Alterations in prefrontal cortical neuregulin-1 levels in post-pubertal rats with neonatal ventral hippocampal lesions.

Genetic studies in humans have implicated the gene encoding neuregulin-1 (NRG-1) as a candidate susceptibility gene for schizophrenia. Furthermore, it has been suggested that NRG-1 is involved in regulating the expression and function of the N-methyl-D-aspartate receptor and the GABAA receptor in several brain areas, including the prefrontal cortex (PFC), the hippocampus, and the cerebellum. Neonatal ventral hippocampal lesioned (NVHL) rats have been considered as a putative model for schizophrenia with characteristic post-pubertal alteration in response to stress and neuroleptics. In this study, we examined NRG-1, erb-b2 receptor tyrosine kinase 4 (erbB4), and phospho-erbB4 (p-erbB4) levels in the PFC and the distribution of NRG-1 in the NVHL rats by using immunoblotting and immunohistochemical analyses. Neonatal lesions were induced by bilateral injection of ibotenic acid in the ventral hippocampus of postnatal day 7 Sprague-Dawley (SD)-rats. NVHL rats showed significantly decreased levels of NRG-1 and p-erbB4 in the PFC compared to sham controls at post-pubertal period, while the level of erbB4 did not differ between sham and NVHL rats. Moreover, microinjection of NRG-1 into the mPFC improved NVHL-induced prepulse inhibition deficits. Our study suggests PFC NRG-1 alteration as a potential mechanism in schizophrenia-like behaviors in the NVHL model.

Long-term effects of filmed social contact or internet-based self-study on mental health-related stigma: a 2-year follow-up of a randomised controlled trial.

PURPOSE: There is a critical need to clarify the long-term effects of anti-stigma interventions. The study aimed to assess the long-term effects of repeated filmed social contact or internet-based self-study on mental health-related stigma through a randomised controlled trial with 2-year follow-up. METHODS: We randomly allocated 259 university or college students to a filmed social contact group, an internet-based self-study group, or a control group. The filmed social contact and internet-based self-study groups each received a 30-min initial intervention followed by emailed interventions every 2 months over a 12-month period. The Japanese version of the Reported and Intended Behaviour Scale (RIBS-J) and the Mental Illness and Disorder Understanding Scale (MIDUS) were used to assess behaviour, behavioural intentions (attitudes), and knowledge regarding mental health. RESULTS: Of the 259 original participants, 187 completed the 24-month follow-up assessment. Mean scores for the RIBS-J future domain and MIDUS peaked at 1 month after initial intervention. Compared with baseline, at 24-month follow-up, we found a significant difference in RIBS-J future domain scores between the filmed social contact and control groups at 24-month follow-up (B = 0.95, 95% CI = 0.01,1.90, p = 0.049), while MIDUS scores in the filmed social contact group (B = - 4.59, 95%CI = - 6.85, - 2.33, p < 0.001) and the internet-based self-study group (B = - 4.51, 95%CI = - 6.86, - 2.15, p < 0.001) significantly decreased compared with the control group. CONCLUSION: While outcome scores peaked at 1 month after initial intervention, results suggest that filmed social contact might have a long-term effect on behavioural intentions, and both filmed social contact and internet-based self-study may contribute to improved knowledge of mental health.

Mental-health-related stigma among Japanese children and their parents and impact of renaming of schizophrenia.

AIM: Mental-health-related stigma affects help-seeking behavior and service utilization among young people. Whether mental-health-related stigma is different or correlated between parents and their children is unknown. It is also unknown whether the name change of schizophrenia in 2002 has had long-term effects on reducing stigma for adults in the general population. METHODS: We recruited 143 parent-child pairs (mean ages [SD]: 51.5 [3.6] and 21.2 [1.2] years, respectively) to complete self-report questionnaires regarding mental-health-related stigma and experience. We also assessed negative stereotypes for three psychiatric disease names (old and new names of schizophrenia, and depression), and for diabetes mellitus as a physical illness comparison. The questionnaires also asked respondents to identify the old and new names of schizophrenia and dementia, respectively, among 10 names for mental and physical illnesses and conditions. RESULTS: Parents showed lower stigma levels toward mental illness and diabetes mellitus, but similar or greater stigma levels toward schizophrenia, compared with their children. Stigma levels toward mental illness in parents and their children were significantly correlated. The rate of correct identification of the old and new names for schizophrenia was higher in parents than in their children (64.7% vs 41.4%, P < 0.001). Parents who responded correctly endorsed more negative stereotypes toward the new name of schizophrenia compared with those who responded incorrectly (P = 0.049). CONCLUSION: The present findings suggest that stigma toward mental illness is shared between family members, and the name change of schizophrenia has effectively reduced stigma levels toward this disorder in adults of various ages.

