ارتباط بین بهزیستن ذهنی و عملکرد جلو مغزی در طول یک کار شناختی در اسکیزوفرنی: مطالعه طیف سنجی چند کاناله نزدیک مادون قرمز

Abstract The purpose of this study was to examine the relationship between subjective well-being and prefrontal function during a cognitive task in schizophrenia. Twenty-four patients with clinically stable schizophrenia participated in the study. We measured the change in hemoglobin concentration in the prefrontal region during a verbal fluency task (VFT) by using 52-channel near-infrared spectroscopy (NIRS). The subjective well-being of participants was assessed using the Subjective Well-being under Neuroleptic drug treatment Short form (SWNS). A significant positive relationship was observed between the SWNS score and frontopolar, left ventrolateral, and bilateral dorsolateral prefrontal function during the VFT. These results suggest that the frontopolar and left ventrolateral and bilateral dorsolateral prefrontal cortical regions are associated with the subjective well-being of clinically stable patients with schizophrenia and that NIRS may be an efficient medical tool for monitoring these characteristics.

Introduction In parallel to the steady improvement in the methods for treatment of patients with schizophrenia, the desired outcome has evolved from symptom management to maximization of quality of life (QOL) and functional recovery (Burns, 2007). Schizophrenia considerably affects the QOL of patients beyond impairing psychosocial functioning through positive and negative symptoms (Hofer et al., 2004). Earlier research had focused on QOL from a physician's perspective by using suitable questionnaires. Recent interest in the patient's own perspective of QOL has resulted in the development of questionnaires assessing well-being from a patient's perspective. Recently, new avenues of neuroimaging and electrophysiological research have been initiated to determine the neurobiological substrate of the individual's own experiences in schizophrenia. Striatal dopamine depletion can lead to negative subjective states that frequently impact the QOL, especially the ability of the person to experience pleasure (Voruganti and Awad, 2006). Functional brain imaging has provided empirical evidence for the neural basis of cognitive and affective states, which are known to affect QOL (Kurtz et al., 2008, Kurtz and Tolman, 2011 and Tolman and Kurtz, 2012). Recent electrophysiological studies have reported an association between local brain activity (P300) in the superior temporal gyrus and prefrontal cortex (PFC) and functional outcomes, including QOL (Higuchi et al., 2008 and Sumiyoshi et al., 2009). To date, only one neuroimaging study has shown an association between QOL and brain activity (Boyer et al., 2012) in patients with schizophrenia, and to our knowledge, no studies have evaluated the relationship between the subjective well-being and brain activity of these patients. A neurobiological understanding of subjective well-being may enhance the scientific foundation of the construct and allow development of appropriate scales and accurate interpretation of data. A recently developed functional neuroimaging technology, multi-channel near-infrared spectroscopy (NIRS; ETG-4000, Hitachi Medical Co.), enables the noninvasive, restraint-free detection of spatiotemporal characteristics of brain function near the brain surface by using near-infrared light (Strangman et al., 2002a and Boas et al., 2004). NIRS has enabled bedside measurement of the concentration of oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) in micro-blood vessels. Assuming that the hematocrit is constant, the changes in oxy-Hb, deoxy-Hb, and total Hb (the sum of oxy-Hb and deoxy-Hb) are correlated with the changes in the regional cerebral blood volume (rCBV), as shown by simultaneous NIRS and positron emission tomography (PET) measurements (Hock et al., 1997, Villringer et al., 1997 and Ohmae et al., 2006). The Subjective Well-being under Neuroleptic drug treatment scale (SWN) is one of the most useful tools for assessing subjective well-being—the major component of QOL. The SWN scale is a questionnaire used to subjectively assess a patient's QOL (Naber, 1995 and Naber et al., 2001). This questionnaire has been widely used to assess QOL in patients with schizophrenia (de Haan et al., 2002 and Kluge et al., 2005Naber et al., 2005 and Lambert et al., 2006). SWN was developed by Naber, D. in 1995, and was found to be significantly correlated to D2 blockade by the antipsychotic drugs (de Haan et al., 2000 and Mizrahi et al., 2009), stronger D2 blockade in ventral striatum leading to lower scores, and also earlier improvement in SWN predicted better long-term outcome (de Haan et al., 2008). SWN Short form (SWNS) was created in 2001. SWNS is a 20-item scale for evaluating a patient's subjective well-being; the reliability and validity of its Japanese version have subsequently been confirmed (Watanabe and Matsumura, 2003). Each item is scored from 1 to 6, corresponding to minimal and maximal subjective well-being, with a total score ranging from 20 to 120. The SWNS consists of 5 subscales: emotional regulation, self-control, mental functioning, social integration, and physical functioning (Naber et al., 2001). The primary objective of the present study was to investigate the relationship between the hemodynamic response in the PFC and the SWNS total scores in stable schizophrenia, by using a 52-channel NIRS machine. Subjective well-being refers to how people experience the quality of their lives and includes both emotional reactions and cognitive judgments (Diener, 1984). There are electrophysiological measures specifically related to well-being: resting EEG activity in the left PFC has been reported to be higher in individuals with greater eudaimonic and hedonic well-being (Urry et al., 2004). Asymmetrical hemispheric activation in the PFC is perhaps the most studied neural correlate of self-reported well-being (for a review, see Davidson, 2004). Recently, we showed the association of reduced task-related oxy-Hb activation in the PFC region with functional impairment assessed by social adaptation self-evaluation scale scores in major depressive disorder patients (Pu et al., 2008 and Pu et al., 2012). These findings suggest that hemodynamic response in the PFC region during a cognitive task may reflect the subjective aspects of their functioning. It is of interest to test whether similar findings could be obtained for other psychiatric disorders, which may indicate universal relevance of the PFC to subjective aspects of functioning. Furthermore, Takizawa et al. (2008) demonstrated the association of reduced oxy-Hb activation in the frontopolar cortex region induced by verbal fluency task with functional impairment assessed by global assessment of functioning scores in schizophrenia patients. Although psychosocial functioning is not necessarily related to subjective well-being in schizophrenia (Brekke et al., 1993 and Awad et al., 1997), taking into consideration our findings on patients with depression, we may well hypothesize that the activity in the PFC associated with a cognitive process measured by NIRS is related to subjective well-being in patients with stable schizophrenia.

. Conclusions Our study suggests that frontopolar, left ventrolateral, and bilateral dorsolateral PFC function during a VFT is associated with subjective well-being in clinically stable patients with schizophrenia; thus, NIRS may be an efficient medical tool for monitoring these characteristics. Role of funding source Funding agencies had no role in study delineation, data collection and analysis, decision to submit the paper to the present journal, or preparation of the manuscript. Contributors Shenghong Pu, Kazuyuki Nakagome and Koichi Kaneko designed the study and wrote the protocol. Shenghong Pu, Kazuyuki Nakagome and Koichi Kaneko undertook the statistical analysis. Shenghong Pu, Takeshi Yamada, Katsutoshi Yokoyama, Megumi Itakura, Takahiro Satake, Hisahito Ishida, Izumi Nagata and Koichi Kaneko conducted data acquisition. Shenghong Pu, Kazuyuki Nakagome and Koichi Kaneko analyzed the data. Shenghong Pu, Kazuyuki Nakagome and Koichi Kaneko wrote the first draft of the manuscript, and the other authors revised it critically for important intellectual content. All authors have approved the final version of the manuscript. Conflict of interest All the authors declare that they have no conflicts of interest with respect to this study or its publication.