Olaoluwa Okusaga

Toxoplasma gondii antibody titers and history of suicide attempts in patients with schizophrenia

Toxoplasma gondii (T. gondii) a widespread neurotropic parasite, has been previously associated with schizophrenia and more recently with suicidal behavior. However, no previous study has examined the association of T. gondii with suicidal behavior in schizophrenia patients. 950 individuals diagnosed with schizophrenia by SCID were recruited from the Munich area of Germany. Solid-enzyme immunoassay methods were used to measure IgG plasma antibodies to T. gondii, other neurotropic pathogens and gliadin. Logistic regression models were developed to analyze the association of T. gondii seropositivity or serointensity with history of suicidal behavior. In those younger than the median age of the sample, 38, T. gondii serointensity was associated with history of suicidal behavior (p = 0.02), while in the older patients the relationship was not significant (p = 0.21). Seropositivity was also associated with history of suicide attempt in younger patients, odds ratio 1.59 (95% CI 1.06 to 2.40), p = 0.03. Seropositivity for CMV (p = 0.22), HSV-1 (p = 0.36) and gliadin (p = 0.92) was not related to history of suicide attempt in the entire sample or any age subgroup. T. gondii serology might become, with interaction with vulnerability genes, a candidate biomarker for a subgroup of schizophrenia patients prone to attempting suicide.

Toxoplasma gondii Immunoglobulin G Antibodies and Nonfatal Suicidal Self-Directed Violence

OBJECTIVE The primary aim was to relate Toxoplasma gondii seropositivity and serointensity to scores on the self-rated Suicide Assessment Scale (SUAS-S). Another aim was to reevaluate the previously reported positive association between T gondii serointensity and a history of nonfatal suicidal self-directed violence. METHOD This cross-sectional, observational study compared T gondii serointensity and seropositivity in plasma from 54 adult suicide attempters (inpatients at Lund University Hospital, Lund, Sweden) and 30 adult control subjects (randomly selected from the municipal population register in Lund, Sweden) recruited between 2006 and 2010. The potential of patients and controls for self-directed violence was evaluated with the SUAS-S. Psychiatric diagnoses were made according to DSM-IV criteria. Plasma samples were tested for immunoglobulin G antibodies to T gondii, cytomegalovirus, and herpes simplex virus type 1. Data were analyzed using multivariable logistic regression to investigate the association between T gondii serointensity or seropositivity and a history of nonfatal suicidal self-directed violence; multivariable linear regression was used to explore the relationship between T gondii serointensity or seropositivity and the SUAS-S. Both regression models included sex, age, and body mass index as covariates. RESULTS Seropositivity of T gondii (adjusted odds ratio [OR] = 7.12; 95% CI, 1.66-30.6; P = .008) and serointensity of T gondii (adjusted OR = 2.01; 95% CI, 1.09-3.71; P = .03) were positively associated with a history of nonfatal suicidal self-directed violence. Seropositivity of T gondii was associated with higher SUAS-S scores, a relationship significant for the whole sample (P = .026), but not for suicide attempters only. No significant associations with other pathogens were identified. CONCLUSIONS These results are consistent with previous reports on the association between T gondii infection and nonfatal suicidal self-directed violence. Confirming these results in future large longitudinal studies and including suicide as an outcome may lead to novel individualized approaches in suicide prevention.

Seasonality of suicidal behavior

A seasonal suicide peak in spring is highly replicated, but its specific cause is unknown. We reviewed the literature on suicide risk factors which can be associated with seasonal variation of suicide rates, assessing published articles from 1979 to 2011. Such risk factors include environmental determinants, including physical, chemical, and biological factors. We also summarized the influence of potential demographic and clinical characteristics such as age, gender, month of birth, socioeconomic status, methods of prior suicide attempt, and comorbid psychiatric and medical diseases. Comprehensive evaluation of risk factors which could be linked to the seasonal variation in suicide is important, not only to identify the major driving force for the seasonality of suicide, but also could lead to better suicide prevention in general.

Decreased interleukin-10 serum levels in first-episode drug-naïve schizophrenia: Relationship to psychopathology

Many lines of findings support the hypothesis of the inflammation-related pathways in the multifactorial pathogenesis of schizophrenia (SZ). Interleukin-10 (IL-10), a potential anti-inflammatory cytokine, was found to be altered in chronic patients with SZ. The aim of this study was to assess the serum levels of IL-10 in first-episode and drug-naïve (FEDN) patients with SZ and its relationships with the psychopathological parameters. Serum IL-10 levels were analyzed using established procedures in 128 FEDN patients with SZ and 62 healthy controls. Schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) with cognitive factor derived from the five factor model of the PANSS. Compared to the healthy controls, the patients exhibited a significant decrease in IL-10 levels. Serum IL-10 was inversely correlated with the PANSS negative symptom, as well as with the PANSS cognitive factor subscores in patients. Our results suggested that decreased IL-10 may be implicated in the negative symptom and cognitive impairment at the acute stage of schizophrenia episode.

Elevated gliadin antibody levels in individuals with schizophrenia

Abstract Objectives. We aimed to replicate, in a larger sample and in a different geographical location, the previously reported elevation of anti-gliadin IgG antibodies in schizophrenia. Methods. A total of 950 adults with schizophrenia (severity assessed by PANSS) and 1000 healthy controls were recruited in the Munich metropolitan area. Anti-gliadin IgG antibodies were analyzed with ELISA. χ2-tests and logistic regression were used to analyze the association of schizophrenia with elevated anti-gliadin IgG. A multivariable general linear model was used to compare anti-gliadin IgG levels between patients and controls. Results. The odds ratio of having elevated anti-gliadin IgG antibodies in the schizophrenia group was 2.13 (95% CI 1.57 to 2.91, p < 0.0001). Mean anti-gliadin IgG levels were higher in schizophrenia patients (0.81 ± 0.79 vs. 0.52 ± 0.56, t = 9.529, df = 1,697, p < 0.0001) and the difference persisted after adjusting for potential confounders. Conclusions. Our study, limited by its cross sectional design, confirmed an association between anti-gliadin IgG antibodies and schizophrenia. Replication in longitudinal studies, clinical trials of gluten free diet and mechanistic investigation could lead to novel treatment targets, preventive and therapeutic considerations in schizophrenia.

