Delineating the functional neuroanatomy of illness denial or anosognosia in schizophrenia

Abstract

The constructs of illness denial and anosognosia (lack of illness awareness) represent two sides of the same coin. The former implies an active psychological process whereas the latter suggests a neurological deficit. Although the neural mechanisms of illness denial are not understood, its counterpart anosognosia is commonly associated with right hemispheric damage secondary to stroke, neurodegeneration or brain injury. In cases of anosognosia secondary to stroke, patients are not only unaware of their condition, but when confronted with their

deficits they deny their hemiparesis, confabulate, and may experience so- matoparaphrenia – the delusional attribution of the paralyzed limb to

someone else, such as the doctor, nurse or family member. Schizophrenia spectrum disorders are characterized by gross misperceptions of reality, hallucinations and bizarre delusions in combination with anosognosia and

denial of need for treatment, which contributes significantly to the ill- ness’ morbidity. This population, in which illness denial is a characteristic

feature of the disorder, provides an extraordinary opportunity to explore the functional neuroanatomy of this phenomenon. In accordance with the literature demonstrating a relationship between lack of illness awareness and right hemisphere lesions, anosognosia in schizophrenia is associated with volumetric reductions within right frontal regions, specifically the OFC, dlPFC, and anterior cingulate cortices, and also the right parietal lobe in studies that used a region of interest approach. A recent hemisphere asymmetry analysis by our group found anosognosia was associated with relatively reduced right frontotemporoparietal volume. Based on these findings, we hypothesized denial of illness would be associated with left hemisphere activation in the mPFC, dlPFC and temporoparietaoccipital junction (TPO).