Elsevier

Psychiatry Research

Volume 149, Issues 1–3, 15 January 2007, Pages 297-302
Psychiatry Research

Brief report
Plasma homovanillic acid correlates inversely with history of learning problems in healthy volunteer and personality disordered subjects

https://doi.org/10.1016/j.psychres.2006.05.009Get rights and content

Abstract

Central dopaminergic activity is critical to the functioning of both motor and cognitive systems. Based on the therapeutic action of dopaminergic agents in treating attention deficit hyperactivity disorder (ADHD), ADHD symptoms may be related to a reduction in central dopaminergic activity. We tested the hypothesis that dopaminergic activity, as reflected by plasma homovanillic acid (pHVA), may be related to dimensional aspects of ADHD in adults. Subjects were 30 healthy volunteer and 39 personality disordered subjects, in whom morning basal pHVA concentration and a dimensional measure of childhood ADHD symptoms (Wender Utah Rating Scale: WURS) were obtained. A significant inverse correlation was found between WURS Total score and pHVA concentration in the total sample. Among WURS factor scores, a significant inverse relationship was noted between pHVA and history of “childhood learning problems”. Consistent with the dopaminergic dysfunction hypothesis of ADHD and of cognitive function, pHVA concentrations were correlated with childhood history of ADHD symptoms in general and with history of “learning problems” in non-ADHD psychiatric patients and controls. Replication is needed in treated and untreated ADHD samples to confirm these initial results.

Introduction

Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder whose symptoms and associated impairments often persist into adulthood (Zametkin and Liotta, 1998). Symptoms of ADHD, such as inattention, distractibility, and impulsivity, however, are not specific to ADHD and occur in many psychiatric disorders besides ADHD. In individuals with ADHD these symptoms are frequently treated with dopamine and norepinephrine agonists (Elia et al., 1999). Consequently, dopamine and other catecholamines have been thought to play a significant role in the pathophysiology of ADHD and dopamine transmission is hypothesized to be low in subjects with ADHD (Pliszka et al., 1996).

In the current study, we sought to evaluate the relationship between history of ADHD symptoms, but not the full ADHD syndrome, and plasma homovanillic acid (pHVA) concentration in adults with personality disorders and normal controls to test the hypothesis that some behavioral components of ADHD would be associated with a hypodopaminergic state. HVA, a primary metabolite of dopamine, has been studied in various compartments (urine, cerebrospinal fluid, plasma) in human subjects, in general, as an index of central dopaminergic functioning (Amin and Friedhoff, 1997). To date, HVA in urine and in cerebrospinal fluid has been studied in children and adults with ADHD and has been observed to be reduced in concentration, compared with controls, in at least two studies to date (Shaywitz et al., 1977, Shekim et al., 1982). Because collection of urinary or cerebrospinal HVA is often difficult and inconvenient, pHVA is often the preferred method of assessing HVA in clinically oriented studies. Plasma HVA is thought to reflect central dopamine activity provided that certain factors, such as physical activity and stress, diet, cigarette smoking, and time of day of sampling, are controlled as they are in the present study (Amin and Friedhoff, 1997). Moreover, because noradrenergic neurons in the periphery may also produce pHVA (Amin and Friedhoff, 1997), we measured plasma levels of the major norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), so that this factor could be examined simultaneously. Finally, since stimulant treatment may affect dopamine transporter density and subsequently decrease dopaminergic activity (Dresel et al., 2000, Volkow et al., 2002), we studied only personality disordered subjects and controls without a history of ADHD so that there was little chance of prior exposure to stimulant treatment in the study group. Childhood ADHD symptoms were assessed dimensionally using the Wender Utah Rating Scale (WURS; Ward et al., 1993). While not directly mapping onto the DSM-IV definition of ADHD, the psychometric properties and clinical utility of the WURS and specific factor scores (Stein et al., 1995, Levitan et al., 2004) have been investigated in several studies.

Section snippets

Subjects

This article reports data from 30 healthy controls and 39 subjects with personality disorder in whom both pHVA, and data regarding history of ADHD symptoms were collected. All subjects were systematically evaluated as part of a larger program designed to study the biological correlates of personality traits in personality disordered and healthy control subjects. Study subjects (58 male, 11 female; 39 personality disorder, 30 healthy control) were recruited by newspaper and public service

Controls and personality disordered subjects

Healthy control subjects differed from personality disordered subjects with regard to age and the WURS total and factor scores but not with regard to gender, race, or socio-economic status (Table 1). The difference between the two groups in log[pHVA] concentration approached, but did not reach, statistical significance (healthy controls: 0.93 ± 0.17 vs. personality disorder: 0.87 ± 0.13 ng/ml; t67 = 1.83, P = 0.072). Regardless, age did not correlate significantly with log[pHVA] concentration (r =  

Discussion

The results of the present study demonstrate a modest, but statistically significant, inverse relationship between plasma pHVA and the total WURS score and with a self-reported history of “childhood learning problems”, specifically. If so, these data suggest that reduced dopaminergic function may be associated with a self-reported history of childhood symptoms of ADHD and learning problems, more specifically, even in a treatment-naïve group of adults (regardless of psychiatric diagnosis) with

Acknowledgments

This project was supported in part by NIMH Grants RO1MH46948 and KO2MH00951 (Dr. Coccaro). There are no conflicts of interest with regards to this work.

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