Increased neural response related to neutral faces in individuals at risk for psychosis
Introduction
The reliable expression and perception of emotions are essential for adequate social interaction and momentous to subjective well-being. Disturbances of emotion expression are key features of schizophrenia, such as flattened affect and parathymia. Several studies have demonstrated that emotion perception – like the discrimination of facial emotions – is also impaired in schizophrenia (e.g., Kohler et al., 2003, Schneider et al., 2006) and that such dysfunctions may have severe consequences for social functioning and functional outcome (Kee et al., 2003). In facial emotion discrimination, particularly specificity – the ability to identify a facial expression as neutral or a non-target emotion – is impaired, while sensitivity to detect the target emotion may be preserved (Schneider et al., 2006).
Deficits in emotion processing were reported to correlate with the severity of psychotic symptoms (Kohler et al., 2000, Schneider et al., 1995), underlining the clinical significance of emotional dysfunctions. They tend to be stable over the course of illness (Kohler et al., 2003) and are already present in healthy individuals with an increased risk to develop schizophrenia due to genetic liability or risk factors like schizotypal personality traits (Kee et al., 2004, van 't Wout et al., 2004). Thus, emotional dysfunctions may represent trait markers or early signs of the disease.
An increasing number of imaging studies dealt with the neurobiological correlates underlying deficits in emotion processing observed in schizophrenia. Structural imaging and neuropathological studies predominantly reported changes in neuronal cell integrity and volume reductions in the amygdala, insula, thalamus and the hippocampus (Wright et al., 2000), which are key regions for emotion processing. Functional neuroimaging studies have demonstrated a failure to activate the amygdala and hippocampal regions in response to emotive stimuli, as well as abnormalities in the prefrontal cortex, the cingulate cortex and the occipital gyri (e.g., Gur et al., 2002a, Hempel et al., 2003, Holt et al., 2006a, Schneider et al., 1998, Taylor et al., 2002). Interestingly, hyperactivations in temporal (hippocampus, amygdala) and frontal regions (e.g., Hempel et al., 2003, Holt et al., 2006a, Kosaka et al., 2002, Russell et al., 2007) have also been observed and are interpreted as compensation for dysfunctions in the underlying neural network.
An important topic currently debated is the question whether alterations in structure and/or function associated with the manifest disorder are already present before its onset, which could point to trait markers and be used as endophenotypes for future genetic studies. Further, the influence of the manifest disorder on brain function could be detected and individuals at risk be further characterized. This issue has been addressed by examining individuals genetically at risk for psychosis as well as clinical high-risk subjects, employing tasks that probe, e.g., working memory and executive functions. Changes in widespread networks underlying these processes have been found, in detail in prefrontal, parietal and temporal regions, the anterior cingulate cortex, the thalamus, the cerebellum and the striatum (e.g., MacDonald et al., 2006, Morey et al., 2005, Seidman et al., 2006, Vink et al., 2006, Whalley et al., 2004; for review see Fusar-Poli et al., 2007).
Although behavioral and neuroimaging findings point to emotion dysfunctions as trait markers of the disorder, the influence of illness onset and course on emotion recognition and its neural correlates have not yet been addressed. Trait markers have been suggested for the neural correlates of emotion experience, manifest in an amygdala hypoactivation in non-affected brothers of schizophrenia patients during mood induction (Habel et al., 2004). Therefore, cerebral dysfunctions in core ‘emotional’ regions were already present in genetic high-risk individuals. Hence, data on subjects with clinical risk factors would add important information in research on emotion processing in early psychosis.
In conclusion, the present study intended to further characterize emotional dysfunctions in psychosis by examining individuals in the putatively prodromal state of the illness. Applying an fMRI facial emotion discrimination paradigm we hypothesized to find altered brain function in areas related to emotion and face processing that have previously been reported to be dysfunctional in schizophrenia patients, such as the amygdala (Gur et al., 2002a, Habel et al., 2004, Hempel et al., 2003, Holt et al., 2006a, Kosaka et al., 2002, Schneider et al., 1998), the insula (Crespo-Facorro et al., 2001), the hippocampus (Gur et al., 2002a, Hempel et al., 2003, Holt et al., 2006a), the prefrontal cortex (Habel et al., 2004, Hempel et al., 2003), the anterior cingulate gyrus (Hempel et al., 2003) and the fusiform gyrus (Taylor et al., 2002).
Section snippets
Subjects
Twelve subjects (10 men, 2 women) clinically at risk for developing psychosis were recruited from an outpatient setting at the Cologne Early Recognition and Intervention Center (German acronym FETZ), Department of Psychiatry and Psychotherapy, University of Cologne, and the Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany. Twelve healthy volunteers were recruited by means of local advertisements, followed by a detailed screening, and were matched pairwise to the
Behavioral data
Analysis of sensitivity revealed a significant main effect for the factor ‘emotion’ (F = 19.41, df = 3, 20; p < .001). No main effect of ‘group’ nor an interaction ’emotion*group’ was observed. Post hoc tests revealed significant differences in sensitivity for happy versus angry faces (t = 5.67, df = 23, p < .001), happy versus fearful faces (t = 6.24, df = 23, p < .001) and sad versus fearful faces (t = 5.42, df = 23, p < .001).
A similar pattern resulted for analysis of specificity (‘emotion’: F = 12.87, df = 3, 20; p <
Discussion
This study intended to examine the neural correlates of facial emotion discrimination in subjects clinically at risk for psychosis in comparison to control subjects by means of fMRI. In summary, the main findings are that emotion discrimination independent of the specific emotional content was associated with hyperactivations in high-risk subjects in the right lingual and fusiform gyrus as well as the left middle occipital gyrus. Further, high-risk subjects exhibited stronger activation related
Acknowledgments
This work was supported by grants from the Federal Ministry of Education and Research (Brain Imaging Center West, 01GO0204) and the German Research Foundation (Schn 362/13-1/-2). Ms. Seiferth was supported by a fellowship for doctoral students from the German National Academic Foundation. This work is a part of the thesis of Ms. Seiferth.
We thank Volker Backes, Petra Engels, Sabrina Weber, Martina Reske, Kathrin Koch, Tony Stöcker, Barbara Elghahwagi, Gaby Oefler, Bianca Hoppmann and Julia
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