RESUMO
The hypothalamus is key to body homeostasis, including regulating cortisol, testosterone, vasopressin, and oxytocin hormones, modulating aggressive behavior. Animal studies have linked the morphology and function of the hypothalamus to aggression and affiliation, with a subregional pattern reflecting the functional division between the hypothalamic nuclei. We explored the relationship between hypothalamic subunit volumes in violent offenders with (PSY-V) and without (NPV) a psychotic disorder, and the association with psychopathy traits. 3T MRI scans (n = 628, all male 18-70 years) were obtained from PSY-V, n = 38, NPV, n = 20, non-violent psychosis patients (PSY-NV), n = 134, and healthy controls (HC), n = 436. The total hypothalamus volume and its eleven nuclei were delineated into five subunits using Freesurfer v7.3. Psychopathy traits were assessed with Psychopathy Checklist-revised (PCL-R). ANCOVAs and linear regressions were used to analyze associations with subunit volumes. Both groups with a history of violence exhibited smaller anterior-superior subunit volumes than HC (NPV Cohen's d = 0.56, p = 0.01 and PSY-V d = 0.38, p = 0.01). There were no significant differences between HC and PSY-NV. PCL-R scores were positively associated with the inferior tubular subunit on a trend level (uncorrected p = 0.045, Cohen's d = 0.04). We found distinct hypothalamic subunit volume reductions in persons with a history of violence independent of concomitant psychotic disorder but not in persons with psychosis alone. The results provide further information about the involvement of the hypothalamus in aggression, which ultimately may lead to the development of targeted treatment for the clinical and societal challenge of aggression and violent behavior.
RESUMO
Toxoplasma gondii (TOXO) infection typically results in chronic latency due to its ability to form cysts in the brain and other organs. Latent toxoplasmosis could promote innate immune responses and impact brain function. A large body of evidence has linked TOXO infection to severe mental illness (SMI). We hypothesized that TOXO immunoglobulin G (IgG) seropositivity, reflecting previous infection and current latency, is associated with increased circulating neuron-specific enolase (NSE), a marker of brain damage, and interleukin-18 (IL-18), an innate immune marker, mainly in SMI. We included 735 patients with SMI (schizophrenia or bipolar spectrum) (mean age 32 years, 47% women), and 518 healthy controls (HC) (mean age 33 years, 43% women). TOXO IgG, expressed as seropositivity/seronegativity, NSE and IL-18 were measured with immunoassays. We searched for main and interaction effects of TOXO, patient/control status and sex on NSE and IL-18. In the whole sample as well as among patients and HC separately, IL-18 and NSE concentrations were positively correlated (p < 0.001). TOXO seropositive participants had significantly higher NSE (3713 vs. 2200 pg/ml, p < 0.001) and IL-18 levels (1068 vs. 674 pg/ml, p < 0.001) than seronegative participants, and evaluation within patients and HC separately showed similar results. Post-hoc analysis on cytomegalovirus and herpes simplex virus 1 IgG status showed no associations with NSE or IL-18 which may suggest TOXO specificity. These results may indicate ongoing inflammasome activation and neuronal injury in people with TOXO infections unrelated to diagnosis.
Assuntos
Toxoplasma , Toxoplasmose , Humanos , Feminino , Adulto , Masculino , Inflamassomos , Interleucina-18 , Imunoglobulina GRESUMO
OBJECTIVE: Auditory mismatch negativity (MMN) impairment is a candidate endophenotype in psychotic disorders, yet the genetic underpinnings remain to be clarified. Here, we examined the relationships between auditory MMN and polygenic risk scores (PRS) for individuals with psychotic disorders, including schizophrenia spectrum disorders (SSD) and bipolar disorder (BD) and in healthy controls (HC). METHODS: Genotyped and clinically well-characterized individuals with psychotic disorders (n = 102), including SSD (n = 43) and BD (n = 59), and HC (n = 397) underwent a roving MMN paradigm. In addition MMN, we measured the memory traces of the repetition positivity (RP) and the deviant negativity (DN), which is believed to reflect prediction encoding and prediction error signals, respectively. SCZ and BD PRS were computed using summary statistics from the latest genome-wide association studies. The relationships between the MMN, RP, and DN and the PRSs were assessed with linear regressions. RESULTS: We found no significant association between the SCZ or BD PRS and grand average MMN in the psychotic disorders group or in the HCs group (all p > 0.05). SCZ PRS and BD PRS were negatively associated with RP in the psychotic disorders group (ß = -0.46, t = -2.86, p = 0.005 and ß = -0.29, t = -0.21, p = 0.034, respectively). No significant associations were found between DN and PRS. CONCLUSION: These findings suggest that genetic variants associated with SCZ and BD may be associated with MMN subcomponents linked to predictive coding among patients with psychotic disorders. Larger studies are needed to confirm these findings and further elucidate the genetic underpinnings of MMN impairment in psychotic disorders.