Comparison of prefrontal hemodynamic responses and cognitive deficits between adult patients with autism spectrum disorder and schizophrenia.

Autism spectrum disorder (ASD) and schizophrenia share many phenotypic characteristics, but their association with prefrontal function have not been directly compared. The aim of this study is to compare cognitive profiles and their association with the prefrontal function between the two groups. We explored prefrontal dysfunction among adult individuals with ASD (n = 32), schizophrenia (n = 87), and healthy controls (HCs; n = 50). We assessed cognitive function in all participants using the Brief Assessment of Cognition in Schizophrenia (BACS). The BACS data of patients with schizophrenia were entered into hierarchical cluster analyses to assign subjects to a specific subgroup based on individual profiles. Using near-infrared spectroscopy, we measured hemodynamic responses in the fronto-temporal regions during a working memory task. Among the patients with schizophrenia, we defined 4 neurocognitive subgroups, including a global impairment, a mild impairment, and 2 selective impairment groups. Compared to the HCs, the ASD and schizophrenia groups had much weaker hemodynamic responses in the left DLPFC, left frontopolar cortex (FPC), and left inferior frontal gyrus. The ASD group showed a similar level of cognitive impairment with the mild level subgroup of schizophrenia. Additionally, the two groups shared reduced activity in the left DLPFC and left FPC during the task compared to HCs. Moreover, the BACS composite scores correlated positively with hemodynamic responses in a broad area involving fronto-temporal regions in the total patient sample. This research indicates considerable similarity in the left PFC dysfunction and its association with cognitive deficits between the disorders. These findings may guide future studies that investigate pathophysiological similarities between ASD and schizophrenia.

Association between social functioning and prefrontal cortex function during a verbal fluency task in schizophrenia: A near-infrared spectroscopic study.

AIM: Impaired social functioning is a common characteristic of patients with schizophrenia. Social functioning requires the complex operation of various executive functions. Deficits in the prefrontal cortex (PFC) have been implicated in executive dysfunction. Here we aimed to clarify the relation between subjectively and objectively assessed social functioning, and their associations with PFC function in patients with schizophrenia. METHODS: Twenty-three patients and 22 age- and sex-matched healthy controls (HC) were assessed. In the schizophrenia group, self- and caregiver-rated social functioning were measured using the Specific Level of Functioning Assessment (SLOF). The hemodynamic responses elicited by a verbal fluency task (VFT) in three regions of interest in the frontotemporal area were measured using multi-channel near-infrared spectroscopy (NIRS). We also investigated psychiatric symptoms, neurocognition, and cognitive insight to assess possible confounding factors. RESULTS: Significant positive correlations were found between self- and caregiver-rated SLOF composite scores and three subdomain scores. Self- and caregiver-rated SLOF composite scores were significantly associated with dorsolateral PFC and frontopolar cortex (DLPFC/FPC) activation during the VFT. Psychiatric symptoms, global functioning, neurocognition, and cognitive insight were not associated with NIRS signals. General psychopathology was associated with NIRS signals in the ventrolateral PFC and the anterior temporal cortex. DLPFC and FPC activity may be associated with social functioning in patients with schizophrenia. CONCLUSION: Our results suggest that the two distinct assessments of social functioning were significantly correlated. Moreover, DLPFC and FPC function was strongly associated with social functioning and the ability to carry out daily life in patients with schizophrenia.

Comparison of neurocognitive function in major depressive disorder, bipolar disorder, and schizophrenia in later life: A cross-sectional study of euthymic or remitted, non-demented patients using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J).

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) are associated with cognitive dysfunction both in adulthood and in later life. In this study, we directly compared neurocognitive function between these three conditions in later life, employing stringent definitions of euthymia and symptomatic remission. Cognitive function in 60 elderly outpatients with MDD, BD, or SZ (20 patients per group) was assessed using the Japanese version of the Brief Assessment of Cognition in Schizophrenia. Patients with MDD had significantly higher z scores than both the other groups with large or moderately large effect sizes, for verbal fluency, attention and speed of information processing, and composite scores. In contrast, there were no significant differences in the degree of neurocognitive impairment between patients with BD and SZ. In later life, patients with BD and SZ showed a similar degree of neurocognitive impairment, while patients with MDD showed smaller impairments in several neurocognitive domains compared to patients with either of the other two disorders.

