Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior.

Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglial Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglial BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administering doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological function in the mPFC, whereas normalizing BDNF from later ages (p45-p50) did not normalize electrophysiological abnormalities in the mPFC, despite the improved sociability. To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible proxy for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. In summary, our study demonstrated the influence of microglial BDNF on the development of experience-dependent social behaviors in mice, emphasizing its specific impact on the maturation of mPFC function, particularly during the juvenile period. Furthermore, our results propose a translational implication by suggesting a potential link between BDNF secretion from macrophages and childhood experiences in humans.

Juvenile social isolation immediately affects the synaptic activity and firing property of fast-spiking parvalbumin-expressing interneuron subtype in mouse medial prefrontal cortex.

A lack of juvenile social experience causes various behavioral impairments and brain dysfunction, especially in the medial prefrontal cortex (mPFC). Our previous studies revealed that juvenile social isolation for 2 weeks immediately after weaning affects the synaptic inputs and intrinsic excitability of fast-spiking parvalbumin-expressing (FSPV) interneurons as well as a specific type of layer 5 (L5) pyramidal cells, which we termed prominent h-current (PH) cells, in the mPFC. However, since these changes were observed at the adult age of postnatal day 65 (P65), the primary cause of these changes to neurons immediately after juvenile social isolation (postnatal day 35) remains unknown. Here, we investigated the immediate effects of juvenile social isolation on the excitability and synaptic inputs of PH pyramidal cells and FSPV interneurons at P35 using whole-cell patch-clamp recording. We observed that excitatory inputs to FSPV interneurons increased immediately after juvenile social isolation. We also found that juvenile social isolation increases the firing reactivity of a subtype of FSPV interneurons, whereas only a fractional effect was detected in PH pyramidal cells. These findings suggest that juvenile social isolation primarily disturbs the developmental rebuilding of circuits involving FSPV interneurons and eventually affects the circuits involving PH pyramidal cells in adulthood.

Discontinuation and remission rates and social functioning in patients with schizophrenia receiving second-generation antipsychotics: 52-week evaluation of JUMPs, a randomized, open-label study.

AIM: Globally, evidence from short-term studies is insufficient for the guidelines to uniformly recommend a particular antipsychotic(s) for the maintenance treatment of schizophrenia. Therefore, long-term comprehensive evaluation of antipsychotics is required from a social rehabilitation perspective, especially for drugs that have not yet been studied. The Japan Useful Medication Program for Schizophrenia (JUMPs) is a large-scale, long-term naturalistic study to present pivotal 52-week data on the continuity of second-generation antipsychotics (SGA: aripiprazole, blonanserin, and paliperidone). METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 52-week study. Enrolled patients had schizophrenia, were ≥20 years old, and required antipsychotic treatment or switched from previous therapy. The primary endpoint was treatment discontinuation rate over 52 weeks. Secondary outcomes included remission rate, social functioning, and quality-of-life scores [Personal and Social Performance Scale (PSP) and EuroQol-5 dimensions], and safety. RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). The discontinuation rate (P = 0.9771) and remission rates (P > 0.05) over 52 weeks did not differ significantly between the three treatment groups. The discontinuation rates were 68.3%, 68.2%, and 65.5% in the aripiprazole, blonanserin, and paliperidone groups, respectively. Significant improvements (all P < 0.05) from baseline in PSP scores were observed at start of monotherapy, week 26, and week 52 in the overall cohort and blonanserin group and at week 26 in the aripiprazole group. The adverse event profile favored blonanserin. CONCLUSION: All three SGAs evaluated in this study showed similar treatment discontinuation rates in patients with chronic schizophrenia in Japan.

Increased Dendritic Orientation Dispersion in the Left Occipital Gyrus is Associated with Atypical Visual Processing in Adults with Autism Spectrum Disorder.

