A functional anatomic study of emotion in schizophrenia☆
Introduction
Brain regions thought to subserve emotion, often referred to as limbic brain, have long been implicated in the pathophysiology of schizophrenia Chiodo and Bunney, 1983, Stevens, 1973, although surprisingly little work has examined the functional anatomy of abnormal emotion in the illness. Schizophrenia impairs emotional processing in tasks requiring recognition of facial emotion Archer et al., 1992, Kohler et al., 2000, Walker et al., 1984, or in applied aspects of emotion, e.g. social cognition (Penn et al., 1997), although some authors have suggested that these emotional deficits may represent manifestations of broader performance deficits Archer et al., 1992, Kerr and Neale, 1993, Salem et al., 1996. Functional imaging studies have investigated possible links between abnormal emotion and anatomy, finding correlations between affective flattening/psychomotor poverty and reduced activity in the lateral prefrontal cortex during resting conditions Kawasaki et al., 1996, Liddle et al., 1992, Wolkin et al., 1992, although this relationship has not been replicated in other studies Gur et al., 1995, Siegel et al., 1993. However, this earlier work did not employ emotional probes known to activate relevant limbic structures of the brain.
Several authors have suggested that the amygdala should exhibit abnormal activity in schizophrenia, as well as a relationship with positive symptoms Fudge et al., 1998, Grace et al., 1998, Grossberg, 2000. Positive symptoms often represent an inappropriate attribution of relevance to insignificant stimuli, as in a delusion of reference. Since the amygdaloid nuclei respond to affectively relevant stimuli Everitt et al., 1991, Kapp et al., 1992, functional abnormalities of this limbic structure might be predicted. Grace and colleagues Grace et al., 1998, Moore et al., 1999 have hypothesized that schizophrenia involves a disturbance of hippocampal and prefrontal gating of information flow through the nucleus accumbens, leading to inappropriate biasing by amygdaloid projections to the accumbens. Using a mood induction paradigm known to activate the amygdala, as visualized by BOLD fMRI, Schneider and colleagues reported a failure of schizophrenic patients to activate this limbic structure (Schneider et al., 1998). While an intriguing finding, the difficulty of assessing task compliance in the patient group complicates the interpretation of their failure to activate, although the finding that the patients reported similar levels of mood induction is congruent with other studies of emotion in schizophrenia Berenbaum and Oltmanns, 1992, Earnst and Kring, 1999, Kring et al., 1993.
In the study reported here, we employed emotionally salient visual stimuli to probe neural activity in schizophrenia. Using evocative visual stimuli in healthy subjects, several groups have demonstrated activation of basal forebrain, including the extended amygdala Liberzon et al., 2000, Paradiso et al., 1999, Reiman et al., 1997, Taylor et al., 2000, and medial prefrontal cortex (MPFC) Lane et al., 1997b, Simpson et al., 2000, Teasdale et al., 1999. Minimal performance demands are placed on the subjects, thereby reducing the possibility that performance differences might confound our results. We predicted that amygdaloid activity would correlate with positive symptoms, and patients would fail to activate medial prefrontal cortex.
Section snippets
Subjects
Fourteen schizophrenic subjects were recruited from a university-staffed community mental health center to participate in the study. Patients underwent a Structured Clinical Interview for DSM-IV (First et al., 1996) to establish a diagnosis of schizophrenia according to DSM-IV criteria (American Psychiatric Association, 1994). All patients were outpatients, on stable doses of medication, at the time of the study, free of significant medical or neurological illness. They underwent assessment
Behavioral results
Subjects tolerated exposure to the images without significant difficulty, except for the single control subject who withdrew from the study. On-line ratings of aversive stimuli by both control and patient groups were nearly identical (Table 2). One schizophrenic subject with significant disorganization could not give valid ratings, but EOG showed similar scanning of the visual field and SCR showed a moderate skin conductance response; therefore, we included his PET data in the analysis. Of the
Discussion
Employing a neurobehavioral probe of emotion, our findings suggest abnormalities of the circuitry which processes emotion in schizophrenia. The schizophrenic subjects exhibited reduced activation to non-aversive, salient stimuli (NA–BL), and nearly normal or above-normal activation to the strong, aversive stimuli (AV–NA). We found reduced activation in the right amygdala, replicating prior work (Schneider et al., 1998), as well as reduced activation of left orbitofrontal cortex, both of which
Acknowledgements
The authors gratefully acknowledge assistance in construction of the stimulus sets and data analysis from David Badre and Greta Lorge.
Supported by grants from the National Alliance for Research in Schizophrenia and Depression and the National Institute of Mental Health (K08 MH01258) to S.F.T. Additional support provided by the Ann Arbor Veterans Administration Medical Center.
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This work was previously presented at the International Congress for Schizophrenia Research, Santa Fe, NM, April 1999.