Aamar Sleemi

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.

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.

Pollen-specific immunoglobulin E positivity is associated with worsening of depression scores in bipolar disorder patients during high pollen season

Manalai P, Hamilton RG, Langenberg P, Kosisky SE, Lapidus M, Sleemi A, Scrandis D, Cabassa JA, Rogers CA, Regenold WT, Dickerson F, Vittone BJ, Guzman A, Balis T, Tonelli LH, Postolache TT. Pollen‐specific immunoglobulin E positivity is associated with worsening of depression scores in bipolar disorder patients during high pollen season. Bipolar Disord 2012: 14: 90–98.

Vitamin D: a potential role in reducing suicide risk?

Abstract Suicide attempts are known to peak in the spring, overlapping with the time of year when 25-hydroxyvitamin D [25(OH)D] levels are at their nadir in the northern hemisphere because of negligible skin production of vitamin D owing to low levels of ultraviolet B radiation. Low levels of 25(OH)D, the vitamin D metabolite used to diagnose vitamin D deficiency, have been associated with certain pro-suicidal factors such as exacerbation of depression, anxiety, psychosis, and certain medical conditions. Therefore, we hypothesize that vitamin D deficiency could also be associated with increased risk of completed suicides. Here, we briefly review the literature on vitamin D, its deficiency, and its reported association with certain risk factors for suicide.

Improvement in depression scores after 1 hour of light therapy treatment in patients with seasonal affective disorder.

Abstract The purpose of this study was to investigate possible rapid effects of light therapy on depressed mood in patients with seasonal affective disorder. Participants received 1 hour of bright light therapy and 1 hour of placebo dim red light in a randomized order crossover design. Depressed mood was measured at baseline and after each hour of light treatment using two self-report depression scales (Profile of Mood States–Depression-Dejection [POMS-D] subscale and the Beck Depression Inventory II [BDI-II]). When light effects were grouped for the two sessions, there was significantly greater reduction in self-report depression scores by −1.3 (p = 0.02) on the BDI-II and −1.2 (p = 0.02) on the POMS-D. A significant but modest improvement was detected after a single active light session. This is the first study, to our knowledge, to document an immediate improvement with light treatment using a placebo-controlled design with a clinical sample of depressed individuals.

Seasonality of mood and behavior in the Old Order Amish

BACKGROUND/OBJECTIVE We examined seasonality and winter seasonal affective disorder (SAD) in the Old Order Amish of Lancaster County, Pennsylvania, a unique population that prohibits use of network electric light in their homes. METHODS We estimated SAD using the seasonal pattern assessment questionnaire (SPAQ) in 1306 Amish adults and compared the frequencies of SAD and total SAD (i.e., presence of either SAD or subsyndromal-SAD) between men and women, young and old, and awareness of (ever vs. never heard about) SAD. Heritability of global seasonality score (GSS) was estimated using the maximum likelihood method, including a household effect to capture shared environmental effects. RESULTS The mean (±SD) GSS was 4.36 (±3.38). Prevalence was 0.84% (95% CI: 0.36-1.58) for SAD and 2.59% (95% CI: 1.69-3.73) for total SAD. Heritability of GSS was 0.14±0.06 (SE) (p=0.002) after adjusting for age, gender, and household effects. LIMITATIONS Limitations include likely overestimation of the rates of SAD by SPAQ, possible selection bias and recall bias, and limited generalizability of the study. CONCLUSIONS In the Amish, GSS and SAD prevalence were lower than observed in earlier SPAQ-based studies in other predominantly Caucasian populations. Low heritability of SAD suggests dominant environmental effects. The effects of awareness, age and gender on SAD risk were similar as in previous studies. Identifying factors of resilience to SAD in the face of seasonal changes in the Amish could suggest novel preventative and therapeutic approaches to reduce the impact of SAD in the general population.

Test-retest reliability of the Seasonal Pattern Assessment Questionnaire in Old Order Amish

Abstract Background: Research on test-retest reliability of the Season Pattern Assessment Questionnaire (SPAQ) is sparse, and to date, has not been done with subgroups such as the Old Order Amish. Methods: We examined the test-retest reliability of the SPAQ in a sample of Old Order Amish. A total of 68 Old Order Amish participants completed the SPAQ twice, with 4 months between administrations. Quantitative data analyses were carried out to determine respective strengths of test-restest reliability for two variables [i.e., Global Seasonality Score (GSS), and Problem Rating Score (PRS)]. Results and conclusions: Results revealed the test-retest reliability of the SPAQ in this population to be strong within the respective variables (GSS, α=0.87; and PRS, α=0.79) using Cronbach’s alpha.

Light treatment for seasonal Winter depression in African-American vs Caucasian outpatients.

