Low-Density Lipoprotein Cholesterol Is a Possible Blood Biomarker of Schizoid Personality Traits among Females.

Lower serum levels of low-density lipoprotein cholesterol (LDL-C) have been suggested to indicate higher suicide risk and various psychiatric symptoms. Previously, we reported that lower serum LDL-C levels are associated with loneliness, social phobia, isolated life with little social support, and lower trust in others among young non-clinical females. Thus, we hypothesize that schizoid personality traits may be associated with lower serum LDL-C. We here verified this hypothesis using non-clinical data and clinical data with schizophrenia. Using the database from the Midlife in Japan (MIDJA), a cohort of residents living in Tokyo, we analyzed whether schizoid-related interpersonal characteristics were associated with LDL-C. In addition, we assessed the association between blood biomarkers including LDL-C and schizoid personality traits in 101 adult non-clinical volunteers. Finally, we evaluated the interaction between LDL-C and social decision making of patients with schizophrenia. In female non-clinical volunteers, serum LDL-C level was a predictive factor and negatively correlated with schizoid personality traits. Female patients with schizophrenia, whose serum LDL-C levels were lower, tended not to trust other females. The present findings suggest that LDL-C may influence schizoid personality traits in females, which provide a basis for further investigation into the biological aspects of schizoid personality disorder.

Plasma acetylcholine and nicotinic acid are correlated with focused preference for photographed females in depressed males: an economic game study.

Interpersonal difficulties are often observed in major depressive disorder (MDD), while the underlying psychological and biological mechanisms have not yet been elucidated. In the present case-control study, a PC-based trust game was conducted for 38 drug-free MDD patients and 38 healthy controls (HC). In the trust game, participants invested money in a partner (trusting behaviors), and also rated each partner's attractiveness (preference for others). In addition, blood biomarkers including metabolites were measured. Both MDD and HC males exhibited more trusting behaviors compared to females. MDD males' preference for ordinary-attractive partners (lay-person photographs) was lower than HC males, whereas their preference for high-attractive females (fashion-model photographs) was similar levels to HC males. This tendency in MDD males could reflect a "focused (narrowed) preference for females". As for blood biomarker analysis, the levels of 37 metabolites including acetylcholine, AMP, GMP, nicotinic acid and tryptophan were significantly different between two groups. Interestingly, among male participants, acetylcholine and nicotinic acid were negatively correlated with the level of focused preference for photographed females. In sum, we have revealed some behavioral, psychological and biological traits of trusting behaviors and preference for others especially in MDD males. Larger studies should be conducted to validate our preliminary findings.

Socio-Ecological Hypothesis of Reconciliation: Cultural, Individual, and Situational Variations in Willingness to Accept Apology or Compensation.

The main goal of the present research is to examine socio-ecological hypothesis on apology and compensation. Specifically, we conducted four studies to test the idea that an apology is an effective means to induce reconciliation in a residentially stable community, whereas compensation is an effective means in a residentially mobile community. In Studies 1, 2a, and 2b, American and Japanese participants (national difference in mobility; Study 1) or non-movers and movers (within-nation difference in mobility; Studies 2a and 2b) imagined the situations in which they were hurt by their friends and rated to what extent they would be willing to maintain their friendships upon receipt of apology or compensation. The results showed that compensation was more effective in appeasing residentially mobile people (i.e., Americans and movers) than stable people (i.e., Japanese and non-movers), while apology was slightly more effective appeasing residentially stable people than residentially mobile people (significant in Study 1; not significant in Studies 2a and 2b). In Study 3, by conducting an economics game experiment, we directly tested the hypothesis that mobility would impair the effectiveness of apology and enhance the effectiveness of compensation. The results again partially supported our hypothesis: In the high mobility condition, compensation increased one's willingness to continue the relationship with the offender, when compared to willingness in the low mobility condition. The importance of socio-ecological perspective on the forgiveness literature is discussed.

Can Brain Waves Really Tell If a Product Will Be Purchased? Inferring Consumer Preferences From Single-Item Brain Potentials.

