Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-28T08:19:50.547Z Has data issue: false hasContentIssue false
  • English
  • Français

Neurocognitive and familial moderators of psychiatric risk in velocardiofacial (22q11.2 deletion) syndrome: a longitudinal study

Published online by Cambridge University Press:  14 November 2014

W. R. Kates ,
N. Russo ,
W. M. Wood ,
K. M. Antshel ,
S. V. Faraone  and
W. P. Fremont
W. R. Kates*
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, USA
N. Russo
Affiliation:
Department of Psychology, Syracuse University, Syracuse, NY, USA
W. M. Wood
Affiliation:
Department of Psychology, Syracuse University, Syracuse, NY, USA
K. M. Antshel
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, USA Department of Psychology, Syracuse University, Syracuse, NY, USA
S. V. Faraone
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, USA
W. P. Fremont
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, USA
*
* Address for correspondence: W. R. Kates Ph.D., Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Although risk for psychosis in velocardiofacial (22q11.2 deletion) syndrome (VCFS) is well established, the cognitive and familial factors that moderate that risk are poorly understood.

Method

A total of 75 youth with VCFS were assessed at three time points, at 3-year intervals. Time 1 (T1) psychiatric risk was assessed with the Behavior Assessment System for Children (BASC). Data reduction of BASC scores yielded avoidance–anxiety and dysregulation factors. Time 2 (T2) neuropsychological and family function and time 3 (T3) prodromal/overt psychosis were assessed. Poisson regression models tested associations between T3 positive prodromal symptoms/overt psychosis and T1 psychiatric risk, T2 cognitive and familial factors, and their interactions.

Results

T1 avoidance–anxiety ratings predicted T3 prodromal/overt psychosis. T2 verbal learning scores moderated this association, such that individuals with low avoidance–anxiety scores and stronger verbal learning skills were the least likely to demonstrate prodromal/overt psychosis at T3. Low scores on a T2 visual vigilance task also predicted T3 prodromal/overt psychosis, independently of the effect of T1 avoidance–anxiety scores. T1 dysregulation scores did not predict T3 prodromal/overt psychosis in a linear manner. Instead, the association between dysregulation and prodromal/overt psychosis was amplified by T2 levels of family organization, such that individuals with low dysregulation scores and low family organization scores were the most likely to exhibit T3 prodromal/overt psychosis.

Conclusions

Significant moderators of psychiatric risk in VCFS include verbal learning skills as well as levels of family organization, carrying implications for early identification and preventative treatment of youth with VCFS at highest risk for psychosis.

