Role Of Symptom Severity Research Articles

S709 Factors Influencing Physician Consultation in Retrograde Cricopharyngeus Dysfunction (R-CPD): The Role of Symptom Severity and Social Implications

S709 Factors Influencing Physician Consultation in Retrograde Cricopharyngeus Dysfunction (R-CPD): The Role of Symptom Severity and Social Implications

The role of free vitamin D and vitamin D binding protein in SARS-Cov-2 infection in children.

Many studies have discussed the effects of serum vitamin D deficiency in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. This study aimed to investigate the relationship between SARS-CoV-2 infection severity and free vitamin D (FVD) and bioavailable vitamin D (BAVD) levels in children. A prospective case-control study design was used. Participants were divided into three groups based on the World Health Organization COVID-19 Clinical Progression Scale. Serum 25-hydroxyvitamin D (ng/mL), albumin (g/L), and vitamin D binding protein (ng/mL) levels were evaluated to investigate the relationship between disease severity and FVD and BAVD levels. In total, 82 participants were included in the study. Of those, 24.4% were uninfected (n = 20), 50% had a mild case of SARS-CoV-2 (n = 41), and 25.6% had a moderate case (n = 21). There was a statistically significant difference in FVD and BAVD levels between the groups (p = 0.026). Median FVD (p = 0.007, Cohen's d = 0.84) and BAVD (p = 0.007, Cohen's d = 0.86) levels were significantly higher in the mild group compared to the moderate group. FVD and BAVD metabolites were moderately positively correlated with lymphocyte counts (FVD: r = 0.437, p < 0.001; BAVD: r = 0.439, p < 0.001). This is the first study to demonstrate a relationship between SARS-CoV-2 symptom severity and FVD and BAVD levels. The relationship between FVD and BAVD levels and lymphocyte counts could play an important role in symptom severity and should be evaluated in further studies.

0693 A Characterization of Social Rhythms in Obsessive-Compulsive Disorder

Abstract Introduction Recent evidence has shown that obsessive-compulsive disorder (OCD) is linked to shifts in biologically driven sleep timing, indicating the role of biological rhythms within the disorder. Specifically, initial evidence suggests that biological disruptions in OCD may play a role in symptom severity and OCD treatment efficacy. Germane to the study of biological rhythmicity is the consideration of social rhythms within OCD. Disruptions in social rhythmicity are found in other psychological disorders associated with biological rhythm vulnerabilities (i.e., Bipolar Spectrum Disorder, Depression, and Post-Traumatic Stress Disorder.) Given the shared features and high rates of comorbidity between OCD and these disorders, it is reasonable that social rhythm disruptions would be found in OCD as well. As no research to date has examined this, we sought to examine the regularity and distribution of social rhythm in individuals with clinically significant obsessive-compulsive symptoms. Further, we examined the role of affect and symptom severity across OCD subtypes. Methods 19 adults meeting criteria for a primary diagnosis of obsessive-compulsive disorder completed the Social Rhythm Metric at home for a period of 7 days. As part of a larger study, participants completed measures of sleep (Pittsburgh Sleep Quality Index), affect (Positive and Negative Affect Schedule), and obsessive-compulsive symptom severity and subtype (Obsessive-Compulsive Inventory) following diagnosis. Results We found the mean social rhythmicity in those with an OCD diagnosis to be 3.05 (SD=1.14.), similar to means found previously in other psychiatric disorders such as Bipolar Spectrum Disorder and Post-Traumatic Stress Disorder. Individuals with OCD who also reported delayed bedtimes were shown to have significantly lower social rhythmicity (p=.005) than those without delayed bedtimes. Additionally, we found that social rhythmicity correlated similarly across OCD subtypes and was not strongly correlated with negative affect. Conclusion In the current study, we provide a preliminary characterization of social rhythmicity in those with OCD. Results suggest that social rhythm may play a role in OCD similar to bipolar disorder and further study is warranted. Overall, this study contributes to burgeoning research into the association between biological rhythms and OCD. Support (If Any)

Cognitive impairment is associated with greater preoperative symptoms, worse health-related quality of life, and reduced likelihood of recovery after cervical and lumbar spine surgery

