Prefrontal dysfunction associated with a history of suicide attempts among patients with recent onset schizophrenia.

Suicide is a major cause of death in patients with schizophrenia, particularly among those with recent disease onset. Although brain imaging studies have identified the neuroanatomical correlates of suicidal behavior, functional brain activity correlates particularly in patients with recent-onset schizophrenia (ROSZ) remain unknown. Using near-infrared spectroscopy (NIRS) recording with a high-density coverage of the prefrontal area, we investigated whether prefrontal activity is altered in patients with ROSZ having a history of suicide attempts. A 52-channel NIRS system was used to examine hemodynamic changes in patients with ROSZ that had a history of suicide attempts (n = 24) or that lacked such a history (n = 62), and age- and sex-matched healthy controls (n = 119), during a block-design letter fluency task (LFT). Patients with a history of suicide attempts exhibited decreased activation in the right dorsolateral prefrontal cortex compared with those without such a history. Our findings indicate that specific regions of the prefrontal cortex may be associated with suicidal attempts, which may have implications for early intervention for psychosis.

Altered expression of microRNA-223 in the plasma of patients with first-episode schizophrenia and its possible relation to neuronal migration-related genes.

Recent studies have shown that microRNAs (miRNAs) play a role as regulators of neurodevelopment by modulating gene expression. Altered miRNA expression has been reported in various psychiatric disorders, including schizophrenia. However, the changes in the miRNA expression profile that occur during the initial stage of schizophrenia have not been fully investigated. To explore the global alterations in miRNA expression profiles that may be associated with the onset of schizophrenia, we first profiled miRNA expression in plasma from 17 patients with first-episode schizophrenia and 17 healthy controls using microarray analysis. Among the miRNAs that showed robust changes, the elevated expression of has-miR-223-3p (miR-223) was validated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using another independent sample set of 21 schizophrenia patients and 21 controls. To identify the putative targets of miR-223, we conducted a genome-wide gene expression analysis in neuronally differentiated SK-N-SH cells with stable miR-223 overexpression and an in silico analysis. We found that the mRNA expression levels of four genes related to the cytoskeleton or cell migration were significantly downregulated in miR-223-overexpressing cells, possibly due to interactions with miR-223. The in silico analysis suggested the presence of miR-223 target sites in these four genes. Lastly, a luciferase assay confirmed that miR-223 directly interacted with the 3' untranslated regions (UTRs) of all four genes. Our results reveal an increase in miR-223 in plasma during both the first episode and the later stage of schizophrenia, which may affect the expression of cell migration-related genes targeted by miR-223.

Severity-dependent and -independent brain regions of major depressive disorder: A long-term longitudinal near-infrared spectroscopy study.

BACKGROUND: Long-term longitudinal studies are necessary to establish neuroimaging indicators which contribute to the detection of severity changes over time in patients with major depressive disorder (MDD). METHODS: One hundred sixty-five patients with MDD underwent clinical assessments and near-infrared spectroscopy (NIRS) examination at the initial evaluation (T0). After 1.5 years, 45 patients who visited for the follow-up evaluation (T1.5) were included in the analysis. The authors conducted analyses using the 17-item Hamilton Rating Scale for Depression (HAMD) scores and mean oxy-hemoglobin concentration ([oxy-Hb]) changes during a cognitive task in NIRS at T0 (T0_HAMD, T0_[oxy-Hb]) and at T1.5 (T1.5_HAMD, T1.5_[oxy-Hb]), and their intra-individual longitudinal changes (ΔHAMD = T1.5_HAMD - T0_HAMD, Δ[oxy-Hb] = T1.5_[oxy-Hb] - T0_[oxy-Hb]). RESULTS: For severity-dependent regions, the Δ[oxy-Hb] in the right inferior frontal gyrus (IFG) was negatively correlated with the ΔHAMD. For severity-independent regions, the intra-class correlation coefficients between T0_ and T1.5_[oxy-Hb] were moderate in the bilateral middle frontal gyri (MFG). LIMITATIONS: The percentage of patients included in the follow-up examination was relatively small. CONCLUSIONS: Brain activation in the right IFG and the bilateral MFG as measured by NIRS may differentially indicate clinical severity and trait-related abnormalities in MDD.