In autism spectrum disorder (ASD), the complexity-specific hypothesis explains that atypical visual processing is attributable to selective functional changes in visual pathways. We investigated dendritic microstructures and their associations with functional connectivity (FC). Participants included 28 individuals with ASD and 29 typically developed persons. We explored changes in neurite orientation dispersion and density imaging (NODDI) and brain areas whose FC was significantly correlated with NODDI parameters in the explored regions of interests. Individuals with ASD showed significantly higher orientation dispersion index (ODI) values in the left occipital gyrus (OG) corresponding to the secondary visual cortex (V2). FC values between the left OG and the left middle temporal gyrus (MTG) were significantly negatively correlated with mean ODI values. The mean ODI values in the left OG were significantly positively associated with low registration of the visual quadrants of the Adolescent/Adult Sensory Profile (AASP), resulting in a significant positive correlation with passive behavioral responses of the AASP visual quadrants; additionally, the FC values between the left OG and the left MTG were significantly negatively associated with reciprocal social interaction. Our results suggest that abnormal V2 dendritic arborization is associated with atypical visual processing by altered intermediation in the ventral visual pathway.

A retrospective study of factors associated with persistent delirium.

BACKGROUND: It has been reported that delirium causes various problems. Many researchers have reported the risk factors associated with the onset of delirium; however, there are few reports focused on persistent delirium. This study aimed to identify the risk factors associated with persistent delirium. METHODS: A total of 573 patients hospitalised in Nara Prefecture General Medical Centre from October 2014 through September 2017 who were referred to the psychiatry consultation service were included in this study. Persistent delirium was defined as delirium lasting for 14 days or more. A retrospective study was carried out based on the patients' records. The relationship between various background factors and persistent delirium was statistically analysed. RESULTS: Of the 573 hospitalised patients, 295 were diagnosed as having delirium. Forty-six patients with persistent delirium and 181 patients with nonpersistent delirium were included in this study. Multivariable logistic regression analyses revealed that male gender, opioid analgesics use, non-opioid analgesics use, and low serum sodium were significantly and independently associated with persistent delirium. Ramelteon or trazodone was used significantly more in persistent delirium, although each use was not significant. CONCLUSION: This is the first study to reveal that male gender and use of analgesics were associated with persistent delirium in general hospital. However, as this is a case-control study and may contain bias, future cohort studies and intervention studies are needed. It is also necessary to investigate the relevance of the 'degree of pain' behind the use of analgesics.

Effect of assertive case management intervention on suicide attempters with comorbid Axis I and II psychiatric diagnoses: secondary analysis of a randomised controlled trial.

BACKGROUND: Most suicide attempters suffer from psychiatric disorders, which are often comorbid with personality disorders. The effects of intervention on patients who have attempted suicide with comorbid Axis I and II diagnoses have not been fully elucidated. We evaluated whether assertive case management can reduce the repetition of suicidal behaviours in patients who had attempted suicide with comorbid Axis I and II diagnoses. METHODS: This study was a secondary analysis of a randomised controlled trial investigating whether assertive case management could reduce the repetition of suicide attempts, compared with enhanced usual care. Subjects were divided into those who had comorbid Axis I and II diagnoses (Axis I + II group), and those who had an Axis I diagnosis without Axis II comorbidity (Axis I group). Outcome measures were compared between patients receiving a case management intervention and patients receiving enhanced usual care, as allocated. The primary outcome measure was the incidence proportion of the first episode of recurrent suicidal behaviour at 6 months after randomisation. We calculated risk ratios (RR) with 95% confidence intervals (CI) at 6 months and 12 months after randomisation of patients in the Axis I and Axis I + II groups. RESULTS: Of 914 enrolled patients, 120 (13.1%) were in the Axis I + II group, and 794 (86.9%) were in the Axis I group. Assertive case management was significantly effective for the Axis I group on the primary outcome at 6 months (risk ratio [RR] 0.51, 95% confidence intervals [CI] 0.31 to 0.84). The RR of the Axis I + II group was 0.44 (95% CI 0.14 to 1.40). CONCLUSIONS: Assertive case management not only had an effect on patients who had attempted suicide with only Axis I disorders but may also have a similar effect on patients with comorbid Axis I and II disorders.

