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John W Stiller

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Director of the Neurology Consultation Dervice at St. Elizabeths Hospital/Department of Behavioral Health, Washington, DC. Chief Physician and Neurologist, Maryland State Athletic CommissionMember of the Mood and Anxiety Program (MAP) research team, The University of Maryland

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Papers by John W Stiller

Age-Adjusted Means for Winter Sleep Duration and Summer Sleep Duration, by Sex, Ethnicity, and Winter Diagnosis Group Winter Sleep Summer Sleep

Duration of nocturnal melatonin secretion, a marker of "biological night" that relates ... more Duration of nocturnal melatonin secretion, a marker of "biological night" that relates to sleep duration, is longer in winter than in summer in patients with seasonal affective disorder (SAD), but not in healthy controls. In this study of African and African American college students, we hypothesized that students who met criteria for winter SAD or subsyndromal SAD (S-SAD) would report sleeping longer in winter than in summer. In addition, based on our previous observation that Africans report more "problems" with change in seasons than African Americans, we expected that the seasonal changes in sleep duration would be greater in African students than in African American students. Based on Seasonal Pattern Assessment Questionnaire (SPAQ) responses, African American and African college students in Washington, D.C. (N = 575) were grouped into a winter SAD/S-SAD group or a no winter diagnosis group, and winter and summer sleep length were determined. We conducted a ...

Biological and Psychological Factors Determining Neuropsychiatric Outcomes in COVID-19

Current Psychiatry Reports, 2021

Purpose of Review We present biological and psychological factors implicated in psychiatric manif... more Purpose of Review We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology. Recent Findings Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem. Most common psychiatric manifestations include delirium, mood disorders, anxiety disorders, and posttraumatic stress disorder. "Long-COVID" non-syndromal presentations include "brain-fogginess," autonomic instability, fatigue, and insomnia. Summary SARS-CoV-2 infection can trigger prior vulnerabilities based on the priming of microglia and other cells, induced or perpetuated by aging and mental and physical illnesses. COVID-19 could further induce priming of neuroimmunological substrates leading to exacerbated immune response and autoimmunity targeting structures in the central nervous system (CNS), in response to minor immune activating environmental exposures, including stress, minor infections, allergens, pollutants, and traumatic brain injury. Keywords COVID-19 • SARS-CoV-2 • Neuroinflammation • Neuroinvasion • Neuropsychiatric • Priming Abbreviations ACE2 Angiotensin I-converting enzyme 2 ACEI Angiotensin-converting enzyme inhibitor ADEM Acute disseminated encephalomyelitis AHLE Acute hemorrhagic leukoencephalomyelitis ANA Antinuclear antibodies ANE Acute necrotizing encephalopathy anti-dsDNA Anti-double-stranded deoxyribonucleic acid ARBs Angiotensin receptor blockers AST Aspartate aminotransferase BBB Blood-brain barrier BMI Body mass index CBT Cognitive behavioral therapy CD Cluster of differentiation CDC Center for Disease Control and Prevention CCL2 CC motif chemokine ligand 2, also known as monocyte chemotactic protein (MCP)-1 CEC Circulating endothelial cells CNS Central nervous system CORONADO Coronavirus-SARS-CoV-2 and diabetes outcomes COVID-19 Coronavirus disease 2019 CoVs Coronaviruses Cr Creatinine CRP C-reactive protein CSF Cerebrospinal fluid CT Computed tomography CTSL Cathepsin L CVD Cardiovascular disease DCLO Diffusing capacity of the lungs for carbon monoxide DSM-IV Diagnostic and Statistical Manual of Mental Disorders, fourth edition EEG Electroencephalogram This article is part of the Topical Collection on Complex Medical-Psychiatric Issues.