Recent research has shown that event-related brain potentials (ERPs) recorded while participants view lists of different consumer goods can be modulated by their preferences toward these products. However, it remains largely unknown whether ERP activity specific to a single consumer item can be informative about whether or not this item will be preferred in a shopping context. In this study, we examined whether single-item ERPs could reliably predict consumer preferences toward specific consumer goods. We recorded scalp EEG from 40 participants while they were viewing pictures of consumer goods and we subsequently asked them to indicate their preferences for each of these items. Replicating previous results, we found that ERP activity averaged over the six most preferred products was significantly differentiated from ERP activity averaged across the six least preferred products for three ERP components: The N200, the late positive potential (LPP) and positive slow waves (PSW). We also found that using single-item ERPs to infer behavioral preferences about specific consumer goods led to an overall predictive accuracy of 71%, although this figure varied according to which ERPs were targeted. Later positivities such as the LPP and PSW yielded relatively higher predictive accuracy rates than the frontal N200. Our results suggest that ERPs related to single consumer items can be relatively accurate predictors of behavioral preferences depending on which type of ERP effects are chosen by the researcher, and ultimately on the level of prediction errors that users choose to tolerate.

Development and validation of the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22).

AIM: Understanding premorbid personality is important, especially when considering treatment selection. Historically, the premorbid personality of patients with major depression in Japan was described as Shuchaku-kishitsu [similar to Typus melancholicus], as proposed by Shimoda in the 1930s. Since around 2000, there have been increased reports in Japan of young adults with depression who have had premorbid personality differing from the traditional type. In 2005, Tarumi termed this novel condition 'dysthymic-type depression,' and more recently the condition has been called Shin-gata/Gendai-gata Utsu-byo [modern-type depression (MTD)]. We recently developed a semi-structured diagnostic interview to evaluate MTD. Development of a tool that enables understanding of premorbid personality in a short time, especially at the early stage of treatment, is desirable. The object of this study was to develop a self-report scale to evaluate the traits of MTD, and to assess the scale's psychometric properties, diagnostic accuracy, and biological validity. METHODS: A sample of 340 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis. Diagnostic accuracy of the MTD traits was compared against a semi-structured interview. RESULTS: The questionnaire contained 22 items across three subscales, thus we termed it the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22). Internal consistency, test-retest reliability, and convergent validity were all satisfactory. Among patients with major depression, the area under the curve was 0.757 (sensitivity of 63.1% and specificity of 82.9%) and the score was positively correlated with plasma tryptophan. CONCLUSION: The TACS-22 possessed adequate psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its ability to support clinical assessment of MTD is warranted.

Blood biomarkers of Hikikomori, a severe social withdrawal syndrome.

Hikikomori, a severe form of social withdrawal syndrome, is a growing social issue in Japan and internationally. The pathophysiology of hikikomori has not yet been elucidated and an effective treatment remains to be established. Recently, we revealed that avoidant personality disorder is the most common comorbidity of hikikomori. Thus, we have postulated that avoidant personality is the personality underpinning hikikomori. First, we herein show relationships between avoidant personality traits, blood biomarkers, hikikomori-related psychological features, and behavioural characteristics assessed by a trust game in non-hikikomori volunteers. Avoidant personality traits were negatively associated with high-density lipoprotein cholesterol (HDL-C) and uric acid (UA) in men, and positively associated with fibrin degeneration products (FDP) and high sensitivity C-reactive protein (hsCRP) in women. Next, we recruited actual individuals with hikikomori, and compared avoidant personality traits, blood biomarkers, and psychological features between individuals with hikikomori and age-matched healthy controls. Individuals with hikikomori had higher avoidant personality scores in both sexes, and showed lower serum UA levels in men and lower HDL-C levels in women compared with healthy controls. This is the first report showing possible blood biomarkers for hikikomori, and opens the door to clarify the underlying biological pathophysiology of hikikomori.

Neural signals of selective attention are modulated by subjective preferences and buying decisions in a virtual shopping task.

We investigated whether well-known neural markers of selective attention to motivationally-relevant stimuli were modulated by variations in subjective preference towards consumer goods in a virtual shopping task. Specifically, participants viewed and rated pictures of various goods on the extent to which they wanted each item, which they could potentially purchase afterwards. Using the event-related potentials (ERP) method, we found that variations in subjective preferences for consumer goods strongly modulated positive slow waves (PSW) from 800 to 3000 milliseconds after stimulus onset. We also found that subjective preferences modulated the N200 and the late positive potential (LPP). In addition, we found that both PSW and LPP were modulated by subsequent buying decisions. Overall, these findings show that well-known brain event-related potentials reflecting selective attention processes can reliably index preferences to consumer goods in a shopping environment. Based on a large body of previous research, we suggest that early ERPs (e.g. the N200) to consumer goods could be indicative of preferences driven by unconditional and automatic processes, whereas later ERPs such as the LPP and the PSW could reflect preferences built upon more elaborative and conscious cognitive processes.

Solving the second-order free rider problem in a public goods game: An experiment using a leader support system.