Residual Symptoms Were Differentially Associated with Brain Function in Remitted Patients with Major Depressive Disorders.

BACKGROUND: The desirable goals of the treatment of major depressive disorder (MDD) are considered both to achieve symptom remission and to help the patients be restored to their premorbid levels of functioning. Remission has often been defined clinically as a threshold using standardized scales. Such a definition, however, allows several residual symptoms to be present in the remitted state. The aim of this study was to examine the relationship between the levels of residual symptoms and social functioning and also the relationship between residual symptoms and brain function. METHODS: The subjects were 21 patients with MDD in remission, defined operationally using clinician-rated 17-item Hamilton Depression Scale. Depressive symptoms and social functioning were self-assessed with the Japanese versions of the Center for Epidemiologic Studies Depression Scale (CES-D) and the Social Adaptation Self-evaluation Scale (SASS), respectively. Brain function was measured by the changes in concentration of oxy-hemoglobin ([oxy-Hb]) in the prefrontal and temporal cortices during verbal fluency task using near-infrared spectroscopy (NIRS). RESULTS: The mean CES-D total score was 18.0, s = 13.2, indicating that they have on average mild depression. Scores of CES-D total and those of its four factors showed a significantly negative correlation with the SASS total score. Among the four factors, "Interpersonal problems" factor showed the strongest correlation with it. CES-D total score and those of its three factors, "Depressed affect", "Somatic and retarded activity" and "Positive affect", showed significantly negative correlations with the mean [oxy-Hb] changes mainly in the left hemisphere, whereas "Interpersonal problems" factor showed a significantly positive correlation with the size of NIRS activation predominantly in right prefrontal regions. CONCLUSION: Our results indicate that remitted patients with MDD possibly have residual symptoms which are most likely to impair their social functioning and that these symptoms are differentially associated with brain function measured with NIRS.

Effects of donepezil and serotonin reuptake inhibitor on acute regression during adolescence in Down syndrome.

A 14-year-old boy with Down syndrome (DS) showed a gradual decline in his daily activities and feeding capacities, and a marked deterioration triggered by a streptococcal infection was observed at the age of 15 years. He became bedridden, accompanied by sleep disturbance, sustained upward gaze, and generalized rigidity. Magnetic resonance imaging showed unremarkable findings, but antiglutamate receptor autoantibodies were positive in his cerebrospinal fluid. Treatment with thiamine infusion and steroid pulse therapy showed little effect, but gross motor dysfunction and appetite loss were ameliorated by the administration of l-DOPA and serotonin reuptake inhibitors. Thereafter, autistic behaviors predominated, including loss of social interaction, oral tendency, water phobia, and aggressiveness. Initiation of donepezil, an acetylcholinesterase inhibitor, resulted in the disappearance of these symptoms and total recovery of the patient to his previous psychosocial levels. We hypothesize that the acute regression in adolescence represents a process closely related to the defects of serotonergic and cholinergic systems that are innate to DS brains and not just a nonspecific comorbidity of depression or limbic encephalitis.

Suicidal ideation is associated with reduced prefrontal activation during a verbal fluency task in patients with major depressive disorder.