Preliminary evidence of altered neural response during intertemporal choice of losses in adult attention-deficit hyperactivity disorder.

Impulsive behaviours are common symptoms of attention-deficit hyperactivity disorder (ADHD). Although previous studies have suggested functional models of impulsive behaviour, a full explanation of impulsivity in ADHD remains elusive. To investigate the detailed mechanisms behind impulsive behaviour in ADHD, we applied an economic intertemporal choice task involving gains and losses to adults with ADHD and healthy controls and measured brain activity by functional magnetic resonance imaging. In the intertemporal choice of future gains, we observed no behavioural or neural difference between the two groups. In the intertemporal choice of future losses, adults with ADHD exhibited higher discount rates than the control participants. Furthermore, a comparison of brain activity representing the sensitivity of future loss in the two groups revealed significantly lower activity in the striatum and higher activity in the amygdala in adults with ADHD than in controls. Our preliminary findings suggest that an altered size sensitivity to future loss is involved in apparent impulsive choice behaviour in adults with ADHD and shed light on the multifaceted impulsivity underlying ADHD.

Lack of correlation between phonetic magnetic mismatch field and plasma d-serine levels in humans.

OBJECTIVE: Uncovering molecular bases for auditory language processing in the human brain is a fundamental scientific challenge. The power and latency of the magnetic mismatch field (MMF) elicited by phoneme change, which are magnetoencephalographic indices of language function in its early stage of information processing, are theoretically thought to be modulated by N-methyl-d-aspartate-type glutamate receptor (NMDAR) function, but no study has yet assessed this possibility. We have thus sought to demonstrate an association between phonetic MMF power/latency and levels of plasma d-serine, an intrinsic co-agonist of glycine binding sites on NMDAR, in adults. METHODS: The MMF response to phoneme changes was recorded using 204-channel magnetoencephalography in 61 healthy, right-handed, Japanese adults. Plasma levels of d- and l-serine were measured for each participant. RESULTS: We did not find a significant correlation between MMF power/latency and plasma serine levels. CONCLUSIONS: Despite a sufficient sample size, we failed to find an association between the physiological markers of the early stage of information processing of language in the auditory cortex and biomarkers indexing glutamatergic function. SIGNIFICANCE: Our study did not indicate that a molecular index of glutamatergic function could be a surrogate marker for the early stage of information processing of language in humans.

Deficient neural activity subserving decision-making during reward waiting time in intertemporal choice in adult attention-deficit hyperactivity disorder.

AIM: Impulsivity, which significantly affects social adaptation, is an important target behavioral characteristic in interventions for attention-deficit hyperactivity disorder (ADHD). Typically, people are willing to wait longer to acquire greater rewards. Impulsivity in ADHD may be associated with brain dysfunction in decision-making involving waiting behavior under such situations. We tested the hypothesis that brain circuitry during a period of waiting (i.e., prior to the acquisition of reward) is altered in adults with ADHD. METHODS: The participants included 14 medication-free adults with ADHD and 16 healthy controls matched for age, sex, IQ, and handedness. The behavioral task had participants choose between a delayed, larger monetary reward and an immediate, smaller monetary reward, where the reward waiting time actually occurred during functional magnetic resonance imaging measurement. We tested for group differences in the contrast values of blood-oxygen-level dependent signals associated with the length of waiting time, calculated using the parametric modulation method. RESULTS: While the two groups did not differ in the time discounting rate, the delay-sensitive contrast values were significantly lower in the caudate and visual cortex in individuals with ADHD. The higher impulsivity scores were significantly associated with lower delay-sensitive contrast values in the caudate and visual cortex. CONCLUSION: These results suggest that deficient neural activity affects decision-making involving reward waiting time during intertemporal choice tasks, and provide an explanation for the basis of impulsivity in adult ADHD.