Keywords

22q11 Deletion syndromefamily environmentmoderatorspsychosisrisk
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 8 , June 2015 , pp. 1629 - 1639
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Allen, TM, Hersch, J, Schoch, K, Curtiss, K, Hooper, SR, Shashi, V (2014). Association of the family environment with behavioral and cognitive outcomes in children with chromosome 22q11.2 deletion syndrome. Journal of Intellectual Disability Research 58, 31–47.CrossRefGoogle ScholarPubMed
Antshel, KM, Aneja, A, Strunge, L, Peebles, J, Fremont, WP, Stallone, K, Abdulsabur, N, Higgins, AM, Shprintzen, RJ, Kates, WR (2007 a). Autistic spectrum disorders in velo-cardio facial syndrome (22q11.2 deletion). Journal of Autism and Developmental Disorders 37, 1776–1786.CrossRefGoogle ScholarPubMed
Antshel, KM, Faraone, SV, Fremont, W, Monuteaux, MC, Kates, WR, Doyle, A, Mick, E, Biederman, J (2007 b). Comparing ADHD in velocardiofacial syndrome to idiopathic ADHD: a preliminary study. Journal of Attention Disorders 11, 64–73.CrossRefGoogle ScholarPubMed
Antshel, KM, Fremont, W, Roizen, NJ, Shprintzen, R, Higgins, AM, Dhamoon, A, Kates, WR (2006). ADHD, major depressive disorder, and simple phobias are prevalent psychiatric conditions in youth with velocardiofacial syndrome. Journal of the American Academy of Child and Adolescent Psychiatry 45, 596–603.CrossRefGoogle ScholarPubMed
Antshel, KM, Shprintzen, R, Fremont, W, Higgins, AM, Faraone, SV, Kates, WR (2010). Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study. Journal of the American Academy of Child and Adolescent Psychiatry 49, 333–344.Google ScholarPubMed
Bassett, AS, Chow, EW, AbdelMalik, P, Gheorghiu, M, Husted, J, Weksberg, R (2003). The schizophrenia phenotype in 22q11 deletion syndrome. American Journal of Psychiatry 160, 1580–1586.CrossRefGoogle ScholarPubMed
Baum, KM, Walker, EF (1995). Childhood behavioral precursors of adult symptom dimensions in schizophrenia. Schizophrenia Research 16, 111–120.CrossRefGoogle ScholarPubMed
Bebbington, P, Kuipers, L (1994). The predictive utility of expressed emotion in schizophrenia: an aggregate analysis. Psychological Medicine 24, 707–718.CrossRefGoogle ScholarPubMed
Botto, LD, May, K, Fernhoff, PM, Correa, A, Coleman, K, Rasmussen, SA, Merritt, RK, O'Leary, LA, Wong, LY, Elixson, EM, Mahle, WT, Campbell, RM (2003). A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics 112, 101–107.CrossRefGoogle ScholarPubMed
Cornblatt, B, Obuchowski, M, Roberts, S, Pollack, S, Erlenmeyer-Kimling, L (1999). Cognitive and behavioral precursors of schizophrenia. Developmental Psychopathology 11, 487–508.CrossRefGoogle ScholarPubMed
DeHerdt, A, Wampers, M, Vancampfort, D, De Hert, M, Vanhees, L, Demunter, H, Van Bouwel, L, Brunner, E, Probst, M (2013). Neurocognition in clinical high risk young adults who did or did not convert to a first schizophrenic psychosis: a meta-analysis. Schizophrenia Research 149, 48–55.CrossRefGoogle Scholar
Delis, DC, Kramer, JH, Kaplan, E, Ober, BA (1994). California Verbal Learning Test – Children's Version. Psychological Corporation: San Antonio, TX.Google Scholar
Dragt, S, Nieman, DH, Scultze-Lutter, F, van der Meer, F, Becker, H, de Haan, L, Dingemans, PM, Birchwood, M, Patterson, P, Salokangas, RK, Heinimaa, M, Heinz, A, Juckel, G, Graf von Reventlow, H, French, P, Stevens, H, Ruhrmann, S, Klosterkötter, J, Linszen, DH (2012). Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis. Acta Psychiatrica Scandinavica 125, 45–53.CrossRefGoogle ScholarPubMed
