Hostname: page-component-586b7cd67f-t8hqh Total loading time: 0 Render date: 2024-11-26T14:04:26.509Z Has data issue: false hasContentIssue false
  • English
  • Français

Insular pathology in young people with high-functioning autism and first-episode psychosis

Published online by Cambridge University Press:  24 April 2017

M. Parellada ,
L. Pina-Camacho ,
C. Moreno ,
Y. Aleman ,
M.-O. Krebs ,
M. Desco ,
J. Merchán-Naranjo ,
A. Del Rey-Mejías ,
L. Boada  and
C. Llorente
...Show all authors
M. Parellada*
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM. Ibiza 43, 28009 Madrid, Spain
L. Pina-Camacho
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM. Ibiza 43, 28009 Madrid, Spain Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, SE5 8AF, London, UK
C. Moreno
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM. Ibiza 43, 28009 Madrid, Spain
Y. Aleman
Affiliation:
Department of Experimental Medicine, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, Ibiza 43, 28009 Madrid, Spain
M.-O. Krebs
Affiliation:
INSERM, U894, “Psychophysiology of psychiatric disorders Lab,” Center for psychiatry and neurosciences, University Paris Descartes, Sorbonne Paris Cité; Institut de Psychiatrie-GDR 3557; and Service Hospitalo-Universitaire, Centre Hospitalier Sainte-Anne, Paris, France
M. Desco
Affiliation:
Department of Experimental Medicine, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, Ibiza 43, 28009 Madrid, Spain Department of Bioengineering and Aerospace Engineering, Universidad Carlos III de Madrid, Madrid, Spain
J. Merchán-Naranjo
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM. Ibiza 43, 28009 Madrid, Spain
A. Del Rey-Mejías
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM. Ibiza 43, 28009 Madrid, Spain Department of Methodology, School of Psychology, Universidad Complutense, Madrid, Spain
L. Boada
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM. Ibiza 43, 28009 Madrid, Spain
C. Llorente
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM. Ibiza 43, 28009 Madrid, Spain
D. Moreno
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM. Ibiza 43, 28009 Madrid, Spain
C. Arango
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM. Ibiza 43, 28009 Madrid, Spain
J. Janssen
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM. Ibiza 43, 28009 Madrid, Spain Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands
*
*Address for correspondence: M. Parellada, M.D., Ph.D., Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Ibiza 43, 28009 Madrid, Spain. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Autism Spectrum Disorders (ASD) and psychosis share deficits in social cognition. The insular region has been associated with awareness of self and reality, which may be basic for proper social interactions.

Methods

Total and regional insular volume and thickness measurements were obtained from a sample of 30 children and adolescents with ASD, 29 with early onset first-episode psychosis (FEP), and 26 healthy controls (HC). Total, regional, and voxel-level volume and thickness measurements were compared between groups (with correction for multiple comparisons), and the relationship between these measurements and symptom severity was explored.

Results

Compared with HC, a shared volume deficit was observed for the right (but not the left) anterior insula (ASD: p = 0.007, FEP: p = 0.032), and for the bilateral posterior insula: (left, ASD: p = 0.011, FEP: p = 0.033; right, ASD: p = 0.004, FEP: p = 0.028). A voxel-based morphometry (VBM) conjunction analysis showed that ASD and FEP patients shared a gray matter volume and thickness deficit in the left posterior insula. Within patients, right anterior (r = −0.28, p = 0.041) and left posterior (r = −0.29, p = 0.030) insular volumes negatively correlated with the severity of insight deficits, and left posterior insular volume negatively correlated with the severity of ‘autistic-like’ symptoms (r = −0.30, p = 0.028).

Conclusions

The shared reduced volume and thickness in the anterior and posterior regions of the insula in ASD and FEP provides the first tentative evidence that these conditions share structural pathology that may be linked to shared symptomatology.

