Cognitive decrements in 1991 Gulf War veterans: associations with Gulf War illness and neurotoxicant exposures in the Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) cohorts.

BACKGROUND: During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of deficit emerge with more power to detect such differences. A group of researchers and clinicians with expertise in the area of GWI have identified common data elements (CDE) for use in research samples to compare data sets. At the same time, a subgroup of researchers created a new repository to share these cognitive data and biospecimens within the GWI research community. METHODS: The present study aimed to compare cognitive measures of attention, executive functioning, and verbal memory in a large sample of GWI cases and healthy GW veteran controls using neuropsychological tests recommended in the CDEs. We additionally subdivided samples based on the specific neurotoxicant exposures related to cognitive deficits and compared exposed versus non-exposed veterans regardless of case criteria status. The total sample utilized cognitive testing outcomes from the newly collated Boston, Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI. RESULTS: Participants included 411 GW veterans, 312 GWI (cases) and 99 healthy veterans (controls). Veterans with GWI showed significantly poorer attention, executive functioning, learning, and short-and-long term verbal memory than those without GWI. Further, GW veterans with exposures to acetylcholinesterase inhibiting pesticides and nerve gas agents, had worse performance on executive function tasks. Veterans with exposure to oil well fires had worse performance on verbal memory and those with pyridostigmine bromide anti-nerve gas pill exposures had better verbal memory and worse performance on an attention task compared to unexposed veterans. CONCLUSIONS: This study replicates prior results regarding the utility of the currently recommended CDEs in determining impairments in cognitive functioning in veterans with GWI in a new widely-available repository cohort and provides further evidence of cognitive decrements in GW veterans related to war-related neurotoxicant exposures.

Genetic association between the APOE ε4 allele, toxicant exposures and Gulf war illness diagnosis.

INTRODUCTION: Exposure to nerve agents, pyridostigmine bromide (PB), pesticides, and oil-well fires during the 1991 Gulf War (GW) are major contributors to the etiology of Gulf War Illness (GWI). Since the apolipoprotein E (APOE) ε4 allele is associated with the risk of cognitive decline with age, particularly in the presence of environmental exposures, and cognitive impairment is one of the most common symptoms experienced by veterans with GWI, we examined whether the ε4 allele was associated with GWI. METHODS: Using a case-control design, we obtained data on APOE genotypes, demographics, and self-reported GW exposures and symptoms that were deposited in the Boston Biorepository and Integrative Network (BBRAIN) for veterans diagnosed with GWI (n = 220) and healthy GW control veterans (n = 131). Diagnosis of GWI was performed using the Kansas and/or Center for Disease Control (CDC) criteria. RESULTS: Age- and sex-adjusted analyses showed a significantly higher odds ratio for meeting the GWI case criteria in the presence of the ε4 allele (Odds ratio [OR] = 1.84, 95% confidence interval [CI = 1.07-3.15], p ≤ 0.05) and with two copies of the ε4 allele (OR = 1.99, 95% CI [1.23-3.21], p ≤ 0.01). Combined exposure to pesticides and PB pills (OR = 4.10 [2.12-7.91], p ≤ 0.05) as well as chemical alarms and PB pills (OR = 3.30 [1.56-6.97] p ≤ 0.05) during the war were also associated with a higher odds ratio for meeting GWI case criteria. There was also an interaction between the ε4 allele and exposure to oil well fires (OR = 2.46, 95% CI [1.07-5.62], p ≤ 0.05) among those who met the GWI case criteria. CONCLUSION: These findings suggest that the presence of the ε4 allele was associated with meeting the GWI case criteria. Gulf War veterans who reported exposure to oil well fires and have an ε4 allele were more likely to meet GWI case criteria. Long-term surveillance of veterans with GWI, particularly those with oil well fire exposure, is required to better assess the future risk of cognitive decline among this vulnerable population.

Boston biorepository, recruitment and integrative network (BBRAIN): A resource for the Gulf War Illness scientific community.

AIMS: Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. MAIN METHODS: BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. KEY FINDINGS: To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. SIGNIFICANCE: The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.

Acute phase proteins disturbances indicate uncompensated obesity declining physical fitness.