Dragt, S, Nieman, DH, Veltman, D, Becker, HE, van de Fliert, R, de Haan, L, Linszen, DH (2011). Environmental factors and social adjustment as predictors of a first psychosis in subjects at ultra high risk. Schizophrenia Research 125, 69–76.CrossRefGoogle ScholarPubMed
Feinstein, C, Eliez, S, Blasey, C, Reiss, AL (2002). Psychiatric disorders and behavioral problems in children with velocardiofacial syndrome: usefulness as phenotypic indicators of schizophrenia risk. Biological Psychiatry 51, 312–318.CrossRefGoogle ScholarPubMed
Golden, CJ (1978). Stroop Color and Word Test. Stoelting: Chicago, IL.Google Scholar
Golding-Kushner, KJ, Weller, G, Shprintzen, RJ (1985). Velo-cardio-facial syndrome: language and psychological profiles. Journal of Craniofacial Genetics and Developmental Biology 5, 259–266.Google ScholarPubMed
Gordon, M, McClure, FD, Aylward, GP (1989). Gordon Diagnostic System. Gordon Diagnostic Systems: Dewitt, NY.Google Scholar
Gothelf, D, Feinstein, C, Thomson, T, Gu, E, Penniman, L, Van Stone, E, Kwon, H, Eliez, S, Reiss, AL (2007). Risk factors for the emergence of psychotic disorders in adolescents with 22q11.2 deletion syndrome. American Journal of Psychiatry 164, 663–669.CrossRefGoogle ScholarPubMed
Gothelf, D, Frisch, A, Munitz, H, Rockah, R, Laufer, N, Mozes, T, Hermesh, H, Weizman, A, Frydman, M (1999). Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome. Schizophrenia Research 35, 105–112.CrossRefGoogle ScholarPubMed
Gothelf, D, Gruber, R, Presburger, G, Dotan, I, Brand-Gothelf, A, Burg, M, Inbar, D, Steinberg, T, Frisch, A, Apter, A, Weizman, A (2003). Methylphenidate treatment for attention-deficit/hyperactivity disorder in children and adolescents with velocardiofacial syndrome: an open-label study. Journal of Clinical Psychiatry 64, 1163–1169.CrossRefGoogle ScholarPubMed
Gothelf, D, Lombrosso, PJ (2001). Genetics of childhood disorders: XXV. Velocardiofacial syndrome. Journal of the American Academy of Child and Adolescent Psychiatry 40, 489–491.CrossRefGoogle ScholarPubMed
Heaton, RK, Chelune, GJ, Talley, JL, Kay, GG, Curtiss, G (1993). Wisconsin Card Sort Test Manual: Revised and Expanded. Psychological Assessment Resources, Inc.: Odessa, FL.Google Scholar
Johnstone, EC, Ebmeier, KP, Miller, P, Owens, DG, Lawrie, SM (2005). Predicting schizophrenia: findings from the Edinburgh High-Risk Study. British Journal of Psychiatry 186, 18–25.CrossRefGoogle ScholarPubMed
Kaufman, J, Birmaher, B, Brent, D, Rao, U, Flynn, C, Moreci, P, Williamson, D, Ryan, N (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry 36, 980–988.CrossRefGoogle ScholarPubMed
Khandaker, GM, Barnett, JH, White, IR, Jones, PB (2011). A quantitative meta-analysis of population-based studies of premorbid intelligence and schizophrenia. Schizophrenia Research 132, 220–227.CrossRefGoogle ScholarPubMed
Kim, HS, Shin, NY, Kim, E, Park, HY, Hong, KS, Kwon, JS (2011). Social cognition and neurocognition as predictors of conversion to psychosis in individuals at ultra-high risk. Schizophrenia Research 130, 170–175.CrossRefGoogle ScholarPubMed
Kohler, CG, Turner, TH, Gur, RE, Gur, RC (2004). Recognition of facial emotions in neuropsychiatric disorders. CNS Spectrums 9, 267–274.CrossRefGoogle ScholarPubMed
Lajiness-O'Neill, RR, Beaulieu, I, Titus, JB, Asamoah, A, Bigler, ED, Bawle, EV, Pollack, R (2005). Memory and learning in children with 22q11.2 deletion syndrome: evidence for ventral and dorsal stream disruption? Child Neuropsychology 11, 55–71.CrossRefGoogle ScholarPubMed
Lencz, T, Smith, CW, McLaughlin, D, Auther, A, Nakayama, E, Hovey, L, Cornblatt, BA (2006). Generalized and specific neurocognitive deficits in prodromal schizophrenia. Biological Psychiatry 59, 863–871.CrossRefGoogle ScholarPubMed