A case report of mania with abnormal cerebral blood flow and cognitive impairment 24 years after head trauma.

BACKGROUND: Mania usually occurs secondary to organic etiologies such as head trauma within a short time of the primary condition's onset; however, there have been a few cases reported in the literature of long time spans before the manifestation of mania. The orbitofrontal cortex has been reported to be associated with manic states in bipolar disorder and with mania-inducing lesions. Head trauma commonly disrupts various cognitive functions, including attention and information processing. Traumatic brain injury patients have been shown to have greater posterior cingulate cortex and precuneus functional connectivity to the rest of the default mode network. We describe a case of secondary mania after head trauma 24 years ago with low blood flow in the orbitofrontal cortex, high blood flow in the posterior cingulate cortex, and impaired cognitive functioning, including impaired attention and lowered processing speed. CASE PRESENTATION: We describe a 30-year-old Japanese man with secondary mania and a medical history of head trauma 24 years ago. After head trauma at 6 years of age, the patient first showed apathy as a sign of frontal lobe impairment. After recovering, he experienced no psychiatric problems during adolescence, although he did show disinhibited behavior. At the onset of mania, low blood flow in the OFC and high blood flow in the PCC were observed as well as impaired cognitive function, including inattention and lowered processing speed. Abnormal cerebral blood flow was less prominent and cognitive dysfunction was partially recovered following recovery from mania, but his processing speed remained low. CONCLUSIONS: Although functional recovery from head trauma in childhood is better than that in adulthood, the brain may remain vulnerable for a long time. The risk of psychotic symptoms such as mania should be considered, even if sufficient superficial brain functional recovery is shown.

Uncinate fasciculus disruption relates to poor recognition of negative facial emotions in Alzheimer's disease: a cross-sectional diffusion tensor imaging study.

BACKGROUND: Recognising facial emotions involves visual and emotional information processing. Patients with dementia, including dementia of Alzheimer's type (DAT), are known to poorly recognise facial emotions, especially negative facial emotions. In this study, we aimed to assess if DAT patients exhibit poor facial emotional recognition, and to identify a neural basis for how poor facial emotional recognition might occur. METHODS: Magnetic resonance imaging and diffusion tensor imaging (DTI) analysis were conducted in 20 DAT patients and 15 cognitive normal (CN) subjects. The uncinate fasciculus (UF), inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus were delineated by deterministic tractography. DTI parameters were calculated for each fibre. Facial emotion recognition was evaluated with the Facial Emotion Selection Test (FEST). The relationships between FEST scores and DTI parameters in each fibre were measured by partial correlation analyses with age, gender, and the Mini-Mental State Examination as covariates. Group-wise comparisons between DAT and CN subjects were performed for each DTI parameter in each fibre. RESULTS: DAT patients showed lower FEST negative emotion scores than CN subjects (P < 0.05). The score of negative emotion subscale was negatively correlated (r = -0.770, P < 0.001) to mean diffusivity of the left UF in DAT patients. There were no relationships between negative emotion subscale and the other fibre tracts. DAT patients showed no differences in the DTI parameters for each fibre compared to CN subjects. CONCLUSIONS: DAT-related prefrontal-limbic network dysfunction is associated with poor recognition of unpleasant emotions; consequently, worse facial recognition of negative emotion is observed in DAT patients.

Neurobiology and treatment of social cognition in schizophrenia: Bridging the bed-bench gap.

Social cognition refers to the psychological processes involved in the perception, encoding, storage, retrieval, and regulation of information about others and ourselves. This process is essential for survival and reproduction in complex social environments. Recent evidence suggests that impairments in social cognition frequently occur in schizophrenia, mainly contributing to poor functional outcomes, including the inability to engage in meaningful work and maintain satisfying interpersonal relationships. With the ambiguous definition of social cognition, the neurobiology underlying impaired social cognition remains unknown, and the effectiveness of currently available intervention strategies in schizophrenia remain limited. Considering the advances and challenges of translational research for schizophrenia, social cognition has been considered a high-priority domain for treatment development. Here, we describe the current state of the framework, clinical concerns, and intervention approaches for social cognition in schizophrenia. Next, we introduce translatable rodent models associated with schizophrenia that allow the evaluation of different components of social behaviors, providing deeper insights into the neural substrates of social cognition in schizophrenia. Our review presents a valuable perspective that indicates the necessity of building bridges between basic and clinical science researchers for the development of novel therapeutic approaches in impaired social cognition in schizophrenia.

