, Fight or Flight Emotional Dysregulation, Allostatic Load?

4 Anxiety Not IQ Predicts Adaptive Function Angkustsiri et al., J. Dev. Beh, Peds., q: N=99; r=-0.04; p=0.71 TD: N=45; r=0.5; p=0.002 Unlike TD children, FSIQ is NOT related to adaptive function in children with 22q11.2DS aged 7-14 years

5 Anxiety Not IQ Predicts Adaptive Function Angkustsiri et al., J. Dev. Beh, Peds., q11.2, N=62; r=-0.34, p=0.007 Copers Strugglers In children with 22q11.2DS aged 7-14 years, adaptive function is strongly and negatively related to anxiety levels

6 One Critical Cognitive Impairment Fix your eyes on the cross on left. Count the bars on the right without moving eyes Reduced resolution of spatial/temporal attention e.g. Intriligator & Cavanagh, 2001 Individual unit representations lost via crowding Hypergranularity hypothesis for NDDs - Simon, 2008 unclear relation to higher spatial and temporal frequencies

7 Reduced Spatiotemporal Resolution Adaptive threshold adjustment when comparing test magnitudes to fixed reference magnitude 22q11.2DS group requires a significantly greater difference to perform as accurately as typically developing children. impairment even greater for temporal task no differences in auditory pitch task 7

8 ORIGINAL RESEARCH ARTICLE published: 10 June 2014 doi: /fpsyg Executive Function Impairments The development of cognitive control in children with chromosome 22q11.2 deletion syndrome Go/NoGo Task adapted from Casey et al Heather M. Shapiro 1*, Flora Tassone 1,2, Nimrah S. Choudhary 2 and Tony J. Simon Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California at Davis, Sacramento, CA, USA Department of Biochemistry and Molecular Medicine, University of California at Davis, Sacramento, CA, USA Go trials (75%): press a button as quickly as possible to Chromosome 22q11.2 Deletion Syndrome (22q11.2DS) is caused by the most common human microdeletion, and it is associated with cognitive impairments across many whack the mole domains. While impairments in cognitive control have been described in children with 22q11.2DS, the nature and development of these impairments are not clear. Children No-Go trials and (25%): do NOT press button to avoid with 22q11.2DS typically developing children (TD) were tested on four well-validated tasks aimed at measuring specific foundational components of cognitive control: response inhibition, cognitive flexibility, and working memory. Molecular assays were also squashing the vegetable conducted in order to examine genotype of catechol-o-methyltransferase (COMT), a gene located within the deleted region in 22q11.2DS and hypothesized to play a role in cognitive Preceded by regression 1, 3, or 5 Go trials control. Mixed model analyses were used to examine group differences, as Edited by: Yusuke Moriguchi, Joetsu University of Education, Japan Reviewed by: Carmelo Mario Vicario, Bangor, UK Koichi Haishi, Saitama University, Japan *Correspondence: Heather M. Shapiro, MIND Institute, th Street, Room 1357, Sacramento, CA 95817, USA hmshapiro@ucdavis.edu well as age-related effects on cognitive control component processes in a cross-sectional analysis. Regression models with COMT genotype were also conducted in order to 5 examine potential effects of the different variants of the gene. Response inhibition, cognitive flexibility, and working memory were impaired in children with 22q11.2DS 3 relative to TD children, even after accounting for global intellectual functioning (as measured by full-scale IQ). When compared with TD individuals, children with 22q11.2DS demonstrated atypical age-related patterns of response inhibition and cognitive flexibility. 1 Both groups demonstrated typical age-related associations with working memory. The results of this cross-sectional analysis suggest a specific aberration in the development of systems mediating response inhibition in a sub-set of children with 22q11.2DS. It will be important to follow up with longitudinal analyses to directly examine these developmental trajectories, and correlate neurocognitive variables with clinical and adaptive outcome measures. Keywords: 22q11.2 deletion syndrome, cognitive control, executive function, childhood cognitive development, developmental disorders, catechol-o-methyltransferase (COMT)

9 Executive Function Impairments Shapiro et al. Atypical response inhibition in 22q11.2DS Shapiro et al. Atypical response inhibition in 22q11.2DS FIGURE 2 Proactive response inhibition was typical in children with 22q11.2DS. (A) Accuracy and (B) response time on Go trials did not differ between groups. Go trials, respectively). Diagnostic group, No-Go trial type, and gender were regressed on accuracy and RT. We found a signifi- FIGURE 4 Age effects on response inhibition. (A) Improved accuracy and (B) faster RT were associated with age on Go trials. There were no group differences in these relationships. (C) Reactive response inhibition was better FIGURE 3 Reactive response inhibition was atypical in children with 22q11.2DS. (A) TD children demonstrated better No-Go accuracy as a function of more preceding Go trials, while children with 22q11.2DS did not demonstrate this pattern. (B) There were no group differences in response time on incorrect No-Go trials (false alarms). in older TD children relative to younger, but this was not the case in children with 22q11.2DS. (D) Both groups demonstrated a similar relationship of faster No-Go (false alarm) RT and age. August 2013

10 Prognostic Power of Anxiety Gothelf et al year longitudinal study 125 with 22q The predictive value of having an anxiety disorder at baseline for later development of psychosis was quite robust, as 9 of 10 patients with emerging psychotic disorder in our sample were diagnosed with an anxiety disorder at baseline. Tang et al cross-sectional study 112 with 22q 8-45 years We also found that those with psychotic features were more likely to have a lifetime diagnosis of mood or anxiety disorder Perhaps individuals with significant anxiety are at even higher risk than the 22q11DS population at large.

11 A Whole New Research Direction! This entire picture was generated by the MIND Inst. culture intensive family/clinician/researcher interactions Q: does coper/struggler experience modulate psychosis risk? New grant: Cognition, affect, stress reactivity interactions to identify psychosis-proneness risk/protection predictors 22q11.2DS=100, TD=50, 12-18yrs old twice 2.5 yrs apart Hot/Cold EF tasks, some with ERPs MRI to examine SN/CEN/DMN integrity Clinical interview to asses psychosis-proneness severity Simon, Luck, Ferrer, Niendam, Carter, Popa

12 Thanks Kids who participated & their families!! Majority of the work presented here was done by: Courtney Durdle, Jordan Garner, Abbie Popa, Josh Cruz, Nina Cung, Dave Reyes, Margie Cabaral, Freddy Bassal, Heather Shapiro Ph.D., Ling Wong Ph.D., Andrea Quintero, Ph.D., Elliott Beaton Ph.D., Michelle Deng Ph.D., Joel Stoddard, M.D., Danielle Harvey, Ph.D., Naomi Hunsaker, Ph.D., Kathy Angkustsiri M.D., Ingrid Leckliter Ph.D., Janice Enriquez Ph.D., Nicole Tartaglia M.D., Khyati Brahmbatt, M.D., Paul Wadell, M.D. UCD MIND Institute IDDRC UC Davis Center of Excellence in Developmental Disabilities Dempster Family Foundation National Institutes of Health: NICHD, NIMH