Associations between plasma levels of 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) and negative symptoms or cognitive impairments in early‐stage schizophrenia

Abstract

Schizophrenic patients demonstrate a variety of cognitive deficits, including attention, executive functions, and working memory, even in the early stage of disease. In the present study, we examined the association between blood levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), or brain-derived neurotrophic factor (BDNF) and scores on the Wisconsin Card Sorting Test (WCST) in patients with early-stage schizophrenia. We also investigated the association between frontal GABA levels using 1H-magnetic resonance spectroscopy (MRS) at 3T and scores on the WCST in the same patients. Blood levels of BDNF and catecholamine metabolites and brain GABA levels using 1H-MRS were measured in 18 schizophrenic patients (nine males, nine females; age range 13-52 year). A significantly positive correlation was observed between plasma MHPG levels and %PEM (rho = -0.686, p = 0.0047). A trend toward negative correlation was found between frontal lobe GABA levels and the per cent of preservation error (%PEM) in the early stage of schizophrenia (rho = -0.420, p = 0.0836). These results suggest that noradrenergic neurons might be involved in neuropsychological functions in early-stage of schizophrenia.

Variability of Plasma Homovanillic Acid Over 13 Months in Patients with Schizophrenia; Relationship with the Clinical Response and the Wisconsin Card Sort Test

“…pHVA and Performance in the WCST We did not find significant relationships between the scores of the WCST and the concentrations or variability in the pHVA, which is in accordance with the results of Goto et al [25]. There was only a non-significant trend to make more perseverative errors with higher concentrations of pHVA.…”

“…In other studies, there was a relationship between a higher concentration of plasma adrenaline and fewer errors in the WCST in healthy control groups, and there was no relationship with the values of noradrenaline [24]. There was also an association between an increased number of perseverative errors and a lower concentration of plasma noradrenaline metabolites in schizophrenic patients [25]. It is important to note that the memory processes and performance needed to test the WCST are extremely complex and involve different neurotransmitter systems and multiple brain areas [52].…”

“…This region is relevant in the inactivation of dopamine through catechol-O-methyltransferase, an enzyme involved in the synthesis of HVA, because there is virtually no inactivation of dopamine via reuptake. Furthermore, different relationships have been found between plasma concentrations of monoamines and their metabolites and cognitive functions in schizophrenic patients [24][25][26].…”

The Role of Norepinephrine and Its α-Adrenergic Receptors in the Pathophysiology and Treatment of Major Depressive Disorder and Schizophrenia: A Systematic Review

“…Baseline levels of MHPG in saliva were shown to positively correlate with a high Beck Depression Inventory score in men (19), which provides support to the findings that MHPG concentrations in CSF were correlated with a lifetime burden of mood swings (18). In addition, plasma MHPG has been shown to correlate with negative symptoms and cognitive impairment during early-stage schizophrenia (91). …”

Blood biomarkers predict the cognitive effects of aripiprazole in patients with acute schizophrenia

“…Several studies of schizophrenia have noted that the behavioral response to antipsychotic drugs, such as a decrease in psychosis, parallels a decrease in plasma HVA levels in schizophrenic patients over time [10][11][12][13][14][15][16][17][18][19][20]. Atypical antipsychotics increase the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and are associated with negative symptoms and cognitive functions [19,21,22]. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophic factor in the brain, the levels of which have been associated with schizophrenia.…”