The interplay between BDNF and oxidative stress in chronic schizophrenia

Neurodegenerative processes may be involved in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF), the most widely distributed neurotrophin and oxidative stress (OS) may be critical for several pathological manifestations of neurodegenerative disorders. Accumulating evidence suggests that both BDNF and OS may be involved in the pathophysiology of schizophrenia. However, the possible interaction between BDNF and OS has been under-investigated. Serum BDNF, plasma malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were analyzed using established procedures in 164 chronic medicated schizophrenia and 50 healthy controls. Schizophrenic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) with cognitive and depressive factors derived from the five factor model of the PANSS. Compared to the control group, the patients exhibited a significant decrease in BDNF levels, in the activities of SOD and GSH-Px but a significant increase in MDA levels. In patients, but not in controls, we observed a significant negative correlation between BDNF and SOD. Furthermore, the interaction between BDNF and CAT was associated with the PANSS cognitive factor, and the interaction between BDNF and GSH-Px with the PANSS depressive factor. Both decreased BDNF levels and OS may be implicated in the pathophysiology of chronic schizophrenia. Their inverse association only in the schizophrenia group may reflect a pathological mechanism involving an interaction of oxidative damage and neurotrophin dysfunction. Moreover, OS may interact with the BDNF system to influence the clinical symptoms and cognitive impairment in schizophrenia, which is line with the neurodevelopmental hypothesis of schizophrenia.

Accelerated Aging in Schizophrenia Patients: The Potential Role of Oxidative Stress

Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.

Association of seropositivity for influenza and coronaviruses with history of mood disorders and suicide attempts.

Abstract Background Anecdotal reports of mood disorder following infection with common respiratory viruses with neurotropic potential have been in existence since the last century. Nevertheless, systematic studies on the association between these viruses and mood disorders are lacking. Methods Influenza A, B and coronavirus antibody titers were measured in 257 subjects with recurrent unipolar and bipolar disorder and healthy controls, by SCID. Pearsons χ² tests and logistic regression models were used to analyze associations between seropositivity for coronaviruses, influenza A and B viruses and the following: a) history of recurrent mood disorders b) having attempted suicide in the past c) uni- vs. bi-polarity and d) presence of psychotic symptoms during mood episodes. Results Seropositivity for influenza A (p =0.004), B (p <0.0001) and coronaviruses (p <0.0001) were associated with history of mood disorders but not with the specific diagnosis of unipolar or bipolar depression. Seropositivity for influenza B was significantly associated with a history of suicide attempt (p =0.001) and history of psychotic symptoms (p =0.005). Limitations The design was cross-sectional. Socioeconomic factors, inflammatory markers, and axis II psychopathology were not assessed. Conclusions The association of seropositivity for influenza and coronaviruses with a history of mood disorders, and influenza B with suicidal behavior require replication in larger longitudinal samples. The need for these studies is additionally supported by the high incidence of these viral infections, the high prevalence of mood disorders, and resilience of suicide epidemics.

The potential association between obesity and bipolar disorder: A meta-analysis

BACKGROUND Several epidemiological studies have found that the prevalence of bipolar disorder (BD) is significantly higher in obese population than non-obese population. However, no meta-analysis has been published to quantitatively summarize the related literature. METHODS In this study, we conducted a meta-analysis to explore the association between obesity and BD by combining 9 cross-sectional studies with a total of 12,259 BD cases and 615,490 non-BD controls. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled odds ratio (OR), while the heterogeneity was assessed using I(2) and Q statistic. RESULTS Our meta-analysis suggests that obesity is associated with increased prevalence of BD by a random-effect model (OR=1.77, 95% CI: 1.40-2.23; Q=44.62, P<0.001, I(2)=82.1%). LIMITATION Without prospective studies, we cannot determine whether obesity increased the risk of developing BD or vice-versa. CONCLUSION Obesity is positively associated with BD.

Combined Toxoplasma gondii seropositivity and high blood kynurenine – Linked with nonfatal suicidal self-directed violence in patients with schizophrenia

Toxoplasma gondii (T. gondii) chronic infection and elevated kynurenine (KYN) levels have been individually associated with non-fatal suicidal self-directed violence (NF-SSDV). We aimed to test the hypothesis that the association between T. gondii seropositivity and history of NF-SSDV would be stronger in schizophrenia patients with high plasma KYN levels than in those with lower KYN levels. We measured anti-T. gondii IgG antibodies and plasma KYN in 950 patients with schizophrenia, and used logistic regression to evaluate the relationship between NF-SSDV and KYN in patients who were either seropositive or seronegative for T. gondii. For those with KYN levels in the upper 25th percentile, the unadjusted odds ratio for the association between NF-SSDV history and KYN in T. gondii seropositive patients was 1.63 (95% CI 1.01 to 2.66), p = 0.048; the adjusted odds ratio was 1.95 (95% CI 1.15 to 3.30), p = 0.014. Plasma KYN was not associated with a history of NF-SSDV in T. gondii seronegative patients. The results suggest that T. gondii and KYN may have a nonlinear cumulative effect on the risk of NF-SSDV among those with schizophrenia. If confirmed by future longitudinal studies, this result is expected to have both theoretical and clinical implications for the prevention and treatment of suicidal behavior.