Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-18T20:58:38.308Z Has data issue: false hasContentIssue false
  • English
  • Français

Amygdala volume in a population with special educational needs at high risk of schizophrenia

Published online by Cambridge University Press:  07 September 2009

K. A. Welch ,
A. C. Stanfield ,
T. W. Moorhead ,
K. Haga ,
D. C. G. Owens ,
S. M. Lawrie  and
E. C. Johnstone
K. A. Welch*
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK
A. C. Stanfield
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK
T. W. Moorhead
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK
K. Haga
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK
D. C. G. Owens
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK
S. M. Lawrie
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK
E. C. Johnstone
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK
*
*Address for correspondence: K. A. Welch, Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

The mildly learning disabled population has a three-fold elevated risk for schizophrenia. It has been proposed that in some individuals this cognitive limitation is a pre-psychotic manifestation of early onset schizophrenia. We examined clinical and neuroanatomical measures of a putative extended phenotype of schizophrenia in an adolescent population receiving special educational assistance. We predicted that people with intellectual impairment and schizotypal features would exhibit amygdala volume reduction as one of the neuroanatomical abnormalities associated with schizophrenia.

Method

Assessment by clinical interview, neuropsychological assessment and magnetic resonance imaging scanning was carried out in 28 intellectually impaired individuals identified as being at elevated risk of schizophrenia due to the presence of schizotypal traits, 39 intellectually impaired controls and 29 non-intellectually impaired controls. Amygdala volume was compared in these three groups and the relationship between symptomatology and amygdala volume investigated.

Results

Right amygdala volume was significantly increased in the elevated risk group compared with the intellectually impaired controls (p=0.05). A significant negative correlation was seen between left amygdala volume and severity of negative symptoms within this group (p<0.05), but not in either control group.

Conclusions

Intellectually impaired subjects judged to be at elevated risk of schizophrenia on the basis of clinical assessment exhibit structural imaging findings which distinguish them from the generality of learning disabled subjects. Within this population reduced amygdala volume may be associated with negative-type symptoms and be part of an extended phenotype that reflects particularly elevated risk and/or early manifestations of the development of psychosis.

Keywords

Amygdalacognitive impairmenthigh risklearning disabilitymagnetic resonance imagingschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 40 , Issue 6 , June 2010 , pp. 945 - 954
Copyright
Copyright © Cambridge University Press 2009