Levene, JE, Lancee, W, Seeman, MV, Skinner, H, Freeman, SJ (2009). Family and patient predictors of symptomatic status in schizophrenia. Canadian Journal of Psychiatry 54, 446–451.CrossRefGoogle ScholarPubMed
McNeil, BJ, Hanley, JA (1984). Statistical approaches to the analysis of receiver operating characteristic (ROC) curves. Medical Decision Making 4, 137–150.CrossRefGoogle Scholar
Michie, PT, Kent, A, Stienstra, R, Castine, R, Johnston, J, Dedman, K, Wichmann, H, Box, J, Rock, D, Rutherford, E, Jablensky, A (2000). Phenotypic markers as risk factors in schizophrenia: neurocognitive functions. Australian and New Zealand Journal of Psychiatry 34 (Suppl.), S74–S85.CrossRefGoogle ScholarPubMed
Miettunen, J, Tormanen, S, Murray, GK, Jones, PB, Maki, P, Ebeling, H, Moilanen, I, Taanila, A, Heinimaa, M, Joukamaa, M, Veijola, J (2008). Association of cannabis use with prodromal symptoms of psychosis in adolescence. British Journal of Psychiatry 192, 470–471.CrossRefGoogle ScholarPubMed
Miller, TJ, McGlashan, TH, Rosen, JL, Cadenhead, K, Cannon, T, Ventura, J, McFarlane, W, Perkins, DO, Pearlson, GD, Woods, SW (2003). Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophrenia Bulletin 29, 703–715.CrossRefGoogle ScholarPubMed
Miller, TJ, McGlashan, TH, Woods, SW, Stein, K, Driesen, N, Cocoran, CM, Hoffman, R, Davidson, L (1999). Symptom assessment in schizophrenic prodromal states. Psychiatric Quarterly 70, 273–287.CrossRefGoogle ScholarPubMed
Moos, RH, Moos, BM (2009). Family Environment Scale Manual and Sampler Test: Development, Applications, and Research, 4th edn. Mind Garden, Inc.: Palo Alto, CA.Google Scholar
Murphy, KC (2002). Schizophrenia and velo-cardio-facial syndrome. Lancet 359, 426–430.CrossRefGoogle ScholarPubMed
Murphy, KC, Owen, MJ (2001). Velo-cardio-facial syndrome: a model for understanding the genetics and pathogenesis of schizophrenia. British Journal of Psychiatry 179, 397–402.CrossRefGoogle Scholar
O'Brien, MP, Gordon, JL, Bearden, CE, Lopez, S, Kopelowicz, A, Cannon, TD (2006). Positive family environment predicts improvement in symptoms and social functioning among adolescents at imminent risk for onset of psychosis. Schizophrenia Research 81, 269–275.CrossRefGoogle ScholarPubMed
Oskarsdottir, S, Belfrage, M, Sandstedt, E, Viggedal, G, Uvebrant, P (2005). Disabilities and cognition in children and adolescents with 22q11 deletion syndrome. Developmental Medicine and Child Neurology 47, 177–184.CrossRefGoogle ScholarPubMed
Pukrop, R, Ruhrmann, S, Schultze-Lutter, F, Bechdolf, A, Brockhaus-Dumke, A, Klosterkötter, J (2007). Neurocognitive indicators for a conversion to psychosis: comparison of patients in a potentially initial prodromal state who did or did not convert to a psychosis. Schizophrenia Research 92, 116–125.CrossRefGoogle Scholar
Reininghaus, U, Morgan, C, Simpson, J, Dazzan, P, Morgan, K, Doody, G, Bhugra, D, Leff, J, Jones, P, Murray, R, Fearon, P, Craig, T (2008). Unemployment, social isolation, achievement-expectation mismatch and psychosis: findings from the AESOP study. Social Psychiatry and Psychiatric Epidemiology 43, 743–751.CrossRefGoogle ScholarPubMed
Reynolds, CR, Kamphaus, RW (1992). Behavior Assessment System for Children. American Guidance Service: Circle Pines, MN.Google Scholar
Rubin, DB, Schenker, N (1991). Multiple imputation in health-care databases: an overview and some applications. Statistics in Medicine 10, 585–598.CrossRefGoogle ScholarPubMed