AIM To compare adherence, response, and remission with light treatment in African-American and Caucasian patients with Seasonal Affective Disorder. METHODS Seventy-eight study participants, age range 18-64 (51 African-Americans and 27 Caucasians) recruited from the Greater Baltimore Metropolitan area, with diagnoses of recurrent mood disorder with seasonal pattern, and confirmed by a Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV, were enrolled in an open label study of daily bright light treatment. The trial lasted 6 wk with flexible dosing of light starting with 10000 lux bright light for 60 min daily in the morning. At the end of six weeks there were 65 completers. Three patients had Bipolar II disorder and the remainder had Major depressive disorder. Outcome measures were remission (score ≤ 8) and response (50% reduction) in symptoms on the Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-SAD) as well as symptomatic improvement on SIGH-SAD and Beck Depression Inventory-II. Adherence was measured using participant daily log. Participant groups were compared using t-tests, chi square, linear and logistic regressions. RESULTS The study did not find any significant group difference between African-Americans and their Caucasian counterparts in adherence with light treatment as well as in symptomatic improvement. While symptomatic improvement and rate of treatment response were not different between the two groups, African-Americans, after adjustment for age, gender and adherence, achieved a significantly lower remission rate (African-Americans 46.3%; Caucasians 75%; P = 0.02). CONCLUSION This is the first study of light treatment in African-Americans, continuing our previous work reporting a similar frequency but a lower awareness of SAD and its treatment in African-Americans. Similar rates of adherence, symptomatic improvement and treatment response suggest that light treatment is a feasible, acceptable, and beneficial treatment for SAD in African-American patients. These results should lead to intensifying education initiatives to increase awareness of SAD and its treatment in African-American communities to increased SAD treatment engagement. In African-American vs Caucasian SAD patients a remission gap was identified, as reported before with antidepressant medications for non-seasonal depression, demanding sustained efforts to investigate and then address its causes.

Prediction of outcome of bright light treatment in patients with seasonal affective disorder: Discarding the early response, confirming a higher atypical balance, and uncovering a higher body mass index at baseline as predictors of endpoint outcome

BACKGROUND We tested the hypothesis that the early improvement in mood after the first hour of bright light treatment compared to control dim-red light would predict the outcome at six weeks of bright light treatment for depressed mood in patients with Seasonal Affective Disorder (SAD). We also analyzed the value of Body Mass Index (BMI) and atypical symptoms of depression at baseline in predicting treatment outcome. METHODS Seventy-eight adult participants were enrolled. The first treatment was controlled crossover, with randomized order, and included one hour of active bright light treatment and one hour of control dim-red light, with one-hour washout. Depression was measured on the Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH-SAD). The predictive association of depression scores changes after the first session. BMI and atypical score balance with treatment outcomes at endpoint were assessed using multivariable linear and logistic regressions. RESULTS No significant prediction by changes in depression scores after the first session was found. However, higher atypical balance scores and BMI positively predicted treatment outcome. LIMITATIONS Absence of a control intervention for the six-weeks of treatment (only the first session in the laboratory was controlled). Exclusion of patients with comorbid substance abuse, suicidality and bipolar I disorder, and patients on antidepressant medications, reducing the generalizability of the study. CONCLUSION Prediction of outcome by early response to light treatment was not replicated, and the previously reported prediction of baseline atypical balance was confirmed. BMI, a parameter routinely calculated in primary care, was identified as a novel predictor, and calls for replication and then exploration of possible mediating mechanisms.

In patients with schizophrenia, non-fatal suicidal self-directed violence is positively associated with present but not past smoking

An increased prevalence of smoking has been consistently reported in patientswith schizophrenia (de Leon et al., 1995; Kalman et al., 2005; Kao et al., 2011) who may use cigarette smoking for self-medicating their previously reported nicotinergic dysfunction (Adler et al., 1993; Kumari and Postma, 2005; Leonard et al., 2007). Previous studies have also documented an association of smoking with suicidal behavior in patients with schizophrenia. However, most of these studies involved small samples (Malone et al., 2003; Iancu et al., 2006; Rihmer et al., 2007; Kao et al., 2011). One larger study (Potkin et al., 2003), included patients with schizoaffective disorder. We therefore attempted to replicate these findings in a larger and diagnostically homogeneous sample. Additionally, we compared history of nonfatal-suicidal-selfdirected-violence (NF-SSDV), the strongest predictor of suicide, in current vs. past smokers. Patients from inpatient and outpatient settings with a diagnosis of schizophrenia validated by the Structured Clinical Interview for DSM-IV Diagnosis (SCID; First et al., 1997) were recruited in Munich, Germany. We also obtained history of NF-SSDV, severity of symptoms by PANSS (Kay et al., 1987), chlorpromazine equivalent of antipsychotics, and BMI. Smoking was assessed by the Fagerstrom Nicotine Dependence Test (Heatherton et al., 1991). Patients were divided into 3 categories: (1) nonsmoker — who smoked less than 100 cigarettes in a lifetime; (2) current smoker — over 100 cigarettes/lifetime and any amount in the last week; and (3) past smoker — smoked over 100 cigarettes/lifetime, no cigarettes last week. NF-SSDV was compared between these three groups (secondary analysis) but, for the primary replicating analysis, current and past smokers were combined and referred to as smokers. Statistical analyses included chi-square tests and multivariate logistic regression. The sample included 950 patients, with 920 patients having available data for full adjustments; 681 (74%) were smokers [i.e. current smokers, 551 (60%) and past smokers, 130 (14%)] and 239 (26%) were nonsmokers. By crude analysis smoking was associated with NF-SSDV (χ 4.15, p = 0.042), with 38% increased odds of NF-SSDV history in smokers compared to nonsmokers (OR 1.38, 95% CI 1.01 to 1.89, p = 0.042), a finding that persisted after controlling for age, sex, education and PANSS score (OR 1.39, 95% CI 1.01 to 1.93, p = 0.046). While differences between past smokers and nonsmokerswere not statistically significant (crude: χ 0.34, p = 0.560 and adjusted OR 1.17, 95% CI 0.72 to 1.90, p = 0.52), current smokers had an increased history of NF-SSDV when compared with the other two groups. Based