BackgroundCognitive impairment (CI) is associated with prolonged hospital stays and increased complications; however, its role in symptom severity and health-related quality of life (HRQoL) among spine patients is unknown. We determined 1) prevalence of preoperative CI; 2) associations between CI and preoperative pain, disability, and HRQoL; and 3) association between CI and postoperative improvements in HRQoL. MethodsThis is a prospective cohort study of 453 consecutive adult spine surgery patients between October 2019 and March 2021. We compared pain (Numeric Rating Scale, NRS), pain-related disability (Oswestry/Neck Disability Index, O/NDI), and HRQoL (PROMIS-29 profile, version 2.0) among participants having severe (PROMIS-29 Cognitive Abilities score ≤30), moderate (31–35), or mild CI (36–40) or who were unimpaired (score >40), using analysis of variance. Likelihood of clinical improvement given the presence of any CI was estimated using logistic regression. All comparisons were adjusted for age, gender, comorbidity, and use of opioid medication during the last 30 days. Alpha=.05. ResultsEighty-five respondents endorsed CI (38 mild; 27 moderate; 20 severe). Preoperatively, those with CI had more severe back pain (p=.005) and neck pain (p=.025) but no differences in leg or arm pain. Those with CI had greater disability on ODI (p<.001) and NDI (p<.001) and worse HRQoL in all domains (all, p<.001). At 6 and 12 months postoperatively, those with CI were less likely to experience clinical improvement in disability and HRQoL (anxiety, pain interference, physical function, and satisfaction with ability to participant in social roles) (all, p<.05). ConclusionsCI was present in nearly 20% of spine patients before surgery and was independently associated with worse preoperative back and neck pain, disability, and HRQoL. Those with CI had approximately one-half the likelihood of achieving meaningful clinical improvement postoperatively. These results indicate a need to evaluate spine patients’ cognitive impairment prior to surgery. Level of EvidenceIII

Persistent Symptoms, Lyme Disease, and Prior Trauma.

One prior study suggests that traumatic events before Lyme disease play an important role in symptom severity. We examined this hypothesis among 60 individuals with persistent symptoms after Lyme disease using validated measures of trauma history, mental and physical symptoms, and functional status. Analysis of variance with Tukey-Kramer multiple comparisons test revealed that a greater number of traumatic events were significantly associated with greater symptom severity on the scales of mood (stress, depression, and anxiety), cognition, multisystem symptom burden, and functional status (mental and physical), but not on measures of pain and fatigue. The effect sizes-meaningful but not large (0.17-0.29)-were mostly produced by comparison with individuals reporting multiple prior traumatic events, representing half of the posttreatment Lyme disease syndrome (PTLDS) group. In conclusion, although PTLDS may be exacerbated by past trauma, trauma plays a role in only a subgroup of PTLDS. Whether addressing prior trauma can improve outcomes in this subgroup requires study.

Utilization of machine learning for identifying symptom severity military-related PTSD subtypes and their biological correlates

We sought to find clinical subtypes of posttraumatic stress disorder (PTSD) in veterans 6–10 years post-trauma exposure based on current symptom assessments and to examine whether blood biomarkers could differentiate them. Samples were males deployed to Iraq and Afghanistan studied by the PTSD Systems Biology Consortium: a discovery sample of 74 PTSD cases and 71 healthy controls (HC), and a validation sample of 26 PTSD cases and 36 HC. A machine learning method, random forests (RF), in conjunction with a clustering method, partitioning around medoids, were used to identify subtypes derived from 16 self-report and clinician assessment scales, including the clinician-administered PTSD scale for DSM-IV (CAPS). Two subtypes were identified, designated S1 and S2, differing on mean current CAPS total scores: S2 = 75.6 (sd 14.6) and S1 = 54.3 (sd 6.6). S2 had greater symptom severity scores than both S1 and HC on all scale items. The mean first principal component score derived from clinical summary scales was three times higher in S2 than in S1. Distinct RFs were grown to classify S1 and S2 vs. HCs and vs. each other on multi-omic blood markers feature classes of current medical comorbidities, neurocognitive functioning, demographics, pre-military trauma, and psychiatric history. Among these classes, in each RF intergroup comparison of S1, S2, and HC, multi-omic biomarkers yielded the highest AUC-ROCs (0.819–0.922); other classes added little to further discrimination of the subtypes. Among the top five biomarkers in each of these RFs were methylation, micro RNA, and lactate markers, suggesting their biological role in symptom severity.

Identification of Subgenomic DNAs Associated with Wheat Dwarf Virus Infection in Iran.

