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.