シンポジウム
40 社会的ひきこもり（hikikomori）における意思決定の回路・計算・臨床
40 Circuit, computation, and clinic in decision-making with social withdrawal (hikikomori)
座長：疋田 貴俊（大阪大学蛋白質研究所）・本田 直樹（広島大学 統合生命科学研究科） |
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| 2022年6月30日 16:12～16:35 ラグナガーデンホテル 羽衣：東 第8会場
1S08e-01
ひきこもり研究外来による多面的な評価と支援法開発：ひきこもり者の血液バイオマーカー
Blood biomarkers of hikikomori: Development of support system for hikikomori based on findings from the hikikomori-research clinic.
*加藤 隆弘(1)、瀬戸山 大樹(2)、康 東天(2)
1. 九州大学大学院医学研究院精神病態医学、2. 九州大学大学院医学研究院臨床検査医学
*Takahiro A. Kato(1), Daiki Setoyama(2), Dongchon Kang(2)
1. Dept. Neuropsychiatry, Grad.Sch.Med.Sci., Kyushu Univ., Japan, 2. Dept. Clin. Chem. Lab. Med., Grad.Sch.Med.Sci., Kyushu Univ., Japan
Keyword: depression, hikikomori, metabolome analysis, arginine
Background: Hikikomori, pathological social withdrawal, is a crucial mental health issue worldwide. The pathophysiology of hikikomori has not been clarified, and biological traits that objectively characterize it remain unexplored.
Methods: We have established the hikikomori-research system to understand multidimensional aspects of hikikomori based on bio-psycho-social analyses in Kyushu University Hospital. Drug-free patients with hikikomori conditions (n=42) and healthy controls (n=41) were recruited. Psychological assessments for the severity of hikikomori (HQ-25) and depression (PHQ-9 and HAMD-17) were conducted. Blood biochemical tests and plasma metabolome analysis were performed. Based on the integrated information, machine-learning models were created to discriminate cases of hikikomori from healthy controls, predict hikikomori severity, stratify the cases, and identify metabolic signatures that contribute to each model.
Results: Long-chain acylcarnitine levels were remarkably higher in patients with hikikomori; bilirubin, arginine, ornithine, and serum arginase were significantly different in male patients with hikikomori. The discriminative random forest model was highly performant, exhibiting an area under the ROC curve of 0.854. To predict hikikomori severity, a partial least squares PLS-regression model was successfully created with high linearity and practical accuracy. Additionally, blood serum uric acid and plasma cholesterol esters contributed to the stratification of cases.
Conclusions: These findings reveal the blood metabolic signatures of hikikomori, which are key to elucidating the pathophysiology of hikikomori. In addition, we believe that these data will shed new light on considering the biological meanings of social-distance and social isolation in the COVID-19 era. | | 2022年6月30日 16:35～16:58 ラグナガーデンホテル 羽衣：東 第8会場
1S08e-02
思春期ひきこもりの心理行動特性ー日仏比較研究から
Psycho-behavioral characteristics of the Japanese and French Social Withdrawal (Hikikomori) in Adolescents
*濱崎 由紀子(1)
1. 京都女子大学
*Yukiko Hamasaki(1)
1. kyoto women's university
Keyword: Social withdrawal, Hikikomori, Adolescence, Comparative Study
Social withdrawal (hikikomori) has become an internationally recognized phenomenon, yet its psychopathology and related factors remain to be clarified. Hence, we conducted a preliminary comparative study between Japanese and French adolescents with hikikomori to identify universal/culturally dependent psychopathology and related risk factors of hikikomori. Parents of middle school students who underwent outpatient mental health treatment for hikikomori (n=20 in Japan, n=10 in France) and control group parents (n=88 in Japan, n=115 in France) completed the Child Behavior Checklist to evaluate their children’s psycho-behavioral characteristics; the Parental Assessment of Environment and Hikikomori Severity Scales were also used. We compared descriptive statistics and intergroup differences in both the countries. Additionally, multiple regression analyses were conducted using environmental independent variables to identify predictors of hikikomori severity in France and Japan. Comparisons revealed no differences in the psycho-behavioral characteristics of hikikomori between Japan and France. More specifically, both studies showed similarly higher scores for all eight symptom scales (i.e., withdrawn, somatic complaints, anxious/depressed, social problems, thought problems, attention problems, delinquent