Associations of childhood experiences with event-related potentials in adults with autism spectrum disorder.

Childhood maltreatment is defined as experiencing of physical, emotional and sexual abuse and neglect in childhood. Maltreatment in childhood leads to substantial psychosocial problems later in life in the general population. Individuals with autism spectrum disorder (ASD) have a higher risk of experiencing stressful and traumatic events, such as maltreatment, during childhood. Although childhood maltreatment reportedly leads to psychosocial problems in adults with ASD, the biological associations between childhood experiences and brain function in this population remain understudied. Here, we evaluated the relationships between childhood experiences and event-related potential (ERP) components during the auditory odd-ball task in adults with ASD (N = 21) and typically developed (TD) individuals (N = 22). We found that the higher the severity of sexual abuse, the larger the amplitude of P300 at Fz, Cz, C3, and C4 in individuals with ASD. Conversely, the severity of child maltreatment was associated with P300 latency at Cz and C3 in TD individuals. Moreover, full IQ was significantly associated with the MMN amplitude at Fz, Cz, C3, and C4 in TD individuals. These findings provide the first evidence that ERPs could be used to study the impacts childhood experiences on the brain of individuals with ASD and that childhood sexual abuse has salient impacts on brain function in this population.

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.

Geissoschizine methyl ether, an alkaloid from the Uncaria hook, improves remyelination after cuprizone-induced demyelination in medial prefrontal cortex of adult mice.

Accumulating evidence indicates that the medial prefrontal cortex (mPFC) is a site of myelin and oligodendrocyte abnormalities that contribute to psychotic symptoms of schizophrenia. The development of therapeutic approaches to enhance remyelination, a regenerative process in which new myelin sheaths are formed on demyelinated axons, may be an attractive remedial strategy. Geissoschizine methyl ether (GM) in the Uncaria hook, a galenical constituent of the traditional Japanese medicine yokukansan (Yi-gan san), is one of the active components responsible for the psychotropic effects of yokukansan, though little is known about the mechanisms underlying the effects of either that medicine or GM itself. In the present study, we employed a cuprizone (CPZ)-induced demyelination model and examined the cellular changes in response to GM administration during the remyelination phase in the mPFC of adult mice. Using the mitotic marker 5-bromo-2'-deoxyuridine (BrdU), we demonstrated that CPZ treatment significantly increased the number of BrdU-positive NG2 cells, as well as microglia and mature oligodendrocytes in the mPFC. Newly formed oligodendrocytes were increased by GM administration after CPZ exposure. In addition, GM attenuated a decrease in myelin basic protein immunoreactivity caused by CPZ administration. Taken together, our findings suggest that GM administration ameliorated the myelin deficit by mature oligodendrocyte formation and remyelination in the mPFC of CPZ-fed mice. The present findings provide experimental evidence supporting the role for GM and its possible use as a remedy for schizophrenia symptoms by promoting the differentiation of progenitor cells to and myelination by oligodendrocytes.

Effects of osmotic-release methylphenidate in attention-deficit/hyperactivity disorder as measured by event-related potentials.

AIM: Attention-deficit/hyperactivity disorder (ADHD) is a relatively common central nervous system disorder in school-age children, which may involve a specific disorder in cognition and/or information processing. Event-related potentials (ERP) are commonly used as physiological measures of cognitive function as they are easily measured and non-invasive. Thus, in the present study, we examined the effects of osmotic-release methylphenidate (MPH) (Concerta), a common treatment for childhood attention-deficit/hyperactivity disorder (ADHD), in ADHD children as measured by ERP. METHODS: Ten ADHD children participated after giving consent. Based on the guidelines for evoked potential measurement, mismatch negativity (MMN) and P300 were obtained by auditory odd-ball tasks. We measured both MMN and P300 in the drug-naive condition and after intake of osmotic-release MPH. RESULTS: The MMN amplitudes after intake of osmotic-release MPH were significantly greater than those in the drug-naive situation at Pz and C4. The P300 amplitudes after intake of osmotic-release MPH were significantly greater than those in the drug-naive situation at Cz and Pz. CONCLUSION: MMN and P300 are sensitive tools for measuring the pharmacological effects of osmotic-release MPH in ADHD children.

Tai Chi exercise versus rehabilitation for the elderly with cerebral vascular disorder: a single-blinded randomized controlled trial.

BACKGROUND: Cerebral vascular disorder (CVD) might result in a quantifiable decrease in quality of life, which is determined not only by the neurological deficits but also by impairment of cognitive functions. There are few studies that report on the cognitive effect of Tai Chi exercise (Tai Chi) on the elderly with CVD. The purpose of the present study was to examine the cognitive effect of Tai Chi on the elderly with CVD using P300 measurement, in addition to the General Health Questionnaire (GHQ) and Pittsburgh Sleep Quality Index (PSQI). METHODS: A total of 34 patients with CVD were recruited from outpatient Akistu-Kounoike Hospital and randomly assigned to receive Tai Chi (n= 17) or rehabilitation (n= 17) in group sessions once a week for 12 weeks. To examine the time courses of each score (P300 amplitude, P300 latency, GHQ score and PSQI score), repeated-measures analysis of variance was carried out with groups and time as factors. RESULTS: For the time courses of P300 amplitudes and latencies, there were no significant effects of interaction between group and time. However, significant time-by-group interactions were found for Sleep Quality (P= 0.006), GHQ total score (P= 0.005), anxiety/insomnia score (P= 0.034), and severe depression score (P= 0.020). CONCLUSIONS: Tai Chi might therefore be considered a useful non-pharmacological approach, along with rehabilitation, for the maintenance of cognitive function in the elderly with CVD and might be a more useful non-pharmacological approach for the improvement of sleep quality and depressive symptoms in the elderly with CVD than rehabilitation.

Olanzapine increases cell mitotic activity and oligodendrocyte-lineage cells in the hypothalamus.

Weight gain is increasingly recognized as an unwanted side effect of atypical antipsychotic drugs. To explore the mechanisms underlying this side effect, we examined the effects of olanzapine, an atypical antipsychotic drug, on cellular proliferation and differentiation in the adult mouse hypothalamus. A 6-week treatment with olanzapine resulted in a significant increase in body weight. The sizes and numbers of olanzapine-treated mouse adipocytes were significantly larger than those of control mice. No significant differences were observed in the levels of blood insulin, cholesterol, triglyceride, leptin, and ghrelin among olanzapine-, haloperidol-treated and control mice with an exception that adiponectin was significantly higher in olanzapine group than control group. Body temperature and the level of uncoupling protein 2 were also comparable between the olanzapine-treated and control groups. We found that the treatment increased BrdU-incorporating cell numbers in the hypothalamus, while the same regimen with haloperidol or control had little effect on cellular proliferation. Double-labeling immunohistochemistry revealed that the majority of the BrdU-positive cells were also Olig2- or APC-positive, indicating that oligodendrocyte-lineage cells were generated in response to olanzapine treatment. Enhancement of hypothalamic cellular proliferation after intracerebroventricular infusion of cytosine arabinoside coincided with elevated food intake and weight gain. These findings suggest a possible link between gliogenesis in the hypothalamus and weight gain following olanzapine treatment.

Yi-gan san restores behavioral alterations and a decrease of brain glutathione level in a mouse model of schizophrenia.

The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.