Application of functional near infrared spectroscopy as supplementary examination for diagnosis of clinical stages of psychosis spectrum.

AIM: Research efforts aiming at neuroimaging-aided differential diagnosis for psychiatric disorders have been progressing rapidly. A previous multisite study has developed a supplementary diagnostic system using functional near-infrared spectroscopy (fNIRS) that can be easily applied to clinical settings. However, few neuroimaging biomarkers have been developed for the psychosis spectrum with various clinical stages. METHODS: We employed the fNIRS as a clinical examination device for 143 participants, comprising 47 ultra-high risk for psychosis (UHR) individuals, 30 patients with first-episode psychosis (FEP), 34 patients with chronic schizophrenia (ChSZ), and 33 healthy controls, who were independent of the previous study. A 12-month follow-up measurement was also carried out on 34 UHR individuals (72%), 21 patients with FEP (70%), and 33 controls. The fNIRS algorithm variables used for classification were the intensity and timing of prefrontal activation following the start of the cognitive task as used in the previous multisite study. RESULTS: The discrimination rate by timing of activation was modest but it became acceptable after adjusting confounding factors. Discrimination by intensity of activation was not improved by similar adjustment. A total of 63.8%, 86.7%, and 81.3% patients were classified as UHR, FEP, and ChSZ, respectively; and 85.1%, 86.7%, and 71.9% of patients in these groups, respectively, were classified as being on the psychosis spectrum. In the follow-up measurement, 88.2% of individuals with UHR and 95.0% of patients with FEP were successfully classified into the psychosis spectrum group. CONCLUSION: The fNIRS for supplementary clinical examination could be validly applied to differentiating people with the psychosis spectrum in various clinical stages. The fNIRS is a candidate biological marker for aiding diagnosis of psychosis spectrum in routine clinical settings.

Familial Influences on Mismatch Negativity and Its Association with Plasma Glutamate Level: A Magnetoencephalographic Study in Twins.

Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch negativity; MMNm) is regarded as a promising biomarker for schizophrenia. Previous electroencephalographic studies of MMN have demonstrated a moderate-to-high heritability for MMN amplitudes. N-methyl-D-aspartate receptor-dependent glutamatergic neurotransmission is implicated in MMN generation. We hypothesized that the differences between identical twins in MMNm variables might be associated with differences in plasma levels of amino acids involved in glutamatergic neurotransmission. Thirty-three pairs of monozygotic (MZ) and 10 pairs of dizygotic (DZ) twins underwent MMNm recording. The MMNm in response to tone duration changes, tone frequency changes, and phonemic changes was recorded using 204-channel magnetoencephalography. Of these, 26 MZ and 7 DZ twin pairs underwent blood sampling for determination of plasma amino acid levels. MMNm peak strength showed relatively high correlations in both MZ and DZ twin pairs. The differences in MMNm latencies tended to correlate with the differences in plasma amino acid levels within MZ pairs, while no significant correlation was observed after the Bonferroni correction. We observed a familial trait in MMNm strength. The differences in MMN latency in MZ twins might be influenced by changes in glutamate levels and glutamate-glutamine cycling; however, the results need to be replicated.

Development of a neurofeedback protocol targeting the frontal pole using near-infrared spectroscopy.