OBJECTIVE: The correlation between physical fitness and health indicators still requires a research aimed at improving the knowledge about physical fitness and the impact of obesity on the health status in children and adolescents. The aim of this study is an analysis of the results of the EUROFIT battery tests in relation to routine laboratory parameters and the inflammation markers. PATIENTS AND METHODS: In the group of 123 Polish adolescents the routine parameters of lipid metabolism and acute phase proteins were investigated, and compared with EUROFIT motor fitness tests results, expressed as percentiles of the results achieved by healthy Polish population. RESULTS: Most of the EUROFIT tests battery were performed by overweight adolescent girls on an insufficient level. Children who were described by parameters indicating more advanced obesity performed the EUROFIT tests worse. There was showed a negative correlation between the concentration of HDL cholesterol and the long jump (rho=-0.304) as well as with the speed of limb movement (rho=-0.277). There was a positive correlation between the speed of limb movement and the concentration of triglycerides (rho=0.335), LDL cholesterol (rho=0.305) and the percentage of the A4 (rho=0.239). CONCLUSIONS: Disturbed lipid parameters, as well as altered glycosylation profiles of acute phase proteins, were observed in all overweight children, and the intensity of alterations correlated with worse fitness.

Health-related quality of life in morphoea.

BACKGROUND: Little is known about the health-related quality of life (HRQoL) of patients with morphoea, and previous studies have yielded conflicting results. OBJECTIVES: To determine the impact of morphoea on HRQoL, and clinical and demographic correlates of HRQoL in adults. METHODS: This was a cross-sectional survey (n = 73) of the Morphea in Adults and Children cohort. RESULTS: Morphoea impairs HRQoL in adults. Patients were most impaired by emotional well-being and concerns that the disease would progress to internal organs. Patients with morphoea had worse skin-specific HRQoL than those with nonmelanoma skin cancer, vitiligo and alopecia (lowest P < 0·01). Participants had significantly worse global HRQoL scores than the general U.S. population for all subscales (all P < 0·01), with the exception of bodily pain. Comorbidity (r = 0·35-0·51, all P < 0·01), and symptoms of pruritus (r = 0·38-0·64, all P < 0·01) and pain (r = 0·46-0·74, all P < 0·01) were associated with impairment in multiple domains of skin-specific and global HRQoL. Physician-based measures of disease severity correlated with patient-reported HRQoL. CONCLUSIONS: Patients with morphoea experience a negative impact on HRQoL, particularly if symptoms (pruritus and pain) or concerns regarding internal manifestations are present. Providers should be aware of this when evaluating and treating patients.

Myalgic encephalomyelitis: International Consensus Criteria.

The label 'chronic fatigue syndrome' (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization's International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.

Chronic fatigue syndrome is associated with diminished intracellular perforin.

Chronic fatigue syndrome (CFS) is an illness characterized by unexplained and prolonged fatigue that is often accompanied by abnormalities of immune, endocrine and cognitive functions. Diminished natural killer cell cytotoxicity (NKCC) is a frequently reported finding. However, the molecular basis of this defect of in vitro cytotoxicy has not been described. Perforin is a protein found within intracellular granules of NK and cytotoxic T cells and is a key factor in the lytic processes mediated by these cells. Quantitative fluorescence flow cytometry was used to the intracellular perforin content in CFS subjects and healthy controls. A significant reduction in the NK cell associated perforin levels in samples from CFS patients, compared to healthy controls, was observed. There was also an indication of a reduced perforin level within the cytotoxic T cells of CFS subjects, providing the first evidence, to our knowledge, to suggest a T cell associated cytotoxic deficit in CFS. Because perforin is important in immune surveillance and homeostasis of the immune system, its deficiency may prove to be an important factor in the pathogenesis of CFS and its analysis may prove useful as a biomarker in the study of CFS.

Relative preservation of natural killer cell cytotoxicity and number in healthy AIDS patients with low CD4 cell counts.

OBJECTIVE: This study examines whether there may be an immune component that protects a relatively rare group of HIV-infected people with very low CD4 cell counts (< or = 50 x 10(6)/l) who have prolonged asymptomatic periods. DESIGN/METHODS: Three groups were recruited in Miami: (i) healthy low CD4 cell count patients (HLC; n = 30) who, for 9 months had < 50 x 10(6) CD4 cells/l, were asymptomatic and were not on protease inhibitors during that time; (ii) HIV comparison group (Comp; n = 60) who had CD4 cell counts predominantly 150 x 10(6) to 400 x 10(6)/l and never had AIDS Category C symptoms; this group was also followed for CD4 cell count and viral load change over 6 months; and (iii) healthy community controls (n = 33). The study was replicated at the University of California at Los Angeles (UCLA) with HLC (n = 31) versus HIV-negative laboratory controls (n = 28). RESULTS: The HLC patients were significantly higher than the Comp group on natural killer cell cytotoxicity (NKCC) and natural killer cell number (NK#) despite their lower CD4 cell numbers and higher viral loads. In fact, there was no difference between the HLC group and the healthy community control group in NK# or NKCC. The NK findings were replicated at UCLA. A retrospective analysis showing that higher NKCC was related to fewer prior symptoms in the HLC group, and prospective analysis in the Comp group showing that NK# predicted a lower increase in viral load over 6 months further supported the importance of NK# and NKCC. CONCLUSIONS: Non-specific cellular immunity may be a factor protecting the health of HIV sero-positive individuals with very low CD4 cell counts.

Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors.

The literature is reviewed and data are presented that relate to a model we have developed to account for the perpetuation of the perplexing disorder currently termed chronic fatigue syndrome (CFS). In patients with CFS there is chronic lymphocyte overactivation with cytokine abnormalities that include perturbations in plasma levels of proinflammatory cytokines and decrease in the ratio of Type 1 to Type 2 cytokines produced by lymphocytes in vitro following mitogen stimulation. The initiation of the syndrome is frequently sudden and often follows an acute viral illness. Our model for the subsequent chronicity of this disorder holds that the interaction of psychological factors (distress associated with either CFS-related symptoms or other stressful life events) and the immunologic dysfunction contribute to (a) CFS-related physical symptoms (e.g., perception of fatigue and cognitive difficulties, fever, muscle and joint pain) and increases in illness burden and (b) impaired immune surveillance associated with cytotoxic lymphocytes with resulting activation of latent herpes viruses.

Autonomic and cardiovascular function in HIV spectrum disease: early indications of cardiac pathophysiology.

Autonomic dysfunction in persons with acquired immune deficiency syndrome (AIDS) has been reported previously but its incidence in early stage HIV infection and its relation to cardiovascular function have not been fully examined. The present study evaluated cardiovascular and autonomic function in 55 HIV-seronegative, and 52 HIV-asymptomatic and 31 HIV-symptomatic seropositive men. Measures of hemodynamic and autonomic function were obtained at rest and during a standardized battery of autonomic tests. Results were compared across groups while controlling for age, body mass, and physical activity. Analyses indicated that measures of autonomic function did not differ among groups. However, at rest, both HIV seropositive groups exhibited diminished stroke volume and elevated diastolic blood pressure, albeit within normotensive levels. In addition, the ability to sustain a blood pressure response during prolonged challenge and the relationship between stroke volume and baroreceptor/vagal responsiveness were disrupted in the HIV-symptomatic group. Therefore, in the pre-AIDS stages of infection, autonomic functioning appeared intact; yet alterations in baroreceptor/vagal function associated with depressed myocardial function may be an early warning signal reflecting cardiovascular pathological processes potentially exacerbated by HIV spectrum disease.

Enhancing adherence to combination antiretroviral therapy in non-adherent HIV-positive men.

This paper describes a preliminary study aimed at testing the efficacy of a brief medication counselling and behavioural intervention in improving adherence to combination antiretroviral medication therapy and prophylactic treatment among non-adherent men living with HIV. Twenty-one non-adherent HIV-positive men obtaining primary care clinical services at a Veterans Affairs Medical Center were recruited by health care providers. Intervention participants were primarily African-Americans with histories of intravenous drug use. During a period of five months, participants were provided with monthly medication counselling and a weekly medication pill organizer. Participants were compared with 21 non-adherent matched controls receiving standard pharmacy care including review of medications. Intervention and control subjects were compared on several variables: medication refill timeliness, appointment attendance, hospitalizations and opportunistic infections. Medical information was obtained from hospital and pharmacy records at baseline and post-intervention. Pre- to post-intervention rates of adherence to medication refills and clinic appointments increased significantly among intervention participants. Relative to matched controls, intervention participants also significantly increased drop-in visits and showed fewer hospitalizations. Intervention participants also showed significant decreases in the number of opportunistic infections. Results suggest that exposure to medication counselling and behavioural interventions increase adherence, with associated reductions in negative clinical outcomes.

Cognitive-behavioral stress management reduces distress and 24-hour urinary free cortisol output among symptomatic HIV-infected gay men.

