Poster

Poster 7 Others ポスター 7 その他

P7-1 Maternal Behavior of CD38 Knockout Dams is Improved by Social Support 社会的支援によって改善するCD38ノックアウトマウスの養育行動についての研究 Tsuji Takahiro（辻隆宏）^1,2，辻知陽² ¹Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui ²Department of Basic research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan Negative health state of mothers has a lifelong negative effect on their offspring. Preventing emotional dysfunction, such as depression and anxiety disorder, of the mother during pregnancy and lactation leads to the offspring’s wellbeing. It is important to point out that stress, which may lead to emotional dysfunction, is attenuated by the effect of social interaction called social buffering. This effect is mediated by oxytocin, but the precise neuroendocrinolological mechanism remains to be investigated. We previously reported CD38 knockout (KO) mice have deficit in oxytocin release and the CD38 KO dams show impaired maternal behavior. However, we have not yet examined weather housing conditions of the dams alone or with the sires during pregnancy affect maternal behavior. Here, we show the CD38 KO dams housed with sires showed significantly shorter latency to retrieve the pups than the dams that were housed alone during pregnancy. This result suggests that social buffing may overcome the deficit of maternal behavior of CD38 knockout dams.		P7-2 How lateralization indices of fMRI show concordances across language tasks fMRIのラテラリティ指標が言語課題間でどのくらい一致するか Matsuo Kayako（松尾香弥子）¹，藤井久彌子²，尾関祐二²，下田和孝²，高野賢太³，楫靖⁴，秋山一文¹ ¹Dept of Biol. Psychi. Neurosci., Dokkyo Med. Univ. ²Dept of Psychi., Dokkyo Med. Univ. ³Dokkyo Med. Univ. ⁴Dept of Radiol., Dokkyo Med. Univ. 背景加齢や精神疾患によって両側的な言語処理が増加する。言語側性化（ラテラリティ）は言語課題のfMRIによって調べられる。どのような課題を行うかは問題であるが、新たに開発した側性化指標（AveLI, Matsuo et al., 2012）では、従来の計算法よりも課題間の一致度が高いことが示唆された。目的 4種類の言語課題のfMRIを行い、AveLIの一致度を従来法と比較する。方法言語課題：被験者（16名、非右利き者含）は次の4つの言語課題のfMRIに参加した：（a）朗読聴取、（b）動詞生成、（c）単語判断（音声提示）、（d）単語判断（視覚提示）。指標の計算：SPM12による前処理および統計処理に続き、左右下前頭回三角部につき、次の6つの側性化指標を計算した：（1）AveLI（画素voxelの統計値contrast estimateを使用）、（2）AveLI_v（同一アルゴリズムだが画素数を使用）、（3）baseLI（AveLIの重み付けを行わない計算法）、（4）baseLI_v（同、画素数を使用）、（4）p001unc（一般的な閾値であるp<0.001, uncorrectedを適用し、画素の統計値について、（左-右）／（左＋右）を計算）、（6）p001unc_v（同、画素数を使用）。従来法は（6）のp001unc_vである。いずれも1が最左、-1が最右となる。統計：各指標につき、課題間におけるケンドールの一致係数（W）を計算する。また左右優位判定数を集計する。結果一致係数は、AveLI（0.586）、baseLI（0.582）、p001unc（0.567）、AveLI_v（0.565）、p001unc_v（0.560）、baseLI_v（0.367）の順に高く、また聴覚提示課題（a~c）のみでは、baseLI（0.772）、AveLI_v（0.737）、AveLI（0.720）、p001unc（0.632）、p001unc_v（0.623）、baseLI_v（0.526）の順であった。さらに、指標0.2以上を左優位、-0.2以下を右優位、その間を両側と定義して、4課題間で判定が一致した被験者数を集計したところ、AveLIでは16名中7、AveLI_vおよびbaseLI_vでは6、他は5であった。討論いずれにおいても、AveLIでは従来法（p001unc_v）よりも一致度は高く、少なくとも下前頭回三角部においては、AveLIはより高い安定性を有していた。外れ値やノイズの影響を抑制できるアルゴリズムを考慮すると、AveLIの適用が推奨される。