Social Isolation During the Critical Period Reduces Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Cell in Mouse Prefrontal Cortex.

Juvenile social experience is crucial for the functional development of forebrain regions, especially the prefrontal cortex (PFC). We previously reported that social isolation for 2 weeks after weaning induces prefrontal cortex dysfunction and hypomyelination. However, the effect of social isolation on physiological properties of PFC neuronal circuit remained unknown. Since hypomyelination due to isolation is prominent in deep-layer of medial PFC (mPFC), we focused on 2 types of Layer-5 pyramidal cells in the mPFC: prominent h-current (PH) cells and nonprominent h-current (non-PH) cells. We found that a 2-week social isolation after weaning leads to a specific deterioration in action potential properties and reduction in excitatory synaptic inputs in PH cells. The effects of social isolation on PH cells, which involve reduction in functional glutamatergic synapses and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate charge ratio, are specific to the 2 weeks after weaning and to the mPFC. We conclude that juvenile social experience plays crucial roles in the functional development in a subtype of Layer-5 pyramidal cells in the mPFC. Since these neurons project to subcortical structures, a deficit in social experience during the critical period may result in immature neural circuitry between mPFC and subcortical targets.

Neural changes following cognitive remediation therapy for schizophrenia.

Patients with schizophrenia experience cognitive impairments that relate to poorer social functioning even after amelioration of positive symptoms. Pharmacological treatment and cognitive remediation are the two important therapeutic approaches for cognitive impairment in schizophrenia. Cognitive remediation therapy (CRT) for schizophrenia improves cognitive functioning and induces neuroplasticity, but different approaches and durations of CRT and different neuroimaging devices have led to varying results in meta-analyses. The objective of this review was to explore the impact of CRT on neurobiology. Several studies have provided evidence of increased activation in the frontal brain regions, such as the prefrontal cortex, anterior cingulate cortex, and parietal and occipital regions during working memory or executive function tasks after CRT. Two studies have shown alterations in resting-state connectivity between the prefrontal cortex and temporal regions. Two studies have reported that CRT induces changes in gray matter volume in the hippocampus. Further, one study observed that patients who had received CRT had elevated fractional anisotropy in the basal ganglia. We conclude that neuroimaging studies assessing CRT in patients with schizophrenia showed functional, structural, and connectivity changes that were positively correlated with cognitive improvements despite heterogeneous CRT approaches. Future studies that combine multiple modalities are required to address the differences, effects of intrinsic motivation, and pharmacological augmentation of CRT. Further understanding of the biological basis might lead to predictions of the CRT response in patients with schizophrenia and contribute to identification of schizophrenia patients for future interventions.

Guanfacine monotherapy for ADHD/ASD comorbid with Tourette syndrome: a case report.

BACKGROUND: Patients with attention deficit/hyperactivity disorder (ADHD) often experience comorbid conditions, such as autism spectrum disorder (ASD) and Tourette syndrome (TS). Although pharmacotherapies are effective for treating ADHD, they are likely to elicit a variety of adverse effects. It is, thus, important to select an effective and well-tolerated pharmacotherapeutic treatment for patients with ADHD/ASD comorbid with TS. CASE PRESENTATION: We report the case of a 10-year-old boy with ADHD/ASD comorbid with TS who was treated with guanfacine (GUAN). He experienced several side effects of atomoxetine (ATX) and methylphenidate (MPH) before being treated with GUAN. In the presented case, symptoms of ADHD as well as tic symptoms were improved by treatment with GUAN. CONCLUSION: GUAN might be effective and well tolerated in the treatment of patients with ADHD/ASD comorbid with TS who experience side effects of ATX and MPH.

