Schizophrenia with Violence Linked to Reduced Left Frontal Gray Matter, Higher TSH

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New data demonstrates that patients with violence in schizophrenia had lower gray matter volume in the left frontal pole and greater thyroid-stimulating hormone (TSH) levels than patients who were not exhibiting violence.¹

Frontal lobe gray matter changes are linked to violence in schizophrenia.² However, not a lot is known about the relationship between thyroid dysfunction and frontal lobe gray matter volume, so investigators sought to assess whether TSH was associated with frontal lobe gray matter volume in male patients with violent schizophrenia.¹

“To the best of our knowledge, this is the first study to investigate the relationship between thyroid hormone levels and frontal lobe [gray matter volume] associated with violence in male patients with [violence in schizophrenia],” wrote investigators, led by Tao Yu, from Anhui Mental Health Center at Hefei Fourth People's Hospital in People's Republic of China.

The study included 29 male patients with violent schizophrenia and 26 without violence who were enrolled in a general psychiatry ward at the Hefei Fourth People’s Hospital in Anhui from December 2021 to March 2022. Violent behavior was defined as aggression toward objects, oneself, and others. Patients were included if they were male, right-handed, did not drink or smoke, and had no neurological diseases; they were excluded if they had substance dependence, history of severe head trauma, mental retardation, and MRI contraindications.

As part of their regular treatment regimen, participants took risperidone (n = 19), paliperidone (n = 8), olanzapine (n = 11), sulfamethoxide (n = 8), clozapine (n = 16), ziprasidone (n = 5) piropilone (n = 5) aripiprazole (n = 3), quetiapine (n = 2), and perphenazine (n = 2). The antipsychotics used were switched to the equivalent chlorpromazine.

Twenty-four hours after admission, patients with violence had their aggression evaluated with the 5-point Modified Overt Aggression Scale, which contained 4 subscales: verbal aggression, aggression against objects, physical aggression against oneself, and physical aggression against others. Participants also had a fasting venous blood sample collected on the morning of the second day of admission so investigators could analyze the concentrations of triiodothyronine (T3), thyroxine (T4), TSH, free triiodothyronine (fT3), and free thyroxine (fT4). Moreover, participants underwent structural resonance imaging (sMRI).

The study discovered significant differences in age and total brain volume between patients with and without violence. For patients with violence, the older they were, the lower total brain volume they had. The research did not find differences between the dosage of chlorpromazine in patients with and without violence.

Investigators saw patients with violence had greater TSH levels than patients without violence.

“[This suggests] that alterations in TSH levels may be involved in [violence in schizophrenia] through changing the frontal pole [gray matter volume],” investigators wrote. “The underlying mechanisms might be that the normal levels of TSH are crucial to the regulation of neuronal differentiation and synaptic plasticity.”

The frontal lobe controls cognitive functions, such as decision-making and problem-solving. When gray matter volume becomes abnormal, individuals experience persecutory delusions that are closely associated with violence.

Investigators wrote high TSH levels might be harmful to the brain structure, resulting in lower levels of T3 and T4 in the brain which are closely related to neurotransmitter release, protein synthesis, and gene transportation. They theorized an inadequate amount of T3 and T4 could impact the gray matter volume in the frontal lobe, although the study found T3, T4, fT3, and fT4 did not differ between patients with and without violence.

Additionally, patients with violence had reduced gray matter volume in the left frontal pole role, compared with those without violence. Even after controlling for total brain volume and age, the reduced gray matter volume in the left frontal pole was still linked to violence in schizophrenia.

“These findings provide valuable insights into the important role of reduced frontal [gray matter volume] in violence among patients with schizophrenia,” investigators wrote. “Additionally, the practical implications are that several potential factors that may lead to increased levels of TSH associated with violence in schizophrenia should be heeded to reduce the risk of violence in schizophrenia. Therefore, alterations in thyroid hormone levels in [violence in schizophrenia] patients should be emphasized.”

References

1. ^{Yu T, Pei W, Zhang X, Deng C. Associations Between Thyroid Hormones Levels and Gray Matter Volume of Frontal Lobe Involved into Violence in Male Schizophrenia Patients. Neuropsychiatr Dis Treat. 2024 Nov 18;20:2169-2175. doi: 10.2147/NDT.S481875. PMID: 39583013; PMCID: PMC11583757.}
2. ^{Gou N, Lu J, Zhang S, Liang X, Guo H, Sun Q, Zhou J, Wang X. Structural Deficits in the Frontotemporal Network Associated With Psychopathic Traits in Violent Offenders With Schizophrenia. Front Psychiatry. 2022 Apr 12;13:846838. doi: 10.3389/fpsyt.2022.846838. PMID: 35492688; PMCID: PMC9039223.}