AIM: Neurofeedback has been studied with the aim of controlling cerebral activity. Near-infrared spectroscopy is a non-invasive neuroimaging technique used for measuring hemoglobin concentration changes in cortical surface areas with high temporal resolution. Thus, near-infrared spectroscopy may be useful for neurofeedback, which requires real-time feedback of repeated brain activation measurements. However, no study has specifically targeted neurofeedback, using near-infrared spectroscopy, in the frontal pole cortex. METHODS: We developed an original near-infrared spectroscopy neurofeedback system targeting the frontal pole cortex. Over a single day of testing, each healthy participant (n = 24) received either correct or incorrect (Sham) feedback from near-infrared spectroscopy signals, based on a crossover design. RESULTS: Under correct feedback conditions, significant activation was observed in the frontal pole cortex (P = 0.000073). Additionally, self-evaluation of control and metacognitive beliefs were associated with near-infrared spectroscopy signals (P = 0.006). CONCLUSION: The neurofeedback system developed in this study might be useful for developing control of frontal pole cortex activation.

Detection of resting state functional connectivity using partial correlation analysis: A study using multi-distance and whole-head probe near-infrared spectroscopy.

Multichannel near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that enables easy-to-use and noninvasive measurement of changes in blood oxygenation levels. We developed a clinically-applicable method for estimating resting state functional connectivity (RSFC) with NIRS using a partial correlation analysis to reduce the influence of extraneural components. Using a multi-distance probe arrangement NIRS, we measured resting state brain activity for 8min in 17 healthy participants. Independent component analysis was used to extract shallow and deep signals from the original NIRS data. Pearson's correlation calculated from original signals was significantly higher than that calculated from deep signals, while partial correlation calculated from original signals was comparable to that calculated from deep (cerebral-tissue) signals alone. To further test the validity of our method, we also measured 8min of resting state brain activity using a whole-head NIRS arrangement consisting of 17 cortical regions in 80 healthy participants. Significant RSFC between neighboring, interhemispheric homologous, and some distant ipsilateral brain region pairs was revealed. Additionally, females exhibited higher RSFC between interhemispheric occipital region-pairs, in addition to higher connectivity between some ipsilateral pairs in the left hemisphere, when compared to males. The combined results of the two component experiments indicate that partial correlation analysis is effective in reducing the influence of extracerebral signals, and that NIRS is able to detect well-described resting state networks and sex-related differences in RSFC.

Magnetoencephalographic recording of auditory mismatch negativity in response to duration and frequency deviants in a single session in patients with schizophrenia.

AIM: Auditory mismatch negativity (MMN) and its magnetoencephalographic (MEG) counterpart (MMNm) are an established biological index in schizophrenia research. MMN in response to duration and frequency deviants may have differential relevance to the pathophysiology and clinical stages of schizophrenia. MEG has advantage in that it almost purely detects MMNm arising from the auditory cortex. However, few previous MEG studies on schizophrenia have simultaneously assessed MMNm in response to duration and frequency deviants or examined the effect of chronicity on the group difference. METHODS: Forty-two patients with chronic schizophrenia and 74 matched control subjects participated in the study. Using a whole-head MEG, MMNm in response to duration and frequency deviants of tones was recorded while participants passively listened to an auditory sequence. RESULTS: Compared to healthy subjects, patients with schizophrenia exhibited significantly reduced powers of MMNm in response to duration deviant in both hemispheres, whereas MMNm in response to frequency deviant did not differ between the two groups. These results did not change according to the chronicity of the illness. CONCLUSION: These results, obtained by using a sequence-enabling simultaneous assessment of both types of MMNm, suggest that MEG recording of MMN in response to duration deviant may be a more sensitive biological marker of schizophrenia than MMN in response to frequency deviant. Our findings represent an important first step towards establishment of MMN as a biomarker for schizophrenia in real-world clinical psychiatry settings.

Association between rostral prefrontal cortical activity and functional outcome in first-episode psychosis: a longitudinal functional near-infrared spectroscopy study.