Background: Wheat dwarf virus (WDV) is a leafhopper-transmitted DNA virus which causes yellowing and stunting in wheat and barley fields leading to considerable crop loss around the world. Mainly, two host-specific forms of WDV have been characterized in wheat and barley (WDV-Wheat and WDV-Barley, respectively).Objectives: This study was aimed to amplify, sequence and describe subgenomic DNAs (sgDNAs) associated with WDV infection among wheat and barley plants. The nucleotide sequence of sgDNAs were then compared to that of parental genomic DNAs (gDNAs) and the differences were shown.Materials and Methods: A total of 65 symptomatic plants were surveyed for WDV infection using double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) and polymerase chain reaction (PCR). Rolling circle amplification followed by restriction analysis (RCA-RA) was applied to identify both gDNAs and sgDNAs in the infected wheat and barley plants. Nucleotide sequence of eight full-length WDV genomes and five sgDNAs were determined.Results: Genomic sequences of WDV-Wheat and WDV-Barley isolates obtained in this study were identified as WDV-F and WDV-B, respectively, forming a separate cluster in the phylogenetic tree with the highest bootstrap support (100%). Sequence analysis of sgDNA molecules revealed that they have undergone different mutation events including deletions in viral genes, duplication of coding regions, and insertion of host-derived sequencesConclusions: The association of different types of sgDNAs were found in WDV-infected wheat and barley plants. The sgDNAs exhibited remarkable changes compared to their parental molecules and they might play a role in symptom severity, host genome evolution and emergence of new virus variants/species.

Association of prior depressive symptoms and suicide attempts with subsequent victimization: analysis of population-based data from the Adult Psychiatric Morbidity Survey

Symptoms of mental disorder, particularly schizophrenia, predispose to victimization. Much less is known about the relationship between depressive symptoms and later victimization in the general population, the influence of these symptoms on types of subsequent victimization, or the role of symptom severity. We investigated this in nationally representative data from the United Kingdom. Data were from the Adult Psychiatric Morbidity Survey 2007. Multivariable logistic regressions estimated association between (a) prior depressive symptoms, (b) prior depressive symptoms with suicide attempt, and types of more recent victimization. Gender-specific associations were estimated using multiplicative interactions. Prior depressive symptoms were associated with greater odds of any recent intimate partner violence (IPV), emotional IPV, sexual victimization, workplace victimization, any victimization, and cumulative victimization (adjusted odds ratio [aOR] for increasing types of recent victimization: 1.47, 95% confidence interval [CI]: 1.14, 1.89). Prior depressive symptoms with suicide attempt were associated with any recent IPV, emotional IPV, any victimization, and cumulative victimization (aOR for increasing types of recent victimization: 2.33, 95% CI: 1.22, 4.44). Self reported recalled data on previous depressive symptoms may have limited accuracy. Small numbers of outcomes for some comparisons results in imprecision of these estimates. Aside from severe mental illness such as schizophrenia, previous depressive symptoms in the general population are associated with greater subsequent victimization. Men and women with prior depressive symptoms may be vulnerable to a range of types of victimization, and may benefit from interventions to reduce this vulnerability.

New Somatic Treatments for Child and Adolescent Depression.

Depression is a common clinical problem in youth, with prevalence increasing significantly during the adolescent period. Although several evidence-based treatments are currently available for treating depression in adults, only a subset of these have been investigated in a pediatric sample. Unfortunately, even well-established, first-line interventions do not lead to sufficient treatment response for many children and adolescents suffering from depression. However, recent research has been conducted in the area of somatic treatments for youth with depression. This review focuses on current (past three years, including published results and ongoing studies) research on somatic treatments for adolescent depression in the following categories: psychopharmacology, nutraceuticals, interventions implicating motor and sensory systems, and neuromodulation. Results from recent randomized, controlled trials testing psychopharmacological options suggest that while antidepressants that have been recently approved for adult patients are safe and tolerable in children and adolescents, none have yet outperformed performed placebo in efficacy. Nutraceuticals, motor-sensory interventions, and neuromodulation techniques, present safe and promising results, but few have been tested against controls to support effectiveness over current treatment options. This review of research on pediatric depression treatment from the past 3 years highlights some disappointments (negative results following some of the well-designed clinical trials) and gaps (preliminary studies in need of follow up with robust methodology) but also some promising directions in research of the efficacyof these treatments in a pediatric sample. We offer suggestions for future research including consideration of treatment timing, sequencing, the role of symptom severity in directing treatment selection, the potential value of combined treatments, consideration of how to best account for high placebo response rates, and the incorporation of neurobiological assessments to examine mechanisms and biomarker predictors of treatment response.