Keywords

Autism spectrum disordersfirst-episode psychosisinsulamorphologycortical thicknessvolume
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 14 , October 2017 , pp. 2472 - 2482
Copyright
Copyright © Cambridge University Press 2017 

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

Anderson, JS, Lange, N, Froehlich, A, Dubray, MB, Druzgal, TJ, Froimowitz, MP, Alexander, AL, Bigler, ED, Lainhart, JE (2010). Decreased left posterior insular activity during auditory language in autism. AJNR American Journal of Neuroradiology 31, 131–139.Google Scholar
Andreasen, NC, Pressler, M, Nopoulos, P, Miller, D, Ho, BC (2010). Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs. Biological Psychiatry 67, 255–262.Google Scholar
Buchanan, RW, Heinrichs, DW (1989). The Neurological Evaluation Scale (NES): a structured instrument for the assessment of neurological signs in schizophrenia. Psychiatry Research 27, 335–350.CrossRefGoogle Scholar
Cabanis, M, Pyka, M, Mehl, S, Muller, BW, Loos-Jankowiak, S, Winterer, G, Wolwer, W, Musso, F, Klingberg, S, Rapp, AM, Langohr, K, Wiedemann, G, Herrlich, J, Walter, H, Wagner, M, Schnell, K, Vogeley, K, Kockler, H, Shah, NJ, Stocker, T, Thienel, R, Pauly, K, Krug, A, Kircher, T (2013). The precuneus and the insula in self-attributional processes. Cognitive Affective & Behavioral Neuroscience 13, 330–345.CrossRefGoogle ScholarPubMed
Couture, SM, Penn, DL, Losh, M, Adolphs, R, Hurley, R, Piven, J (2010). Comparison of social cognitive functioning in schizophrenia and high functioning autism: more convergence than divergence. Psychological Medicine 40, 569–579.Google Scholar
Craig, AD (2009). How do you feel--now? The anterior insula and human awareness. Nature Reviews Neuroscience 10, 59–70.Google Scholar
Craig, AD (2011). Significance of the insula for the evolution of human awareness of feelings from the body. Annals of the New York Academy of Sciences 1225, 72–82.Google Scholar
Di Martino, A, Shehzad, Z, Kelly, C, Roy, AK, Gee, DG, Uddin, LQ, Gotimer, K, Klein, DF, Castellanos, FX, Milham, MP (2009). Relationship between cingulo-insular functional connectivity and autistic traits in neurotypical adults. American Journal of Psychiatry 166, 891–899.Google Scholar
Ebisch, SJ, Gallese, V, Willems, RM, Mantini, D, Groen, WB, Romani, GL, Buitelaar, JK, Bekkering, H (2011). Altered intrinsic functional connectivity of anterior and posterior insula regions in high-functioning participants with autism spectrum disorder. Human Brain Mapping 32, 1013–1028.CrossRefGoogle ScholarPubMed
Ellison-Wright, I, Glahn, DC, Laird, AR, Thelen, SM, Bullmore, E (2008). The anatomy of first-episode and chronic schizophrenia: an anatomical likelihood estimation meta-analysis. American Journal of Psychiatry 165, 1015–1023.Google Scholar
Endicott, J, Spitzer, RL, Fleiss, JL, Cohen, J (1976). The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Archives General Psychiatry 33, 766–771.Google Scholar
Fett, AK, Shergill, SS, Krabbendam, L (2015). Social neuroscience in psychiatry: unravelling the neural mechanisms of social dysfunction. Psychological Medicine 45, 1145–1165.Google Scholar
Goodkind, M, Eickhoff, SB, Oathes, DJ, Jiang, Y, Chang, A, Jones-Hagata, LB, Ortega, BN, Zaiko, YV, Roach, EL, Korgaonkar, MS, Grieve, SM, Galatzer-Levy, I, Fox, PT, Etkin, A (2015). Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry 72, 305–315.Google Scholar
