Dipika Vaswani

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.

Chronotype and seasonality: Morningness is associated with lower seasonal mood and behavior changes in the Old Order Amish

BACKGROUND Several studies documented that lower scores on the Morningness-Eveningness Questionnaire (MEQ) are associated with a higher global seasonality of mood (GSS). As for the Modern Man artificial lighting predominantly extends evening activity and exposure to light, and as evening bright light phase is known to delay circadian rhythms, this chronic exposure could potentially lead to both lower Morningness as well as higher GSS. The aim of the study was to investigate if the MEQ-GSS relationship holds in the Old Order Amish of Lancaster County, PA, a population that does not use network electrical light. METHODS 489 Old Order Amish adults (47.6% women), with average (SD) age of 49.7 (14.2) years, completed both the Seasonal Pattern Assessment Questionnaire (SPAQ) for the assessment of GSS, and MEQ. Associations between GSS scores and MEQ scores were analyzed using linear models, accounting for age, gender and relatedness by including the relationship matrix in the model as a random effect. RESULTS GSS was inversely associated with MEQ scores (p=0.006, adjusted). LIMITATIONS include a potential recall bias associated with self-report questionnaires and no actual light exposure measurements. CONCLUSION We confirmed the previously reported inverse association between MEQ scores and lower seasonality of mood, for the first time in a population that does not use home network electrical lighting. This result suggests that the association is not a byproduct of exposure to network electric light, and calls for additional research to investigate mechanisms by which Morningness is negatively associated with seasonality.

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 shows evidence for polygenic architecture and genetic correlation with schizophrenia and bipolar disorder.

OBJECTIVE To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. METHOD Genome-wide association studies (GWASs) were conducted in Australian (between 1988 and 1990 and between 2010 and 2013) and Amish (between May 2010 and December 2011) samples in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered, and the results were meta-analyzed in a total sample of 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder, major depressive disorder (MDD), and schizophrenia were calculated to test for overlap in risk between psychiatric disorders and seasonality. RESULTS The most significant association was with rs11825064 (P = 1.7 × 10⁻⁶, β = 0.64, standard error = 0.13), an intergenic single nucleotide polymorphism (SNP) found on chromosome 11. The evidence for overlap in risk factors was strongest for schizophrenia and seasonality, with the schizophrenia genetic profile scores explaining 3% of the variance in log-transformed global seasonality scores. Bipolar disorder genetic profile scores were also associated with seasonality, although at much weaker levels (minimum P value = 3.4 × 10⁻³), and no evidence for overlap in risk was detected between MDD and seasonality. CONCLUSIONS Common SNPs of large effect most likely do not exist for seasonality in the populations examined. As expected, there were overlapping genetic risk factors for bipolar disorder (but not MDD) with seasonality. Unexpectedly, the risk for schizophrenia and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and schizophrenia.

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.

Seasonality patterns of mood and behavior in the Old Order Amish.

Abstract Background: Although humans have become partially isolated from physical seasonal environmental changes through artificial lighting and temperature control, seasonal changes in mood and behavior have been described across hemispheres, continents, ethnicities and occupations. The Old Order Amish are more exposed than the general population to environmental seasonal changes both occupationally as well as through their limited use of electric light in the winter and air conditioning in the summer; yet, their seasonal changes in mood and behavior have not been previously studied. Methods: The aim of this study was to analyze seasonal patterns in mood and behavior in the Old Order Amish of Lancaster County, Pennsylvania, who returned completed Seasonal Pattern Assessment Questionnaires (SPAQ). Monthly seasonal patterns were analyzed with repeated measures ANOVAs, followed by a post hoc t-test if significant. The χ2 was used for presence or absence of seasonal patterns for each item. Results: More than 75% of the participants reported at least one seasonal change. More than 75% endorsed seasonality in “feeling best” but only <25% did so for “feeling worst”. Mood-wise, the best month was May, and the worst months were January and February. Conclusions: There were significant seasonal patterns for all mood and behavior items reported by the majority of participants. The results were consistent with an overall winter pattern of seasonality previously consistently reported in predominantly Caucasian populations.

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.