John W. Stiller

Elevated cytokine expression in the orbitofrontal cortex of victims of suicide.

Objective:  Based on the reported association between cytokines with depression and suicide, and evidence of increased markers of inflammation in the brain of suicide victims, the present study examined the expression of cytokines in the orbitofrontal cortex of suicide victims.

Tree pollen peaks are associated with increased nonviolent suicide in women

SIR—Research on seasonality of suicide has identified a highly replicated and robust peak in late spring and a somewhat less consistent peak in late summer and early fall. While a number of psychosocial and environmental factors, such as increased exposure to light in the spring, have been suggested to be associated with the spring peak, none satisfactorily explains the temporal association of the peak in suicide with the proposed environmental trigger. Based on the influence of cytokines on mood, cognition, and behavior in healthy individuals and patients with medical and psychiatric conditions, the reciprocal immune–brain interactions, and the cytokine expression during allergic reactions, we hypothesized that tree pollen (which peaks in spring) and ragweed pollen (which peaks in late summer/ early fall) may act as environmental triggers for suicide in vulnerable individuals. We explored this hypothesis by comparing the suicide rates before, during and after periods of peak atmospheric pollen. Tree and ragweed pollen data were obtained from the American Academy of Allergy, Asthma, & Immunology for the years 1995–1998 for the continental US and Canada. Periods of allergen exposure were derived from histograms expressing pollen counts as particles per cubic meter (p/m) on a log scale from 0 to 1000 (y-axis) by months (x-axis) within each year. Raters identified three periods for each allergen in time units of quartermonths at each location for up to 4 years divided as follows: a prepollen period (pollen countso10p/m3 for trees and omid-way on the log scale between 1 and 10p/m for ragweed), a peak-pollen period (4100p/m for trees and4mid-way on the log scale between 10 and 100p/m for ragweed), and a postpollen period when concentrations returned to the prepollen levels. Intervals with intermediate pollen counts were discarded. Suicide data were obtained from the General Mortality Database compiled by the National Center for Health Statistics. Each suicide was classified by county and state of occurrence, date, sex, age, and type (violent, nonviolent, other, or unknown) based on the ICD-9 codes. Suicides by other or unknown means accounted for 6% of the total. For annual rates, person-years were estimated by summing each county’s population from the 2000 Census across the years of observation by sex and age categories. For the analysis of rates and relative rates (RRs) by allergen season and pollen-level period, person-years were estimated by multiplying the population for each age and sex category in each county by the total number of days in each pollen-level period (1⁄4number of quarter months days per quarter month (1⁄47.6 days)) summed across years of observation and divided by 365.25 days per year. Annual and seasonal suicide rates, RRs, and their standard errors were estimated in Poisson’s regression models. RRs for each allergen season and suicide type were estimated setting the prepollen period as the referent and peak and postpollen periods as indicator variables. Since interaction by sex and age was found to be significant, rates and RRs for the effect of allergen exposure were calculated separately by the four age by sex strata. A post hoc analysis of a possible confounding effect of light (using a proxy measure, ‘sunshine’) was performed for the specific pollen periods that showed significant differences in suicide rates using mixed effects repeated measures ANOVAwith pollenperiod and year as within-location effects. The total population of these counties in 2000 was 37 824174 (Table 1). The total number of quarter months of peak-pollen was 670 in the tree season (mean1⁄414.3) and 476 in the ragweed season (mean1⁄49.5). In 92705 505 person-years, 9528 suicides were recorded (rate1⁄410.3/100 000 personyears, 95% confidence interval (CI)1⁄410.1, 10.5) (Table 2). As in other population-based samples of completed suicide, the rate in males was greater than in females (RR1⁄4 4.1, 95% CI1⁄43.9, 4.3), and greater in older people compared with younger (RR1⁄41.4, 95% CI1⁄41.3, 1.5). The rate in older males was greater than in younger males (RR1⁄41.8, 95% CI1⁄4 1.7, 1.9). No difference by age was seen in females. A total of 2417 suicides were recorded in the tree season and 1811 in the ragweed season (Table 3). During the tree allergy season, there was a two-fold increase in the rate of nonviolent suicides among younger females in the peak-pollen period compared with the prepollen period (95% CI1⁄4 1.3, 3.0) (Table 3). There was no difference between the postpollen period and the prepollen period. In older females, the rate of nonviolent suicide in the postpollen period was 4.6 times that of the prepollen period (95% CI1⁄41.2, 17.8), with no increase in the peak-pollen period relative to the prepollen period (Table 3). It is unlikely that a greater exposure to natural light during the peak-pollen season would have spuriously increased suicide rates in younger women, because a greater suicide rate was found in the peak-pollen period, while a greater ‘sunshine’ was found in the postpollen period. However, in older women, it is possible that a greater light exposure during the postpollen period could have spuriously inflated the rate of suicide during that period. The differences in the tree pollen period effect between younger and older women may also represent a consequence of Molecular Psychiatry (2005) 10, 232–238 & 2005 Nature Publishing Group All rights reserved 1359-4184/05