Different Effects of Cisplatin and Transplatin on the Higher-Order Structure of DNA and Gene Expression.

Despite the effectiveness of cisplatin as an anticancer agent, its trans-isomer, transplatin, is clinically ineffective. Although both isomers target nuclear DNA, there is a large difference in the magnitude of their biological effects. Here, we compared their effects on gene expression in an in vitro luciferase assay and quantified their effects on the higher-order structure of DNA using fluorescence microscopy (FM) and atomic force microscopy (AFM). The inhibitory effect of cisplatin on gene expression was about 7 times that of transplatin. Analysis of the fluctuation autocorrelation function of the intrachain Brownian motion of individual DNA molecules showed that cisplatin increases the spring and damping constants of DNA by one order of magnitude and these visco-elastic characteristics tend to increase gradually over several hours. Transplatin had a weaker effect, which tended to decrease with time. These results agree with a stronger inhibitory effect of cisplatin on gene expression. We discussed the characteristic effects of the two compounds on the higher-order DNA structure and gene expression in terms of the differences in their binding to DNA.

Decreased perfusion of the posterior cingulate gyri shown by a cingulate island score is a possible marker of vulnerability to behavioural and psychological symptoms of Alzheimer's disease: a pilot study.

BACKGROUND: The cingulate island score (CIScore), which indicates the Z-score ratio of the posterior cingulate gyri to the medial occipital area, has been shown to be useful for differentiating dementia with Lewy bodies from Alzheimer's disease (AD). Our aim was to investigate associations between the clinical symptoms of AD and the CIScore as an index of the relative decrease in perfusion of the posterior cingulate gyri that occurs in the early stages of AD. METHODS: Seventeen patients with early-stage AD and 13 patients with amnesic mild cognitive impairment were examined. Z-score maps of technetium-99m ethyl cysteinate dimer single-photon emission computed tomography images acquired from the patients were converted, and the CIScore was determined by using the easy Z-score imaging system. The relationships between the CIScore and clinical symptom scores were tested. RESULTS: A significant correlation was identified between the CIScore and the Neuropsychiatric Inventory Questionnaire score. No significant correlations were identified between the CIScore and other measures of cognitive function. Based on a CIScore of 0.39, we correctly differentiated patients with and without behavioural and psychological symptoms of dementia (BPSD), with a sensitivity of 72.2% and specificity of 75.0%. DISCUSSION: Using technetium-99m ethyl cysteinate dimer single-photon emission computed tomography, we observed that decreased posterior cingulate gyri perfusion, relative to the medial occipital area, in prodromal and early AD was closely associated with behavioural and psychological symptoms of dementia. Therefore, our findings suggest that CIScore is not only useful for discriminating dementia with Lewy bodies from AD, but it can also be clinically used as a specific indicator of the vulnerability to behavioural and psychological symptoms of dementia in the early stages of AD.

Detection of brain amyloid-ß deposits due to the repetitive head trauma in a former karate player.

Head trauma is a well-established epidemiological risk factor for Alzheimer's disease, but a study of early detection of its pathology has not yet been performed in human patients in vivo. To address this issue, we performed 11 C-labelled Pittsburgh compound B-positron emission tomography on a right-handed 30-year-old man with cognitive deterioration after repetitive head trauma during karate matches. Structural magnetic resonance imaging was also performed on this patient. The same positron emission tomography analysis was performed on elderly healthy controls (15 men, mean age: 70.7 ± 6.2 years). To analyze grey matter volume, structural magnetic resonance imaging was performed on age-matched healthy controls (15 men, mean age: 28.5 ± 3.6 years). The cognitive deterioration in our patient was fixed and partially improved in the 10 years after the repetitive head trauma. However, Pittsburgh compound B-non-displaceable binding potential was significantly elevated in the patient. Volume reduction was shown in the medial temporal region, cerebellum, and the basal frontal cortex, while amyloid-ß increase was shown in the bilateral prefrontal cortex. This is the first study to show an early degenerative process due to head trauma in the prefrontal cortex, where structural damage is not yet visible. Early recognition of the degenerative pathology due to repetitive head trauma by amyloid and possibly tau imaging would help clinicians determine how to treat those with early symptoms.