Punishment of non-cooperators-free riders-can lead to high cooperation in public goods games (PGG). However, second-order free riders, who do not pay punishment costs, reduce the effectiveness of punishment. Here we introduce a "leader support system," in which one group leader can freely punish group followers using capital pooled through the support of group followers. In our experiment, participants engage in three stages repeatedly: a PGG stage in which followers decide to cooperate for their group; a support stage in which followers decide whether to support the leader; and a punishment stage in which the leader can punish any follower. We compare a support-present condition with a no-support condition, in which there is an external source for the leader's punishment. The results show that punishment occurs more frequently in the support-present condition than the no-support condition. Within the former, both higher cooperation and higher support for a leader are achieved under linkage-type leaders-who punish both non-cooperators and non-supporters. In addition, linkage-type leaders themselves earn higher profits than other leader types because they withdraw more support. This means that leaders who effectively punish followers could increase their own benefits and the second-order free rider problem would be solved.

Internet addiction and self-evaluated attention-deficit hyperactivity disorder traits among Japanese college students.

AIM: Internet addiction (IA), also referred to as Internet use disorder, is a serious problem all over the world, especially in Asian countries. Severe IA in students may be linked to academic failure, attention-deficit hyperactivity disorder (ADHD), and forms of social withdrawal, such as hikikomori. In this study, we performed a survey to investigate the relation between IA and ADHD symptoms among college students. METHODS: Severity of IA and ADHD traits was assessed by self-report scales. Subjects were 403 college students (response rate 78%) who completed a questionnaire including Young's Internet Addiction Test (IAT) and the Adult ADHD Self-Report Scale-V1.1. RESULTS: Out of 403 subjects, 165 were male. The mean age was 18.4 ± 1.2 years, and mean total IAT score was 45.2 ± 12.6. One hundred forty-eight respondents (36.7%) were average Internet users (IAT < 40), 240 (59.6%) had possible addiction (IAT 40-69), and 15 (3.7%) had severe addiction (IAT ≥ 70). Mean length of Internet use was 4.1 ± 2.8 h/day on weekdays and 5.9 ± 3.7 h/day on the weekend. Females used the Internet mainly for social networking services while males preferred online games. Students with a positive ADHD screen scored significantly higher on the IAT than those negative for ADHD screen (50.2 ± 12.9 vs 43.3 ± 12.0). CONCLUSION: Our results suggest that Internet misuse may be related to ADHD traits among Japanese youth. Further investigation of the links between IA and ADHD is warranted.

Multidimensional anatomy of 'modern type depression' in Japan: A proposal for a different diagnostic approach to depression beyond the DSM-5.

Japan's prototype of depression was traditionally a melancholic depression based on the premorbid personality known as shuchaku-kishitsu proposed by Mitsuzo Shimoda in the 1930s. However, since around 2000, a novel form of depression has emerged among Japanese youth. Called 'modern type depression (MTD)' by the mass media, the term has quickly gained popularity among the general public, though it has not been regarded as an official medical term. Likewise, lack of consensus guidelines for its diagnosis and treatment, and a dearth of scientific literature on MTD has led to confusion when dealing with it in clinical practice in Japan. In this review article, we summarize and discuss the present situation and issues regarding MTD by focusing on historical, diagnostic, psychosocial, and cultural perspectives. We also draw on international perspectives that begin to suggest that MTD is a phenomenon that may exist not only in Japan but also in many other countries with different sociocultural and historical backgrounds. It is therefore of interest to establish whether MTD is a culture-specific phenomenon in Japan or a syndrome that can be classified using international diagnostic criteria as contained in the ICD or the DSM. We propose a novel diagnostic approach for depression that addresses MTD in order to combat the current confusion about depression under the present diagnostic systems.

Relationship between trusting behaviors and psychometrics associated with social network and depression among young generation: a pilot study.

Maladaptive social interaction and its related psychopathology have been highlighted in psychiatry especially among younger generations. In Japan, novel expressive forms of psychiatric phenomena such as "modern-type depression" and "hikikomori" (a syndrome of severe social withdrawal lasting for at least six months) have been reported especially among young people. Economic games such as the trust game have been utilized to evaluate real-world interpersonal relationships as a novel candidate for psychiatric evaluations. To investigate the relationship between trusting behaviors and various psychometric scales, we conducted a trust game experiment with eighty-one Japanese university students as a pilot study. Participants made a risky financial decision about whether to trust each of 40 photographed partners. Participants then answered a set of questionnaires with seven scales including the Lubben Social Network Scale (LSNS)-6 and the Patient Health Questionnaire (PHQ)-9. Consistent with previous research, male participants trusted partners more than female participants. Regression analysis revealed that LSNS-family (perceived support from family) for male participants, and item 8 of PHQ-9 (subjective agitation and/or retardation) for female participants were associated with participants' trusting behaviors. Consistent with claims by social scientists, our data suggest that, for males, support from family was negatively associated with cooperative behavior toward non-family members. Females with higher subjective agitation (and/or retardation) gave less money toward males and high attractive females, but not toward low attractive females in interpersonal relationships. We believe that our data indicate the possible impact of economic games in psychiatric research and clinical practice, and validation in clinical samples including modern-type depression and hikikomori should be investigated.