Parkinson’s disease-related motor and non-motor symptoms are not more prevalent in the Lancaster Amish

IntroductionPrevious studies have suggested that the Amish may experience a relatively high preva... more IntroductionPrevious studies have suggested that the Amish may experience a relatively high prevalence of Parkinson’s disease (PD) and/or parkinsonian-motor signs.MethodsWe assessed the frequency of PD-related motor and no-motor symptoms in a large sample from the Amish Community in Lancaster County, Pennsylvania age ≥ 18 y.ResultsOf 430 participants ≥ 60 years, five (1.2%) reported a PD diagnosis, a prevalence similar to estimates in the general older adult populations. Of those without a PD diagnosis, 10.5% reported ≥ 1 and 1.2% ≥ 4 motor symptoms for the nine-item PD screening questionnaire. We also used questionnaires to assess non-motor symptoms. Constipation was reported in 0.7%, and daytime sleepiness in 8.1% of the participants. These frequencies are similar to, or lower than, corresponding frequencies reported in the US National Health and Nutrition Examination Surveys.DiscussionThese data neither support a markedly higher PD prevalence in the Lancaster Amish, nor do they s...

Increased brain vitamin D receptor expression and decreased expression of cathelicidin antimicrobial peptide in individuals who died by suicide

Journal of Psychiatric Research, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Toxoplasma gondii IgG associations with sleepwake problems, sleep duration and timing

Pteridines, 2019

Background: Evidence links Toxoplasma gondii (T. gondii), a neurotropic parasite, with schizophre... more Background: Evidence links Toxoplasma gondii (T. gondii), a neurotropic parasite, with schizophrenia, mood disorders and suicidal behavior, all of which are associated and exacerbated by disrupted sleep. Moreover, low-grade immune activation and dopaminergic overstimulation, which are consequences of T. gondii infection, could alter sleep patterns and duration. Methods: Sleep data on 833 Amish participants [mean age (SD) = 44.28 (16.99) years; 59.06% women] were obtained via self-reported questionnaires that assessed sleep problems, duration and timing. T. gondii IgG was measured with ELISA. Data were analyzed using multivariable logistic regressions and linear mixed models, with adjustment for age, sex and family structure. Results: T. gondii seropositives reported less sleep problems (p < 0.005) and less daytime problems due to poor sleep (p < 0.005). Higher T. gondii titers were associated with longer sleep duration (p < 0.05), earlier bedtime (p < 0.005) and earlier ...

Heritability of plasma neopterin levels in the Old Order Amish

Journal of neuroimmunology, Jan 15, 2017

We examined the heritability of neopterin, a biomarker for cell-mediated immunity and oxidative s... more 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. Plasma neopterin levels were determined in 2015 Old Order Amish adults. Quantitative genetic procedures were used to estimate heritability of neopterin. 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). 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.

Sparring and Neurological Function in Professional Boxers

Frontiers in Public Health, 2014

Despite increased interest regarding the potentially long-term negative impact of chronic traumat... more 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.

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

Journal of affective disorders, Jan 28, 2014

Several studies documented that lower scores on the Morningness-Eveningness Questionnaire (MEQ) a... more 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. 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. GSS w...

Tree pollen peaks are associated with increased nonviolent suicide in women

Molecular Psychiatry, 2004

Elevated cytokine expression in the orbitofrontal cortex of victims of suicide

Acta Psychiatrica Scandinavica, 2008

Objective-Based on the reported association between cytokines with depression and suicide, and ev... more 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. Method-In a postmortem sample obtained from the Brodman area 11 of suicides (n = 34) and controls (n = 17), real-time RT-PCR was used to compare the expression of mRNA species for tumor necrosis factor-a (TNF-α), interleukin (IL)-1β, 4, 5, 6, and 13. Results-Increased expression of IL-4 was found in women suicide victims and IL-13 in men suicide victims. Elevated but not significant cytokine expression was also observed for TNF-α in women suicide victims. Conclusion-To our knowledge, these results provide the first evidence of the presence of mRNA transcripts of type 2 T-helper cytokines in the human orbitofrontal cortex and their increased expression in the brain of suicides. Keywords suicide; postmortem; gene expression; brain; neuroimmune Significant outcomes • Neuroimmune abnormalities in the brains of suicide completers are associated with type-2 (TH2) cytokines. • These results are consistent with the reported association between allergies and suicide.