Left dorsolateral prefrontal cortex atrophy is associated with frontal lobe function in Alzheimer's disease and contributes to caregiver burden.

OBJECTIVE: Caregivers of patients with dementia experience physical and mental deterioration. We have previously reported a correlation between caregiver burden and the Frontal Assessment Battery (FAB) total scores of patients with Alzheimer's disease (AD), especially regarding the dependency factor from the Zarit Burden Interview. The present study aimed to identify an objective biomarker for predicting caregiver burden. METHODS: The participants were 26 pairs of caregivers and patients with AD and mild-to-moderate dementia. Correlations between regional gray matter volumes in the patients with AD and the FAB total scores were explored by using whole-brain voxel-based morphometric analysis. Path analysis was used to estimate the relationships between regional gray matter volumes, FAB total scores, and caregiver burden based on the Zarit Burden Interview. RESULTS: The voxel-based morphometric revealed a significant positive correlation between the FAB total scores and the volume of the left dorsolateral prefrontal cortex. This positive correlation persisted after controlling for the effect of general cognitive dysfunction, which was assessed by using the Mini-Mental State Examination. Path analysis revealed that decreases in FAB scores, caused by reduced frontal lobe volumes, negatively affected caregiver burden. CONCLUSIONS: The present study revealed that frontal lobe function, based on FAB scores, was affected by the volume of the left dorsolateral prefrontal cortex. Decreased scores were associated with greater caregiver burden, especially for the dependency factor. These findings may facilitate the development of an objective biomarker for predicting caregiver burden.

Computer-assisted cognitive remediation therapy increases hippocampal volume in patients with schizophrenia: a randomized controlled trial.

BACKGROUND: Cognitive remediation therapy (CRT) effectively reduces neurocognitive impairment in patients with schizophrenia, but few studies have used structural neuroimaging methods to assess its neuroanatomical effects. We investigated these effects, as well as the association between changes in cortical volume and neurocognitive performance. METHOD: Between August 2013 and September 2016, we performed a randomized controlled study comprising a CRT group (16 individuals) and a treatment-as-usual (TAU) group (15 individuals) of patients with schizophrenia. CRT participants engaged in twice-weekly computer-assisted CRT sessions and weekly group meetings for 12 weeks. T1-weighted magnetic resonance imaging was performed before and after the intervention period, and whole-brain voxel-based morphometric analysis was used to detect significant cortical gray matter volume changes. We also assessed the correlation between cortical volume changes and CRT-derived neurocognitive improvements. RESULTS: The CRT group exhibited significantly greater improvements than the TAU group in verbal fluency (P = 0.012) and global cognitive scores (P = 0.049). The CRT group also exhibited significantly greater increases in right hippocampal volume than the TAU group (P < 0.001). Changes in verbal fluency scores and right hippocampal volumes were positively correlated (r = 0.53, P = 0.001). CONCLUSION: We found that CRT significantly increased right hippocampal volumes and that these enhancements were positively correlated with changes in verbal fluency scores. Our results indicate that CRT induces cognitive improvement through hippocampal plasticity. TRIAL REGISTRATION: Registration number: UMIN000026146 , 2017/02/15, retrospectively registered.

Reduced prefrontal hemodynamic response in adult attention-deficit hyperactivity disorder as measured by near-infrared spectroscopy.