P7-3 Moderation of sensitivity to parental behaviors during characterization of personality traits by mu-opioid receptor polymorphism 人格形成過程におけるμオピオイド受容体多型による両親の養育行動に対する感受性の調整 Suzuki Akihito（鈴木昭仁）¹，松本祥彦¹，白田稔則¹，高橋奈那¹，能登契介¹，後藤薫薫²，大谷浩一¹ ¹Department of Psychiatry, Yamagata University School of Medicine ²Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata, Japan Attachment experiences with parents in childhood influence the characerization of personality traits. Meanwhile, mu-opioid receptor function is involved in human attachment. Furthermore, a few studies suggest that the A118G single nucleotide polymorphism in the mu-opioid receptor gene (OPRM1) is associated with altered mu-opioid receptor function. Thus, we examined if this polymorphism moderates the sensitivity to partental behaviors and thereby contributes to the characerization of personality traits. The subjects were 725 healthy Japanese. Parenting practices of their parents were assessed by the Parental Bonding Instrument which has care and protection subscales. Personality was assessed by the Temperament and Character Inventory (TCI) consisting of 7 dimensions. The OPRM1 polymorphism was detected by a PCR method. This study was approved by the Ethics Committee of Yamagata University School of Medicine, and all subjects gave written informed consent to participate. In multiple regression analyses, main effects of the OPRM1 genotype on the TCI scores were not significant, but interaction effects between the OPRM1 genotype and maternal protection were significant on scores of the self-directedness and cooperativeness. In subsequent analyses, the effects of maternal protection on these personality dimensions were genotype-specific, i.e., there were significant negative correlations between maternal protection scores and these dimensional scores in the A/A and A/G genotypes with higher correlation coefficients in the former, but not in the G/G genotype. The present study suggests that the OPRM1 polymorphism contributes to the characterization of personality traits by moderating the sensitivity to parental behaviors, especially maternal protection.		P7-4 Neurocognitive profile in Anorexia Nervosa 神経性やせ症の認知機能障害 Tamiya Hiroko（田宮裕子）¹，大内淳¹，陳潤舒¹，宮澤志保²，秋元頼孝³，兼田康宏⁴，曽良一郎¹ ¹Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan ²Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan ³Department of Information & Management Systems Engineering, Nagaoka University of Technology, Nagaoka, Japan ⁴Department of Psychiatry, Iwaki Clinic, Tokushima, Japan Objective: To evaluate cognitive function impairment in patients with anorexia nervosa (AN) of either the restricting (ANR) or binge-eating/purging (ANBP) subtype. Method: We administered the Japanese version of the MATRICS Consensus Cognitive Battery to 22 patients with ANR, 18 patients with ANBP, and 69 healthy control subjects. Our participants were selected from among the patients at the Kobe University Hospital and community residents. Written consent was obtained from all participants. We also obtained the written informed parental consent for participants under the age 16. The study was conducted according to the standards of the Declaration of Helsinki and was approved by the Kobe University Hospital Ethics Committee. Results: Compared to the healthy controls, the ANR group had significantly lower visual learning and social cognition scores, and the ANBP group had significantly lower processing speed, attention/vigilance, visual learning, reasoning/problem-solving, and social cognition scores. Compared to the ANR group, the ANBP group had significantly lower attention/vigilance scores. Discussion: The AN subtypes differed in cognitive function impairments. Participants with ANBP, which is associated with higher mortality rates than ANR, exhibited greater impairment severities, especially in the attention/vigilance domain, confirming the presence of impairments in continuous concentration. This may relate to the impulsivity, an ANBP characteristic reported in the personality research. Future studies can further clarify the cognitive impairments of each subtype by addressing the subtype cognitive functions and personality characteristics.