Neuron-glia interaction as a possible glue to translate the mind-brain gap: a novel multi-dimensional approach toward psychology and psychiatry.

Neurons and synapses have long been the dominant focus of neuroscience, thus the pathophysiology of psychiatric disorders has come to be understood within the neuronal doctrine. However, the majority of cells in the brain are not neurons but glial cells including astrocytes, oligodendrocytes, and microglia. Traditionally, neuroscientists regarded glial functions as simply providing physical support and maintenance for neurons. Thus, in this limited role glia had been long ignored. Recently, glial functions have been gradually investigated, and increasing evidence has suggested that glial cells perform important roles in various brain functions. Digging up the glial functions and further understanding of these crucial cells, and the interaction between neurons and glia may shed new light on clarifying many unknown aspects including the mind-brain gap, and conscious-unconscious relationships. We briefly review the current situation of glial research in the field, and propose a novel translational research with a multi-dimensional model, combining various experimental approaches such as animal studies, in vitro & in vivo neuron-glia studies, a variety of human brain imaging investigations, and psychometric assessments.

Minocycline, a microglial inhibitor, reduces 'honey trap' risk in human economic exchange.

Recently, minocycline, a tetracycline antibiotic, has been reported to improve symptoms of psychiatric disorders and to facilitate sober decision-making in healthy human subjects. Here we show that minocycline also reduces the risk of the 'honey trap' during an economic exchange. Males tend to cooperate with physically attractive females without careful evaluation of their trustworthiness, resulting in betrayal by the female. In this experiment, healthy male participants made risky choices (whether or not to trust female partners, identified only by photograph, who had decided in advance to exploit the male participants). The results show that trusting behaviour in male participants significantly increased in relation to the perceived attractiveness of the female partner, but that attractiveness did not impact trusting behaviour in the minocycline group. Animal studies have shown that minocycline inhibits microglial activities. Therefore, this minocycline effect may shed new light on the unknown roles microglia play in human mental activities.

Minocycline modulates human social decision-making: possible impact of microglia on personality-oriented social behaviors.

BACKGROUND: Microglia, one of the glial cells, play important roles in various brain pathologies including psychiatric disorders. In addition, microglia have recently been proved to monitor synaptic reactions via direct-touching even in normal brain. Human microglia may modulate various social/mental functions, while microglial social/mental roles remain unresolved especially in healthy humans. There is no known drug with the specific effect of modulating microglia. Therefore, using minocycline, a tetracycline antibiotic and the most famous microglial inhibitor, is one of the best alternative approaches to clarify microglial functions on human social/mental activities. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a double-blind randomized trial of trust game, a monetary decision-making experiment, with ninety-nine human adult males who decided how much to trust an anonymous partner after a four-day administration of minocycline. Our previous pilot trial indicated a positive effect of minocycline, while the underlying mechanisms were not clarified. Therefore, in this trial with larger samples, we additionally measured the effects of anxiety and personality. The monetary score in trust game was significantly lower in the minocycline group. Interestingly, participants' ways of decision-making were significantly shifted; cooperativeness, one component of personality, proved to be the main modulating factor of decision-making in the placebo group, on the other hand, the minocycline group was mainly modulated by state anxiety and trustworthiness. CONCLUSIONS/SIGNIFICANCE: Our results suggest that minocycline led to more situation-oriented decision-making, possibly by suppressing the effects of personality traits, and furthermore that personality and social behaviors might be modulated by microglia. Early-life events may activate human microglia, establish a certain neuro-synaptic connection, and this formation may determine each human's personality and personality- oriented social behaviors in later life. To explore these mechanisms, further translational research is needed. TRIAL REGISTRATION: UMIN clinical trial center UMIN000004803.

Effects of facial expression and gaze direction on approach-avoidance behaviour.