Seasonal Changes in Sleep Duration in African American and African College Students Living In Washington, D.C

The Scientific World JOURNAL, 2007

Duration of nocturnal melatonin secretion, a marker of “biological night” that relates to sleep d... more Duration of nocturnal melatonin secretion, a marker of “biological night” that relates to sleep duration, is longer in winter than in summer in patients with seasonal affective disorder (SAD), but not in healthy controls. In this study of African and African American college students, we hypothesized that students who met criteria for winter SAD or subsyndromal SAD (S-SAD) would report sleeping longer in winter than in summer. In addition, based on our previous observation that Africans report more “problems” with change in seasons than African Americans, we expected that the seasonal changes in sleep duration would be greater in African students than in African American students. Based on Seasonal Pattern Assessment Questionnaire (SPAQ) responses, African American and African college students in Washington, D.C. (N = 575) were grouped into a winter SAD/S-SAD group or a no winter diagnosis group, and winter and summer sleep length were determined. We conducted a 2 (season) × 2 (sex)...

Summer SAD and Diastolic BP Reactivity to the Cold Pressor Test

Biological Psychiatry

Winter Pattern of Seasonality is Associated With a Blunted Systolic Blood Pressure Response to the Cold Pressor Test

Biological Psychiatry

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

Psychiatry research, Jan 22, 2018

Previously, we reported that Toxoplasma gondii (T. gondii)-seropositivity is associated with high... more 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 ...

$Research paper thumbnail of {"__content__"=>"Positive association between IgG serointensity and current dysphoria/hopelessness scores in the Old Order Amish: a preliminary study.", "i"=>{"__content__"=>"Toxoplasma gondii"}}$

{"__content__"=>"Positive association between IgG serointensity and current dysphoria/hopelessness scores in the Old Order Amish: a preliminary study.", "i"=>{"__content__"=>"Toxoplasma gondii"}}

Pteridines, 2017

Toxoplasma gondii (T. gondii) IgG seropositivity and serointensity have been previously associate... more 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.

$Research paper thumbnail of {"__content__"=>"Sleep onset insomnia, daytime sleepiness and sleep duration in relationship to IgG seropositivity and serointensity.", "i"=>{"__content__"=>"Toxoplasma gondii"}}$

{"__content__"=>"Sleep onset insomnia, daytime sleepiness and sleep duration in relationship to IgG seropositivity and serointensity.", "i"=>{"__content__"=>"Toxoplasma gondii"}}

Pteridines, 2017

Toxoplasma gondii (T. gondii) infects central nervous tissue and is kept in relative dormancy by ... more 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.

Mental Health in Allergic Rhinitis: Depression and Suicidal Behavior

Current Treatment Options in Allergy

A high proportion of suicides visit their medical provider in the month prior to death, but depre... more A 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 much needed basic and clinical research to guide clinical approach for patients with comorbid allergic rhinitis and depression, the simple steps recommended here are expected to improved clinical outcomes in depression, including, on a large scale, reduced premature deaths by suicide.

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

Journal of affective disorders, Nov 22, 2017

We tested the hypothesis that the early improvement in mood after the first hour of bright light ... more 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. 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. No signific...

Magnesium Deficiency in Fibromyalgia Syndrome

Since patients with either fibromyalgia syndrome (FS) or low magnesium (Mg) levels can have fatig... more Since patients with either fibromyalgia syndrome (FS) or low magnesium (Mg) levels can have fatigue, sleep disturbance and anxiety, it was necessary to determine if some patients with FS also have low Mg levels. Both red blood cell (RBC) and plasma Mg levels were measured in 100 consecutive FS patients and 12 osteoarthritis (OA) control patients. Compared to reference laboratory and OA controls, FS patients had significantly lower RBC Mg levels. The plasma Mg levels of FS patients were no different than the reference laboratory or OA controls. Some FS patients have low Mg levels, a problem that is potentially correctable.

Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals

Journal of psychiatry & neuroscience : JPN, Oct 11, 2016

Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a ... more Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology. We used postmortem brain tissue from the ventrolateral prefrontal cortex (VLPFC) to assess tissue levels of tryptophan and KP metabolites, the expression of several KP enzymes and a series of cytokines as well as tissue pathology, including microglial activation. Tissue samples came from nonpsychiatric controls (n = 36) and individuals with depressive disorder not otherwise specified (DD-NOS, n = 45) who died of natural c...