BACKGROUND: Few biomarkers can be used easily and noninvasively to measure clinical condition and future outcome in patients with first-episode psychosis (FEP). To develop such biomarker using multichannel functional near-infrared spectroscopy (fNIRS), cortical function in the prefrontal cortex was longitudinally measured during a verbal fluency task. METHODS: Sixty-nine fNIRS measurements and 77 clinical assessments were obtained from 31 patients with FEP at baseline, 6-month, and 12-month follow-ups. Sixty measurements were obtained from 30 healthy controls matched for age, sex, and premorbid IQ. We initially tested signal changes for 12 months, and then investigated the relationship between fNIRS signals and clinical assessments. RESULTS: Signal changes from baseline to 12-month follow-up were not evident in any group. Patients with FEP had significant positive correlation coefficients between 6-month fNIRS signals and the 12-month Global Assessment of Functioning (GAF) score in the left middle frontal gyrus (FDR-corrected p=.0016-.0052, r=.65-.59). fNIRS signals at the 12-month follow-up were associated with 12-month GAF score in the bilateral superior and middle frontal gyri (FDR-corrected p=.00085-.018, r=.72-.55), and with the difference between baseline and 12-month GAF scores in the right superior frontal gyrus (FDR-corrected p=.000067-.00012, r=.80-.78). These associations were significant even after controlling for demographic variables. No association between baseline fNIRS signals and later GAF scores was found. DISCUSSION: fNIRS measurement can potentially be used as a biomarker to aid sequential assessment of neuro-clinical conditions through the early stage of psychosis.

Characterizing prefrontal cortical activity during inhibition task in methamphetamine-associated psychosis versus schizophrenia: a multi-channel near-infrared spectroscopy study.

Methamphetamine abuse and dependence, frequently accompanied by schizophrenia-like psychotic symptoms [methamphetamine-associated psychosis (MAP)], is a serious public health problem worldwide. Few studies, however, have characterized brain dysfunction associated with MAP, nor investigated similarities and differences in brain dysfunction between MAP and schizophrenia. We compared prefrontal cortical activity associated with stop-signal inhibitory task in 21 patients with MAP, 14 patients with schizophrenia and 21 age- and gender-matched healthy controls using a 52-channel near-infrared spectroscopy (NIRS) system. Both the MAP and the schizophrenia groups showed significantly reduced activation in the bilateral ventrolateral prefrontal cortex compared with controls; however, only the MAP group showed reduced activation in the frontopolar prefrontal cortex. The MAP group demonstrated significant positive correlations between task performance and hemodynamic responses in the bilateral ventrolateral, polar and left dorsolateral regions of the prefrontal cortex. The MAP and schizophrenia groups demonstrated a significant difference in the relationship of impulsivity to hemodynamic changes in the bilateral premotor cortex. These findings characterize similarities and differences in prefrontal cortical dysfunction between psychosis associated with methamphetamine and schizophrenia. The reduced hemodynamic changes in the bilateral ventrolateral prefrontal cortex suggest a common underlying pathophysiology of MAP and schizophrenia, whereas those in the frontopolar prefrontal cortex point to an impaired state that is either inherent or caused specifically by methamphetamine use.

Social Function and Frontopolar Activation during a Cognitive Task in Patients with Bipolar Disorder.

BACKGROUND: It is important to understand the neural basis of functional impairments in patients with bipolar disorder (BD) in order to be able to address the recovery. Recently, neurocognitive impairment emerged as a predictor of psychosocial function. A number of functional brain imaging studies have shown that social function is associated with activation of the prefrontal cortex during a cognitive task in healthy adults, and in patients with major depressive disorder and schizophrenia. However, few studies have been conducted in patients with BD. METHODS: We performed multichannel near-infrared spectroscopy (NIRS) imaging to investigate the activation of the prefrontal cortex during a verbal fluency task (VFT). We also used the Social Adaptation Self-Evaluation Scale (SASS) to assess social functioning in patients with BD. Thirty-three depressed patients with BD and 65 age-, gender- and task performance-matched healthy controls (HCs) participated in this study. RESULTS: Depressed patients with BD showed reduced activation in the broader bilateral prefrontal cortex during the VFT compared to HCs. Moreover, a significant positive correlation was observed between the total SASS scores and right prefrontal activation in patients with BD. In the SASS subscores, the interest and motivation factor was also positively correlated with frontopolar activation. CONCLUSIONS: These results suggest an association between social function and prefrontal activation in depressed patients with BD. The present study provides evidence that NIRS imaging could be helpful in understanding the neural basis of social function.

