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

Summary: Hikikomori is a mental health disorder that is defined as pathological social withdrawal. Researchers have discovered a number of blood biomarkers 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 distinguish between healthy individuals and hikikomori patients as well as determine the severity of the condition.

According to the Japanese Ministry of Health, Labor, and Welfare, a hikikomori is a condition in which individuals do not leave their home and isolate themselves from society and the family for a period of more than six months.

Also known as “pathological social withdrawal,” hikikomori is estimated to affect more than 1 million people in Japan today.

Although it has historically been identified as a syndrome associated with Japanese culture, evidence over the past few decades has shown that it has become a global phenomenon, with some fearing the COVID-19 pandemic spurring a global wave of hikikomori patients.

In 2013, Kyushu University Hospital established the world’s first hikikomori research outpatient clinic in hopes of developing support systems for patients through biological, psychological, and social understanding of the condition.

In a report published in Dialogues in Clinical Neuroscienceprincipal investigator Takahiro A. Kato of Kyushu University’s School of Medical Sciences explains that while the social underpinnings of the condition are carefully studied, there are still significant gaps in understanding the biological aspects of hikikomori.

Mental illnesses such as depression, schizophrenia, and social anxiety disorder are sometimes seen in hikikomori. However, our previous research shows that it is not that simple, and that it is a complex condition with different psychological and non-psychological elements overlapping,” Cato explains.

“Understanding what happens biologically will help us greatly in identifying and treating hikikomori.”

The team conducted blood biochemical tests and collected data on plasma metabolites — small molecules found in the blood such as sugars, amino acids and proteins — from 42 untreated hikikomori and compared it to data from 41 healthy volunteers. In total, 127 molecules data were analyzed.

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

“In both male and female patients, levels of long-chain acylcarnitine were higher. Furthermore, when these data were further analyzed and categorized, we were able to distinguish between healthy individuals and hikikomori individuals, and even predict their severity.”

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

Bilirubin is formed when the liver breaks down red blood cells and is often used as a marker of healthy liver function. Patients with major depression and seasonal affective disorder have been reported to have low serum bilirubin levels.

This shows a woman sitting alone on the dock
Although it has historically been identified as a syndrome associated with Japanese culture, evidence over the past few decades has shown that it has become a global phenomenon, with some fearing the COVID-19 pandemic spurring a global wave of hikikomori patients. The image is in the public domain

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

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

Kato says, “Identification of hikikomori biomarkers is the first step in uncovering the biological roots of the condition and correlating it with its severity. We hope that these findings will lead to specialized treatments and better support for hikikomori.”

see also

This shows a woman sitting under a tree

“Many questions remain, including understanding the root causes behind these biomarkers. Today, hikikomori are spread all over the world, and therefore, we must conduct international investigations to understand the similarities and differences between hikikomori patients globally,”

About this research psychology news

author: press office
source: Kyushu University
Contact: Press Office – Kyushu University
picture: The image is in the public domain

original search: open access.
Metabolic signatures of hikikomori in the blood, pathological social withdrawalBy Daiki Setoyama et al. Dialogues in Clinical Neuroscience


Metabolic signatures of hikikomori in the blood, pathological social withdrawal


A severe form of pathological social withdrawal, hikikomori, was recognized in Japan, has spread worldwide, and has become a global health problem. The pathophysiology of hikikomori has not been elucidated, and its biological features remain undiscovered.


hikikomori patients (n= 42) and healthy controls (n= 41) They were recruited. Psychological assessments of hikikomori severity and depression were performed. Blood biochemical examinations and plasma metabolism analysis were performed. Building on the integrated information, machine learning models were generated to distinguish hikikomori cases from healthy controls, predict hikikomori severity, stratify cases, and identify metabolic signatures that contribute to each model.


Levels of long-chain acylcarnitine were significantly higher in hikikomori patients. Serum bilirubin, arginine, ornithine and arginase were significantly different in male patients with hikikomori. The discriminative random forest model was high-performance, showing an area under the ROC curve of 0.854 (secret interval = 0.648–1,000). To predict hikikomori sharpness, 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 the stratification of cases.


These results reveal metabolic signatures of hikikomori in the blood, which are fundamental to elucidating the pathophysiology of hikikomori and also useful as an indicator for monitoring the course of rehabilitation therapy.