مجوز علائم در روان پریشی اپیزود اول: مطالعه ضخامت قشر مغز

One dimension of insight in psychosis is the ability to attribute correctly one's symptoms to a mental disorder. Recent work suggests that gray matter volumes of the orbitofrontal cortex (OFC) are correlated with aggregate symptom attribution scores in first-episode schizophrenia. Whether regions beyond the OFC are important for symptom attribution remains to be established. Further, whether common or separable neural systems underlie attribution of specific symptoms (e.g., delusions, asociality) has not been studied. In the current magnetic resonance imaging study, 52 people with a first-episode psychosis (FEP) were rated with the Scale for Assessment of Unawareness of Mental Disorder on attribution of hallucinations, delusions, flat affect and asociality. Attribution ratings were regressed on cortical thickness at 81,924 vertices. Mapping statistics revealed that delusion misattribution was associated with thickness in the OFC [Brodmann's area (BA) 11/47]. Delusion, flat affect and asociality misattribution were associated with cortical thinness in the dorsolateral prefrontal cortex (BA 9/46). Differential associations emerged between each attribution item and cortical thickness/thinness in a variety of frontal, temporal, parietal and occipital areas. The results imply a selective role for the OFC in delusion misattribution in FEP. Evidence for cortical thickness covariation in a variety of regions suggests partial independence in the neural architecture underlying attribution for different symptoms in FEP.

Lack of insight is a central clinical characteristic of schizophrenia (Carpenter et al., 1973) and other psychoses (Amador et al., 1994 and Ghaemi and Rosenquist, 2004). Although early theoretical models suggested that insight can be split into an all or nothing phenomenon (Carpenter et al., 1973 and Van Putten et al., 1976), more recent evidence suggests that insight is a continuous construct composed of several related but partially independent elements (David et al., 1992 and Amador et al., 1993). Insight elements typically involve awareness of illness, awareness of treatment effects, and an ability to label unusual mental events as pathological and attributable to a mental disorder (David, 1990, David et al., 1992 and Amador et al., 1993). Consistent with current multidimensional models, neuroimaging studies suggest the existence of partially separable neural systems underlying different insight dimensions in psychosis. These studies have employed voxel-based or region-of-interest-based analyses of magnetic resonance images (MRIs) to estimate gray matter volume or concentration. Two aspects of insight that have received attention in the literature include awareness of illness and awareness of treatment effects. Proposed brain regions relevant for illness awareness include bilateral dorsolateral prefrontal cortex (DLPFC) (Flashman et al., 2001, Shad et al., 2004, Shad et al., 2006a and Buchy et al., 2011) and the gyrus rectus (Flashman et al., 2001). To understand these findings, it has been conceptualized that alterations in regional gray matter likely disturb their subserved cognitive functions, and this presumably contributes to poor insight. Shad and colleagues (Shad et al., 2004 and Shad et al., 2006a) have hypothesized that the DLPFC may mediate poor insight via deficits in conceptual organization and self-monitoring. Flashman et al. (2001) have hypothesized that the DLPFC and gyrus rectus orchestrate comparison of current and past experiences for accurate symptom interpretation. Awareness of treatment effects, on the other hand, may engage left precuneus and inferior temporal cortex (Buchy et al., 2011). The precuneus may support accurate reflection on one's mental states or adopting another's mental perspective to judge correctly one's mental health (Cavanna and Trimble, 2006, Hassabis et al., 2007 and Wolf et al., 2009), while decreased coordination of the left temporal cortex–DLPFC pathway may lead to insight-associated memory and executive dysfunctions in psychosis (Aleman et al., 2006 and Buchy et al., 2011). A third insight dimension, the ability to attribute symptoms to a mental disorder, has been relatively understudied. The only study examining this question found that symptom misattribution was associated with increased left orbitofrontal cortex (OFC) volume in first-episode schizophrenia (Shad et al., 2006a). The authors suggested that a larger OFC, vis-à-vis its direct connections with limbic structures, may confer aberrant salience to symptom-related perceptions and experiences causing incorrect attribution. However, symptom misattribution as measured by the Scale to Assess Unawareness of Mental Disorder (SUMD) (Amador et al., 1993) was quantified with an aggregate score from attribution ratings on many different symptoms, and this may limit interpretation of results. First, a global rating may obfuscate potential associations between misattribution for any one symptom and structural neuroanatomy. Second, modern theorists have argued that insight can be modality-specific, in that patients may express insight into particular signs and symptoms of their illness but not others (Amador et al., 1994 and Pini et al., 2001), and this is presumably due to dissociable features of their pathophysiology. Third, investigations taking a specific symptom-awareness approach suggest that different cognitive and psychopathological processes contribute to different dimensions of insight, for example, that insight into delusions and hallucinations results from different processes (Amador et al., 1994, Beck et al., 2004 and Buchy et al., 2009). Fourth, functional and structural MRI data suggest that neural networks underlying different schizophrenia symptoms are partially overlapping but not homogeneous (Kasai et al., 2002, Gur et al., 2007, Hulshoff Pol and Kahn, 2008, Knobel et al., 2008 and Harvey et al., 2010). Another relevant point here is that healthy adults activate qualitatively dissociable neural networks to different attributional tasks, for example, during internal versus external attribution for events (Blackwood et al., 2000), and to attributions about one's own versus others' emotional states (Ochsner et al., 2004). This presents a strong case for a symptom-specific approach to studying the neural architecture of insight. In the present work, we used a fully automated, objective measure of cortical thickness across the entire cerebrum to address whether common or separable neural systems underlie misattribution for symptoms seen in people with psychosis (delusions, hallucinations, flat affect, asociality). The measurement of cortical thickness confers several benefits over previously employed manual analyses: it provides a direct quantitative index in millimeters of cortical integrity and reflects the structure, density and arrangement of cells (Zilles, 1990 and Parent and Carpenter, 1995). In line with the literature, we (1) predicted that greater OFC thickness would be associated with higher misattribution for one or more symptoms, and (2) tested a general hypothesis that the regional distribution of cortical thickness or thinness would be partially dissociable across the four symptom attribution items.