Neural circuitry underlying
impaired insight in schizophrenia
Mark D. Benton1, Mujeeb U.
Shad2, Vaibhav
A. Diwadkar2, Rajaprabhakaran Rajarethinam1, Richard J. Genik II1, Jeffrey A. Stanley1, Matcheri S.
Keshavan1
1Brain Research and Imaging
Neuroscience Division, Wayne State University, Detroit, MI USA
2Deptartment of Psychiatry,
University of Pittsburgh School of Medicine, Pittsburgh, PA USA
Objective: A substantial proportion of schizophrenia patients may
have impairments in insight. Insight is a multidimensional construct, involving
self-awareness and attribution components. Recent data in schizophrenia,
including our work, implicate prefrontally mediated neurocognitive deficits related to the lack of
self-awareness component of poor insight. These observations led us to examine
prefrontal alterations in patients with and without insight deficits using
magnetic resonance imaging (MRI). Specifically, we examined the volume of the dorsolateral prefrontal cortex (DLPFC). Additionally,
functional MRI studies of healthy participants have suggested a primary role
for the right DLPFC in self-awareness (Schmitz 2004). Therefore, we have
undertaken the logical next step of investigating whether the functional
correlates of lack of self-awareness in schizophrenia can be measured with an fMRI paradigm designed to evoke self-reflection.
Methods: A series of consenting first episode antipsychotic-naive
subjects with a DSM-IV diagnosis of first episode schizophrenia were included.
Insight was assessed using a structured rating scale. In our MRI studies
conducted in a 1.5T GE scanner, prefrontal structure was compared between
first-episode schizophrenia subjects with good (n = 17) and poor insight (n =
18). Morphometric measurements of the DLPFC and
intracranial volume (ICV) were based on MRI scans by trained raters blind to
clinical information. A pilot fMRI study was
conducted in 3 healthy male controls in a 4T Bruker MedSpec scanner using a self-referential metacognitive evaluation paradigm developed by Schmitz and
colleagues (2004). In this blocked task, subjects are required to make yes or
no decisions regarding trait adjectives in three different conditions
(evaluating oneself, a close friend or relative, and
semantic positivity).
Results & Discussion: First-episode schizophrenia subjects with poor
insight showed decreased right DLPFC volumes relative to those with good
insight, using ANCOVA after covarying for ICV. In
healthy controls, fMRI data showed that separate
comparisons of both the self- and other-evaluation conditions to the semantic positivity condition produced similar activation patterns,
specifically activating the medial prefrontal and retrosplenial
cortices. When the self- and other-referential conditions were directly
contrasted, self-evaluation showed increased activation in the right DLPFC. The
results of this fMRI pilot study are extremely
consistent with previously published reports.
Conclusions: Our findings suggest that structural and biochemical
alterations of the DLPFC may underlie decreased awareness in schizophrenia.
Poor insight in schizophrenia may be a function of specific prefrontally
mediated neurocognitive deficits, especially the
ability to reflect on oneself. Preliminary fMRI data suggest that right DLPFC participates in this
function. The fMRI paradigm in this study can be
applied to investigate the neural circuitry underlying impaired insight in
schizophrenia and related neuropsychiatric disorders.
References & Acknowledgements: Schmitz TW, et al. NeuroImage 22, 941 (2004).