P7-5 Effect of perampanel on acute itch in mice 急性の痒みに対するペランパネルの効果 Haruta-Tsukamoto Ayaka（治田彩香），船橋英樹，宮原裕，西森利數，石田康 Dept. of Psychiatry, Faculty of Medicine, Univ. of Miyazaki Glutamate is an excitatory amino acid in the central nervous system, and it plays crucial roles by binding to the NMDA receptor, AMPA/kainate receptor or metabotropic glutamate receptor. Recently, it has been reported that the pretreatment with CNQX, an AMPA/kainate receptor antagonist, attenuates acute itch induced by chloroquine, a pruritogen (Koga et al., 2011; Akiyama et al., 2014), indicating that the AMPA/kainate receptor is involved in pruriceptive processing. Interestingly, perampanel is an anticonvulsant that elicits its effect by attenuating AMPA/kainate receptor activity (Zwart et al., 2014). Taken together with these previous data, it seems likely that perampanel may have the antipruritic effect; however, there is no available information on the antipruritic effect of perampanel. Thus, the objectives of the present study were determined to clarify whether perampanel exhibits the antipruritic effect on animal model with acute itch.A solution of perampanel (5 μg / 5 μL) dissolved in dimethyl sulfoxide (DMSO) was administered into the subarachnoid space under isoflurane anesthesia, and then chloroquine (200 μg/50 μL) was subcutaneously injected into the nape of the neck at different times after intrathecal administration of perampanel. The number of scratching behavior with hind-paws after administration of chloroquine was counted for 30 min in mice pretreated with DMSO, and was considered as the basal level of chloroquine-induced scratching behavior. Compared with the basal level, the induction of scratching by chloroquine was significantly attenuated by intrathecal injection of perampanel, suggesting that perampanel may be a candidate for antipruritic drugs.		P7-6 Development of innovative wide-view mapping of synaptic ensemble in the psychiatric model 精神疾患の神経回路異常の解明にむけた革新的な機能的コネクトミクス法の開発 Obi Kisho（小尾紀翔），宮本成美，佐藤壮泰，杉順子，三宅隆平，千葉久実，林（高木）朗子 Lab of medical neuroscience, Institute for Molecular and Cellular Regulation, Gunma University The dysregulation of dendritic spines, protrusions of neural connectivity, is thought to be involved in the pathophysiology of a variety of psychiatric disorders, but the links between spines and psychiatric disorders have been largely correlational because of lacks of a technique for manipulating individual spine. To overcome this problem, we developed a novel synaptic optoprobe, AS-PaRac1 (Activated Synapse targeting PhotoActivatable Rac1), which is unique not only because it can specifically label the recently potentiated spine, but can also selectively induce shrinkage in just those spines containing AS-PaRac1. This indicates AS-PaRac1 specifically visualizes the synaptic plasticity, which can be erased by blue light.Here, we aim to visualize the potentiated neuronal circuits by simultaneous three colour imaging of an activity-dependent expression of the presynaptic marker Vamp2-mTurquoise2, the postsynaptic neuron markers tdTomato, together with AS-mClover as a potentiated synaptic marker.To identify the ideal probe with a proper temporal regulation, the selection of promoter and protein degradation sequences were extensively compared in the mice. We transduced various kinds of constructs into layer 2/3 pyramidal neurons in the V1 cortex. Two days after dark rearing, 2 hours light exposure was performed. Time-course of an activity-dependent tdTomato and mTq2 expression and subsequent transportation into ipsilateral V1 cortex were compared and we finished the selection of ideal probes. With the development and application of these tools, studies on synaptic ensemble will pioneer new discoveries, eventually leading to a comprehensive understanding of how the brain works.

P7-7 Biological mechanism of time discount disability in psychiatric disorders: a systematic review 精神障害における時間割引に関する神経生物学的メカニズム：システマティックレヴュー Muhammad Elsalhy，進一郎中島，高広宮崎，將三村，賀大野田 Department of Neuropsychiatry, Keio University Graduate School of Medicine Background: Time discount (TD) refers to the discount of the reward value with delay when comparing a certain reward with the current reward value. TD was increased with impulsivity in patients with attention deficit/hyperactivity disorder (ADHD) or behavioral and substance addiction, whereas TD was decreased in patients with anorexia nervosa. Here, mainly two neural networks associated with the actions of short-term interests and long-term benefits are identified in the TD process. However, the detailed neurobiological mechanisms of TD still remain unelucidated in these populations.Methods: A systematic review was conducted following the PRISMA statement to investigate the neurobiological mechanisms of TD in psychiatric disorders, setting specific search terms on PubMed. Results: Out of 503 records, 31 studies were identified, all of which employed a magnetic resonance imaging. Various neurobiological correlations with TD were observed in patients with pathological conditions. However, there were two neurobiological networks associated with TD which were observed among patients with ADHD or behavioral and substance addiction as follows: one is the neural network implicated in evaluating the value of the reward while the other is the network linked to engagement of prospective thought and future planning. Brain regions involved in these two brain systems during delay discounting task were the prefrontal cortex, insular cortex, ventral striatum, cingulate cortex, parietal cortex, and midbrain. Conclusion: This review generated consistent findings in the neural basis of TD in patients with psychiatric disorders. Such neurobiological differences of TD between patients and healthy subjects may represent the potential pathophysiology of these psychiatric disorders.