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

Achenbach, TM (1991). Integrative Guide for the 1991 CBCL/4-18, YSR, and TRF Profiles. Department of Psychiatry, University of Vermont: Burlington, VT.Google Scholar
Bonnici, HM, Moorhead, TWJ, Stanfield, AC, Harris, JM, Owens, DG, Johnstone, EC, Lawrie, SM (2007). Pre-frontal lobe gyrification index in schizophrenia, mental retardation and comorbid groups: an automated study. NeuroImage 35, 648–654.CrossRefGoogle ScholarPubMed
Borgwardt, SJ, McGuire, PK, Aston, J, Berger, G, Dazzan, P, Gschwandtner, U, Pfluger, M, D'Souza, M, Radue, E-W, Riecher-Rossler, A (2007). Structural brain abnormalities in individuals with an at-risk mental state who later develop psychosis. British Journal of Psychiatry 191 (Suppl.), S69–S75.CrossRefGoogle Scholar
Chance, SA, Esiri, MM, Crow, TJ (2002). Amygdala volume in schizophrenia: post-mortem study and review of magnetic resonance imaging findings. British Journal of Psychiatry 180, 331–338.CrossRefGoogle ScholarPubMed
Convit, A, McHugh, P, Wolf, OT, de Leon, MJ, Bobinski, M, De Santi, S, Roche, A, Tsui, W (1999). MRI volume of the amygdala: a reliable method allowing separation from the hippocampal formation. Psychiatry Research: Neuroimaging 90, 113–123.CrossRefGoogle ScholarPubMed
Cooper, SA, Smiley, E, Morrison, J, Williamson, A, Allan, L (2007). Mental ill-health in adults with intellectual disabilities: prevalence and associated factors. British Journal of Psychiatry 190, 27–35.CrossRefGoogle ScholarPubMed
Cunningham Owens, DG, Johnstone, EC (1980). The disabilities of chronic schizophrenia – their nature and the factors contributing to their development. British Journal of Psychiatry 136, 384–395.CrossRefGoogle ScholarPubMed
Doody, GA, Johnstone, EC, Sanderson, TL, Owens, DG, Muir, WJ (1998). ‘Pfropfschizophrenie’ revisited. Schizophrenia in people with mild learning disability. British Journal of Psychiatry 173, 145–153.CrossRefGoogle ScholarPubMed
Duvernoy, H (1999). The Human Brain: Surface, Three-Dimensional Sectional Anatomy with MRI, and Blood Supply. Springer-Verlag: New York.CrossRefGoogle Scholar
Grossberg, S (2000). The imbalanced brain: from normal behavior to schizophrenia. Biological Psychiatry 48, 81–98.CrossRefGoogle ScholarPubMed
Gur, RE, Loughead, J, Kohler, CG, Elliott, MA, Lesko, K, Ruparel, K, Wolf, DH, Bilker, WB, Gur, RC (2007). Limbic activation associated with misidentification of fearful faces and flat affect in schizophrenia. Archives of General Psychiatry 64, 1356–1366.CrossRefGoogle ScholarPubMed
Honea, R, Crow, TJ, Passingham, D, Mackay, CE (2005). Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. American Journal of Psychiatry 162, 2233–2245.CrossRefGoogle ScholarPubMed
Hassiotis, A, Ukoumunne, O, Tyrer, P, Piachaud, J, Gilvarry, C, Harvey, K, Fraser, J (1999). Prevalence and characteristics of patients with severe mental illness and borderline intellectual functioning. Report from the UK700 randomised controlled trial of case management. British Journal of Psychiatry 175, 135–140.CrossRefGoogle ScholarPubMed
Johnstone, EC, Cosway, R, Lawrie, SM (2002). Distinguishing characteristics of subjects with good and poor early outcome in the Edinburgh High-Risk Study. British Journal of Psychiatry 181 (Suppl.), S26–S29.CrossRefGoogle Scholar
Johnstone, EC, Ebmeier, KP, Miller, P, Owens, DGC, Lawrie, SM (2005). Predicting schizophrenia: findings from the Edinburgh High-Risk Study. British Journal of Psychiatry 186, 18–25.CrossRefGoogle ScholarPubMed
Johnstone, EC, Owens, DGC, Hoare, P, Gaur, S, Spencer, MD, Harris, J, Moffat, V, Brearley, N, Miller, P, Lawrie, SM, Muir, WJ (2007). Schizotypal cognitions as a predictor of psychopathology in adolescents with mild intellectual impairment. British Journal of Psychiatry 191, 484–492.CrossRefGoogle ScholarPubMed
Kapur, S (2003). Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 160, 13–23.CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA (1987). The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.CrossRefGoogle ScholarPubMed
Kendler, KS, Lieberman, JA, Walsh, D (1989). The Structured Interview for Schizotypy (SIS): a preliminary report. Schizophrenia Bulletin 15, 559–571.CrossRefGoogle Scholar
Lawrie, SM, Abukmeil, SS (1998). Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. British Journal of Psychiatry 172, 110–120.CrossRefGoogle ScholarPubMed
Lawrie, SM, McIntosh, AM, Hall, J, Owens, DGC, Johnstone, EC (2008). Brain structure and function changes during the development of schizophrenia: the evidence from studies of subjects at increased genetic risk. Schizophrenia Bulletin 34, 330–340.CrossRefGoogle ScholarPubMed
Lawrie, SM, Whalley, HC, Abukmeil, SS, Kestelman, JN, Donnelly, L, Miller, P, Best, JJK, Owens, DGC, Johnstone, EC (2001). Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia. Biological Psychiatry 49, 811–823.CrossRefGoogle ScholarPubMed
