Brief reportPlasma homovanillic acid correlates inversely with history of learning problems in healthy volunteer and personality disordered subjects
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.
References (29)
- et al.
Striatal dopamine and learning strategy—an 123I-FP-CIT SPECT study
Neuropsychologia
(2004) - et al.
Cerebrospinal fluid monoamine metabolites in boys with attention-deficit hyperactivity disorder
Psychiatry Research
(1994) - et al.
Simultaneous quantification of homovanillic acid and 5-hydroxyindolacetic acid in cerebrospinal fluid by mass fragmentography
Life Sciences
(1974) Mass fragmentographic determination of homovanillic acid and 4-hydroxy-3-methoxy mandelic acids in 50 μl plasma
Clinica Chimica Acta
(1983)- et al.
Catecholamines in attention-deficit hyperactivity disorder: current perspectives
Journal of the American Academy of Child and Adolescent Psychiatry
(1996) - et al.
Cerebrospinal fluid homovanillic acid and 5-hydroxy-indoleacetic acid in adults with attention deficit disorder, residual type
Psychiatry Research
(1984) - et al.
CSF monoamine metabolites in children with minimal brain dysfunction: evidence for alteration of brain dopamine. A preliminary report
Journal of Pediatrics
(1977) Diagnostic and Statistical Manual of Mental Disorders
(1994)- et al.
Plasma homovanillic acid as a tool to investigate brain dopaminergic activity
- et al.
Cerebrospinal fluid homovanillic acid predicts behavioral response to stimulants in 45 boys with attention deficit/hyperactivity disorder
Neuropsychopharmacology
(1996)