Seasonal affective disorder and seasonal changes in weight and sleep duration are inversely associated with plasma adiponectin levels.

Overlapping pathways between mood and metabolic regulation have increasingly been reported. Although impaired regulation of adiponectin, a major metabolism-regulating hormone, has been implicated in major depressive disorder, its role in seasonal changes in mood and seasonal affective disorder-winter type (SAD), a disorder characterized by onset of mood impairment and metabolic dysregulation (e.g., carbohydrate craving and weight gain) in fall/winter and spontaneous alleviation in spring/summer, has not been previously studied. We studied a convenience sample of 636 Old Order Amish (mean (± SD), 53.6 (±14.8) years; 50.1% males), a population with self-imposed restriction on network electric light at home, and low prevalence of total SAD (t-SAD = syndromal + subsyndromal). We calculated the global seasonality score (GSS), estimated SAD and subsyndromal-SAD after obtaining Seasonal Pattern Assessment Questionnaires (SPAQs), and measured overnight fasting plasma adiponectin levels. We then tested associations between plasma adiponectin levels and GSS, t-SAD, winter-summer difference in self-reported sleep duration, and self-reported seasonal weight change, by using analysis of co-variance (ANCOVA) and linear regression analysis after adjusting for age, gender, and BMI. Participants with t-SAD (N = 14; 2.2%) had significantly lower plasma adiponectin levels (mean ± SEM, 8.76 ± 1.56 µg/mL) than those without t-SAD (mean ± SEM, 11.93 ± 0.22 µg/mL) (p = 0.035). In addition, there was significant negative association between adiponectin levels and winter-summer difference in self-reported sleep duration (p = 0.025) and between adiponectin levels and self-reported seasonal change in weight (p = 0.006). There was no significant association between GSS and adiponectin levels (p = 0.88). To our knowledge, this is the first study testing the association of SAD with adiponectin levels. Replication and extension of our findings longitudinally and, then, interventionally, may implicate low adiponectin as a novel target for therapeutic intervention in SAD.

Toxoplasma gondii Serointensity and Seropositivity: Heritability and Household-Related Associations in the Old Order Amish.

Toxoplasma gondii (T. gondii) is an intracellular parasite infecting one third of the world's population. Latent T. gondii infection has been associated with mental illness, including schizophrenia and suicidal behavior. T. gondii IgG antibody titers were measured via ELISA. The heritability of T. gondii IgG was estimated using a mixed model that included fixed effects for age and sex and random kinship effect. Of 2017 Old Order Amish participants, 1098 had positive titers (54.4%). The heritability for T. gondii serointensity was estimated to be 0.22 (p = 1.7 × 10-8 and for seropositivity, it was estimated to be 0.28 (p = 1.9 × 10-5). Shared household environmental effects (i.e., household effects) were also determined. Household effects, modeled as a random variable, were assessed as the phenotypic covariance between any two individuals who had the same current address (i.e., contemporaneous household), and nuclear household (i.e., the phenotypic covariance between parents and children only, not other siblings or spouses). Household effects did not account for a significant proportion of variance in either T. gondii serointensity or T. gondii seropositivity. Our results suggest a significant familial aggregation of T. gondii serointensity and seropositivity with significant heritability. The shared household does not contribute significantly to family aggregation with T. gondii, suggesting that there are possible unmeasured non-household shared and non-shared environmental factors that may play a significant role. Furthermore, the small but significant heritability effects justify the exploration of genetic vulnerability to T. gondii exposure, infection, virulence, and neurotropism.

Heritability of plasma neopterin levels in the Old Order Amish.

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.

Sleep onset insomnia, daytime sleepiness and sleep duration in relationship to Toxoplasma gondii IgG seropositivity and serointensity.

Toxoplasma gondii (T. gondii) infects central nervous tissue and is kept in relative dormancy by a healthy immune system. Sleep disturbances have been found to precipitate mental illness, suicidal behavior and car accidents, which have been previously linked to T. gondii as well. We speculated that if sleep disruption, particularly insomnia, would mediate, at least partly, the link between T. gondii infection and related behavioral dysregulation, then we would be able to identify significant associations between sleep disruption and T. gondii. The mechanisms for such an association may involve dopamine (DA) production by T. gondii, or collateral effects of immune activation necessary to keep T. gondii in check. Sleep questionnaires from 2031 Old Order Amish were analyzed in relationship to T. gondii-IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). Toxoplasma gondii seropositivity and serointensity were not associated with any of the sleep latency variables or Epworth Sleepiness Scale (ESS). A secondary analysis identified, after adjustment for age group, a statistical trend toward shorter sleep duration in seropositive men (p = 0.07). In conclusion, it is unlikely that sleep disruption mediates links between T. gondii and mental illness or behavioral dysregulation. Trending gender differences in associations between T. gondii and shorter sleep need further investigation.

In psychiatrically healthy individuals, overweight women but not men have lower tryptophan levels.

Gender differences in tryptophan (TRP) breakdown in obese individuals have been previously reported. This could be both contributory to, as well as a consequence of, gender differences in mood changes among obese people. To exclude the potential effect of depression on TRP breakdown and its levels in obesity, we replicated analyses in psychiatrically healthy individuals. In 1000 participants, plasma kynurenine (KYN), TRP, and the KYN/TRP ratio were compared between overweight/obese and normal-weight individuals using analysis of covariance, with adjustment for age and gender. Bivariate post hoc tests were also conducted. There were no significant relationships between KYN, TRP, or the KYN/TRP ratio and overall overweight/obese status. However, a significant gender by weight category interaction was identified for TRP only, with overweight/obese women having lower TRP than overweight/obese men (p = 0.02). No gender differences in TRP were found in non-obese participants. Our study in psychiatrically healthy individuals suggested that lower TRP levels in obese women were not secondary to depression, strengthening the possibility that TRP levels could mediate depression in vulnerable women. Thus experimental manipulations of TRP levels could be used to advance theoretical knowledge, prevention, and clinical control of depression in obese women.

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, ß = 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.

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.

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

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.

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.

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.