behavior, and aggressive behavior) in the hikikomori group, with no sequence-specific bias. However, statistical predictors of hikikomori severity in France (lack of communication between parents and child, and lack of communication with the community) differed from those in Japan (lack of communication between parents, and internet overuse). Hikikomori in Japan and France could essentially be considered the same phenomenon; moreover, our findings showed the universal non-specificity and unbiasedness of the psychopathology of hikikomori. This suggests that several mental disorders are involved in the hikikomori phenotype and that behavioral characteristics, including decision-making, need to be further explored. Furthermore, it is important to note that there are cultural differences that accelerate or mitigate the progression of hikikomori. Different strategies within different cultures may be required to prevent its onset and progression. | | 2022年6月30日 16:58～17:21 ラグナガーデンホテル 羽衣：東 第8会場
1S08e-03
心の葛藤の行動データ駆動的解読
Data-Driven Decoding of Psychological Conflict
*本田 直樹(1,2)、古仲 裕貴(1)
1. 広島大学大学院統合生命科学研究科、2. 自然科学研究機構生命創成探究センター
*Honda Naoki(1,2), Yuki Konaka(1)
1. Grad Sch Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan, 2. ExCELLS, NINS
Keyword: Decision-making, Mental conflict, Curiosity, Uncertainty
Animals and humans perceive the external world from sensory systems and make decisions. Generally, they cannot optimally make decisions, due to uncertainty of the environment, as well as the computational capacity of the brain and time constraints in decision-making. Indeed, they do irrational actions involved in psychological conflict. For example, people play lotteries and gamble despite low reward expectations. In this case, we face a dilemma between low expected-reward and curiosity of whether reward is acquired. Thus, understanding how animals control the balance between reward and curiosity is important for elucidation of irrational decision-making process with psychological conflict. However, a method to quantify psychological conflict between reward and curiosity has not been established. In this talk, we will introduce a machine learning approach to decode the reward-curiosity conflict from animal behavioral data. | | 2022年6月30日 17:21～17:44 ラグナガーデンホテル 羽衣：東 第8会場
1S08e-04
Neural mechanisms of reward and aversive signaling
*Tom Macpherson(1), Takatoshi Hikida(1)
1. Institute for Protein Research, Osaka University, Osaka, Japan
Keyword: Reward , Aversion, Nucleus Accumbens, Pavlovian Conditioning
The ability to understand and identify stimuli in our environment that are rewarding (e.g. food/sex) or aversive (e.g. pain/danger) is critical for survival. Indeed, dysfunction of such signaling and its effect on behavior is thought to contribute to several psychiatric conditions, including depression, schizophrenia, and hikikomori (Macpherson & Hikida, 2019, PCN, 73(6): 289-301). The nucleus accumbens (NAc) is a key brain structure within a basal ganglia neurocircuit implicated in limbic processing. Neurons of the NAc can largely be divided into two equal populations, dopamine D1 or D2 receptor-expressing medium spiny neurons (D1/D2-MSNs), that our group has previously demonstrated to be critically involved in signaling of rewarding and aversive stimuli, respectively (Hikida et al., 2010, Neuron, 66(6): 896-907; Hikida, et al.., 3013, PNAS, 110(1): 342-347; Macpherson et al., 2016, Learn. Mem, 23(7): 359-364; Macpherson et al., 2018, Front. Neurosci, 12: 418). However, we do not yet have a precise understanding of how these neurons act to signal rewarding and aversive stimuli and whether they act uniformly as a population. Using miniature microscope-based in-vivo calcium imaging of NAc core D1- and D2-MSNs, we recorded the neural activity of NAc D1- and D2-MSNs during performance of a Pavlovian conditioning task in which rewarding (sucrose) and aversive (airpuff) unconditioned stimuli (US) were repeatedly paired with previously neutral auditory stimuli, until these now conditioned auditory stimuli (CS) were able to induce conditioned responses in the form of augmented (reward-paired) or suppressed (aversion-paired) licking responses at a reward delivery spout. We revealed the existence of several