Researchers have discovered a number of biomarkers in the blood associated with Hikikomori


Researchers at Kyushu University have identified a number of key blood biomarkers for 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 Japan’s Ministry of Health, Labour, and Welfare, hikikomori is a condition in which individuals do not leave their dwelling and isolate themselves away from society and family for a period exceeding six months.

Also identified as “pathological social withdrawal,” hikikomori is estimated to afflict more than one million people in Japan today.

While it has been historically identified as a Japanese culture-bound syndrome, evidence over the last few decades has shown that it is becoming a global phenomenon, with some fearing the COVID-19 pandemic catalyzing a global wave of hikikomori patients.

In 2013, the Kyushu University Hospital established the world’s first outpatient clinic for hikikomori research 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 Neuroscience, lead researcher Takahiro A. Kato of Kyushu University’s Faculty of Medical Sciences explains that while the sociological underpinnings of the condition are carefully studied, major gaps remain in the 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 past research shows that it is not that simple, and that it is a complex condition with overlaps of different psychiatric and non-psychiatric elements,” explains Kato.

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

The team conducted blood biochemical tests and collected data on the plasma metabolome – small molecules found in blood such as sugars, amino acids, and proteins – from 42 unmedicated hikikomori individuals and compared it with 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,” states first author of the paper Daiki Setoyama.

“In both men and women patients, long-chain acylcarnitine levels were higher. Moreover, when this data was further analyzed and categorized, we were able to distinguish between healthy and hikikomori individuals, and even predict its 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 bodily functions, including blood pressure regulation and the urea cycle.

Bilirubin is made when the liver breaks down red blood cells and is often used as a marker for proper liver function. Patients with major depression and seasonal affective disorder have been reported to have lower blood bilirubin levels.

Finally, acylcarnitines play an important role in supplying energy to the brain. Its levels decrease 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 are elevated in hikikomori whereas short-chain acylcarnitines remain the same.

Says Kato, “Identifying the biomarkers of hikikomori is the first step in uncovering the biological roots of the condition and connecting them to its severity. We hope these findings will lead to better specialized treatments and support for hikikomori.”

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

Hikikomori is a term that originated in Japan and was used as early as the 1990s [1] to describe people who socially withdraw from society or the phenomenon of their doing so [2]. Other terms, such as socially withdrawn youth [3] or hidden youth [4], have been used to describe this phenomenon in other places.

Individuals with this condition seclude themselves at home for six months or longer, refrain from going to work or school, and do not maintain friendships [5]. These individuals live reclusive lifestyles and usually have face-to-face interactions only with family members [6]. Although the common definition of hikikomori refers to self-seclusion for the mentioned extended period of time, some researchers and organizations have suggested a lower threshold of three months of self-seclusion to aid in early detection and treatment [3, 6, 7]. While Hamasaki et al. [8] have suggested hikikomori as a spectrum continuum of social withdrawal (hikikomori) severity.

Five reviews of research on hikikomori were identified through a literature search. One was a systematic review and the other four were narrative reviews. The aim of the systematic review was to consolidate available research evidence on hikikomori, not to raise research questions or hypotheses [9].

Similar topics discussed in the reviews were the definition, etiology, and diagnosis of hikikomori, and interventions to treat the condition. Three definitions were mentioned in the reviews, with the major differences between them arising from the inclusion of individuals with psychiatric conditions [10, 11] or of those who might leave their home but avoid social interactions [10].

There was also further categorical differentiation into primary and secondary hikikomori, namely, those without psychiatric comorbidity and those with psychiatric comorbidities, respectively [9]. In the reviews, the following similar etiologies were described: adverse or traumatic childhood experiences, bullying, peer rejection, dysfunctional family dynamics, changes in the labor market [11, 12], and overprotective parenting styles [9, 11, 12].

The differences were: psychiatric condition [12], introverted personality, shyness, parental attachment issues, dysfunctional family dynamics, parental psychiatric conditions, poor academic performance and high expectations, technology, globalization, the Internet, the breakdown of social cohesion [13], and the overdependence of children [9]. Common issues of diagnosis mentioned in the reviews were the difficulty of differentiating hikikomori from psychiatric disorders, because those exhibiting socially isolating behaviors could potentially suffer from any one of a spectrum of psychiatric illnesses [12, 13].

There is also uncertainty over whether a psychiatric condition is the cause of hikikomori symptoms or if hikikomori leads to a psychiatric condition [10]. The following Interventions were commonly reported in the reviews: psychotherapy, pharmacological treatment, family therapy, nidotherapy, milieu therapy with the provision of a safe environment for hikikomori, support groups with the avoidance of labeling, rigid schedules, or categorization of role identity [9, 12, 13].

Less commonly reported were the following interventions: group therapy, horse-assisted therapy, communal cooking, online platforms [13], Chinese medicine, narrative therapy, naikan therapy, and engagement with social workers [9]. The following are additional interventions not mentioned in the reviews: animal-assisted therapy [14], jogging therapy [15], and the online mobile game Pokémon Go [16].

Many current interventions in hikikomori care brought up in case reports seem to lack a focal factor to target in order to achieve a recovery. The majority also fail to use a theoretical framework to guide the components of the intervention. It would be beneficial to apply a psychosocial recovery model to the task of developing methods of caring for hikikomori because such a model provides a comprehensive structure and an organized approach to guide a researcher or service provider in determining what areas need to be assessed or measured, or in identifying areas that could be focused on for care [17].

To the best of our knowledge, in only one study [18] has a psychological recovery model or framework for hikikomori care been applied. In their study, Yokoyama et al. [18] combined concepts from dialectic behavior therapy and from the mental health recovery model used by Mental Health America to design online modules for hikikomori, which uses elements of self-realization, caring for oneself, acquiring change, and future planning in the intervention.

Other psychosocial recovery frameworks have not been used in hikikomori interventions. Saito [19] has proposed conceptual models on the power operates in the “hikikomori system” and the vicious circles preventing treatment for hikikomori; however, they were not focusing on psychosocial recovery. After reviewing different psychosocial recovery frameworks such as the Recovery Model [20], Psychosocial Rehabilitation Model [21], Strength Based Model [22], Coach-based Model [23], and the CHIME framework for personal recovery [24], it was concluded that all of the frameworks had something beneficial to offer for hikikomori care, such as a non-linear approach, a focus on the positive attributes of an individual or holistic care.

However, it seems most fitting to apply the CHIME framework for personal recovery to hikikomori care because of the following two reasons. First, the framework was synthesized for psychosocial recovery and hikikomori are in need of psychosocial recovery from a behavioral and etiological perspective. Second, some domains and dimensions of the framework shed light on what hikikomori lack, such as connectedness, identity, or meaningful social roles, which provide accuracy in targeting specific areas requiring re-establishing for hikikomori.

There is awareness that the CHIME framework has been designed for personal recovery in the area of mental health; therefore, some may hypothesize that it may be more applicable to people who have experienced mental health challenges; whereas young people with experience of primary social withdrawal may not have been diagnosed with any mental health issues or exhibited any mental health syndromes. However, the domains of the CHIME framework seem broad and encompassing which may possibly extend its application to individuals without psychiatric disorders but in need of psychosocial recovery.

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Source: Kyushu University


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