Latent toxoplasmosis and psychiatric symptoms – A role of tryptophan metabolism?

Toxoplasma gondii (TOX) is a common parasite which infects approximately one third of the human population. In recent years, it has been suggested that latent toxoplasmosis may be a risk factor for the development of mental disorders, particularly schizophrenia and anxiety. With regards to depression the results have been varied.The main objective of this study was to examine subpopulations from the Danish PRISME and GENDEP populations for TOX IgG antibodies. These consisted of: a group with symptoms of anxiety, a group suffering from burnout syndrome, as well as two different subpopulations with depression of differing severity. The secondary objective of this study was to examine whether tryptophan metabolism was altered in TOX-positive subjects within each subpopulation.Our results show that the anxiety and burnout populations were more likely to be TOX IgG seropositive. Furthermore, we find that the moderate-severe but not mild-moderate depressive subpopulation were associated with TOX seropositivety, suggesting a possible role of symptom severity. Additionally, we found that TOX positive subjects in the anxiety and burnout subpopulations had altered tryptophan metabolism. This relationship did not exist in the mild-moderate depressive subpopulation.These results suggest that TOX seropositivity may be related to anxiety, burnout and potentially to severity of depression. We furthermore show that the psychiatric symptoms could be associated with an altered tryptophan metabolism.

Socioeconomic status is associated with symptom severity and sickness absence in people with infectious intestinal disease in the UK

BackgroundThe burden of infectious intestinal disease (IID) in the UK is substantial. Negative consequences including sickness absence are common, but little is known about the social patterning of these outcomes, or the extent to which they relate to disease severity.MethodsWe performed a cross-sectional analysis using IID cases identified from a large population-based survey, to explore the association between socioeconomic status (SES) and symptom severity and sickness absence; and to assess the role of symptom severity on the relationship between SES and absence. Regression modelling was used to investigate these associations, whilst controlling for potential confounders such as age, sex and ethnicity.ResultsAmong 1164 cases, those of lower SES versus high had twice the odds of experiencing severe symptoms (OR 2.2, 95%CI;1.66–2.87). Lower SES was associated with higher odds of sickness absence (OR 1.8, 95%CI;1.26–2.69), however this association was attenuated after adjusting for symptom severity (OR 1.4, 95%CI;0.92–2.07).ConclusionsIn a large sample of IID cases, those of low SES versus high were more likely to report severe symptoms, and sickness absence; with greater severity largely explaining the higher absence. Public health interventions are needed to address the unequal consequences of IID identified.

Risk and Protective Factors, Perceptions of Family Environment, Ethnicity, and Schizophrenia Symptoms.

The family environment can play either a detrimental or a protective role in symptom severity for people with schizophrenia. The current study examined both patient and caregiver perspectives of the family environment in an ethnically diverse sample of 221 patients with schizophrenia. We hypothesized that environments characterized by high levels of perceived caregiver criticism, low perceived caregiver warmth, and low family cohesion (from both the patient and caregiver perspective) would predict greater symptom severity. As expected, results demonstrated that lower patient ratings of family cohesion and caregiver warmth were associated with greater symptom severity. However, once put into a hierarchical regression analysis, only patient ratings of family cohesion remained significant. Ethnic patterns were also examined and revealed that family cohesion may be particularly protective for ethnic minorities. Study implications are discussed.

Cultural differences in seeking mental health counseling: The role of symptom severity and type in Appalachian Kentucky.

Cultural differences in seeking mental health counseling: The role of symptom severity and type in Appalachian Kentucky.

Severity of Depression Predicts Remission Rates Using Transcranial Magnetic Stimulation.

Multiple factors likely impact response and remission rates in the treatment of depression with repetitive transcranial magnetic stimulation (rTMS). Notably, the role of symptom severity in outcomes with rTMS is poorly understood. This study investigated the predictors of achieving remission in patients suffering from depression who receive ≥3 rTMS treatments per week. Available data on 41 patients treated at Walter Reed National Military Medical Center from 2009 to 2014 were included for analysis. Patients received a range of pulse sequences from 3,000 to 5,000 with left-sided or bilateral coil placement. Primary outcome measures were total score on the Patient Health Questionnaire-9 or the Quick Inventory of Depressive Symptomatology-Self Rated. Remission was defined as a total score less than five, and response was defined as a 50% decrease in the total score on both outcome metrics. Outcomes in patients diagnosed as suffering from mild or moderate depression were compared to those suffering from severe depression. Of the 41 patients receiving treatment, 16 reached remission and 18 reached response by the end of treatment. Remission rate was associated with the initial severity of depression, with patients with mild or moderate depression reaching remission at a significantly higher rate than those with severe depression. Total number of rTMS sessions or length of treatment was not predictors of remission. Patients with a baseline level of depression characterized as mild or moderate had significantly better outcomes following rTMS compared to patients with severe depression.