BACKGROUND: Despite the known relationship between prefrontal function and increased suicidality during major depressive episodes, the links between prefrontal function and suicidality remain unclear in major depressive disorder (MDD). Suicidal ideation usually precedes a suicide attempt. If prefrontal cortex (PFC) activity is a biomarker for suicidal ideation in depression, monitoring it could be useful for suicide prevention. Therefore, in this study, we assessed the association between prefrontal function and suicidal ideation in MDD. METHODS: Prefrontal function in 67 patients with MDD (31 with suicidal ideation and 36 without) and 67 age-, gender-, and intelligence quotient-matched healthy controls (HCs) was evaluated using near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD). RESULTS: Regional hemodynamic changes were significantly smaller in patients with MDD than in HCs in prefrontal and temporal regions. Hemodynamic changes in the right dorsolateral PFC (DLPFC), orbitofrontal cortex (OFC), and right frontopolar cortex (FPC) regions in patients with MDD with suicidal ideation were significantly smaller than in those without suicidal ideation. In addition, hemodynamic changes correlated negatively with the severity of suicidal ideation in the DLPFC, OFC, and FPC in patients with MDD. LIMITATIONS: Further studies with a larger sample size are required to verify our findings. CONCLUSIONS: These results suggest that the DLPFC, OFC, and FPC are brain substrates of suicidal ideation in depressive states in patients with MDD, and that NIRS data can be employed as a clinically useful biomarker for the assessment of suicide risk.

Relationship between hypothalamic-pituitary-adrenal axis dysregulation and insulin resistance in elderly patients with depression.

Cortisol dysregulation has been proposed to be involved in depression. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation associated with major depressive disorder (MDD) was previously reported to be higher in the elderly. Furthermore, insulin resistance and the prevalence of type 2 diabetes are known to increase with aging. The aim of the present study was to determine whether a relationship existed between plasma cortisol levels following the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test and insulin resistance evaluated by the homeostasis model assessment of insulin resistance (HOMA-R) in elderly MDD subjects. Fifteen unmedicated MDD inpatients and 17 age- and sex-matched healthy controls participated in this study. After overnight fasting, blood samples were collected to measure plasma glucose and insulin concentrations, estimate HOMA-R, and perform the DEX/CRH test to evaluate HPA axis function. The value of the area under the time curve of plasma cortisol concentrations (CortAUC) and peak cortisol values (Cortpeak) following the administration of DEX/CRH both correlated with HOMA-R in MDD group. In contrast, neither CortAUC nor Cortpeak correlated with HOMA-R in controls. This is the first study to directly demonstrate the relationship between HPA axis dysregulation assessed with the DEX/CRH test and the index of insulin resistance estimated as HOMA-R in elderly MDD patients.

Prefrontal activation predicts social functioning improvement after initial treatment in late-onset depression.

The activation of oxygenated hemoglobin (oxy-Hb) has been shown to be lacking in the prefrontal cortex (PFC) of patients with late-onset depression (LOD), in verbal fluency task (VFT)-related near-infrared spectroscopy (NIRS). In our previous studies, we have emphasized the connection between the lack of activation in the frontopolar cortex and social functioning disorder in patients with LOD. In this study, we investigated whether the responsiveness to medical treatment of untreated patients with LOD, particularly social functioning improvements, could be predicted by NIRS findings at the initial examination. The subjects were 29 patients with LOD who were diagnosed with major depression at 65 years or older at the initial examination (mean age ± standard deviation, 72.4 ± 5.71 years). We measured the changes in hemoglobin concentration in the prefrontal and temporal cortex regions during a VFT by using 52-channel NIRS. In addition, depression status and social functioning were evaluated with the Hamilton Depression Rating Scale and the Social Adaptation Self-evaluation Scale, respectively, at the initial examination and 8 weeks after the treatment. A negative correlation was found between the NIRS activation in the right ventrolateral PFC region before treatment and the improvement in social functioning. These results suggested that the social functioning improvements were greater in LOD with initially lower NIRS activation in the right ventrolateral PFC region. NIRS is a simple technique that can be used before treatment to evaluate the social functioning levels of patients with LOD, and predict social functioning improvement after treatment.

Association between social functioning and prefrontal hemodynamic responses in elderly adults.