Long-term effect of a name change for schizophrenia on reducing stigma.

BACKGROUND: A name change for schizophrenia was first implemented in Japan for reducing stigma in 2002; however, little is known of its long-term impact. METHODS: Total 259 students from 20 universities answered an anonymous self-administered questionnaire about their mental health-related experiences, and stigma scales including feasible knowledge and negative stereotypes for four specific diseases, including schizophrenia (old and new names), depression, and diabetes mellitus. We also asked to choose the old and new names of schizophrenia and dementia among ten names for mental and physical illnesses and conditions. RESULTS: The participants had more feasible knowledge and fewer negative stereotypes for the new name of schizophrenia than the old name, but were still significantly worse than for depression and diabetes mellitus (p < 0.01). Direct contact experiences with those who have mental health problems were associated with feasible knowledge for schizophrenia but not negative stereotypes (ß = 0.13, p = 0.020). The rate of correct responses for the old and new names of schizophrenia was significantly lower than that of dementia (41 vs. 87%, p < 0.001). Mental health-related experience from media was associated with the recognition of name change for schizophrenia (p = 0.008), which was associated with less feasible knowledge for new name of schizophrenia. DISCUSSION: The name change of schizophrenia has reduced stigma since 12 years have passed. More effective campaigns, educational curricula, and policy making are needed to reduce stigma toward schizophrenia.

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.

Development of a Japanese version of the reported and intended behaviour scale: reliability and validity.

AIM: The Reported and Intended Behaviour Scale (RIBS) was developed in the U.K. to measure mental health-related behavior. The current study aimed to evaluate the applicability, and reliability of a Japanese version of the RIBS (RIBS-J) in a Japanese context, and further examine the construct validity of the RIBS-J. METHODS: The sample included 224 undergraduate and postgraduate students at a Japanese university. Cronbach's alpha was used to assess internal consistency. Pearson's correlation coefficient was used to examine the divergent validity between the RIBS-J and the Mental Health Knowledge Schedule and the convergent validity between the second subscale of the RIBS-J and Japanese version of the Social Distance Scale. Confirmatory factor analysis assessed the goodness of model fit of the RIBS-J. We also examined test-retest reliability with another undergraduate sample (n = 29). RESULTS: Most items exhibited no floor/ceiling effect. High internal consistency (α = 0.83) was reported. The second subscale of the RIBS-J, measuring intended behavior, correlated with the Mental Health Knowledge Schedule (r = 0.33, P < 0.001) and the Japanese version of the Social Distance Scale (r = -0.60, P < 0.001). In addition, confirmatory factor analysis found good model fit for the RIBS-J (χ2 = 41.001, d.f. = 19, P = 0.002, goodness-of-fit index = 0.956, adjusted goodness-of-fit index = 0.916, comparative fit index = 0.955, root mean square error of approximation = 0.072). Overall test-retest reliability (ρc) was 0.71. CONCLUSION: The RIBS-J is an appropriate and psychometrically robust measure of behavior towards individuals with mental health problems in Japan. Further studies using a community sample could assess the generalizability of our findings.

Impaired prefrontal hemodynamic maturation in autism and unaffected siblings.

BACKGROUND: Dysfunctions of the prefrontal cortex have been previously reported in individuals with autism spectrum disorders (ASD). Previous studies reported that first-degree relatives of individuals with ASD show atypical brain activity during tasks associated with social function. However, developmental changes in prefrontal dysfunction in ASD and genetic influences on the phenomena remain unclear. In the present study, we investigated the change in hemoglobin concentration in the prefrontal cortex as measured with near-infrared spectroscopy, in children and adults with ASD during the letter fluency test. Moreover, to clarify the genetic influences on developmental changes in the prefrontal dysfunction in ASD, unaffected siblings of the ASD participants were also assessed. METHODOLOGY/PRINCIPAL FINDINGS: Study participants included 27 individuals with high-functioning ASD, age- and IQ-matched 24 healthy non-affected siblings, and 27 unrelated healthy controls aged 5 to 39 years. The relative concentration of hemoglobin ([Hb]) in the prefrontal cortex was measured during the letter fluency task. For children, neither the [oxy-Hb] change during the task nor task performances differed significantly among three groups. For adults, the [oxy-Hb] increases during the task were significantly smaller in the bilateral prefrontal cortex in ASD than those in control subjects, although task performances were similar. In the adult siblings the [oxy-Hb] change was intermediate between those in controls and ASDs. CONCLUSION/SIGNIFICANCE: Although indirectly due to a cross-sectional design, the results of this study indicate altered age-related change of prefrontal activity during executive processing in ASD. This is a first near-infrared spectroscopy study that implies alteration in the age-related changes of prefrontal activity in ASD and genetic influences on the phenomena.