Guy, W (1976). ECDEU. Assessment Manual for Psychopharmacology, Revised. US Department of Health, Education and Welfare: Rockville, MD.Google Scholar
Hommer, RE, Swedo, SE (2015). Schizophrenia and autism-related disorders. Schizophrenia Bulletin 41, 313–314.Google Scholar
Insel, T, Cuthbert, B, Garvey, M, Heinssen, R, Pine, DS, Quinn, K, Sanislow, C, Wang, P (2010). Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. American Journal of Psychiatry 167, 748–751.Google Scholar
Kastner, A, Begemann, M, Michel, TM, Everts, S, Stepniak, B, Bach, C, Poustka, L, Becker, J, Banaschewski, T, Dose, M, Ehrenreich, H (2015). Autism beyond diagnostic categories: characterization of autistic phenotypes in schizophrenia. BMC Psychiatry 15, 115.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.Google Scholar
Klein, A, Tourville, J (2012). 101 labeled brain images and a consistent human cortical labeling protocol. Frontiers in Neuroscience 6, 171.Google Scholar
Klein, TA, Ullsperger, M, Danielmeier, C (2013). Error awareness and the insula: links to neurological and psychiatric diseases. Frontiers in Human Neuroscience 7, 14.Google Scholar
Kosaka, H, Omori, M, Munesue, T, Ishitobi, M, Matsumura, Y, Takahashi, T, Narita, K, Murata, T, Saito, DN, Uchiyama, H, Morita, T, Kikuchi, M, Mizukami, K, Okazawa, H, Sadato, N, Wada, Y (2010). Smaller insula and inferior frontal volumes in young adults with pervasive developmental disorders. Neuroimage 50, 1357–1363.CrossRefGoogle ScholarPubMed
Lombardo, MV, Chakrabarti, B, Bullmore, ET, Sadek, SA, Pasco, G, Wheelwright, SJ, Suckling, J, Consortium, MA, Baron-Cohen, S (2010). Atypical neural self-representation in autism. Brain, 133, 611–624.CrossRefGoogle ScholarPubMed
Lord, C, Risi, S, Lambrecht, L, Cook, EH Jr, Leventhal, BL, Dilavore, PC, Pickles, A, Rutter, M (2000). The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders 30, 205–223.Google Scholar
Makris, N, Goldstein, JM, Kennedy, D, Hodge, SM, Caviness, VS, Faraone, SV, Tsuang, MT, Seidman, LJ (2006). Decreased volume of left and total anterior insular lobule in schizophrenia. Schizophrenia Research 83, 155–171.Google Scholar
Merchan-Naranjo, J, Mayoral, M, Rapado-Castro, M, Llorente, C, Boada, L, Arango, C, Parellada, M (2012). Estimation of the intelligence quotient using Wechsler Intelligence Scales in children and adolescents with Asperger syndrome. Journal of Autism and Developmental Disorders 42, 116–122.Google Scholar
Modinos, G, Renken, R, Ormel, J, Aleman, A (2011). Self-reflection and the psychosis-prone brain: an fMRI study. Neuropsychology 25, 295–305.Google Scholar
Moran, ME, Weisinger, B, Ludovici, K, McAdams, H, Greenstein, D, Gochman, P, Miller, R, Clasen, L, Rapoport, J, Gogtay, N (2014). At the boundary of the self: the insular cortex in patients with childhood-onset schizophrenia, their healthy siblings, and normal volunteers. International Journal of Developmental Neuroscience 32, 58–63.Google Scholar
Nichols, T, Brett, M, Andersson, J, Wager, T, Poline, JB (2005). Valid conjunction inference with the minimum statistic. Neuroimage 25, 653–660.Google Scholar
Nieuwenhuys, R (2012). The insular cortex: a review. Progress in Brain Research 195, 123–163.Google Scholar
Palaniyappan, L, Liddle, PF (2012). Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction. Journal of Psychiatry & Neuroscience 37, 17–27.Google Scholar
Penfield, W, Faulk, ME Jr (1955). The insula; further observations on its function. Brain, 78, 445–470.CrossRefGoogle ScholarPubMed