BACKGROUND: Stress management interventions can reduce symptoms of distress as well as modulate certain immune system components in persons infected with human immunodeficiency virus (HIV). These effects may occur in parallel with reductions in hypothalamic-pituitary-adrenal (HPA) axis hormones such as cortisol, which has been related in other work to a down-regulation of immune system components relevant to HIV infection. The present study tested the effects of a multimodal cognitive-behavioral stress management (CBSM) intervention on 24-hour urinary free cortisol levels and distressed mood in symptomatic HIV+ gay men. METHODS: Symptomatic HIV-infected gay men who were randomized to either a 10-week group-based CBSM intervention or a 10-week wait-list period provided psychological responses and urine samples pre-post intervention. RESULTS: Of the 59 participants providing matched questionnaire data, men assigned to CBSM (n = 40) showed significantly lower posttreatment levels of self-reported depressed affect, anxiety, anger, and confusion than those in the wait-list control group (n = 19). Among the 47 men providing urine samples (34 CBSM, 13 controls), those assigned to CBSM revealed significantly less cortisol output as compared to controls. At the individual level, depressed mood decreases paralleled cortisol reductions over this period across the entire sample. CONCLUSION: A time-limited CBSM intervention reduced distress symptoms and urinary free cortisol output in symptomatic HIV+ gay men and greater reductions in some aspects of distress, especially depressed mood, paralleled greater decreases in cortisol over the intervention period. If persisting stressors and depressed mood contribute to chronic HPA axis activation in HIV-infected persons, then interventions such as CBSM, which teaches them to relax, alter cognitive appraisals, use new coping strategies, and access social support resources, may decrease distress and depressed mood and normalize HPA axis functioning.

Cognitive-behavioral stress management intervention effects on anxiety, 24-hr urinary norepinephrine output, and T-cytotoxic/suppressor cells over time among symptomatic HIV-infected gay men.

The present study tested the effects of a multimodal cognitive-behavioral stress management (CBSM) intervention on anxious mood, perceived stress, 24-hr urinary catecholamine levels, and changes in T-lymphocyte subpopulations over time in symptomatic HIV+ gay men. Seventy-three men were randomized to either a group-based CBSM intervention (n = 47) or a wait-list control (WLC) condition (n = 26). Men assigned to CBSM showed significantly lower posttreatment levels of self-reported anxiety, anger, total mood disturbance, and perceived stress and less norepinephrine (NE) output as compared with men in the WLC group. At the individual level, anxiety decreases paralleled NE reductions. Significantly greater numbers of T-cytotoxic/suppressor (CD3+CD8+) lymphocytes were found 6 to 12 months later in those assigned to CBSM. Moreover, greater decreases in NE output and a greater frequency of relaxation home practice during the 10-week CBSM intervention period predicted higher CD3+CD8+ cell counts at follow-up.

Cognitive-behavioral stress management increases free testosterone and decreases psychological distress in HIV-seropositive men.

The effects of a 10-week group-based cognitive-behavioral stress management (CBSM) intervention on psychological distress and plasma free testosterone in symptomatic, HIV-seropositive men were examined. Participants were randomized to either CBSM (n = 42) or a wait-list control group (n = 23). Men in the CBSM intervention showed significant increases in testosterone, whereas control participants showed significant decreases. Those participating in CBSM had significant distress reductions, whereas controls showed no such change. Alterations in free testosterone were inversely related to changes in distress states over time, independent of any changes in cortisol. These findings demonstrate that a short-term CBSM intervention increases free testosterone levels among symptomatic, HIV-seropositive men, and alterations in free testosterone are associated with changes in psychological distress observed during CBSM.

Reductions in herpes simplex virus type 2 antibody titers after cognitive behavioral stress management and relationships with neuroendocrine function, relaxation skills, and social support in HIV-positive men.

OBJECTIVE: Coinfection with herpes simplex virus type 2 (HSV-2) is common in individuals infected with human immunodeficiency virus (HIV) and may have health implications. This study examined the effect of a 10-week cognitive behavioral stress management (CBSM) intervention on immunoglobulin G (IgG) antibody titers to HSV-2 in a group of mildly symptomatic HIV-infected gay men and the degree to which these effects were mediated by psychosocial and endocrine changes during the 10-week period. METHODS: Sixty-two HIV+ gay men were randomly assigned to either a 10-week CBSM intervention (N = 41) or a wait-list control condition (N = 21). Anxious mood, social support, cortisol/dehydroepiandrosterone sulfate (DHEA-S) ratio levels, and HSV-2 IgG antibody titers were assessed at baseline and after the 10-week period. CBSM participants also recorded their stress levels before and after at-home relaxation practice. RESULTS: HSV-2 IgG titers were significantly reduced in the CBSM participants but remained unchanged in the control group after the 10-week intervention period. Increases in one type of social support, perceived receipt of guidance, during the 10 weeks was associated with and partially mediated the effect of the intervention on HSV-2 IgG. Similarly, decreases in cortisol/DHEA-S ratio levels were associated with decreases in HSV-2 IgG, and lower mean stress levels achieved after home relaxation practice were associated with greater decreases in HSV-2 IgG among CBSM participants. CONCLUSIONS: These findings suggest that behavioral and psychosocial changes occurring during CBSM interventions, including relaxation, enhanced social support, and adrenal hormone reductions, may help to explain the effects of this form of stress management on immune indices such as HSV-2 antibody titers.

