Brain correlates of verbal fluency in subthreshold psychosis assessed by functional near-infrared spectroscopy
Introduction
Current research proposes that there is a continuum from mental health, to subthreshold and clinical forms of psychosis (Rössler et al., 2011b). The present study focused on the assessment of subthreshold psychotic symptoms in the general population. Symptoms of psychosis (e.g., Paranoid Ideation, Psychoticism) may not exclusively experienced by people with psychiatric disorders, such as schizophrenia. Subthreshold psychotic symptoms also occur in otherwise healthy people, but are less severe and may not necessarily have clinical relevance. Investigating people with subthreshold psychotic symptoms has therefore gained increasing interest to evaluate whether there exist behavioral and neural correlates of subthreshold psychosis.
Subthreshold psychotic symptoms can be identified with standardized scales (e.g., Rössler et al., 2007, Rössler et al., 2013), providing an index of psychosis proneness. A high score of psychosis proneness has been reported to represent a 10% increased risk to develop a schizophrenia-spectrum disorder (Chapman et al., 1994, Hanssen et al., 2005, Meehl, 1990). Subthreshold psychotic symptoms also represent risk factors for subsequent other common mental disorders (Rössler et al., 2011a).
On the behavioral level, studies in individuals with subthreshold psychotic symptoms (Allen et al., 2012, Becker et al., 2010, Bodatsch et al., 2013, Krabbendam et al., 2005) demonstrated that performance on verbal fluency tasks (VFTs) provides a possible predictor for prospective identification of future clinical psychosis. Verbal fluency deficits have been reported to precede psychosis onset up to 30 months (Lencz et al., 2006). Letter and category VFT are common tests to investigate phonemic and semantic processes central to word retrieval. Previous neuroimaging studies applying VFT implicated both frontal and temporal lobe areas, suggesting that letter fluency (phonemic-based word retrieval) is mediated primarily by the frontal cortex, while category fluency (semantic-based word retrieval) is mediated primarily by the temporal cortex (Baldo et al., 2006). Accordingly, pathologies affecting these areas produce behavioral impairments (typically a reduction in the number of items generated) in one or both versions of the task (Ardila et al., 2006). In persons with subthreshold psychotic symptoms and subsequent conversion to schizophrenia, reduced activation in prefrontal brain regions and reduced prefrontal–temporal functional connectivity have been reported during verbal fluency performance (Allen et al., 2012, Fu et al., 2002, Fusar-Poli et al., 2011, Jung et al., 2012, Sabb et al., 2010, Spence et al., 2000).
The present study was conducted in a large community sample. This aspect differentiates the study from other studies conducted in selected populations (Allen et al., 2012, Brent et al., 2014, Fusar-Poli et al., 2010, Fusar-Poli et al., 2011, Jacobson et al., 2010, Jung et al., 2012, Modinos et al., 2011, Sabb et al., 2010). To assess the brain correlates of this community sample, the present study applied functional near-infrared spectroscopy (fNIRS). fNIRS is an optical brain imaging method that measures cortical activity via concentration changes of cortical hemoglobin (Obrig and Villringer, 2003). An advantage of fNIRS over functional magnetic resonance imaging (fMRI) is its low susceptibility to movement artifacts, especially artifacts due to overt speech (Fallgatter et al., 2004, Okamoto et al., 2004, Suto et al., 2004). This fact led to a multitude of studies investigating overt verbal fluency assessed by fNIRS (Ehlis et al., 2007, Herrmann et al., 2003, Herrmann et al., 2004, Herrmann et al., 2005, Herrmann et al., 2006, Kameyama et al., 2006, Matsuo et al., 2000, Matsuo et al., 2002, Matsuo et al., 2004, Matsuo et al., 2005, Schecklmann et al., 2007, Schecklmann et al., 2008a, Schecklmann et al., 2008b, Suto et al., 2004), revealing comparable results to fMRI literature (Basho et al., 2007, Fu et al., 2002). Moreover, fNIRS offers ease of administration, a more convenient setting compared to an fMRI scanner, and a less expensive technology than fMRI. These advantages render fNIRS as a neuroimaging method that allows for the screening of neuropsychological deficits in large samples such as in the context of early diagnostic assessments in psychiatry (Ehlis et al., 2014, Fallgatter et al., 2004).
The first objective of the present study was to examine in this community sample, how VFT performance would differ in subjects with high subthreshold psychotic symptoms compared to a control group. Based on the described previous behavioral studies, we hypothesized that subjects with high compared to low subthreshold psychotic symptoms would exhibit a reduction in the number of items generated in response to the phonemic and semantic VFT.
The second objective was to examine whether there exist differences in cortical correlates of VFT performance, in terms of both hemodynamic responses and connectivity patterns, in subjects with high subthreshold psychotic symptoms compared to a control group. According to previous literature, we hypothesized that subjects with high subthreshold psychotic symptoms would show reduced prefrontal and temporal responses to the phonemic and semantic VFT compared to the control group.
Section snippets
Subjects
Data were obtained from the Epidemiology Survey of the Zurich Program for Sustainable Development of Mental Health Services (ZInEP) (Ajdacic-Gross et al., 2014). The total subsample undergoing fNIRS examination consisted of 188 subjects, who were recruited out of a representative sample of 20–41 years old adults restricted to Swiss residents. The catchment area, the canton of Zurich, is a mixed urban–rural area with a population of 1.35 million, which comprises about one sixth of the total Swiss
VFT data
Repeated measures ANOVA of the behavioral VFT data revealed significant main effects of the between-subject factor ‘group’ (CO, PA, PS, PA–PS) and the within-subject factor ‘condition’ (control vs. phonemic vs. semantic) (Fig. 2). Poorest performance was observed in the group PA–PS as indicated by less ‘production’ compared to the control group (phonemic: F3 = 2.879, p = 0.037, control condition: F3 = 3.419, p = 0.019). No significant group-differences were found in response to the semantic VFT.
Hemodynamic responses
The
Discussion
Neuroimaging studies have reported a number of abnormalities in brain function and structure of people with subthreshold psychotic symptoms (Brent et al., 2014, Jacobson et al., 2010, Lagioia et al., 2010, Modinos et al., 2010, Modinos et al., 2011, Modinos et al., 2013), and suggested that subthreshold psychotic symptoms may be a confounding factor for neuroimaging studies in other clinical populations, such as subclinical depression (Modinos et al., 2013).
Verbal fluency paradigms have been
Role of the funding source
Elsevier listed no existing agreements and policies with the funding sources of this study.
Conflict of interest
All authors declare that they have no conflicts of interest.
Contributors
Authors WR, WK, HH, VA, and AF, designed the study and wrote the protocol. Authors FH, AA, and MM, collected the data. Author LH undertook the statistical analysis. Author LH wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.
Acknowledgments
This work was supported by the Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, and the academic career program Filling the Gap, University of Zurich, Switzerland (Grant number: FTG-1415-007).
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