The right occipital lobe and poor insight in first-episode psychosis

Diana Tordesillas-Gutierrez, Rosa Ayesa-Arriola, Manuel Delgado-Alvarado, Jennifer L Robinson, Javier Lopez-Morinigo, Jesus Pujol, M Encarnación Dominguez-Ballesteros, Anthony S David, Benedicto Crespo-Facorro, Diana Tordesillas-Gutierrez, Rosa Ayesa-Arriola, Manuel Delgado-Alvarado, Jennifer L Robinson, Javier Lopez-Morinigo, Jesus Pujol, M Encarnación Dominguez-Ballesteros, Anthony S David, Benedicto Crespo-Facorro

Abstract

Lack of insight is a core feature of non-affective psychosis and has been associated with poorer outcomes. Brain abnormalities underlying lack of insight have been suggested, mostly in the frontal lobe, although previous research showed mixed results. We used a voxel-based morphometry (VBM) analysis in 108 first-episode non-affective psychosis patients to investigate the pattern of brain structural abnormalities related to lack of insight. In addition, 77 healthy volunteers were compared with the patients classified as having poor and good insight. The shortened version of the Scale to Assess Unawareness of Mental Disorder was used to evaluate insight. Patients with poor insight (n = 68) compared with patients with good insight (n = 40) showed a single significant cluster (kc = 5834; PcFWE = 0.001) of reduced grey matter volume (GMV) in the right occipital lobe extending to its lateral and medial surfaces, the cuneus, and the middle temporal gyrus. In addition, GMV at this cluster showed a negative correlation with the score of the SUMD (r = -0.305; p = 0.001). When comparing patients with poor insight with healthy subjects overall reductions of GMV were found, mainly in frontal and occipital lobes. Hence, poor insight in non-affective psychosis seems to be associated with specific brain abnormalities in the right occipital and temporal cortical regions. Dysfunction in any combination of these areas may contribute to lack of insight in non-affective psychosis. Specifically, the 'right' hemisphere dysfunction underlying impaired insight in our sample is consistent with previously reported similarities between lack of insight in psychosis and anosognosia in neurological disorders.

Trial registration: ClinicalTrials.gov NCT02305823 NCT02534363.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1
(A) In red are shown the results of the VBM contrast FEP patients with good insight vs. FEP with poor insight, cluster extends through the right middle and superior occipital gyri, cuneus and middle temporal gyrus. All results are in MNI space. (B) Correlation analysis: Grey matter values at maximum voxel of the contrast good insight > poor insight and insight.

