Elsevier

General Hospital Psychiatry

Volume 30, Issue 4, July–August 2008, Pages 337-343
General Hospital Psychiatry

Psychiatric–Medical Comorbidity
Cerebrospinal fluid homovanillic acid is correlated to psychotic features in neurological patients with delirium

https://doi.org/10.1016/j.genhosppsych.2008.01.007Get rights and content

Abstract

Objective

The aim of this study was to determine if cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) are related to the clinical features of delirium in a group of patients with acute onset neurological illness.

Methods

Fifty-one patients with probable acute brain infection were classified as delirious and nondelirious according to Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) and Delirium Rating Scale (DRS). CSF HVA concentration was analyzed by high-performance liquid chromatography.

Results

Delirium was present in 60.8% of the total sample. HVA levels were not significantly different between delirious and nondelirious patients. Remarkably, patients with psychotic symptoms shown higher levels of CSF HVA as compared to nonpsychotic patient values. In addition, HVA levels were positively correlated to specific items of DRS such as delusions (r=0.463, P=.001), hallucinations (r=0.438, P=.001), cognitive dysfunction (r=0.286, P=.042) and fluctuation of symptoms (r=0.280, P=.046) in the total sample. Subanalyses excluding patients taking antipsychotic drugs revealed that HVA CSF levels were higher in those patients with delusions, and furthermore, the dopamine metabolite remained positively correlated to delusion subscale of DRS.

Conclusions

Our results suggest that psychotic symptoms in delirious patients may be related to increased dopamine neurotransmission, as reflected by increased CSF HVA concentration, providing direct evidence to support the dopaminergic theory of psychosis.

Introduction

Delirium is an acute neuropsychiatric syndrome characterized by impaired alertness and disturbance of the attentional matrix manifested as impaired consciousness, cognition and perception, with an acute onset and fluctuating course [1] as well as sleep–wake cycle and motor disturbances [2]. It may include psychotic features (hallucinations and/or delusions). It is produced by central nervous system (CNS) infections and other disorders, as well as general medical conditions and the use of some drugs. Neurotransmitter dysfunction has been proposed [3] as a mechanism related to this syndrome: acetylcholine dysfunction could underlie cognitive disturbance, while dopamine dysfunction may be related to psychotic symptoms and psychomotor agitation among other symptoms. Psychotic features (delusions and hallucinations) have been reported to be present in 42.7% of delirious patients [4]. The psychopharmacological approach to delirium has focused on dopamine D2 receptor antagonists: haloperidol, risperidone, olanzapine, ziprasidone and others [5], [6], [7]. Notwithstanding, there is a noticeable lack of studies providing direct evidence on the relationship between excessive dopamine neurotransmission and delirium. A few studies rejecting or supporting this hypothesis have been done in populations as diverse as alcohol withdrawal or dementia patients [8], [9]; however, previous studies suggest that dopaminergic dysfunction is most likely associated to delirium than to dementia [9]. Considering the wide etiologic spectrum as a confounding factor in delirium research, acute brain infections provide us with a natural model for a neurochemical study; there is a rational basis for obtaining cerebrospinal fluid (CSF) in this population, and the vast majority of patients with brain infections will manifest psychiatric disturbances, such as delirium and psychosis [10], [11]. This study explores the relationship between delirium and the main dopamine metabolite, homovanillic acid (HVA), as measured in the CSF from acute neurological patients requiring an extensive evaluation for CNS infection.

Section snippets

Methods

This cross-sectional study was submitted and approved by the ethics committee from the National Institute of Neurology and Neurosurgery of Mexico, a reference neurological hospital in Mexico City. All of the participants' relatives received written information concerning the objective of the present study, and those who agreed to collaborate signed an informed consent. Participants were treated according to the ethics principles described in the Declaration of Helsinki; the procedures applied

Results

As shown in Fig. 1, 51 acute neurological patients were assessed and completed both clinical and neurochemical measures. Patients were 36.4±1.9 (mean±S.E.M.) years old (18–85 years). Patients had 8.3±0.4 (mean±S.E.M.) years of education. Twenty-three patients were female (45.1%). None of the patients had a diagnosis of dementia at the moment of assessment.

CNS infection was confirmed in 43 patients (16 of them were HIV-positive). DSM-IV diagnosis of delirium was established in 31 cases (60.8%)

Discussion

The role of dopamine systems in complex psychiatric phenomena as psychosis or delirium has been a central point of discussion in modern biological psychiatry. Notwithstanding, direct measurements of dopamine metabolism in delirium have rarely been achieved.

The concentration of the main dopamine metabolite HVA is increased in the extracellular fluid following dopamine release [17] and different pharmacological manipulations [18], [19] and, thus, may reflect synaptic activity. For those reasons,

Acknowledgments

The present study was partially supported by CONACyT grants 43974 and 51541. I. Pérez-Neri receives fellowships from CONACyT 186343 and from DGEP (UNAM).

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