Concurrent fNIRS-fMRI measurement to validate a method for separating deep and shallow fNIRS signals by using multidistance optodes.

It has been reported that a functional near-infrared spectroscopy (fNIRS) signal can be contaminated by extracerebral contributions. Many algorithms using multidistance separations to address this issue have been proposed, but their spatial separation performance has rarely been validated with simultaneous measurements of fNIRS and functional magnetic resonance imaging (fMRI). We previously proposed a method for discriminating between deep and shallow contributions in fNIRS signals, referred to as the multidistance independent component analysis (MD-ICA) method. In this study, to validate the MD-ICA method from the spatial aspect, multidistance fNIRS, fMRI, and laser-Doppler-flowmetry signals were simultaneously obtained for 12 healthy adult males during three tasks. The fNIRS signal was separated into deep and shallow signals by using the MD-ICA method, and the correlation between the waveforms of the separated fNIRS signals and the gray matter blood oxygenation level-dependent signals was analyzed. A three-way analysis of variance ([Formula: see text]) indicated that the main effect of fNIRS signal depth on the correlation is significant [[Formula: see text], [Formula: see text]]. This result indicates that the MD-ICA method successfully separates fNIRS signals into spatially deep and shallow signals, and the accuracy and reliability of the fNIRS signal will be improved with the method.

Dysfunction of ventrolateral prefrontal cortex underlying social anxiety disorder: A multi-channel NIRS study.

Social anxiety disorder (SAD) is characterized by strong fear and anxiety during social interactions. Although ventrolateral prefrontal cortex (VLPFC) activity in response to emotional stimuli is related to pathological anxiety, little is known about the relationship between VLPFC activity and social anxiety. This study aimed to investigate whether VLPFC activity was involved in SAD and whether VLPFC activity was related to the level of social anxiety. Twenty-four drug-naïve patients with SAD and 35 healthy controls underwent near-infrared spectroscopy (NIRS) scanning while performing a verbal fluency task (VFT). Results indicated that, compared to the healthy controls, the SAD patients exhibited smaller changes of oxygenated hemoglobin (oxy-Hb) concentrations in the VLPFC during the VFT. Furthermore, the right VLPFC activation was negatively correlated with social avoidance. In contrast to the latter, the healthy controls exhibited a positive correlation between changes of oxy-Hb concentrations in the bilateral VLPFC and social fear. Our findings provide evidence for VLPFC dysfunction in SAD, and indicate that the VLPFC dysfunction may contribute to the difference between normal and abnormal social anxiety.

Neuroimaging-Aided Prediction of the Effect of Methylphenidate in Children with Attention-Deficit Hyperactivity Disorder: A Randomized Controlled Trial.