Age-Adjusted Means for Winter Sleep Duration and Summer Sleep Duration, by Sex, Ethnicity, and Winter Diagnosis Group Winter Sleep Summer Sleep

Duration of nocturnal melatonin secretion, a marker of "biological night" that relates ... more Duration of nocturnal melatonin secretion, a marker of "biological night" that relates to sleep duration, is longer in winter than in summer in patients with seasonal affective disorder (SAD), but not in healthy controls. In this study of African and African American college students, we hypothesized that students who met criteria for winter SAD or subsyndromal SAD (S-SAD) would report sleeping longer in winter than in summer. In addition, based on our previous observation that Africans report more "problems" with change in seasons than African Americans, we expected that the seasonal changes in sleep duration would be greater in African students than in African American students. Based on Seasonal Pattern Assessment Questionnaire (SPAQ) responses, African American and African college students in Washington, D.C. (N = 575) were grouped into a winter SAD/S-SAD group or a no winter diagnosis group, and winter and summer sleep length were determined. We conducted a ...

Biological and Psychological Factors Determining Neuropsychiatric Outcomes in COVID-19

Current Psychiatry Reports, 2021

Purpose of Review We present biological and psychological factors implicated in psychiatric manif... more Purpose of Review We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology. Recent Findings Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem. Most common psychiatric manifestations include delirium, mood disorders, anxiety disorders, and posttraumatic stress disorder. "Long-COVID" non-syndromal presentations include "brain-fogginess," autonomic instability, fatigue, and insomnia. Summary SARS-CoV-2 infection can trigger prior vulnerabilities based on the priming of microglia and other cells, induced or perpetuated by aging and mental and physical illnesses. COVID-19 could further induce priming of neuroimmunological substrates leading to exacerbated immune response and autoimmunity targeting structures in the central nervous system (CNS), in response to minor immune activating environmental exposures, including stress, minor infections, allergens, pollutants, and traumatic brain injury. Keywords COVID-19 • SARS-CoV-2 • Neuroinflammation • Neuroinvasion • Neuropsychiatric • Priming Abbreviations ACE2 Angiotensin I-converting enzyme 2 ACEI Angiotensin-converting enzyme inhibitor ADEM Acute disseminated encephalomyelitis AHLE Acute hemorrhagic leukoencephalomyelitis ANA Antinuclear antibodies ANE Acute necrotizing encephalopathy anti-dsDNA Anti-double-stranded deoxyribonucleic acid ARBs Angiotensin receptor blockers AST Aspartate aminotransferase BBB Blood-brain barrier BMI Body mass index CBT Cognitive behavioral therapy CD Cluster of differentiation CDC Center for Disease Control and Prevention CCL2 CC motif chemokine ligand 2, also known as monocyte chemotactic protein (MCP)-1 CEC Circulating endothelial cells CNS Central nervous system CORONADO Coronavirus-SARS-CoV-2 and diabetes outcomes COVID-19 Coronavirus disease 2019 CoVs Coronaviruses Cr Creatinine CRP C-reactive protein CSF Cerebrospinal fluid CT Computed tomography CTSL Cathepsin L CVD Cardiovascular disease DCLO Diffusing capacity of the lungs for carbon monoxide DSM-IV Diagnostic and Statistical Manual of Mental Disorders, fourth edition EEG Electroencephalogram This article is part of the Topical Collection on Complex Medical-Psychiatric Issues.

