Psychiatric–Medical ComorbidityCerebrospinal fluid homovanillic acid is correlated to psychotic features in neurological patients with delirium
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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Ethanol concentration induces production of 3,4-dihydroxyphenylacetic acid and homovanillic acid in mouse brain through activation of monoamine oxidase pathway
2022, Neuroscience LettersCitation Excerpt :DOPAC, 3-MT, and HVA have been regarded as indicators of different aspects of DA dynamics [9,10]. Some researchers have reported elevated levels of HVA in the urine and cerebrospinal fluid of autistic and psychotic patients [11,12]. The increase in CSF HVA concentration provides evidence to support the dopaminergic theory of psychosis [11].
Biomarkers in delirium: A systematic review
2021, Journal of Psychosomatic ResearchCitation Excerpt :Only Ramirez et al. [25] assessed an amino acid in the setting of pure delirium. HVA was either assessed alone [25], as part of a study involving neuropsychiatric patients, or as part of a suite of other amino acids in either medical [23] or surgical [24] patients. Two of three studies measuring HVA reported no association between this marker and delirium [23–25] while the third study [24] demonstrated elevated levels of HVA in pre-operative and post-operative surgical patients with delirium alongside elevated neopterin [24] as well as, in post-operative patients, phenylalanine to LNAA ratio and citrulline.
Dopaminergic Hyperactivity in Neurological Patients with Delirium
2019, Archives of Medical ResearchCitation Excerpt :However, these hypothetical biochemical abnormalities have been scarcely documented by direct measures in patients with delirium. A study in neurological patients with delirium showed that homovanillic acid (HVA) concentrations in cerebrospinal fluid (CSF), dopamine's main metabolite, were significantly higher in patients with psychotic symptoms (hallucinations and delusions) in the context of delirium, even though a small sample size did not allow to demonstrate the relation between the delirium syndrome and dopaminergic hyperactivity. (10) Other neurotransmission systems relevant to delirium have been explored insufficiently.
Pediatric Delirium
2018, Complex Disorders in Pediatric Psychiatry: A Clinician's GuideEtiologies and delirium rates of elderly ED patients with acutely altered mental status: a multicenter prospective study
2017, American Journal of Emergency Medicine