The relationship between adverse childhood experiences and symptom severity, chronicity, and comorbidity in patients with obsessive-compulsive disorder.

Studies on the relationship between adverse childhood experiences (ACEs) and obsessive-compulsive disorder (OCD) symptom severity are scarce. Available studies leave a considerable degree of uncertainty. The present study examines the relationship between ACEs and symptom severity, chronicity, and comorbidity in a sample of patients with OCD. Baseline data of the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study, in which 382 referred patients with DSM-IV-diagnosed OCD participated, were analyzed. ACEs (physical abuse, sexual abuse, witnessing interparental violence, maternal dysfunction, paternal dysfunction, and early separation from a parent) were measured using a structured interview. Data were collected between September 2005 and November 2009. None of the ACEs were related to OCD symptom severity or chronicity, nor was there a dose-response relationship between ACEs and OCD severity or chronicity, but results of linear regression analysis revealed that ACEs were related to comorbidity in patients with OCD (P < .001), in particular to comorbid affective disorders (P < .01), substance use disorders (P < .01), and eating disorders (P < .01), but not to comorbid anxiety disorders. Results of the study suggest that unlike in other psychiatric disorders, ACEs play no significant role in symptom severity and chronicity of OCD. This study was the first to reveal evidence for a relationship between ACEs and comorbidity in patients with OCD. Conclusions about trauma-relatedness of OCD based on studies finding higher trauma rates or severity among patients with OCD than among healthy controls, should be critically reconsidered, since presence of comorbidity might account for these differences.

The costs of social anxiety disorder: The role of symptom severity and comorbidities

BackgroundSocial anxiety disorder (SAD) is associated with low direct costs compared to other anxiety disorders while indirect costs tend to be high. Mental comorbidities have been identified to increase costs, but the role of symptom severity is still vague. The objective of this study was to determine the costs of SAD, and to explore the impact of symptoms and comorbidities on direct and indirect costs. MethodsBaseline data, collected within the SOPHO-NET multi-centre treatment study (N=495), were used. Costs were calculated based on health care utilization and lost productivity. Symptom severity was measured with the Liebowitz-Social-Anxiety-Scale; comorbidities were included as covariates. ResultsTotal 6-month costs were accrued to €4802; 23% being direct costs. While there was no significant association with SAD symptom severity for direct costs, costs of absenteeism increased with symptom severity in those with costs >0; comorbid affective disorders and eating disorders had an additional effect. Self-rated productivity was lower with more pronounced symptoms even after controlling for comorbidities. LimitationsAs the study was based on a clinical sample total costs were considered, rather than net costs of SAD and no population costs could be calculated. DiscussionThe burden associated with lost productivity was considerable while costs of healthcare utilization were rather low as most patients had not sought for treatment before. Efforts to identify patients with SAD earlier and to provide adequate treatment should be further increased. Mental comorbidities should be addressed as well, since they account for a large part of indirect costs associated with SAD.

Abstract SY31-03: Inflammatory mechanisms of cancer-related fatigue

Abstract Fatigue is one of the most common and disabling side effects of cancer treatment and may persist for months or years after successful treatment completion, causing significant impairment in quality of life. Basic research on neural-immune signaling has demonstrated that proinflammatory cytokines signal the central nervous system to trigger a constellation of behavioral changes that include fatigue as well depression, sleep disturbance, and cognitive impairment. This presentation will review the evidence linking proinflammatory cytokines and fatigue in cancer patients and survivors. In addition, we will consider host factors that influence inflammation and associated symptoms of fatigue, focusing on genetic mechanisms. There is considerable variability in the experience of post-treatment fatigue that cannot be explained by treatment exposure, suggesting that host factors play an important role in symptom severity and persistence. Single nucleotide polymorphisms (SNPs) that influence quantitative gene expression have been identified in the promoter regions of several genes that encode proinflammatory cytokines and examined individually in relation to breast cancer susceptibility and prognosis as well as behavioral symptoms. Here, we will present findings linking SNPs in the promoter regions of three proinflammatory cytokine genes (IL-1β -511 C&amp;gt;T (rs16944), IL6 -174 G&amp;gt;C (rs1800795), and TNF -308 G&amp;gt;A (rs1800629)) to fatigue in breast cancer survivors. Further, we will consider how alterations in glucocorticoid signaling pathways may contribute to persistent cancer-related fatigue. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY31-03. doi:1538-7445.AM2012-SY31-03

