Livio Marchiaro

Decrease of the D4 dopamine receptor messenger RNA expression in lymphocytes from patients with major depression

OBJECTIVES The evaluation of the possible role of dopamine in psychiatric disorders has been limited by the relative inadequacy of tools. A tempting approach to examine alterations of dopaminergic system in major depression is to examine the expression of dopamine receptors in peripheral blood mononuclear cells (PBMC). METHODS D4 dopamine receptor (D4DR) messenger RNA (mRNA) expression in PBMC from 12 patients with major depressive disorder was examined before and after an 8-week treatment with paroxetine at 20-50 mg/day. Ten healthy subjects were analyzed in parallel. The relative content of D4DR mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). using beta-actin as internal standard. RESULTS D4DR mRNA levels were significantly decreased in untreated depressed patients as compared to controls. D4DR mRNA expression returned to control levels after paroxetine treatment, when patients achieved a significant improvement of depressive symptoms. CONCLUSIONS Results of our study suggest the role of PBMC D4DR mRNA expression as a peripheral marker of the central dopaminergic function in major depression.

Neuropsychological correlates of reality distortion in schizophrenic patients

The present study aims at exploring the relationship between content-related aspects of delusions and hallucinations in schizophrenia and the basic domains of cognition, controlling for the other clinical and demographic variables that could produce bias in the interpretation of the results. Seventy stable schizophrenic patients were evaluated through psychiatric assessment and a neuropsychological battery including tests on attention, memory, perceptual-motor speed and executive functions. We found that the severity of negative symptoms was strongly correlated with poor performance in almost all domains of cognitive functions, while only the attentional deficit was correlated with positive symptoms. The relationships between different cognitive domains and specific types of delusions and hallucinations showed that thought insertion, guilt, grandiose, religious and somatic delusions were associated with impairment in different cognitive functions (verbal and visual memory, attention and executive functions). Voices arguing and tactile hallucinations were correlated to delay-recall memory function. Our results suggest that no specific cognitive pattern is associated with typical-content delusions and hallucinations. On the basis of our findings, cognitive impairments associated with delusions and hallucinations, as measured by our battery, seem not to play a central role in the genesis and the maintenance of these symptoms, suggesting a more complex model of pathogenesis.

Donepezil in the treatment of Alzheimer's disease: Long-term efficacy and safety

OBJECTIVES The aim of this study was to evaluate the long-term efficacy, safety and tolerability of donepezil in the treatment of Alzheimers disease (AD). METHODS Twenty-five patients (15 females and 10 males) with mild to moderate AD, according to DSM IV criteria, were recruited in the study. The principal efficacy measures were Alzheimer Disease Assessment Scale-cognitive subscale score (ADAS-cog), Mini Mental State Examination (MMSE) and Physical Self-Maintenance Scale (PSMS). Patients were treated with donepezil 5 mg/day for 1 month, after which an increase to 10 mg/day was encouraged. Evaluations were carried out prior to the start of the treatment and every 3 months for a period of 1 year. RESULTS A significant improvement from baseline score of cognitive performances was seen through Week 24. Beginning with Week 36, performances declined relative to baseline, indicating continued disease progression. CONCLUSIONS Donepezil improved cognition and global functioning and was well tolerated especially considered the long duration of the observation period.

A comparison of paroxetine versus paroxetine plus amisulpride in the treatment of dysthymic disorder: efficacy and psychosocial outcomes

Dysthymic disorder is a chronic depressive condition with considerable psychosocial impairment. Even if DD patients respond to various antidepressant medications, there has been little systematic study on antidepressant-refractory DD. Only a few trials have evaluated the effects of treatment on psychosocial functioning of dysthymic patients. In this 3-month, open-label study, 60 outpatients with DSM-IV criteria for dysthymic disorder who failed to respond to 3-month treatment with paroxetine 20 mg/day were randomly assigned to treatment with paroxetine 40 mg/day or paroxetine 20 mg/day plus amisulpride 50 mg/day. The effects of the two treatments were assessed for both mood symptoms (21-item Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression, severity and improvement) and psychosocial outcomes (DSM-IV Global Assessment of Functioning, Social Adaptation Self-evaluation Scale). Analysis of variance on all rating scales showed that both treatments were effective over this observation period. Response and remission rates did not differ in the treatment groups. A significantly greater psychosocial improvement was observed in the group receiving combined treatment compared with patients receiving paroxetine alone. Both treatments appeared to be effective in our sample of dysthymic subjects. Combined treatment with paroxetine and amisulpride resulted in a better outcome in terms of social functioning.