Lower CSF Homovanillic Acid Levels in Depressed Patients with a History of Alcoholism

Abstract

Major depression and alcoholism are often comorbid, resulting in more impairment and more suicidal behavior compared with either diagnosis alone. This study compared clinical features and cerebrospinal fluid (CSF) monoamine metabolites in depressed subjects with and without a history of alcoholism and healthy volunteers. We hypothesized that depressed subjects with a history of alcoholism would be more aggressive, impulsive, and suicidal than depressed subjects without a history of alcoholism, and would have lower CSF monoamine metabolite levels. We compared 63 subjects with a current major depressive episode (MDE) and a history of alcoholism, 72 subjects with a current MDE but without a history of alcoholism, and 22 healthy volunteers. Participants with a history of alcoholism were in remission for at least 6 months. All subjects were free from prescribed medications known to affect brain serotonin, dopamine, or norepinephrine systems for a minimum of 14 days. Depressive symptoms, lifetime aggression, impulsivity, Axis II disorders, and suicidal behavior were assessed. CSF was sampled and homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were assayed by high-performance lipid chromatography with electrochemical detection. Depressed subjects with a history of alcoholism did not differ from depressed subjects without a history of alcoholism in current severity of depressive symptoms, or in past suicidal behavior. Depressed subjects with a history of alcoholism had lower CSF HVA levels, and higher lifetime aggression and current suicide ideation scale scores and were more likely to be tobacco smokers compared with depressed subjects without a history of alcoholism. Low HVA was present after adjustment for sex, aggression and depression scores, cigarette smoking, antisocial and borderline personality disorders, psychomotor retardation, and delusions. Controls had CSF HVA levels intermediate between the two depressed groups. We found no group difference in CSF 5-HIAA and MHPG levels. In individuals with current MDE, those with a history of comorbid alcoholism had lower CSF HVA levels compared with those without a history of alcoholism. Low CSF HVA suggests that impaired dopaminergic activity is associated with a history of alcoholism in persons with current MDE.

CSF monoamine metabolites and lethality of suicide attempts in depressed patients with alcohol dependence

“…For example, we have demonstrated that in individuals with major depression, those with comorbid alcoholism had lower CSF homovanillic acid (HVA) levels compared with those without comorbid alcoholism (Sher et al, 2003). However, our study did not focus on suicidal behavior.…”

“…Alcoholism is associated with altered CSF monoamine metabolite levels (Ballenger et al, 1979;Banki and Molnar, 1981;Borg et al, 1985;Ratsma et al, 2002;Sher et al, 2003). For example, we have demonstrated that in individuals with major depression, those with comorbid alcoholism had lower CSF homovanillic acid (HVA) levels compared with those without comorbid alcoholism (Sher et al, 2003).…”

“…Current suicidal ideation was measured by the Scale for Suicidal Ideation (SSI) (Beck et al, 1979). Details of lifetime suicide attempts were recorded on the Columbia Suicide History Form, which records all suicide attempts chronologically, including documentation of the method and degree of medical damage (Medical Damage Scale) (Oquendo et al, 2003) and suicide intent by the Beck Suicide Intent Scale (SIS) (Beck et al, 1974b). Patients with medical lethality scores ≥4 were classified as high-lethality suicide attempters, subjects with medical lethality scores <4 were regarded as low-lethality attempters.…”

Personality traits as intermediary phenotypes in suicidal behavior: Genetic issues

“…Although the intricate relationships and the causal links between alcohol abuse and/or dependence, personality traits and suicidal behavior are not clearly understood and still a matter of debate, impulsive and aggressive traits are probably key common predisposing factors [Koller et al, 2002;Sher et al, 2003;Conner and Duberstein, 2004].…”

A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species

“…Levels of HVA have been related to aggressive behavior, wounding, sexual behavior, and social dominance in vervets and macaques (12,(20)(21)(22)(23). Numerous studies suggest associations between CSF MA metabolite concentrations and various human behavioral disorders (15,24,25), but other than relationships of CSF 5-HIAA to suicidal and aggressive behaviors (26), these associations remain mostly equivocal and nonreplicated, in part because of the difficulty in obtaining CSF from sufficient human subjects. In addition, human studies, in contrast to those in NHPs, rely on lumbar CSF, which may less accurately reflect brain MA levels than cisternal CSF (27).…”