Schlosser, DA, Zinberg, JL, Lowey, RL, Casey-Gannon, S, O'Brien, MP, Bearden, CE, Vinogradov, S, Cannon, TD (2010). Predicting the longitudinal effects of the family environment on prodromal symptoms and functioning in patients at-risk for psychosis. Schizophrenia Research 118, 69–75.CrossRefGoogle ScholarPubMed
Seidman, LJ, Giuliano, AJ, Meyer, EC, Addington, J, Cadenhead, KS, Cannon, TD, McGlashan, TH, Perkins, DO, Tsuang, MT, Walker, EF, Woods, SW, Bearden, CE, Christensen, BK, Hawkins, K, Heaton, R, Keefe, RS, Heinssen, R, Cornblatt, BA (2010). North American Prodrome Longitudinal Study (NAPLS) group. Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis. Archives of General Psychiatry 67, 578–588.CrossRefGoogle ScholarPubMed
Shprintzen, R (2008). Velo-cardio-facial syndrome: 30 years of study. Developmental Disabilities Research Reviews 14, 3–10.CrossRefGoogle ScholarPubMed
Swets, JA (1982). Sensitivities and specificities of diagnostic tests. JAMA 248, 548–549.CrossRefGoogle ScholarPubMed
Swets, JA (1986 a). Form of empirical ROCs in discrimination and diagnostic tasks: implications for theory and measurement of performance. Psychological Bulletin 99, 181–198.CrossRefGoogle ScholarPubMed
Swets, JA (1986 b). Indices of discrimination or diagnostic accuracy: their ROCs and implied models. Psychological Bulletin 99, 110–117.CrossRefGoogle ScholarPubMed
Swets, JA, Pickett, RM (1982). Evaluation of Diagnostic Systems: Methods from Signal Detection Theory. Academic Press: New York.Google Scholar
Swillen, A, Vandeputte, L, Cracco, J, Maes, B, Ghesquiere, P, Devriendt, K, Fryns, JP (1999). Neuropsychological, learning and psychosocial profile of primary school aged children with the velo-cardio-facial syndrome (22q11 deletion): evidence for a nonverbal learning disability? Child Neuropsychology 5, 230–241.CrossRefGoogle ScholarPubMed
Thomson, GH (1951). The Factorial Analysis of Human Ability. University of London Press: London.Google Scholar
Vorstman, JA, Morcus, ME, Duijff, SN, Klaassen, PW, Heineman-de Boer, JA, Beemer, FA, Swaab, H, Kahn, RS, van Engeland, H (2006). The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. Journal of the American Academy of Child and Adolescent Psychiatry 45, 1104–1113.CrossRefGoogle ScholarPubMed
Vorstman, JAS, Breetvelt, EJ, Duijff, SN, Eliez, S, Schneider, M, Jalbrzikowski, M et al. and the International 22q11.2 Brain Behavior Consortium (in press). A cognitive decline precedes the onset of psychosis in patients with the 22q11.2 deletion syndrome. JAMA Psychiatry.Google Scholar
Wechsler, D (1991). Wechsler Intelligence Scale for Children, 3rd edn. Psychological Corporation: San Antonio, TX.Google Scholar
Wechsler, D (1994). Wechsler Adult Intelligence Scale, 3rd edn. Psychological Corporation: San Antonio, TX.Google Scholar
Wechsler, D (1997). WMS-III: Wechsler Memory Scale Administration and Scoring Manual, 3rd edn. Psychological Corporation: San Antonio, TX.Google Scholar
Whyte, MC, Brett, C, Harrison, LK, Byrne, M, Miller, P, Lawrie, SM, Johnstone, EC (2006). Neuropsychological performance over time in people at high risk of developing schizophrenia and controls. Biological Psychiatry 59, 730–739.CrossRefGoogle ScholarPubMed
Woodin, M, Wang, PP, Aleman, D, McDonald-McGinn, D, Zackai, E, Moss, E (2001). Neuropsychological profile of children and adolescents with the 22q11.2 microdeletion. Genetics in Medicine 3, 34–39.CrossRefGoogle ScholarPubMed
Yung, AR, Phillips, LJ, Yuen, HP, Francey, SM, McFarlane, CA, Hallgren, M, McGorry, PD (2003). Psychosis prediction: 12-month follow up of a high-risk (“prodromal”) group. Schizophrenia Research 60, 21–32.CrossRefGoogle ScholarPubMed