Although methylphenidate hydrochloride (MPH) is a first-line treatment for children with attention-deficit hyperactivity disorder (ADHD), the non-response rate is 30%. Our aim was to develop a supplementary neuroimaging biomarker for predicting the clinical effect of continuous MPH administration by using near-infrared spectroscopy (NIRS). After baseline assessment, we performed a double-blind, placebo-controlled, crossover trial with a single dose of MPH, followed by a prospective 4-to-8-week open trial with continuous MPH administration, and an ancillary 1-year follow-up. Twenty-two drug-naïve and eight previously treated children with ADHD (NAÏVE and NON-NAÏVE) were compared with 20 healthy controls (HCs) who underwent multiple NIRS measurements without intervention. We tested whether NIRS signals at the baseline assessment or ΔNIRS (single dose of MPH minus baseline assessment) predict the Clinical Global Impressions-Severity (CGI-S) score after 4-to-8-week or 1-year MPH administration. The secondary outcomes were the effect of MPH on NIRS signals after single-dose, 4-to-8-week, and 1-year administration. ΔNIRS significantly predicted CGI-S after 4-to-8-week MPH administration. The leave-one-out classification algorithm had 81% accuracy using the NIRS signal. ΔNIRS also significantly predicted CGI-S scores after 1 year of MPH administration. For secondary analyses, NAÏVE exhibited significantly lower prefrontal activation than HCs at the baseline assessment, whereas NON-NAÏVE and HCs showed similar activation. A single dose of MPH significantly increased activation compared with the placebo in NAÏVE. After 4-to-8-week administration, and even after MPH washout following 1-year administration, NAÏVE demonstrated normalized prefrontal activation. Supplementary NIRS measurements may serve as an objective biomarker for clinical decisions and monitoring concerning continuous MPH treatment in children with ADHD.

Effect of metabotropic glutamate receptor-3 variants on prefrontal brain activity in schizophrenia: An imaging genetics study using multi-channel near-infrared spectroscopy.

BACKGROUND: The glutamatergic system is essential for learning and memory through its crucial role in neural development and synaptic plasticity. Genes associated with the glutamatergic system, including metabotropic glutamate receptor (mGluR or GRM) genes, have been implicated in the pathophysiology of schizophrenia. Few studies, however, have investigated a relationship between polymorphism of glutamate-related genes and cortical function in vivo in patients with schizophrenia. We thus explored an association between genetic variations in GRM3 and brain activation driven by a cognitive task in the prefrontal cortex in patients with schizophrenia. MATERIALS AND METHODS: Thirty-one outpatients with schizophrenia and 48 healthy controls participated in this study. We measured four candidate single nucleotide polymorphisms (rs274622, rs2299225, rs1468412, and rs6465084) of GRM3, and activity in the prefrontal and temporal cortices during a category version of a verbal fluency task, using a 52-channel near-infrared spectroscopy instrument. RESULTS AND DISCUSSION: The rs274622 C carriers with schizophrenia were associated with significantly smaller prefrontal activation than patients with TT genotype. This between-genotype difference tended to be confined to the patient group. GRM3 polymorphisms are associated with prefrontal activation during cognitive task in schizophrenia.

Association between longitudinal changes in prefrontal hemodynamic responses and social adaptation in patients with bipolar disorder and major depressive disorder.

BACKGROUND: Patients with affective disorders exhibit changes in regional brain function and show abnormal social adaptation. However, to our knowledge, no near-infrared spectroscopy (NIRS) study has examined the relationship between these two phenomena longitudinally. This study examined the region-specific functional abnormality associated with bipolar disorder (BD) and major depressive disorder (MDD), and the association between particular longitudinal changes in regional activation and social adaptation. METHODS: We evaluated frontotemporal functioning during a verbal fluency test (VFT) for patients with BD (N=18), those with MDD (N=10), and healthy controls (HCs; N=14) using NIRS. NIRS measurements and the Social Adaptation Self-evaluation Scale (SASS) were administered twice with an interval of approximately 6 months. RESULTS: The BD and MDD groups showed lesser activation than the HCs in the bilateral ventro-lateral prefrontal cortex and the anterior part of the temporal cortex (VLPFC/aTC). Longitudinal changes in SASS scores were positively associated with the extent of change in left VLPFC/aTC activation in the BD group and with right VLPFC/aTC activation in the MDD group. LIMITATIONS: Our small sample size limited statistical power, and the effect of medication and multiple comparisons cannot be excluded, although these effects were considered in the interpretation of the present results. CONCLUSION: Longitudinal increases of VLPFC/aTC activation were associated with improvement in social adaptation in patients with BD and those with MDD. NIRS measurement could be a useful tool for objective evaluation of changes in social adaptation in BD and MDD.