Uttam K. Raheja

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.

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.

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

Abstract 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.

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.

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.

Body Rhythms/Biological Clocks

Chronobiology is the study of biological rhythms. In animals the master biological clock is located in the hypothalamus. Peripheral clocks have also been found in various cells, tissues, and organs. Disruptions of biological rhythms are implicated in general performance decrements and certain medical and psychiatric conditions. Chronotherapeutic modalities include light therapy, wake therapy, shifting of sleep-wake schedules, dark therapy, melatonin, and its synthetic receptor agonists. An improved alignment of biological rhythms with the environmental light-dark exposure and societal demands can have important and broad implications for performance (academic, occupational, and athletic), health, and well-being.

Mood Disorders: Depression and Bipolar Disorder

Mood disorders are one of the most common causes of disability throughout the world. Individuals with intellectual and developmental disabilities (IDD) have impairment in functioning and suffer from social stigma and rejection, which are known triggers of depressive episodes. Comorbid mood disorders augment preexistent disabilities and, although they are treatable, diagnosing them in this population can often be a challenge. They are commonly underdiagnosed and undertreated, treatment is often not individualized, and there is a paucity of evidence-based information. Clinicians who work with this population need a thorough understanding of both disorders and their management in order to maximize functioning and minimize suffering. To that purpose, we succinctly review the epidemiology, diagnosis, and management of mood disorders in individuals with IDD.

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

Abstract 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.