Humans must coordinate approach-avoidance behaviours with the social cues that elicit them, such as facial expressions and gaze direction. We hypothesised that when someone is observed looking in a particular direction with a happy expression, the observer would tend to approach that direction, but that when someone is observed looking in a particular direction with a fearful expression, the observer would tend to avoid that direction. Twenty-eight participants viewed stimulus faces with averted gazes and happy or fearful expressions on a computer screen. Participants were asked to grasp (approach) or withdraw from (avoid) a left- or right-hand button depending on the stimulus face's expression. The results were consistent with our hypotheses about avoidance responses, but not with respect to approach responses. Links between social cues and adaptive behaviour are discussed.

Does minocycline, an antibiotic with inhibitory effects on microglial activation, sharpen a sense of trust in social interaction?

RATIONALE: Minocycline has long been applied to various infectious diseases as a tetracycline antibiotic and recently has found new application in the treatment of brain diseases such as stroke and multiple sclerosis. In addition, minocycline has also been suggested as an effective drug for psychiatric diseases. These suggestions imply that minocycline may modulate our mental activities, while the underlying mechanism remains to be clarified. OBJECTIVE: To investigate how minocycline influences human mental activity, we experimentally examined how minocycline works on human social decision making in a double-blind randomized trial. METHODS: Forty-nine healthy volunteers were administered minocycline or placebo over four days, after which they played (1) a trust game, in which they decided how much to trust an anonymous partner, and (2) a dictator game, in which they decided how to divide resources between themselves and an anonymous partner. RESULTS: The minocycline group did not display increased trusting behavior or more altruistic resource allocation. In fact, the minocycline group displayed a slight reduction in trusting behavior. However, the minocycline group did show a strong positive correlation between the degree of risk taking in the trust game and in a separate evaluation of others' trustworthiness, whereas the placebo group showed no such correlation. CONCLUSIONS: These results suggest that minocycline led to more rational decision-making strategies, possibly by increasing emotion regulation. Since minocycline is a well-known inhibitor of microglial activation, our findings may open a new optional pathway for treating mental states in which a component of rational decision making is impaired.

Cultural grounding of regret: regret in self and interpersonal contexts.

The purpose of this study was to explore cultural similarities and differences in regret, focusing on distinctions between interpersonal and self-situations, and between action and inaction regrets. Japanese and American undergraduates were asked to describe regrets experienced in interpersonal and self-situations. We found that both situational and cultural contexts influenced the likelihood of regretting inactions over actions. Participants were more likely to recall inaction regrets in self-situations than in interpersonal situations, and that the likelihood of recalling inaction regrets was more pronounced for Americans than for Japanese. Furthermore, we examined the intensity of the regret. Whereas American students experienced regret as intense as that of Japanese students in self-situations, Japanese students experienced regret more strongly than American students in interpersonal situations. Detailed content analysis also showed that individuals experienced regret in ways consistent with cultural values. The situational and cultural grounding of regret is discussed.

Polling the face: prediction and consensus across cultures.

Previous work has shown that individuals agree across cultures on the traits that they infer from faces. Previous work has also shown that inferences from faces can be predictive of important outcomes within cultures. The current research merges these two lines of work. In a series of cross-cultural studies, the authors asked American and Japanese participants to provide naïve inferences of traits from the faces of U.S. political candidates (Studies 1 and 3) and Japanese political candidates (Studies 2 and 4). Perceivers showed high agreement in their ratings of the faces, regardless of culture, and both sets of judgments were predictive of an important ecological outcome (the percentage of votes that each candidate received in the actual election). The traits predicting electoral success differed, however, depending on the targets' culture. Thus, when American and Japanese participants were asked to provide explicit inferences of how likely each candidate would be to win an election (Studies 3-4), judgments were predictive only for same-culture candidates. Attempts to infer the electoral success for the foreign culture showed evidence of self-projection. Therefore, perceivers can reliably infer predictive information from faces but require knowledge about the target's culture to make these predictions accurately.

[Regret in individual and group decision making].

We compared the regret that people report in individual and group decision-making in two experimental studies. In the first study, thirty-nine participants were randomly assigned to either an individual or a group decision-making condition, and then failed on an assigned task. They were asked to rate their regret and cognitive variables of controllability, internal and external factors related to their failure. Participants in the group decision condition, reported less regret than in the individual decision condition. In the second study, we added individual and group decision conditions where the participants heard others express regret. Fifty-eight participants played and lost the same game in the four conditions. In the group decision condition, we found that the participants who heard others express regret reported more regret than the participants who did not hear others' regret. These findings suggest that the expression of regret enhances others' regret. Some implications of the findings are discussed.