References

    1. Amador XF, David AS. Insight and Psychosis: Awareness of Illness in Schizophrenia and Related Disorders: OUP Oxford; 2004.
    1. Arango C, Amador X. Lessons learned about poor insight. Schizophr Bull. 2011. January;37(1):27–8. doi:
    1. Crumlish N, Whitty P, Kamali M, Clarke M, Browne S, McTigue O, et al. Early insight predicts depression and attempted suicide after 4 years in first-episode schizophrenia and schizophreniform disorder. Acta Psychiatr Scand. 2005. December;112(6):449–55. doi:
    1. Saeedi H, Addington J, Addington D. The association of insight with psychotic symptoms, depression, and cognition in early psychosis: a 3-year follow-up. Schizophr Res. 2007. January;89(1–3):123–8. doi:
    1. Ayesa-Arriola R, Morinigo JD, David AS, Perez-Iglesias R, Rodriguez-Sanchez JM, Crespo-Facorro B. Lack of insight 3 years after first-episode psychosis: an unchangeable illness trait determined from first presentation? Schizophr Res. 2014. August;157(1–3):271–7. doi:
    1. Buckley PF, Wirshing DA, Bhushan P, Pierre JM, Resnick SA, Wirshing WC. Lack of insight in schizophrenia: impact on treatment adherence. CNS drugs. 2007;21(2):129–41.
    1. Lincoln TM, Lullmann E, Rief W. Correlates and long-term consequences of poor insight in patients with schizophrenia. A systematic review. Schizophr Bull. 2007. November;33(6):1324–42. doi:
    1. Kumar A, Sharma P, Das S, Nath K, Talukdar U, Bhagabati D. Insight in psychotic disorder: relation with psychopathology and frontal lobe function. Psychopathology. 2014;47(1):32–8. doi:
    1. Shad MU, Muddasani S, Prasad K, Sweeney JA, Keshavan MS. Insight and prefrontal cortex in first-episode Schizophrenia. Neuroimage. 2004. July;22(3):1315–20. doi:
    1. Laroi F, Fannemel M, Ronneberg U, Flekkoy K, Opjordsmoen S, Dullerud R, et al. Unawareness of illness in chronic schizophrenia and its relationship to structural brain measures and neuropsychological tests. Psychiatry research. 2000. November 20;100(1):49–58.
    1. Morgan KD, Dazzan P, Morgan C, Lappin J, Hutchinson G, Suckling J, et al. Insight, grey matter and cognitive function in first-onset psychosis. The British journal of psychiatry: the journal of mental science. 2010. August;197(2):141–8.
    1. Cocchini G, Beschin N, Cameron A, Fotopoulou A, Della Sala S. Anosognosia for motor impairment following left brain damage. Neuropsychology. 2009. March;23(2):223–30. doi:
    1. Antonius D, Prudent V, Rebani Y, D'Angelo D, Ardekani BA, Malaspina D, et al. White matter integrity and lack of insight in schizophrenia and schizoaffective disorder. Schizophr Res. 2011. May;128(1–3):76–82. doi:
    1. Bedford NJ, Surguladze S, Giampietro V, Brammer MJ, David AS. Self-evaluation in schizophrenia: an fMRI study with implications for the understanding of insight. BMC Psychiatry. 2012;12:106 doi:
    1. Kim JJ, Ku J, Lee H, Choi SH, Kim IY. Distinct neural responses used to gain insight into hallucinatory perception in patients with schizophrenia. Journal of psychiatric research. 2012. October;46(10):1318–25. doi:
    1. Liemburg EJ, van der Meer L, Swart M, Curcic-Blake B, Bruggeman R, Knegtering H, et al. Reduced connectivity in the self-processing network of schizophrenia patients with poor insight. PLoS One. 2012;7(8):e42707 doi:
    1. Raij TT, Riekki TJ, Hari R. Association of poor insight in schizophrenia with structure and function of cortical midline structures and frontopolar cortex. Schizophr Res. 2012. August;139(1–3):27–32. doi:
    1. van der Meer L, de Vos AE, Stiekema AP, Pijnenborg GH, van Tol MJ, Nolen WA, et al. Insight in schizophrenia: involvement of self-reflection networks? Schizophr Bull. 2013. November;39(6):1288–95.
    1. Bassitt DP, Neto MR, de Castro CC, Busatto GF. Insight and regional brain volumes in schizophrenia. European archives of psychiatry and clinical neuroscience. 2007. February;257(1):58–62. doi:
    1. Cooke MA, Fannon D, Kuipers E, Peters E, Williams SC, Kumari V. Neurological basis of poor insight in psychosis: a voxel-based MRI study. Schizophr Res. 2008. August;103(1–3):40–51. doi:
    1. Ha TH, Youn T, Ha KS, Rho KS, Lee JM, Kim IY, et al. Gray matter abnormalities in paranoid schizophrenia and their clinical correlations. Psychiatry research. 2004. December 30;132(3):251–60. doi:
    1. Berge D, Carmona S, Rovira M, Bulbena A, Salgado P, Vilarroya O. Gray matter volume deficits and correlation with insight and negative symptoms in first-psychotic-episode subjects. Acta Psychiatr Scand. 2011. June;123(6):431–9. doi:
    1. McFarland J, Cannon DM, Schmidt H, Ahmed M, Hehir S, Emsell L, et al. Association of grey matter volume deviation with insight impairment in first-episode affective and non-affective psychosis. European archives of psychiatry and clinical neuroscience. 2013. March;263(2):133–41. doi:
    1. Pelayo-Teran JM, Perez-Iglesias R, Ramirez-Bonilla M, Gonzalez-Blanch C, Martinez-Garcia O, Pardo-Garcia G, et al. Epidemiological factors associated with treated incidence of first-episode non-affective psychosis in Cantabria: insights from the Clinical Programme on Early Phases of Psychosis. Early Interv Psychiatry. 2008. August;2(3):178–87. doi:
    1. First MB, Spitzer RL, Gibbon M, Williams J. Structured clinical interview for DSM-IV-TR Axis I disorders- Non patient edition New York: New York State Psychiatric Institute; 2001.
    1. Andreasen NC, Flaum M, Arndt S. The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. Archives of general psychiatry. 1992. August;49(8):615–23.
    1. Amador XF, Flaum M, Andreasen NC, Strauss DH, Yale SA, Clark SC, et al. Awareness of illness in schizophrenia and schizoaffective and mood disorders. Archives of general psychiatry. 1994. October;51(10):826–36.
    1. Ruiz A, Pousa E, Duno R, Crosas J, Cuppa S, Garcia C. [Spanish adaptation of the Scale to Asses Unawareness of Mental Disorder (SUMD)]. Actas Esp Psiquiatr. 2008. Mar-Apr;36(2):111–1198.
    1. Michel P, Baumstarck K, Auquier P, Amador X, Dumas R, Fernandez J, et al. Psychometric properties of the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia. BMC Psychiatry. 2013. September 22;13:229 doi:
    1. Ayesa-Arriola R, Rodriguez-Sanchez JM, Morelli C, Pelayo-Teran JM, Perez-Iglesias R, Mata I, et al. Insight dimensions in first-episode psychosis patients: clinical, cognitive, pre-morbid and socio-demographic correlates. Early Interv Psychiatry. 2011. May;5(2):140–9. doi:
    1. Trevisi M, Talamo A, Bandinelli PL, Ducci G, Kotzalidis GD, Santucci C, et al. Insight and awareness as related to psychopathology and cognition. Psychopathology. 2012;45(4):235–43. doi:
    1. Overall JE, Gorman DR. The Brief Psychiatric Rating Scale. Psychol. Rep 10:799–821 1962.
    1. Andreasen NC. The Scale for the Assesment of Negative Symptoms (SANS) Iowa City: University of Iowa; 1983.
    1. Andreasen NC. The Scale for the Assesment of Positive Symptoms (SAPS) Iowa City: University of Iowa; 1984.
    1. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971. March;9(1):97–113.
    1. Ashburner J, Friston KJ. Voxel-based morphometry—the methods. Neuroimage. 2000. June;11(6 Pt 1):805–21. doi:
    1. Cuadra MB, Cammoun L, Butz T, Cuisenaire O, Thiran JP. Comparison and validation of tissue modelization and statistical classification methods in T1-weighted MR brain images. IEEE Trans Med Imaging. 2005. December;24(12):1548–65. doi:
    1. Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage. 2007. October 15;38(1):95–113. doi:
    1. Hayasaka S, Phan KL, Liberzon I, Worsley KJ, Nichols TE. Nonstationary cluster-size inference with random field and permutation methods. Neuroimage. 2004. June;22(2):676–87. doi:
    1. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002. January;15(1):273–89. doi:
    1. Tordesillas-Gutierrez D, Koutsouleris N, Roiz-Santianez R, Meisenzahl E, Ayesa-Arriola R, Marco de Lucas E, et al. Grey matter volume differences in non-affective psychosis and the effects of age of onset on grey matter volumes: A voxelwise study. Schizophr Res. 2015. May;164(1–3):74–82. doi:
    1. Buchy L, Ad-Dab'bagh Y, Malla A, Lepage C, Bodnar M, Joober R, et al. Cortical thickness is associated with poor insight in first-episode psychosis. Journal of psychiatric research. 2011. June;45(6):781–7. doi:
    1. Flashman LA, McAllister TW, Johnson SC, Rick JH, Green RL, Saykin AJ. Specific frontal lobe subregions correlated with unawareness of illness in schizophrenia: a preliminary study. J Neuropsychiatry Clin Neurosci. 2001. Spring;13(2):255–7. doi:
    1. Orfei MD, Piras F, Macci E, Caltagirone C, Spalletta G. The neuroanatomical correlates of cognitive insight in schizophrenia. Soc Cogn Affect Neurosci. 2013. April;8(4):418–23. doi:
    1. Sapara A, Cooke M, Fannon D, Francis A, Buchanan RW, Anilkumar AP, et al. Prefrontal cortex and insight in schizophrenia: a volumetric MRI study. Schizophr Res. 2007. January;89(1–3):22–34. doi:
    1. Aleman A, Agrawal N, Morgan KD, David AS. Insight in psychosis and neuropsychological function: meta-analysis. The British journal of psychiatry: the journal of mental science. 2006. September;189:204–12.
    1. Braff DL, Heaton R, Kuck J, Cullum M, Moranville J, Grant I, et al. The generalized pattern of neuropsychological deficits in outpatients with chronic schizophrenia with heterogeneous Wisconsin Card Sorting Test results. Archives of general psychiatry. 1991. October;48(10):891–8.
    1. Drake RJ, Lewis SW. Insight and neurocognition in schizophrenia. Schizophr Res. 2003. July 1;62(1–2):165–73.
    1. Lysaker P, Bell M. Work rehabilitation and improvements in insight in schizophrenia. J Nerv Ment Dis. 1995. February;183(2):103–6.
    1. Osatuke K, Ciesla J, Kasckow JW, Zisook S, Mohamed S. Insight in schizophrenia: a review of etiological models and supporting research. Compr Psychiatry. 2008. Jan-Feb;49(1):70–7. doi:
    1. Mitchell JP, Macrae CN, Banaji MR. Dissociable medial prefrontal contributions to judgments of similar and dissimilar others. Neuron. 2006. May 18;50(4):655–63. doi:
    1. Sapara A, Ffytche DH, Cooke MA, Williams SC, Kumari V. Voxel-based magnetic resonance imaging investigation of poor and preserved clinical insight in people with schizophrenia. World J Psychiatry. 2016. September 22;6(3):311–21. doi:
    1. Yue Y, Kong L, Wang J, Li C, Tan L, Su H, et al. Regional Abnormality of Grey Matter in Schizophrenia: Effect from the Illness or Treatment? PLoS One. 2016;11(1):e0147204 doi:
    1. Berti A, Bottini G, Gandola M, Pia L, Smania N, Stracciari A, et al. Shared cortical anatomy for motor awareness and motor control. Science. 2005. July 15;309(5733):488–91. doi:
    1. Besharati S, Forkel SJ, Kopelman M, Solms M, Jenkinson PM, Fotopoulou A. The affective modulation of motor awareness in anosognosia for hemiplegia: behavioural and lesion evidence. Cortex. 2014. December;61:127–40. doi:
    1. Moro V, Pernigo S, Tsakiris M, Avesani R, Edelstyn NM, Jenkinson PM, et al. Motor versus body awareness: Voxel-based lesion analysis in anosognosia for hemiplegia and somatoparaphrenia following right hemisphere stroke. Cortex. 2016. October;83:62–77. doi:
    1. Maier F, Williamson KL, Tahmasian M, Rochhausen L, Ellereit AL, Prigatano GP, et al. Behavioural and neuroimaging correlates of impaired self-awareness of hypo- and hyperkinesia in Parkinson's disease. Cortex. 2016. September;82:35–47. doi:
    1. Chao LL, Haxby JV, Martin A. Attribute-based neural substrates in temporal cortex for perceiving and knowing about objects. Nat Neurosci. 1999. October;2(10):913–9. doi:
    1. Mesulam MM, Mufson EJ. Insula of the old world monkey. I. Architectonics in the insulo-orbito-temporal component of the paralimbic brain. J Comp Neurol. 1982. November 20;212(1):1–22. doi:
    1. Fan J, Zhong M, Gan J, Liu W, Niu C, Liao H, et al. Spontaneous neural activity in the right superior temporal gyrus and left middle temporal gyrus is associated with insight level in obsessive-compulsive disorder. J Affect Disord. 2017. January 1;207:203–11. doi:
    1. Gilleen J, Greenwood K, David AS. Domains of awareness in schizophrenia. Schizophr Bull. 2011. January;37(1):61–72. doi:
    1. Aldrich MS, Alessi AG, Beck RW, Gilman S. Cortical blindness: etiology, diagnosis, and prognosis. Ann Neurol. 1987. February;21(2):149–58. doi:
    1. Celesia GG, Brigell MG, Vaphiades MS. Hemianopic anosognosia. Neurology. 1997. July;49(1):88–97.
    1. Davatzikos C. Why voxel-based morphometric analysis should be used with great caution when characterizing group differences. Neuroimage. 2004. September;23(1):17–20. doi:
    1. Kubicki M, Shenton ME, Salisbury DF, Hirayasu Y, Kasai K, Kikinis R, et al. Voxel-based morphometric analysis of gray matter in first episode schizophrenia. Neuroimage. 2002. December;17(4):1711–9.

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