Social functioning has received widespread attention as one of the most important outcomes in psychiatric disorders and has been related to cognitive functioning and the underlying brain activity. Cognitive decline, however, appears not only in the psychiatric population but also in aged individuals. In our previous study, we demonstrated a significant relationship between social functioning and prefrontal cortex (PFC) activity in patients with depression. However, it has not been shown whether the above relationship could be extended to healthy populations. The purpose of the present study was to investigate a possible association between social functioning and prefrontal hemodynamic responses in healthy elderly adults by using a non-invasive and low-constraint functional neuroimaging technique, near-infrared spectroscopy (NIRS). Study subjects included 55 healthy, elderly volunteers. We measured hemodynamic responses over prefrontal cortical (PFC) areas during the verbal fluency task by using multi-channel NIRS and analyzed the relationship between task-associated hemodynamic responses and social functioning as measured by the social adaptation self-evaluation scale (SASS). A significant positive relationship was observed between the SASS total score and PFC activation. Our findings suggest that PFC activation is associated with social functioning in healthy elderly adults. Furthermore, hemodynamic responses assessed using non-invasive NIRS could be a useful biological marker of these characteristics.

Milnacipran influences the indexes of I-metaiodobenzylguanidine scintigraphy in elderly depressed patients.

AIM: This study investigated whether or not and how much milnacipran influences the indexes of I-metaiodobenzylguanidine (I-MIBG) scintigraphy, early heart-to-mediastinum (H/M) ratio, delayed H/M ratio, and wash-out rate. METHODS: Six elderly depressed patients participated in the study. All six patients met the diagnostic criteria for a major depressive disorder. They were taking milnacipran for their depression. They needed differential diagnosis for Lewy body diseases due to their symptomatology. I-MIBG scintigraphy was performed twice for each subject, once under prescription of milnacipran and the other without prescription of milnacipran. RESULTS: Both early and delayed phase H/M ratio were significantly lower when taking milnacipran (early phase H/M ratio, P < 0.01, Cohen's d 1.62; delayed phase H/M ratio, P < 0.005, Cohen's d 1.98) than when not taking the drug. Wash-out rate (%) was significantly higher when taking milnacipran (P < 0.05, Cohen's d 2.31) than when off the drug. CONCLUSION: Taking milnacipran substantially influences the indexes of I-MIBG scintigraphy, indicating that taking the drug possibly causes a false-positive result for Lewy body diseases diagnosis.

Association between Fish Consumption and Prefrontal Function during a Cognitive Task in Male Japanese Workers: A Multi-Channel Near-Infrared Spectroscopy Study.

The purpose of this study was to examine the relationship between fish consumption and prefrontal function during a cognitive task in male Japanese workers. The study included 208 male workers who underwent medical health examinations 3 months after a change in their work assignment. We measured the hemoglobin concentration changes in the prefrontal region during working memory tasks using 52-channel near-infrared spectroscopy. The frequency of fish consumption was calculated on the basis of the subjects' self-reported customary intake frequency over the previous 3 months. A significant positive relationship was observed between fish consumption and left dorsolateral prefrontal function during a working memory task. To our knowledge, this is the first study to report an association between fish consumption and functional cortical activity with an ample sample size, suggesting that fish consumption modulates functional activity in the left dorsolateral prefrontal cortex.

Relationship between prefrontal function during a cognitive task and social functioning in male Japanese workers: a multi-channel near-infrared spectroscopy study.

To investigate whether prefrontal function during a cognitive task reflects the social functioning of male Japanese workers, prefrontal function during a working memory task in 181 male workers was measured by multi-channel near-infrared spectroscopy (NIRS). Social functioning was assessed using the Social Adaptation Self-Evaluation Scale (SASS). The results indicated that cortical oxygenation level increases in dorsolateral prefrontal region showed significant positive correlations with the interest and motivation factor scores on the SASS. These results suggest that dorsolateral prefrontal function is associated with the interest and motivation factor in social functioning in male workers and that NIRS could be an addition to the medical tools for monitoring these characteristics on mental health examination.

Association between subjective well-being and prefrontal function during a cognitive task in schizophrenia: a multi-channel near-infrared spectroscopy study.

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.

The relationship between the prefrontal activation during a verbal fluency task and stress-coping style in major depressive disorder: a near-infrared spectroscopy study.