AIM: Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. In pediatric attention-deficit hyperactivity disorder (ADHD), reduced prefrontal hemodynamic responses have been observed with NIRS repeatedly. However, there are few studies of adult ADHD by multi-channel NIRS. Therefore, in this study, we used multi-channel NIRS to examine the characteristics of prefrontal hemodynamic responses during the Stroop Color-Word Task (SCWT) in adult ADHD patients and in age- and sex-matched control subjects. METHODS: Twelve treatment-naïve adults with ADHD and 12 age- and sex-matched healthy control subjects participated in the present study after giving consent. We used 24-channel NIRS to measure the oxygenated hemoglobin (oxy-Hb) changes at the frontal lobes of participants during the SCWT. We compared the oxy-Hb changes between adults with ADHD and control subjects by t-tests with Bonferroni correction. RESULTS: During the SCWT, the oxy-Hb changes observed in the ADHD group were significantly smaller than those in the control group in channels 11, 16, 18, 21, 22, 23, and 24, corresponding to the prefrontal cortex. At channels 16, 21, 23, and 24 of the ADHD group, there were negative correlations between the symptomatic severity and the oxy-Hb changes. CONCLUSION: The present study suggests that adults with ADHD have reduced prefrontal hemodynamic response as measured by NIRS.

Feasibility and effectiveness of a cognitive remediation programme with original computerised cognitive training and group intervention for schizophrenia: a multicentre randomised trial.

Devising new methods to improve neurocognitive impairment through cognitive remediation is an important research goal. We developed an original computer programme termed the Japanese Cognitive Rehabilitation Programme for Schizophrenia (JCORES) that provides cognitive practice across a broad range of abilities. The current study examined for the first time whether a cognitive remediation programme, including both computerised cognitive training using JCORES and group intervention such as enhancing meta-cognition and teaching strategies, is more effective than treatment as usual for improving neurocognitive and social functioning. Sixty-two outpatients with schizophrenia were randomised to either a cognitive remediation group or a control group. Participants engaged in two computerised cognitive training sessions and one group meeting per week for 12 weeks. The average number of total sessions attended (computerised cognitive practice + group intervention) was 32.3 (89.7%). The cognitive remediation group showed significantly more improvements in verbal memory, composite score of the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J), and general psychopathology on the Positive and Negative Syndrome Scale (PANSS) than the control group. These findings demonstrate that a cognitive remediation programme is feasible in Japan and is a more effective way to improve neurocognitive functioning and psychiatric symptoms.

Social isolation impairs remyelination in mice through modulation of IL-6.

Recent studies have revealed that social experience affects myelination. These findings have important implications for disorders that feature abnormal myelination, such as multiple sclerosis (MS), as previous studies have shown that psychosocial stress exacerbates the pathobiology of MS. However, most studies have focused on psychosocial stress during the demyelination phase of MS and have not investigated the effects of social experience on remyelination. Thus, the current study sought to determine whether social experience can alter remyelination after myelin depletion. Myelin in the mouse medial prefrontal cortex was depleted with cuprizone, and the effects of subsequent social isolation on remyelination were evaluated. Remyelination was severely impaired in socially isolated mice. Social isolation also increased IL-6 levels in the medial prefrontal cortex, and administration of an IL-6 inhibitor (ND50 = 0.01-0.03 µg for 0.25 ng/ml IL-6) ameliorated remyelination impairments. Consistent with this result, IL-6 administration (ED50 = 0.02-0.06 ng/ml) disturbed remyelination. In addition, neuron-oligodendrocyte coculture experiments showed that IL-6 treatment (ED50 ≤ 0.02 ng/ml) markedly impeded myelination, which was recovered with IL-6 inhibitor administration (ND50 = 0.01-0.03 µg for 0.25 ng/ml IL-6). This study provides the first direct evidence, to our knowledge, that social experience influences remyelination via modulation of IL-6 expression. These findings indicate that psychosocial stress may disturb remyelination through regulation of IL-6 expression in patients with such demyelinating diseases that involve remyelination as MS.-Makinodan, M., Ikawa, D., Miyamoto, Y., Yamauchi, J., Yamamuro, K., Yamashita, Y., Toritsuka, M., Kimoto, S., Okumura, K., Yamauchi, T., Fukami, S., Yoshino, H., Wanaka, A., Kishimoto, T. Social isolation impairs remyelination in mice through modulation of IL-6.