Peralta, V, Cuesta, M (1994). Validación de la escala de los sindromes positivo y negativo (PANSS) en una muestra de esquizofrénicos españoles. Actas Luso Españolas de Neurología, Psiquiatría y Ciencias afines 22, 171–177.Google Scholar
Perneger, TV (1998). What's wrong with Bonferroni adjustments. BMJ 316, 1236–1238.Google Scholar
Pinkham, AE, Hopfinger, JB, Pelphrey, KA, Piven, J, Penn, DL (2008). Neural bases for impaired social cognition in schizophrenia and autism spectrum disorders. Schizophrenia Research 99, 164–175.CrossRefGoogle ScholarPubMed
Radeloff, D, Ciaramidaro, A, Siniatchkin, M, Hainz, D, Schlitt, S, Weber, B, Poustka, F, Bolte, S, Walter, H, Freitag, CM (2014). Structural alterations of the social brain: a comparison between schizophrenia and autism. PLoS ONE 9, e106539.CrossRefGoogle Scholar
Rais, M, Cahn, W, Schnack, HG, Hulshoff Pol, HE, Kahn, RS, Van Haren, NE (2012). Brain volume reductions in medication-naive patients with schizophrenia in relation to intelligence quotient. Psychological Medicine 42, 1847–1856.Google Scholar
Rapoport, J, Chavez, A, Greenstein, D, Addington, A, Gogtay, N (2009). Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. Journal of the American Academy of Child and Adolescent Psychiatry 48, 10–18.Google Scholar
Rijcken, CA, Monster, TB, Brouwers, JR, De Jong-Van Den Berg, LT (2003). Chlorpromazine equivalents versus defined daily doses: how to compare antipsychotic drug doses?. Journal of Clinical Psychopharmacology 23, 657–659.Google Scholar
Riva, D, Bulgheroni, S, Aquino, D, Di Salle, F, Savoiardo, M, Erbetta, A (2011). Basal forebrain involvement in low-functioning autistic children: a voxel-based morphometry study. AJNR American Journal of Neuroradiology 32, 1430–1435.Google Scholar
Shepherd, AM, Matheson, SL, Laurens, KR, Carr, VJ, Green, MJ (2012). Systematic meta-analysis of insula volume in schizophrenia. Biological Psychiatry 72, 775–784.Google Scholar
Smith, SM, Nichols, TE (2009). Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44, 83–98.CrossRefGoogle ScholarPubMed
Takahashi, T, Wood, SJ, Soulsby, B, McGorry, PD, Tanino, R, Suzuki, M, Velakoulis, D, Pantelis, C (2009). Follow-up MRI study of the insular cortex in first-episode psychosis and chronic schizophrenia. Schizophrenia Research 108, 49–56.CrossRefGoogle ScholarPubMed
Tustison, NJ, Cook, PA, Klein, A, Song, G, Das, SR, Duda, JT, Kandel, BM, Van Strien, N, Stone, JR, Gee, JC, Avants, BB (2014). Large-scale evaluation of ANTs and FreeSurfer cortical thickness measurements. Neuroimage 99, 166–179.Google Scholar
Volkmar, F, Siegel, M, Woodbury-Smith, M, King, B, McCracken, J, State, M, American Academy Of, C. & Adolescent Psychiatry Committee on Quality, I. (2014). Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder. Journal of the American Academy of Child and Adolescent Psychiatry 53, 237–257.Google Scholar
Wang, H, Yushkevich, PA (2013). Groupwise segmentation with multi-atlas joint label fusion. Medical Image Computing and Computer- Assisted Intervention 16, 711–718.Google ScholarPubMed
Wechsler, D (2003). Wechsler Intelligence Scale for Children-IV (WISC-IV). Psychological Corporation: San Antonio, TX.Google Scholar
Winkler, AM, Ridgway, GR, Webster, MA, Smith, SM, Nichols, TE (2014). Permutation inference for the general linear model. Neuroimage 92, 381–397.Google Scholar

Parellada supplementary material

Figures S1-S3

Download Parellada supplementary material(Audio)
Audio 549.8 KB