Appreciating symptoms and deficits in schizophrenia: Right posterior insula and poor insight Lena Palaniyappan ⁎, Pavan Mallikarjun, Verghese Joseph, Peter F. Liddle Division of Psychiatry, University of Nottingham, A Floor, South Block, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom abstract article info Article history: Received 11 November 2010 Received in revised form 3 December 2010 Accepted 8 December 2010 Available online 21 December 2010 Keywords: Insight Insula Interoception MRI Schizophrenia Poor insight is one of the most prominent clinical features of psychosis. Loss of insight in schizophrenia is characterised by abnormalities in awareness and attribution of the origin of pathological mental phenomena. Converging lines of investigations suggest that in healthy individuals, right posterior insula plays an important role in awareness and self-attribution of mental phenomena, contributing to the emergence of a sense of self (Craig, 2002; Farrer et al., 2003). In addition, neuroimaging studies investigating brain morphometry in schizophrenia have consistently reported deficits in the structure of insula (Glahn et al., 2008; Ellison-Wright and Bullmore, 2010). In the present study, we investigated the relationship between the morphometry of posterior insula and degree of insight in a sample of 57 patients in a stable phase of illness using high resolution Magnetic Resonance Imaging. We measured the cortical surface area and local white matter volume of posterior insula. A significant inverse relationship was found between right posterior insular structure and degree of insight in schizophrenia. No such relationship was noted for left posterior insula. Our results highlight the importance of a predominantly right-sided network that includes posterior insula as the neural basis of insight. Abnormalities in interoceptive awareness and self-appraisal of emotional states may contribute to the loss of insight seen in schizophrenia. © 2010 Elsevier Inc. All rights reserved. 1. Introduction Impairment of insight is one of the defining features of psychosis. A number of longitudinal studies have found a significant predictive association between insight and functional outcome in schizophrenia (Lysaker et al., 2002; Mohamed et al., 2009). In this context, insight refers to an awareness of the illness and associated functional changes rather than an internalized stigma or acceptance of stereotyped beliefs about schizophrenia. While the former shows a positive relationship with recovery, the latter may hinder recovery (Lysaker et al., 2007). An emerging view of insight involves the role of metacognitive abilities in generating a personal narrative of the meaning of mental symptoms (Tranulis et al., 2008; Lysaker et al., 2005). Meta-cognition aids in generating a sense of ownership of one's own thoughts and actions. Together with emotional awareness and the ability to discriminate self from others, this forms the basis of self-reflection necessary to generate insight (Dimaggio et al., 2009). Lack of appreciation of one's own symptoms and functional deficits is also seen in neurological disorders resulting from stroke wherein the term anosognosia is commonly used. Anosognosia in neurological disorders often presents in a more striking manner with some patients denying the ownership of paralysed limbs and/or attributing their deficits to a different person (Orfei et al., 2007). These deficits in awareness, sense of agency and ownership of self-generated intentions/actions are similar to some core psychotic symptoms in schizophrenia (Waters and Badcock, 2010). Several lines of evidence suggest an important role for posterior insula in the lack of insight seen in schizophrenia. Both awareness and attribution of mental phenomenon, the two core components of insight in schizophrenia (David et al., 1992; Gilleen et al., 2011), are associated with the function of posterior insula. Firstly, Craig regards insula as one of the cardinal brain regions in modulating interoceptive awareness that is coupled to an appraisal of internal states leading to a sense of self (Craig, 2002, 2009). Interoceptive awareness contributes to the appreciation of the pathological nature of various mental phenomena (Goldstein et al., 2009). In addition, Farrer and Frith's (Farrer et al., 2003; Farrer and Frith, 2002) studies on action attribution have established that right posterior insula is crucial in modulating the experience of agency. When healthy individuals attribute an action to themselves as a result of a sense of self-control, activation in the insular cortex is observed (Farrer et al., 2003). But the same task fails to elicit insular activation in subjects with schizophrenia (Farrer et al., 2004). Finally, Karnath et al. (Karnath et al., 2005; Baier and Karnath, 2008) have demonstrated that lesions in right posterior insula underlie the disturbances in self-awareness of actions and limb ownership seen in anosognosic patients with stroke. Overall, these findings underline the Progress in Neuro-Psychopharmacology & Biological Psychiatry 35 (2011) 523–527 Abbreviations: SSPI, Signs and Symptoms in Psychotic Illness scale; GM, grey matter; WM, white matter; FDR, False Discovery Rate; DSM-IV, Diagnostic Statistical Manual — Fourth edition; MRI, Magnetic Resonance Imaging. ⁎ Corresponding author. Tel.: + 44 115 823 0407; fax: + 44 115 823 0433. E-mail address: Lena.Palaniyappan@nottingham.ac.uk (L. Palaniyappan). 0278-5846/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2010.12.008 Contents lists available at ScienceDirect Progress in Neuro-Psychopharmacology & Biological Psychiatry journal homepage: www.elsevier.com/locate/pnp