Psychophysiological evidence for cortisol-induced reduction in early bias for implicit social threat in social phobia

The stress hormone cortisol is important for the regulation of social motivational processes. High cortisol levels have been associated with social fear and avoidance, which play an important role in social anxiety disorder (SAD), as does hypervigilant processing of social threat. However, causal effects of cortisol on threat processing in SAD remain unclear. In an event-related potential (ERP) study we investigated the effects of cortisol on task-irrelevant (implicit) processing of social threat in SAD, exploring the temporal dynamics as well as the role of symptom severity and stimulus awareness. Angry face processing was measured in participants with clinical SAD after double-blind, within-subject oral administration of cortisol (50mg) and placebo, using a masked and an unmasked emotional Stroop task. Both tasks showed significantly increased P2 midline ERP amplitudes for angry compared to neutral and happy faces in the placebo condition, reflecting an early attentional bias for social threat in SAD. Furthermore, cortisol administration significantly decreased P2 amplitudes for masked angry faces. This effect correlated with social anxiety, showing stronger decreases in patients with higher levels of social anxiety. These results indicate a highly specific effect of cortisol on early motivated attention to social threat and, together with previous findings, highlight the importance of motivational context (stimulus- or task-relevance) as well as symptom severity.

Barriers to Care for Antenatal Depression

Barriers to Care for Antenatal Depression

ADHD: Braun et al. Respond

We appreciate the comments of Brondum, and Konofal and Cortese, and the opportunity to clarify our results (Braun et al. 2006). It is common practice to select variables with a p-value of 0.2 for inclusion in multivariable models (Katz 1999). Although the association of blood lead levels and ADHD appeared “tenuous” in bivariate analysis (i.e., p = 0.19), this was largely an artifact of our decision to categorize blood lead levels. When we entered lead into our multivariable analysis as a continuous variable, we found a 1.2-fold increased odds [95% confidence interval (CI), 1.0–1.4; p = 0.02] of ADHD for each 1.0-μg/dL increase in blood lead levels. The blood lead quintiles were not divided into exactly equal sample sizes because we used weighted percentages to categorize the data. We decided a priori to present the analysis in quintiles to make the results easier to interpret and also to illustrate any dose–response relationships for blood lead levels and ADHD. As we noted in the “Discussion” of our article (Braun et al. 2006), a limitation of our study was the inability to adjust for parental psychopathology. This is an unfortunate trade-off when using a large nationally representative survey. In other studies, prenatal tobacco exposure has been shown to be a risk factor for the development of ADHD after controlling for parental psychopathology (Mick et al. 2002; Weissman et al. 1999). Although there is considerable experimental and epidemiologic evidence linking lead exposure with behaviors consistent with ADHD, future studies of childhood lead exposure will need to confirm our results by accounting for parental psychopathology and other potential confounders. The hypothesis proposed by Konofal and Cortese—that iron deficiency may play a role in symptom severity among children with ADHD—is intriguing. Indeed, it was their original research that prompted us to incorporate ferritin as a measure of iron status (Konofal et al. 2004). It is certainly plausible that iron deficiency may confound or modify the effects of environmental lead exposure on ADHD in children. Alternatively, lead exposure may act as a confounder or modifier for the observed effects of iron deficiency with ADHD. Unfortunately, we were not able to examine whether ferritin (or other indicators of iron status) was associated with ADHD symptom severity using the National Health and Nutrition Examination Survey. Nor did we specifically test for an association between iron deficiency and ADHD. Although iron or other micronutrient supplementation may protect children from lead toxicity, recent evidence from a double-blind randomized trial (Kordas et al. 2005) suggests that iron and zinc supplementation did not appreciably lower blood lead levels or improve child behavior, as measured by the Conners Rating Scales. However, Kordas et al. included only children without anemia in their trial.