This study aimed to identify coping styles used by patients with major depressive disorder (MDD) in comparison with those used by healthy controls, and to explore their association with prefrontal hemodynamic response related to a cognitive task. Regional hemodynamic changes were monitored during a verbal fluency task (VFT) using a 52-channel near-infrared spectroscopy (NIRS) apparatus in 26 MDD patients in depressive state and 30 matched healthy controls, and their correlation with coping styles assessed by Coping Inventory for Stressful Situations (CISS) were examined. We found the Emotion-oriented coping style was significantly higher, whereas the Task-oriented coping and Avoidance-oriented coping style were lower in the MDD group compared with controls. Emotion-oriented coping style positively correlated with subjective assessment of depression severity. Regional hemodynamic changes were significantly smaller in the MDD group than in the control group in prefrontal and temporal regions, and positively correlated with Task-oriented coping (adaptive coping) in the bilateral ventrolateral and dorsolateral prefrontal cortex, and the midline fronto-polar and bilateral orbitofrontal cortex regions. These findings suggest coping styles may be considered an important source of knowledge for patients who struggle with the illness and for mental health professionals who work with MDD patients, and that hemodynamic response in the ventrolateral and dorsolateral prefrontal cortex, midline fronto-polar, and orbitofrontal cortex regions during a VFT may reflect the adaptive coping (Task-oriented coping) style in MDD patients in depressive state.

Reduced prefrontal cortex activation during the working memory task associated with poor social functioning in late-onset depression: multi-channel near-infrared spectroscopy study.

A number of studies have demonstrated impairment of working memory (WM) in patients with major depressive disorder (MDD). However, the relationship between the underlying brain activity associated with impairment of WM function in MDD patients and their clinical characteristics is not yet clear. The objective of this study is to evaluate prefrontal hemodynamic response related to a WM task in patients with late-onset depression (LOD) and to assess the relationship between activation in the prefrontal cortex and clinical characteristics. Thirty-six patients with LOD and 35 age- and gender-matched healthy controls were recruited for the present study. We measured hemoglobin concentration changes in the prefrontal and temporal regions during a WM (2-back, letter version) task using 52-channel near-infrared spectroscopy (NIRS). LOD patients were associated with reduced increase in prefrontal and temporal activation compared with healthy controls. Moreover, reduced activation in the prefrontal and temporal regions was significantly related to lower scores on the Social Adaptation Self-Evaluation Scale (SASS) in the patient group. More specifically, the reduced hemodynamic response in the frontopolar region was associated with functional impairment related to interpersonal relationship factor scores on the SASS. These findings suggest that hemodynamic response in prefrontal and temporal regions during a WM task may act as a biological marker of social functioning in LOD patients.

Fish consumption is positively associated with social functioning: a cross-sectional study in male Japanese workers.

This study investigated the association of fish consumption with social functioning. One hundred forty male Japanese workers completed the social adaptation self-evaluation scale (SASS) and their customary fish consumption was assessed. The total, interest, and motivation factor scores on SASS showed significant positive correlations with fish consumption.

A multi-channel near-infrared spectroscopy study of prefrontal cortex activation during working memory task in major depressive disorder.

Many neuropsychological studies demonstrate impairment of working memory in patients with major depressive disorder (MDD). However, there are not enough functional neuroimaging studies of MDD patients seeking for the underlying brain activity relevant to working memory function. The objective of this study is to evaluate prefrontal hemodynamic response related to working memory function in patients with MDD. Twenty-four subjects with MDD and 26 age- and gender-matched healthy subjects were recruited for the present study. We measured hemoglobin concentration changes in the prefrontal and superior temporal cortical surface areas during the execution of working memory task (WM; 2-back, letter version) using 52-channel near-infrared spectroscopy (NIRS), which enables real-time monitoring of task-related changes in cerebral blood volumes in the cortical surface areas. MDD patients showed a smaller increase in lateral prefrontal and superior temporal cortex activation during the 2-back task and associated poorer task performance than healthy controls. The results coincided with previous findings in terms of working memory deficits and prefrontal cortex dysfunction in MDD patients, but contradicted with some previous fMRI studies that suggested increased cortical activity during the working memory task in patients with depression. The contradiction may, in part, be explained by a relatively low level of cognitive demand imposed on the subjects in the present study.