Aim Hikikomori, a form of severe social withdrawal, is an emerging issue in mental health, for which validated measurement tools are lacking. The object was to develop a self‐report scale of hikikomori, and assess its psychometric properties and diagnostic accuracy.MethodsA sample of 399 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis; diagnostic accuracy was compared against a semi‐structured diagnostic interview.ResultsThe Hikikomori Questionnaire contained 25 items across three subscales representing socialization, isolation, and emotional support. Internal consistency, test–retest reliability, and convergent validity were all satisfactory. The area under the curve was 0.86 (95% confidence interval, 0.80–0.92). A cut‐off score of 42 (out of 100) was associated with a sensitivity of 94%, specificity of 61%, and positive predictive value of 17%.ConclusionThe 25‐item Hikikomori Questionnaire (HQ‐25) possesses robust psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its psychometric properties and ability to support clinical assessment of hikikomori is warranted.

Evaluating the severity of depression (SOD), especially suicidal ideation (SI), is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD)-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ)-9. However, these evaluation systems have relied on a person’s subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS), and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB), betaine, citrate, creatinine, and gamma-aminobutyric acid (GABA)) are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In addition, modification of these metabolites by diet and/or medications may be a novel therapeutic target for depression. To clarify these aspects, clinical trials measuring metabolites before/after interventions should be conducted. Larger cohort studies including non-clinical subjects are also warranted to clarify our pilot findings.

Background: BDNF and Ca 2ϩ mobilization is important for microglial function. Results: We showed BDNF elevates intracellular Ca 2ϩ through TRPC3 channels. Conclusion: TRPC3 is important for BDNF suppression of microglial activation. Significance: TRPC3 might be important for the treatment of psychiatric disorders.

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.

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.