At the boundary of the self: The insular cortex in patients with childhood‐onset schizophrenia, their healthy siblings, and normal volunteers

Abstract

The insular cortex (insula), whose normal function involves delineating the boundary between self and non-self stimuli, has been implicated in the pathophysiology of the positive symptoms of schizophrenia, including hallucinations and delusions. Childhood-onset schizophrenia (COS), that includes the onset of psychosis before age 13, is a severe and continuous form of the illness which shows profound and global progressive cortical brain abnormalities during adolescence which merge in the adult pattern with age. Using prospectively acquired anatomic brain magnetic resonance imaging (MRI) scans, a matched sample of COS patients, their nonpsychotic full siblings and healthy volunteers, we measured insular volume using the FreeSurfer automated software. COS patients (n=98; 234 scans) had significantly lower right (p=0.003), left (p<0.001), and total (p<0.001) insular volumes than healthy volunteers (n=100; 248 scans). Right insular volume negatively correlated with positive symptoms as measured by the Scale for the Assessment of Positive Symptoms (SAPS) (p=0.02), while both left (p=0.01) and right (p=0.006) insula volumes were positively correlated with overall functioning, as measured by the Children's Global Assessment Scale (CGAS) scores. COS siblings (n=71; 153 scans), on the other hand, did not differ significantly from normal volunteers suggesting that the insular deficits are more related to the illness state than a familial endophenotype. These results also highlight the salience of the insula in positive symptoms of schizophrenia perhaps resulting from the inability to discriminate between self from the non-self in COS. Further work to connect insular deficits to other neurocircuitries is warranted.

Bridging disparate symptoms of schizophrenia: a triple network dysfunction theory

“…This may result in a malfunction of this self-attributional tagging system with a consequent misattribution of internal mental states to an external source. Along a somewhat different line, both structural and functional changes within the SN key node, the insular region, correlate with the occurrence of AVH in schizophrenia (Jardri et al, 2011; Palaniyappan et al, 2012a) and positive symptoms in general (Moran et al, 2014). …”

Gray Matter Volume Decrease Distinguishes Schizophrenia From Bipolar Offspring During Childhood and Adolescence

“…Although both samples are first-degree relatives of patients with schizophrenia, our sample of SzO differs from the young schizophrenia siblings 35,39 in that they present clinical markers of heightened risk for the disorder (lower functionality, greater clinical severity, and higher prodromal symptom scores than CcO), thus making it likely that at least a proportion of these participants will go on to develop the disease 40 . This opens the possibility that the regional volumetric abnormalities that we have observed in SzO may in some cases form part of the preclinical phenotype of disease.…”

A Comparison of Neuroimaging Findings in Childhood Onset Schizophrenia and Autism Spectrum Disorder: A Review of the Literature

“…Patients with COS were found to have smaller insular volumes, whereas COS-siblings and controls were not statistically different, suggesting reduced insular size as an indicator of disease state. Additionally, level of functioning and severity of symptoms correlated with insular volume (68). …”