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

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Sparring and neurological function in professional boxers

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.

Positive association between Toxoplasma gondii IgG serointensity and current dysphoria/hopelessness scores in the Old Order Amish: a preliminary study

Despite increased interest regarding the potentially long-term negative impact of chronic traumatic brain injury, limited research has been conducted regarding such injuries and neurological outcomes in real world settings. To increase understanding regarding the relationship between sparring (e.g., training under the tutelage of an experienced boxing coach for the purpose of improving skills and/or fitness) and neurological functioning, professional boxers (n = 237) who competed in Maryland between 2003 and 2008 completed measures regarding sparring exposure (Cumulative Sparring Index, CSI) and performance on tests of cognition (Symbol Digit Modalities Test, SDMT) and balance (Sharpened Romberg Test, SRT). Measures were completed prior to boxing matches. Higher scores on the CSI (increased sparring exposure) were associated with poorer performance on both tests of cognition (SDMT) and balance (SRT). A threshold effect was noted regarding performance on the SDMT, with those reporting CSI values greater than about 150 experiencing a decline in cognition. A history of frequent and/or intense sparring may pose a significant risk for developing boxing associated neurological sequelae. Implementing administration of clinically meaningful tests before bouts, such as the CSI, SDMT, and/or the SRT, as well as documentation of results into the boxer’s physicals or medical profiles may be an important step for improving boxing safety.

Mental Health in Allergic Rhinitis: Depression and Suicidal Behavior

Abstract Toxoplasma gondii (T. gondii) IgG seropositivity and serointensity have been previously associated with suicidal self-directed violence (SSDV). Although associations with unipolar depression have also been investigated, the results have been inconsistent, possibly as a consequence of high heterogeneity. We have now studied this association in a more homogeneous population, [that is (i.e.) Old Order Amish (OOA)] with previously reported high T. gondii seroprevalence. In 306 OOA with a mean age of 46.1±16.7 years, including 191 (62.4%) women in the Amish Wellness Study, we obtained both T. gondii IgG titers (by enzyme-linked immunosorbent assay [ELISA]), and depression screening questionnaires (Patient Health Questionnaire [PHQ-9] [n=280] and PHQ-2 [n=26]). Associations between T. gondii IgG and dysphoria/hopelessness and anhedonia scores on depression screening questionnaires were analyzed using multivariable linear methods with adjustment for age and sex. Serointensity was associated with both current dysphoria/hopelessness (p=0.045) and current combined anhedonia and dysphoria/hopelessness (p=0.043), while associations with simple anhedonia and past/lifelong (rather than current) phenotypes were not significant. These results indicate the need for larger longitudinal studies to corroborate the association between dysphoria/hopelessness and T. gondii IgG-titers. Current hopelessness is a known risk factor for SSDV which responds particularly well to cognitive behavioral therapy, and may be a focused treatment target for T. gondii-positive individuals at high-risk for SSDV.

A Prospective Longitudinal Study of Seasonality in African Students Living in the Greater Washington, D.C. Metropolitan Area

