Contents lists available at ScienceDirect Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad Social withdrawal in major depressive disorder: a case-control study of hikikomori in japan Alan R. Teo a,b,c, ⁎ , Sarah Nelson a , Wynn Strange a , Hiroaki Kubo d , Ryoko Katsuki d , Keita Kurahara d , Shigenobu Kanba d , Takahiro A. Kato d, ⁎ a VA Portland Health Care System, HSR&D Center to Improve Veteran Involvement in Care (CIVIC), 3710 SW US Veterans Hospital Rd (R&D 66), Portland, OR 97239- 2964, USA b Oregon Health & Science University, Department of Psychiatry, 3181 SW Sam Jackson Park Rd (Multnomah Pavilion, Room 2316), Portland, OR 97239-3098, USA c Oregon Health & Science University and Portland State University, School of Public Health, 506 SW Mill St., Suite 450 (OMPH-SCH), Portland, OR 97201, USA d Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan ARTICLE INFO Keywords: Social withdrawal Social isolation Hikikomori Major depressive disorder ABSTRACT Background: Social withdrawal is a feature of a number of psychiatric disorders including major depressive disorder (MDD), yet research examining social withdrawal as a feature of MDD is rare. Methods: This was a retrospective case-control study. Participants (N = 67) were recruited through an out- patient clinic at an academic medical center in Japan. Major depressive disorder (MDD) and social withdrawal were established with the Structured Clinical Interview for DSM-IV Axis I Disorders and a semi-structured psychiatric interview, respectively. Participants also completed self-report measures. Results: We classified 24 participants as cases (MDD with social withdrawal) and 43 participants as controls (MDD without social withdrawal). Cases, on average, were more likely to have lower education level, prior episodes of depression, and higher suicidal ideation at baseline than controls. In unadjusted regression models, cases had significantly less social connection, less reward dependence, less self-directedness, and higher scores on scales of modern-type depression and hikikomori. In adjusted regression models, associations between social withdrawal and hikikomori (p<0.01) and reward dependence (p = 0.03) remained significant. Limitations: The sample was limited in size and drawn from a single site. Conclusions: In patients with MDD, social withdrawal may have subtle associations with clinical symptoms, social connection, and personality traits. Developing a better understanding of social withdrawal's phenotype in depression requires more in-depth examination. 1. Background Major depressive disorder (MDD) is highly prevalent and extremely debilitating disease. Globally, it is the largest contributor to burden of disease among all psychiatric and neurological diseases, and by 2020 is projected to be the number two contributor among all medical condi- tions.(Global Burden of Disease Study 2013 Collaborators) One feature of depression that contributes to its impact on patients’ quality of life is social withdrawal. Social withdrawal may be a sign of depression itself, but can also persist after presumed recovery from depression and be an indicator of residual occupational or other functional impairment. (Porcelli et al., 2019) In Japan, individuals experiencing prolonged periods of social withdrawal are a major societal concern, so much so that it has given rise to the term hikikomori to denote severe cases of social withdrawal.(Kato et al., 2016) In our prior research examining hikikomori, we identified MDD as a commonly co-occurring condition. (Teo et al., 2015) For many years, studies examining social withdrawal have focused on patients with schizophrenia, whereas studies examining social withdrawal as a feature of depression are rare. Moreover, it is unclear if social withdrawal provides an indication of severity of depression or other distinguishing clinical features. Recent research, however, has begun to suggest that psychological characteristics and personality traits—such as indirect expression of emotions and passive ag- gressiveness—may relate to difficulties in coping with social interac- tion, and those features may be distinctive among patients with severe https://doi.org/10.1016/j.jad.2020.06.011 Received 9 December 2019; Received in revised form 29 April 2020; Accepted 5 June 2020 ⁎ Corresponding author at: Core Investigator, VA Portland Health Care System, HSR&D Center to Improve Veteran Involvement in Care (CIVIC) Associate Professor, Oregon Health & Science University, 3710 SW US Veterans Hospital Rd (R&D 66), Portland, OR 97239-2964, USA E-mail addresses: teoa@ohsu.edu (A.R. Teo), takahiro@npsych.med.kyushu-u.ac.jp (T.A. Kato). Journal of Affective Disorders 274 (2020) 1142–1146 Available online 07 June 2020 0165-0327/ Published by Elsevier B.V. T