This shows a teen.
Changes in glutamate levels in the ACC in those individuals at high risk of psychosis, and the relationship between this and the effects of bullying in adolescents has remained unclear. Credit: Neuroscience News

Brains of Bullied Teens Show Chemical Shifts Linked to Psychosis

Summary: A new study revealed a significant link between bullying in adolescents and the early stages of psychosis, associated with lower levels of the neurotransmitter glutamate in the brain’s anterior cingulate cortex (ACC), a region critical for emotion regulation. This finding underscores the potential of targeting glutamate levels for pharmaceutical interventions to mitigate the risk of developing psychotic disorders.

The research utilized magnetic resonance spectroscopy to measure changes in ACC glutamate levels, finding that bullying correlates with increased subclinical psychotic experiences. Highlighting the importance of anti-bullying programs and mental health support, the study opens new avenues for both pharmacological and non-pharmacological interventions aimed at preventing psychosis in bullied adolescents.

Key Facts:

  1. Adolescents experiencing bullying show lower levels of glutamate in the ACC, linking to early signs of psychosis.
  2. The study indicates glutamate as a potential target for interventions to prevent psychotic disorders in bullied youths.
  3. Anti-bullying initiatives and mental health support are crucial for reducing psychosis risk and promoting well-being among adolescents.

Source: University of Tokyo

Researchers have found that adolescents being bullied by their peers are at greater risk of the early stages of psychotic episodes and in turn experience lower levels of a key neurotransmitter in a part of the brain involved in regulating emotions.

The finding suggests that this neurotransmitter — a chemical messenger that transmits nerve impulses for communication by a nerve cell — may be a potential target for pharmaceutical interventions aimed at reducing the risk of psychotic disorders.

Psychosis is a mental state characterized by loss of contact with reality, incoherent speech and behavior, and typically hallucinations and delusions seen in psychiatric disorders such as schizophrenia.

Recent studies investigating links between neurological and psychiatric features of certain disorders have found that individuals who experience their first episode of psychosis or have schizophrenia that remains treatable, have lower-than-normal levels of glutamate, a neurotransmitter in the brain’s anterior cingulate cortex (ACC) region.

The ACC is known to play a crucial role in regulating emotions, decision-making and cognitive control, while glutamate is the most abundant neurotransmitter in the brain and is involved in a wide range of functions, including learning, memory and mood regulation.

Alterations in glutamate levels have been implicated in various psychiatric disorders, including schizophrenia, depression and anxiety, and so measuring ACC glutamate levels can provide valuable insights into the mechanisms of the nervous system underlying these disorders and their treatment.

However, until now, changes in glutamate levels in the ACC in those individuals at high risk of psychosis, and the relationship between this and the effects of bullying in adolescents has remained unclear.

And so researchers at the University of Tokyo used magnetic resonance spectroscopy, or MRS, a type of radiological imaging applied to depict brain structure and function, to measure glutamate levels in the ACC region of Japanese adolescents.

They then measured the glutamate levels at a later point, allowing them to assess changes over time, and compare these changes to experiences with bullying or lack thereof, as well as with any intention on the part of those experiencing bullying to seek help.

Bullying victimization was tracked via questionnaires completed by the adolescents. The researchers then used formalized psychiatric measurement to assess experiences of bullying victimization based on those questionnaires, such as tallying the frequency and assessing the nature of events involving physical or verbal aggression, and also capturing their impact on overall mental health.

They found that bullying was associated with higher levels of subclinical psychotic experiences in early adolescence — those symptoms come close to psychosis but do not meet the full criteria for a clinical diagnosis of a psychotic disorder, such as schizophrenia.

These symptoms or experiences can include hallucinations, paranoia or radical alterations in thinking or behavior and can have a significant impact on well-being and functioning, even in the absence of a psychotic disorder diagnosis.

“Studying these subclinical psychotic experiences is important for us to understand the early stages of psychotic disorders and for identifying individuals who may be at increased risk for developing a clinical psychotic illness later on,” said Naohiro Okada, lead author of the study and project associate professor at the University of Tokyo’s International Research Center for Neurointelligence (a research center under Japan’s World Premier International Research Center Initiative program).

Crucially, the researchers found that higher levels of these subclinical psychotic experiences were associated with lower levels of anterior cingulate glutamate in early adolescence.

“First and foremost, anti-bullying programs in schools that focus on promoting positive social interactions and reducing aggressive behaviors are essential for their own sake and to reduce the risk of psychosis and its subclinical precursors,” said Okada.

“These programs can help create a safe and supportive environment for all students, reducing the likelihood of bullying and its negative consequences.”

Another potential intervention is to provide support and resources for adolescents who have experienced bullying victimization. This might include counseling services, peer support groups and other mental health resources that can help adolescents cope with the negative effects of bullying and develop resilience.

While Okada’s group has identified a potential target of pharmacological interventions, he added that nonpharmacological interventions such as cognitive behavioral therapy or mindfulness-based interventions may also serve to target this neurotransmitter imbalance.


This work is a part of the Tokyo TEEN Cohort Study and was supported by MEXT/JSPS KAKENHI, JST Moonshot R&D, AMED and NIH. This work was also partially supported by WPI-IRCN, UTIAS, and Open Access funding provided by The University of Tokyo.

About this neurodevelopment and psychosis research news

Author: Joseph Krisher
Source: University of Tokyo
Contact: Joseph Krisher – University of Tokyo
Image: The image is credited to Neuroscience News

Original Research: Open access.
Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization” by Naohiro Okada et al. Molecular Psychiatry


Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization

Previous studies reported decreased glutamate levels in the anterior cingulate cortex (ACC) in non-treatment-resistant schizophrenia and first-episode psychosis. However, ACC glutamatergic changes in subjects at high-risk for psychosis, and the effects of commonly experienced environmental emotional/social stressors on glutamatergic function in adolescents remain unclear.

In this study, adolescents recruited from the general population underwent proton magnetic resonance spectroscopy (MRS) of the pregenual ACC using a 3-Tesla scanner. We explored longitudinal data on the association of combined glutamate-glutamine (Glx) levels, measured by MRS, with subclinical psychotic experiences.

Moreover, we investigated associations of bullying victimization, a risk factor for subclinical psychotic experiences, and help-seeking intentions, a coping strategy against stressors including bullying victimization, with Glx levels. Finally, path analyses were conducted to explore multivariate associations.

For a contrast analysis, gamma-aminobutyric acid plus macromolecule (GABA+) levels were also analyzed. Negative associations were found between Glx levels and subclinical psychotic experiences at both Times 1 (n = 219, mean age 11.5 y) and 2 (n = 211, mean age 13.6 y), as well as for over-time changes (n = 157, mean interval 2.0 y).

Moreover, effects of bullying victimization and bullying victimization × help-seeking intention interaction effects on Glx levels were found (n = 156). Specifically, bullying victimization decreased Glx levels, whereas help-seeking intention increased Glx levels only in bullied adolescents.

Finally, associations among bullying victimization, help-seeking intention, Glx levels, and subclinical psychotic experiences were revealed. GABA+ analysis revealed no significant results.

This is the first adolescent study to reveal longitudinal trajectories of the association between glutamatergic function and subclinical psychotic experiences and to elucidate the effect of commonly experienced environmental emotional/social stressors on glutamatergic function.

Our findings may deepen the understanding of how environmental emotional/social stressors induce impaired glutamatergic neurotransmission that could be the underpinning of liability for psychotic experiences in early adolescence.

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