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Neurochemical regulation of auditory information ... - Helda - Helsinki.fi

underlies positive symptoms in schizophrenia, whereas cortical DA hypofunction is

responsible for cognitive disturbances and negative symptoms (for review, see Guillin et

al. 2007). Further, plasma concentrations of homovanillic acid (HVA, a major dopamine

metabolite measured in various body fluids; measured in blood plasma, it is used to

assess brain dopamine neuronal activity) correlate with symptom severity in unmedicated

schizophrenia patients (Davis et al. 1985). Moreover, various changes in the plasma HVA

have a high correlation with the therapeutic response to neuroleptic drugs (Davis et al.

2002).

From another point of view, increasing evidence indicates that the pathophysiology of

mental disorders, including schizophrenia, could be a consequence of the deregulation

of synaptic plasticity (Gratacos et al. 2007). Moreover, DA seems to affect synaptic

plasticity induced within the circuits of certain brain regions (Goto and Grace 2007).

In this way, disturbances in DA neurotransmission impair cognitive functions such as

memory and information processing, which are considered the primary cognitive deficits

in schizophrenia (Braff 1993; Nuechterlein and Dawson 1984; O’Donnell 2007).

Animal studies show long-term effects of antipsychotic drugs on the dopamine D2 receptor

family, which is implicated in the pathophysiology of schizophrenia. For example,

olanzapine and risperidone significantly increased D2 binding in the medial prefrontal

cortex in a study by Tarazi et al. (2001). A number of studies show the negative effect of

typical antipsychotics (especially haloperidol) on cognitive functioning in schizophrenia

patients. Longitudinal studies in humans show impairments in cognitive performance,

related to vigilance and attention tasks, associated with antipsychotic treatment (for review,

see Cassens et al. 1990). Moreover, extra-pyramidal symptoms (EPS), produced by typical

and some atypical antipsychotic drugs through the blockade of D2 receptors in striatum,

could also have negative consequences on procedural learning (Bedard et al. 2000) and

psychomotor performance (e.g. impairments in driving skills could occur) (Rapoport

and Banina 2007). Studying schizophrenia patients, Purdon et al. (2003) observed that

impairment in procedural learning resulted from the use not only of haloperidol, but

also of risperidone. Ramaerkers et al. (1999) found that haloperidol significantly impairs

psychomotor and cognitive performance in healthy volunteers.

Dopaminergic involvement in schizophrenia gives rise to the possibility of dopaminergic

deregulation in schizotypal personality disorder as well (Siever et al. 1993). Preliminary

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