Parkinson’s disease-related motor and non-motor symptoms are not more prevalent in the Lancaster Amish

IntroductionPrevious studies have suggested that the Amish may experience a relatively high preva... more IntroductionPrevious studies have suggested that the Amish may experience a relatively high prevalence of Parkinson’s disease (PD) and/or parkinsonian-motor signs.MethodsWe assessed the frequency of PD-related motor and no-motor symptoms in a large sample from the Amish Community in Lancaster County, Pennsylvania age ≥ 18 y.ResultsOf 430 participants ≥ 60 years, five (1.2%) reported a PD diagnosis, a prevalence similar to estimates in the general older adult populations. Of those without a PD diagnosis, 10.5% reported ≥ 1 and 1.2% ≥ 4 motor symptoms for the nine-item PD screening questionnaire. We also used questionnaires to assess non-motor symptoms. Constipation was reported in 0.7%, and daytime sleepiness in 8.1% of the participants. These frequencies are similar to, or lower than, corresponding frequencies reported in the US National Health and Nutrition Examination Surveys.DiscussionThese data neither support a markedly higher PD prevalence in the Lancaster Amish, nor do they s...

Increased brain vitamin D receptor expression and decreased expression of cathelicidin antimicrobial peptide in individuals who died by suicide

Journal of Psychiatric Research, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Toxoplasma gondii IgG associations with sleepwake problems, sleep duration and timing

Pteridines, 2019

Background: Evidence links Toxoplasma gondii (T. gondii), a neurotropic parasite, with schizophre... more Background: Evidence links Toxoplasma gondii (T. gondii), a neurotropic parasite, with schizophrenia, mood disorders and suicidal behavior, all of which are associated and exacerbated by disrupted sleep. Moreover, low-grade immune activation and dopaminergic overstimulation, which are consequences of T. gondii infection, could alter sleep patterns and duration. Methods: Sleep data on 833 Amish participants [mean age (SD) = 44.28 (16.99) years; 59.06% women] were obtained via self-reported questionnaires that assessed sleep problems, duration and timing. T. gondii IgG was measured with ELISA. Data were analyzed using multivariable logistic regressions and linear mixed models, with adjustment for age, sex and family structure. Results: T. gondii seropositives reported less sleep problems (p < 0.005) and less daytime problems due to poor sleep (p < 0.005). Higher T. gondii titers were associated with longer sleep duration (p < 0.05), earlier bedtime (p < 0.005) and earlier ...

Heritability of plasma neopterin levels in the Old Order Amish

Journal of neuroimmunology, Jan 15, 2017

We examined the heritability of neopterin, a biomarker for cell-mediated immunity and oxidative s... more 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. Plasma neopterin levels were determined in 2015 Old Order Amish adults. Quantitative genetic procedures were used to estimate heritability of neopterin. 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). 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.

Sparring and Neurological Function in Professional Boxers

Frontiers in Public Health, 2014

Despite increased interest regarding the potentially long-term negative impact of chronic traumat... more 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.

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

Journal of affective disorders, Jan 28, 2014

Several studies documented that lower scores on the Morningness-Eveningness Questionnaire (MEQ) a... more 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. 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. GSS w...

Tree pollen peaks are associated with increased nonviolent suicide in women

Molecular Psychiatry, 2004

Elevated cytokine expression in the orbitofrontal cortex of victims of suicide

Acta Psychiatrica Scandinavica, 2008

Objective-Based on the reported association between cytokines with depression and suicide, and ev... more 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. Method-In a postmortem sample obtained from the Brodman area 11 of suicides (n = 34) and controls (n = 17), real-time RT-PCR was used to compare the expression of mRNA species for tumor necrosis factor-a (TNF-α), interleukin (IL)-1β, 4, 5, 6, and 13. Results-Increased expression of IL-4 was found in women suicide victims and IL-13 in men suicide victims. Elevated but not significant cytokine expression was also observed for TNF-α in women suicide victims. Conclusion-To our knowledge, these results provide the first evidence of the presence of mRNA transcripts of type 2 T-helper cytokines in the human orbitofrontal cortex and their increased expression in the brain of suicides. Keywords suicide; postmortem; gene expression; brain; neuroimmune Significant outcomes • Neuroimmune abnormalities in the brains of suicide completers are associated with type-2 (TH2) cytokines. • These results are consistent with the reported association between allergies and suicide.