Electrophysiological abnormalities of spatial attention in adults with autism during the gap overlap task.

OBJECTIVE: We evaluated event-related potentials (ERPs) elicited by attentional disengagement in individuals with autism. METHODS: Sixteen adults with autism, 17 adults with mental retardation and 14 healthy adults participated in this study. We recorded the pre-saccade positive ERPs during the gap overlap task under which a peripheral stimulus was presented subsequent to a stimulus in the central visual field. Under the overlap condition, the central stimulus remained during the presentation of the peripheral stimulus and therefore participants need to disengage their attention intentionally in order to execute the saccade to the peripheral stimulus due to the preservation of the central stimulus. RESULTS: The autism group elicited significantly higher pre-saccadic positivity during a period of 100-70 ms prior to the saccade onset than the other groups only under the overlap condition. The higher amplitude of pre-saccadic positivity in the overlap condition was significantly correlated with more severe clinical symptoms within the autism group. CONCLUSIONS: These results demonstrate electrophysiological abnormalities of disengagement during visuospatial attention in adults with autism which cannot be attributed to their IQs. SIGNIFICANCE: We suggest that adults with autism have deficits in attentional disengagement and the physiological substrates underlying deficits in autism and mental retardation are different.

Neuropeptide Y and somatostatin participate differently in the seizure-generating mechanisms following trimethyltin-induced hippocampal damage.

Trimethyltin (TMT) is an organic metal known to induce neuronal degeneration in the hippocampus, and abnormal behavior characterized by seizures, increased aggression and memory deficits. We administered TMT to rats and studied the changes of neuropeptide Y (NPY) and somatostatin (SOM) in the hippocampus. Phenobarbital (PB) was administered as an anticonvulsant to assess the effect of seizures on neuropeptide expressions in both dorsal and ventral hippocampus. Histochemically, NPY-immunoreactivity increased 4 days after TMT treatment in the hilus of the hippocampus, then progressively decreased and dropped to a level below control 16 days after TMT treatment. Detection of NPY mRNA by in situ hybridization preceded the detection of NPY by immunohistochemistry. NPY mRNA signals increased in the hilus 2 days after TMT treatment. SOM-immunoreactivity also increased in the hilus of the hippocampus 2 days after TMT treatment, then decreased rapidly to a normal level. Similar changes in SOM mRNA were demonstrated by in situ hybridization. PB treatment significantly inhibited changes of NPY in terms of both immunoreactivity and mRNA expression; however, the same treatment failed to affect changes in SOM expression. This suggests that NPY and SOM act by different mechanisms in TMT-induced neurodegeneration.

Impaired sleep during the post-alcohol withdrawal period in alcoholic patients.

Twenty-seven patients who suffered from alcohol dependence syndrome and who were admitted to the Department of Psychiatry at NCNP were investigated for impaired sleep. The incidence of "insomnia night", when a patient has trouble getting sufficient sleep even after taking additional drugs for insomnia, was used as the index for impaired sleep. "Insomnia night" was observed among 51.9% (14 of 27) of the patients during administration; 18.5% (nine of 27) experienced "insomnia night" only during the withdrawal period. The mean incidence was 3.5 nights of 10 nights for 0-9th day after abstinence and 2.0 nights of 10 nights for 10-19th day after abstinence; 33.3% (nine of 27) claimed "insomnia night" even after the withdrawal period and the highest incidence was the 160-169th day after abstinence, average frequency being 4.4 nights of 10 nights. Impaired sleep emerging after the withdrawal period neared the clinical course of Komiyama's protracted withdrawal symptoms, thus suggesting that it might be one of the protracted withdrawal symptoms.