Lawrie, SM, Whalley, HC, Job, DE, Johnstone, EC (2003). Structural and functional abnormalities of the amygdala in schizophrenia. Annals of the New York Academy of Sciences 985, 445–460.CrossRefGoogle ScholarPubMed
Miller, PM, Byrne, M, Hodges, A, Lawrie, SM, Johnstone, EC (2002). Childhood behaviour, psychotic symptoms and psychosis onset in young people at high risk of schizophrenia: early findings from the Edinburgh High Risk Study. Psychological Medicine 32, 173–179.CrossRefGoogle ScholarPubMed
Moorhead, TWJ, Job, DE, Whalley, HC, Sanderson, TL, Johnstone, EC, Lawrie, SM (2004). Voxel-based morphometry of comorbid schizophrenia and learning disability: analyses in normalized and native spaces using parametric and nonparametric statistical methods. NeuroImage 22, 188–202.CrossRefGoogle ScholarPubMed
Moorhead, TWJ, Stanfield, A, Spencer, M, Hall, J, McIntosh, A, Owens, DC, Lawrie, SM, Johnstone, EC (in press). Progressive temporal lobe grey matter loss in adolescents with schizotypal traits and mild intellectual impairment. Psychiatry Research: Neuroimaging.Google Scholar
Morgan, VA, Leonard, H, Bourke, J, Jablensky, A (2008). Intellectual disability co-occurring with schizophrenia and other psychiatric illness: population-based study. British Journal of Psychiatry 193, 364–372.CrossRefGoogle ScholarPubMed
Muir, WJ, Davidson, C, Doody, GA (1998). A complex re-arrangement of karyotype involving chromosomes 2 and 11 detected in a patient with dual diagnosis of schizophrenia and mild learning disability. American Journal of Medical Genetics (Neuropsychiatric Genetics) 81, 552–553.Google Scholar
Nacewicz, BM, Dalton, KM, Johnstone, T, Long, MT, McAuliff, EM, Oakes, TR, Alexander, AL, Davidson, RJ (2006). Amygdala volume and nonverbal social impairment in adolescent and adult males with autism. Archives of General Psychiatry 63, 1417–1428.CrossRefGoogle ScholarPubMed
Niemi, LT, Suvisaari, JM, Tuulio-Henriksson, A, Lönnqvist, JK (2003). Childhood developmental abnormalities in schizophrenia: evidence from high-risk studies. Schizophrenia Research 60, 239–258.CrossRefGoogle ScholarPubMed
Pruessner, JC, Li, LM, Serles, W, Pruessner, M, Collins, DL, Kabani, N, Lupien, S, Evans, AC (2000). Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. Cerebral Cortex 10, 433–442.CrossRefGoogle ScholarPubMed
Sanderson, TL, Best, JJK, Doody, G, Owens, DGC, Johnstone, EC (1999). Neuroanatomy of comorbid schizophrenia and learning disability: a controlled study. Lancet 354, 1867–1871.CrossRefGoogle ScholarPubMed
Schumann, CM, Hamstra, J, Goodlin-Jones, BL, Lotspeich, LJ, Kwon, H, Buonocore, MH, Lammers, CR, Reiss, AL, Amaral, DG (2004). The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. Journal of Neuroscience 24, 6392–6401.CrossRefGoogle Scholar
Shenton, ME, Dickey, CC, Frumin, M, McCarley, RW (2001). A review of MRI findings in schizophrenia. Schizophrenia Research 49, 1–52.CrossRefGoogle ScholarPubMed
Stanfield, AC, McIntosh, AM, Spencer, MD, Philip, R, Gaur, S, Lawrie, SM (2008 a). Towards a neuroanatomy of autism: a systematic review and meta-analysis of structural magnetic resonance imaging studies. European Psychiatry 23, 289–299.CrossRefGoogle ScholarPubMed
Stanfield, AC, Moorhead, TWJ, Harris, JM, Owens, DGC, Lawrie, SM, Johnstone, EC (2008 b). Increased right prefrontal cortical folding in adolescents at risk of schizophrenia for cognitive reasons. Biological Psychiatry 63, 80–85.CrossRefGoogle ScholarPubMed
Turner, TH (1989). Schizophrenia and mental handicap: an historical review, with implications for further research. Psychological Medicine 19, 301–314.CrossRefGoogle ScholarPubMed
Velakoulis, D, Wood, SJ, Wong, MTH, McGorry, PD, Yung, A, Phillips, L, Smith, D, Brewer, W, Proffitt, T, Desmond, P, Pantelis, C (2006). Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. Archives of General Psychiatry 63, 139–149.CrossRefGoogle ScholarPubMed
Vita, A, De Peri, L, Silenzi, C, Dieci, M (2006). Brain morphology in first-episode schizophrenia: a meta-analysis of quantitative magnetic resonance imaging studies. Schizophrenia Research 82, 75–88.CrossRefGoogle ScholarPubMed
Wechsler, D (1992). Wechsler Intelligence Scale for Children – III. Psychological Corporation: New York.Google Scholar
Wechsler, D (1999). Wechsler Adult Intelligence Scale – III. Psychological Corporation: New York.Google Scholar
WHO (1992). The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Description and Diagnostic Guidelines. World Health Organization: Geneva.Google Scholar
Wright, IC, Rabe-Hesketh, S, Woodruff, PWR, David, AS, Murray, RM, Bullmore, ET (2000). Meta-analysis of regional brain volumes in schizophrenia. American Journal of Psychiatry 157, 16–25.CrossRefGoogle ScholarPubMed