Seasonal Changes in Sleep Duration in African American and African College Students Living In Washington, D.C

The Scientific World JOURNAL, 2007

Duration of nocturnal melatonin secretion, a marker of “biological night” that relates to sleep d... more Duration of nocturnal melatonin secretion, a marker of “biological night” that relates to sleep duration, is longer in winter than in summer in patients with seasonal affective disorder (SAD), but not in healthy controls. In this study of African and African American college students, we hypothesized that students who met criteria for winter SAD or subsyndromal SAD (S-SAD) would report sleeping longer in winter than in summer. In addition, based on our previous observation that Africans report more “problems” with change in seasons than African Americans, we expected that the seasonal changes in sleep duration would be greater in African students than in African American students. Based on Seasonal Pattern Assessment Questionnaire (SPAQ) responses, African American and African college students in Washington, D.C. (N = 575) were grouped into a winter SAD/S-SAD group or a no winter diagnosis group, and winter and summer sleep length were determined. We conducted a 2 (season) × 2 (sex)...

Summer SAD and Diastolic BP Reactivity to the Cold Pressor Test

Biological Psychiatry

Winter Pattern of Seasonality is Associated With a Blunted Systolic Blood Pressure Response to the Cold Pressor Test

Biological Psychiatry

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

Psychiatry research, Jan 22, 2018

Previously, we reported that Toxoplasma gondii (T. gondii)-seropositivity is associated with high... more 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 ...

$Research paper thumbnail of {"__content__"=>"Positive association between IgG serointensity and current dysphoria/hopelessness scores in the Old Order Amish: a preliminary study.", "i"=>{"__content__"=>"Toxoplasma gondii"}}$

{"__content__"=>"Positive association between IgG serointensity and current dysphoria/hopelessness scores in the Old Order Amish: a preliminary study.", "i"=>{"__content__"=>"Toxoplasma gondii"}}

Pteridines, 2017

Toxoplasma gondii (T. gondii) IgG seropositivity and serointensity have been previously associate... more 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.

$Research paper thumbnail of {"__content__"=>"Sleep onset insomnia, daytime sleepiness and sleep duration in relationship to IgG seropositivity and serointensity.", "i"=>{"__content__"=>"Toxoplasma gondii"}}$

{"__content__"=>"Sleep onset insomnia, daytime sleepiness and sleep duration in relationship to IgG seropositivity and serointensity.", "i"=>{"__content__"=>"Toxoplasma gondii"}}

Pteridines, 2017

Toxoplasma gondii (T. gondii) infects central nervous tissue and is kept in relative dormancy by ... more 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.

Mental Health in Allergic Rhinitis: Depression and Suicidal Behavior

Current Treatment Options in Allergy

A high proportion of suicides visit their medical provider in the month prior to death, but depre... more A 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 much needed basic and clinical research to guide clinical approach for patients with comorbid allergic rhinitis and depression, the simple steps recommended here are expected to improved clinical outcomes in depression, including, on a large scale, reduced premature deaths by suicide.

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

Journal of affective disorders, Nov 22, 2017

We tested the hypothesis that the early improvement in mood after the first hour of bright light ... more 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. 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. No signific...

Magnesium Deficiency in Fibromyalgia Syndrome

Since patients with either fibromyalgia syndrome (FS) or low magnesium (Mg) levels can have fatig... more Since patients with either fibromyalgia syndrome (FS) or low magnesium (Mg) levels can have fatigue, sleep disturbance and anxiety, it was necessary to determine if some patients with FS also have low Mg levels. Both red blood cell (RBC) and plasma Mg levels were measured in 100 consecutive FS patients and 12 osteoarthritis (OA) control patients. Compared to reference laboratory and OA controls, FS patients had significantly lower RBC Mg levels. The plasma Mg levels of FS patients were no different than the reference laboratory or OA controls. Some FS patients have low Mg levels, a problem that is potentially correctable.

Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals

Journal of psychiatry & neuroscience : JPN, Oct 11, 2016

Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a ... more Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology. We used postmortem brain tissue from the ventrolateral prefrontal cortex (VLPFC) to assess tissue levels of tryptophan and KP metabolites, the expression of several KP enzymes and a series of cytokines as well as tissue pathology, including microglial activation. Tissue samples came from nonpsychiatric controls (n = 36) and individuals with depressive disorder not otherwise specified (DD-NOS, n = 45) who died of natural c...