subpopulations of NAc neurons that were activated or inhibited by the delivery of rewarding or aversive stimuli. Interestingly, many of these subpopulations comprised both D1- and D2-MSNs, which appear to act collaboratively to signal a specific type of CS or US. Our findings suggest remarkable heterogeneity in the responses of NAc core D1- and D2-MSNs and indicate that the previous roles ascribed to these neurons (uniformly controlling reward and aversive signaling, respectively) have been oversimplified. This new understanding of the precise roles of specific NAc subpopulations provides novel insight into reward and aversion signaling in the brain and may help to better identify its dysfunction in psychiatric conditions such as depression and hikikomori. | | 2022年6月30日 17:44～18:07 ラグナガーデンホテル 羽衣：東 第8会場
1S08e-05
ネガティブな選択を回避する意思決定の神経機構
Neural mechanisms for the strategy to avoid a choice that leads to negative outcome in reward-based decision-making
*西岡 忠昭(1)、トム マクファーソン(2)、濱口 航介(3)、疋田 貴俊(2)
1. マウントサイナイ医科大学、2. 大阪大学、3. 京都大学
*Tadaaki Nishioka(1), Tom Macpherson(2), Kosuke Hamaguchi(3), Takatoshi Hikida(2)
1. Icahn School of Medicine at Mount Sinai, 2. Osaka University, 3. Kyoto University
Keyword: nucleus accumbens, decision making, visual discrimination, basal ganglia
Goal-directed behavior can be guided not only by strategies based upon the acquisition of a desireable outcomes, but also by those aimed at reducing undesirable outcomes. Indeed, we are often faced with situations in which the correct behavioral response to acquire a desired outcome is unknown or ambigious, but prior experience of failure can be used to avoid inappropriate responses. The important role that negative outcomes play in guiding avoidance behavior has long been appreciated, dating back from Thorndike’s law of effect to the more recent proposal of loss aversion in the field of behavioral economics. However, the neural mechanisms that underly the use of such avoidance-based strategies for goal-directed behavior are still unclear, and studies to date have primarily focused investigating the reinforcement of behaviors that directly result in rewarding outcomes.
The nucleus accumbens (NAc), in particular the NAc Core subregion, is suggested to play an important role in goal-directed decision making via its role in linking information processing concerning outcome values with that related to goal selection. NAc medium spiny projection neurons (MSN), the major neuron type, are typically anatomically divided into two roughly equal subpopulations; dopamine D1 receptor-expressing MSNs (D1-MSN) that project predominantly to the ventral pallidum (VP) and substantia nigra pars reticulata (SNr), and dopamine D2 receptor-expressing MSNs (D2-MSN) that project predominantly to the VP. While previous studies have demonstrated NAc D1-MSNs to be implicated in reward-related learning and D2-MSNs to be involved in aversion-related learning and behavioral flexibility, the specific role that NAc D1- and D2-MSNs may play in avoidance-based behavior are less clear.
To isolate and measure the ability for avoidance-based goal-directed behavior, we designed a novel visual discrimination-based cue-guided avoidance learning (VD-Avoid) task in which mice were required to avoid an instrumental response at a visual cue known to be associated with a reward omission, and instead respond at a random cue that had not previously been associated with any outcome in order to acquire a liquid reward. In a series of experiments, miniature microscope in vivo calcium imaging was used to investigate the precise activity patterns of D1- and D2-MSNs during the VD-Avoid task, while chemogenetic and time-specific optogenetic silencing of NAc D1-MSN or D2-MSNs during the same task were used to establish whether inactivation of these two subpopulations impairs the utilization of avoidance-based behavioral strategies. Our findings indicate that while D1-MSNs are activated by rewarding outcomes and contribute to the ongoing performance of behaviors directly resulting in rewarding outcomes, D2-MSNs are activated by reward omission and are necessary for avoidance of responses resulting in non-rewarded outcomes. | | | |
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