Cardiopulmonary and CD4 cell changes in response to exercise training in early symptomatic HIV infection.

PURPOSE: The purposes of the present study were to assess the effects of a 12-wk laboratory based aerobic exercise program on cardiopulmonary function, CD4 cell count, and physician-assessed health status among symptomatic pre-AIDS HIV-infected individuals (N = 28) and to assess the degree to which ill health was associated with exercise relapse. METHODS: Responses to graded exercise test, physician-assessed health status, and CD4 cell counts were determined at baseline and 12-wk follow-up for participants randomly assigned to exercise or control conditions, and reasons for exercise noncompliance were recorded. RESULTS: Approximately 61% of exercise-assigned participants complied (> 50% attendance) with the exercise program, and analyses of exercise relapse data indicated that obesity and smoking status, but not exercise-associated illness, differentiated compliant from noncompliant exercisers. Compliant exercisers significantly improved peak oxygen consumption (VO2peak; 12%), oxygen pulse (O2pulse; 13%), tidal volume (TV; 8%), ventilation (VE; 17%), and leg power (25%) to a greater degree than control participants and noncompliant exercisers (all P < 0.05). Although no group differences in health status were found, a significant interaction effect indicated that noncompliant exercisers' CD4 cells declined (18%) significantly, whereas compliant exercisers' cell counts significantly increased (13%; P < 0.05). CONCLUSION: We conclude that although aerobic exercise can improve cardiopulmonary functioning in symptomatic HIV-infected individuals with minimal health risks, attention to factors associated with exercise adherence is warranted.

Disease progression, adherence, and response to protease inhibitor therapy for HIV infection in an Urban Veterans Affairs Medical Center.

Indinavir therapy has demonstrated promise in the treatment of HIV-1 infection in clinical trials; however, its efficacy in a U.S. Veterans Affairs Medical Center, where access to therapy is generally unimpeded, is unknown. A review of the Miami cohort was conducted for the year beginning May 1996 to evaluate response to indinavir plus two nucleoside analogues. Of 483 HIV-1-positive patients (97% male; mean age, 46.7+/-9.7 years), 266 were offered indinavir based on their having CD4 counts <200 cells/microl or viral loads >10,000 copies/ml. Of these patients, 36% were adherent and experienced significant reductions in viral loads (-93,325+/-147,911 copies/ml) and elevations in CD4+ (111+/-103 cells/microl) and CD8+ (225+/-338 cells/microl) T cell counts. Adherent patients with baseline CD4 counts <100 cells/microl were 4.5 times more likely to have follow-up viral loads >10,000 copies/ml than those with CD4 >200 cells/microl. Adherent patients with CD4 counts <100 cells/microl did not show evidence of immune "exhaustion" because they were equal to those with CD4 counts >200 cells/microl in their capacity to replenish CD4 cells. Nonadherence to the regimen resulted in loss of therapeutic benefit and suggested that strategies to enhance adherence may become an essential component of treatment.

Serum neopterin and somatization in women with chemical intolerance, depressives, and normals.

The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is a feature of several controversial polysymptomatic conditions that overlap symptomatically with depression and somatization, i.e., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and Persian Gulf syndrome. These syndromes can involve many somatic symptoms consistent with possible inflammation. Immunological or neurogenic triggering might account for such inflammation. Serum neopterin, which has an inverse relationship with l-tryptophan availability, may offer a marker of inflammation and macrophage/monocyte activation. This study compared middle-aged women with CI (who had high levels of affective distress; n = 14), depressives without CI (n = 10), and normals (n = 11). Groups did not differ in 4 p.m. resting levels of serum neopterin. However, the CI alone had strong positive correlations between neopterin and all of the scales measuring somatization. These preliminary findings suggest the need for additional research on biological correlates of 'unexplained' multiple somatic symptoms in subtypes of apparent somatizing disorders.