Study examines pediatric traumatic brain injury as a potential risk factor for psychotic disorders or symptoms

In a recent study posted to the medRxiv* preprint server, scientists conduct a meta-analysis to assess whether pediatric traumatic brain injury (pTBI) is a potential risk factor for psychotic disorders or symptoms.

Study: Pediatric traumatic brain injury as a risk factor for psychosis and psychotic symptoms: a systematic review and meta-analysis. Image Credit: Karan Bunjean /

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

The long-term neurological effects of TBIs

TBI has been associated with an increased risk of adverse neuropsychiatric outcomes such as anxiety, depression, personality change, post-traumatic stress symptoms, neurodegenerative disorders, and cognitive impairment in adults.

Although several cases of post-TBI psychosis have been reported, the extent of its prevalence is not clear. It is important to understand whether TBI could be considered a reliable risk factor for psychosis. 

There are several contradictory reviews on the incidence of psychotic disorders or symptoms due to brain injury. For example, one review reported that TBI significantly increases the risk of psychotic disorders in the general population; however, this observation was contradicted by other studies.

Likewise, a case-control study indicated an association between TBI and schizophrenia; however, this association was linked with a genetic predisposition.

It is important to determine the possible link between pTBI and psychosis. Several developmental models on psychosis, such as the psychosis-proneness-persistence-impairment and developmental risk factor models, have revealed that adverse experiences impair typical neurodevelopment, which may influence the subsequent development of psychotic disorders.

It is assumed that pTBI could be a vital neurodevelopmental risk factor that influences the incidence of psychosis. However, this risk factor has not been previously subjected to systematic review and meta-analysis. 

About the study

The present systematic review and meta-analysis included studies that recruited participants of any age or gender with a diagnosis of pTBI. All participants were diagnosed with pTBI based on standardized screening tools, medical records reviews, clinical diagnosis, and structured clinical interviews. Relevant studies were obtained from various databases, such as PsycINFO and MEDLINE.

TBIs with severity ranging from mild, such as a concussion, to severe were included in this review. Schizophrenia and related psychotic disorders, as well as psychotic symptoms like psychosis-risk syndromes and psychotic-like experiences were considered.

All peer-reviewed studies, including retrospective or prospective cohort studies, randomized or non-randomized controlled trials, and case-control studies, were included in the current analysis. 

Study findings

A total of 850 articles were identified after the initial screening of the databases, 10 of which were ultimately included in the review, as they fulfilled all eligibility criteria.

Among these ten studies, five were based on case-control designs, and the other five adopted cohort designs. These studies were conducted in the United States, Canada, Denmark, Norway, Finland, and Sweden.

Based on the findings of a pooled sample size of 479,686, pTBI was robustly associated with the prevalence of psychotic disorders and symptoms. However, a moderate between-study heterogeneity was observed. The robustness of the association was validated based on outliers, study quality, and excessively influential studies.

Based on the findings from the developmental models, pTBI could be a plausible risk factor for psychosis. This finding is supported by the fact that pTBI influences neurodevelopment, which influences the incidence of psychosis.

Psychotic symptoms are associated with higher rates of early-life bullying, which indicate the possibility of a reverse or reciprocal association between psychotic spectrum phenomena and acquired brain injury through victimization violence.

Strengths and limitations

The key strength of this study is the use of systematic procedures to obtain relevant studies. Sensitivity analyses were used to assess the robustness of the findings. Importantly, this meta-analysis is available online to ensure openness and reproducibility. 

Nevertheless, the current study has some limitations, including the consideration of heterogeneous studies with respect to their outcomes and the life-stage of measured psychosis outcome, There is also a possibility of publication bias, which could affect the accuracy of the estimate.

None of the studies considered in this review indicated the severity of brain injury. Therefore, the dose-response relationship between TBI and psychosis could not be established.


The current meta-analysis provided evidence supporting the role of pTBI as a risk factor for psychosis. Nevertheless, there is a possibility of reverse causality or shared risk factor pathways.

In the future, a well-designed prospective cohort study is needed to identify the relationships between psychotic symptoms, pTBI, and any potential confounding and/or mediating factors. Furthermore, more research related to the specific location and type of TBI must be conducted better to understand the etiological relationship between pTBI and psychosis.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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