Finding the biological roots of the pathological social withdrawal known as “hikikomori.”


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Summary: Hikikomori is a mental health disorder identified as pathological social withdrawal. Researchers have discovered a number of biomarkers in the blood associated with hikikomori.

Source: Kyushu University

Researchers at Kyushu University have identified a number of key blood biomarkers of pathological social withdrawal, known as hikikomori.

Based on their findings, the team was able to differentiate between healthy individuals and hikikomori patients, as well as determine the severity of the disease.

According to Japan’s Ministry of Health, Labor and Welfare, hikikomori is a condition in which people do not leave their homes and isolate themselves from society and family for a period of more than six months.

Also known as “pathological social withdrawal,” hikikomori is estimated to affect more than a million people in Japan today.

Although historically identified as a Japanese culture-bound syndrome, evidence over the past few decades has shown that it is evolving into a global phenomenon, with some fearing that the COVID-19 pandemic is sparking a global wave of hikikomori sufferers.

In 2013, Kyushu University Hospital established the world’s first Hikikomori Research Outpatient Clinic, hoping to develop patient support systems through biological, psychological, and social understanding of the disease.

In a report published in Dialogues in clinical neuroscienceLead researcher Takahiro A. Kato of Kyushu University School of Medicine explains that while the sociological basis of the disease is carefully studied, there are major gaps in understanding of the biological aspects of hikikomori.

“Mental illnesses such as depression, schizophrenia, and social anxiety disorder are occasionally observed in hikikomori individuals. However, our research to date shows that it is not that simple and that it is a complex condition with an overlap of various psychiatric and non-psychiatric elements,” explains Kato.

“Understanding what’s happening biologically will help us a lot in identifying and treating hikikomori.”

The team performed biochemical blood tests and collected data on the plasma metabolome – small molecules found in the blood, such as sugars, amino acids and proteins – from 42 untreated hikikomori people and compared them to data from 41 healthy volunteers. In total, data for 127 molecules were analyzed.

“Some of our key findings showed that in the blood of men with hikikomori, ornithine levels and serum arginase activity were higher, while bilirubin and arginine levels were lower,” says the paper’s first author Daiki Setoyama.

“Long-chain acylcarnitine levels were higher in both male and female patients. Additionally, when this data was further analyzed and categorized, we were able to distinguish between healthy and hikikomori individuals and even predict severity.”

Ornithine is an amino acid that is produced from the amino acid arginine with the help of the enzyme arginase. These molecules are critical to many bodily functions, including blood pressure regulation and the urea cycle.

Bilirubin is formed when the liver breaks down red blood cells and is often used as a marker of proper liver function. Patients with major depression and seasonal depression have been reported to have lower levels of bilirubin in their blood.

Although historically identified as a Japanese culture-bound syndrome, evidence over the past few decades has shown that it is evolving into a global phenomenon, with some fearing that the COVID-19 pandemic is sparking a global wave of hikikomori sufferers. The image is in the public domain

Finally, acylcarnitines play an important role in supplying the brain with energy. Its levels drop when patients with depression take selective serotonin reuptake inhibitors.

However, patients with hikikomori differ from patients with depression in that only the long-chain acylcarnitines in hikikomori are elevated while short-chain acylcarnitines remain the same.

Kato says: “Identifying the biomarkers of hikikomori is the first step in uncovering the biological roots of the disease and linking them to its severity. We hope these results will lead to better specialized treatments and support for hikikomori.”

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“Many questions remain, including understanding the root causes behind these biomarkers. Today, hikikomori is spreading worldwide, so we need to conduct international research to understand the similarities and differences between patients with hikikomori worldwide,” he concludes.

About this news from psychology research

Author: press office
Source: Kyushu University
Contact: Press Office – University of Kyushu
Picture: The image is in the public domain

Original research: Open access.
“Blood Metabolic Signatures of Hikikomori, Pathological Social Withdrawal” by Daiki Setoyama et al. Dialogues in clinical neuroscience


Blood metabolic signatures of hikikomori, pathological social withdrawal


A severe form of pathological social withdrawal, “hikikomori,” recognized in Japan, is spreading worldwide and becoming a global health problem. The pathophysiology of hikikomori has not yet been elucidated, and its biological features remain unexplored.


Drug-free patients with hikikomori (n= 42) and healthy controls (n= 41) were recruited. Psychological studies on the severity of hikikomori and depression were conducted. Biochemical blood tests and plasma metabolome analyzes were performed. Based on the integrated information, machine learning models were built to distinguish cases of hikikomori from healthy controls, predict hikikomori severity, stratify the cases, and identify metabolic signatures that contribute to each model.


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 performed well, showing an area under the ROC curve of 0.854 (confidential interval = 0.648-1.000). To predict the severity of hikikomori, a partial least squares PLS regression model was successfully constructed with high linearity and practical accuracy. In addition, serum uric acid and plasma cholesterol esters contributed to case stratification.


These results demonstrate the blood metabolic signatures of hikikomori, which are key to elucidating the pathophysiology of hikikomori and are also useful as an index for monitoring the course of treatment for rehabilitation.

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