Opinion statementA high proportion of suicides visit their medical provider in the month prior to death, but depression, suicidal thoughts, and substance use are seldom addressed. For the clinicians routinely treating a substantial patient population with allergic diseases, there are additional concerns, as allergy has been linked with both depression and suicidal behavior. While psychotropic medications may affect diagnosis of allergies, medications used to treat allergies impact mood and behavior. Thus, we present an overview of the overlap of allergic rhinitis with depression and suicidal behavior in adults, based on clinical and epidemiological data, and our research and clinical experience. In summary, we suggest: (1) inquiring among patients with allergies about personal and family history of depression, substance use disorders, suicidal ideation, and attempts; (2) increased mindfulness regarding the potential effects of allergy medications on mood and behavior; and (3) for people identified with certain types of depression or increased suicide risk, a systematic multilevel collaborative approach. While, for practical reasons the majority of patients with depression will continue to be treated by general or family practitioners, the allergy-treating provider should always consider integrated care for bipolar, psychotic, or suicidal depression and incomplete remission, or relapsing and highly recurrent course. While awaiting results of a much needed basic and clinical research to guide the clinical approach to patients with comorbid allergic rhinitis and depression, the simple steps recommended here are expected to lead to improved clinical outcomes in depression, and, perhaps, contributing to lowering the highly resilient suicide mortality.Learning objectives: a) Present overlaps between allergy, allergen exposure, depression, and suicidal behavior in adults and b) Familiarize allergists with the principles of diagnosis and treatment of depression in adults and importance to monitor suicide risk.

Moderation of the relationship between Toxoplasma gondii seropositivity and trait impulsivity in younger men by the phenylalanine-tyrosine ratio

We conducted a prospective, longitudinal study of seasonality in a vulnerable population, i.e., African students who migrated to a temperate climate. Consistent with previous cross-sectional studies, we hypothesized lower mood and energy, and higher appetite and weight, in fall/winter than in spring/summer. Four cohorts of African students attending a year-long nursing school program without vacation in Washington, D.C., were assessed monthly for 1 year. Forty-three subjects (mean age = 33.46 ± 6.25), consisting of predominantly females (76.7%), completed the study. The cohorts began their academic program in different seasons (one each in winter, spring, summer, and fall), inherently minimizing confounding influences on seasonality, such as academic and immigration stress, as well as allowing adjustment for an order effect. At each assessment, students completed three 100-mm visual analog scales for mood, energy, and appetite, and were weighed on a digital scale. For each standardized dependent variable, a repeated measure ANOVA was used and, if a significant effect of month was identified, averages for spring/summer and fall/winter were compared using paired ttests. In addition, a mixed model for repeated measures was applied to raw (nonstandardized) data. Body weight was significantly higher in fall/winter than in spring/summer (p < 0.01). No seasonal differences in mood, energy, or appetite were found. Benefiting from certain unique features of our cohorts allowing adjustment for order effects, this is the first study to identify a seasonal variation in body weight with a peak in winter using longitudinal monthly measurements.

Heritability of plasma neopterin levels in the Old Order Amish

Previously, we reported that Toxoplasma gondii (T. gondii)-seropositivity is associated with higher impulsive sensation seeking in younger men. As dopaminergic and serotonergic signaling regulate impulsivity, and as T. gondii directly and indirectly affects dopaminergic signaling and induces activation of the kynurenine pathway leading to the diversion of tryptophan from serotonin production, we investigated if dopamine and serotonin precursors or the tryptophan metabolite kynurenine interact with the T. gondii-impulsivity association. In 950 psychiatrically healthy participants, trait impulsivity scores were related to T. gondii IgG seropositivity. Interactions were also identified between categorized levels of phenylalanine (Phe), tyrosine (Tyr), Phe:Tyr ratio, kynurenine (Kyn), tryptophan (Trp) and Kyn:Trp ratio, and age and gender. Only younger T. gondii-positive men with a high Phe:Tyr ratio, were found to have significantly higher impulsivity scores. There were no significant associations in other demographic groups, including women and older men. No significant effects or interactions were identified for Phe, Tyr, Kyn, Trp, or Kyn:Trp ratio. Phe:Tyr ratio, therefore, may play a moderating role in the association between T. gondii seropositivity and impulsivity in younger men. These results could potentially lead to individualized approaches to reduce impulsivity, based on combined demographic, biochemical and serological factors.

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 examined the heritability of neopterin, a biomarker for cell-mediated immunity and oxidative stress, and potentially for psychiatric disorders, in the Old Order Amish. METHODS Plasma neopterin levels were determined in 2015 Old Order Amish adults. Quantitative genetic procedures were used to estimate heritability of neopterin. RESULTS Heritability of log-neopterin was estimated at 0.07 after adjusting for age, gender, and household (p=0.03). The shared household effect was 0.06 (p<0.02). CONCLUSIONS We found a low heritability of neopterin and small household effect, suggesting that non-household environmental factors are more important determinants of variance of neopterin levels in the Amish.