Analysis of differential clinical profiles of different antipsychotic molecules in the first psychotic episode: a retrospective study.

Our study starts from the supposition that the ideal pharmacological treatment should improve the patient's global behaviour, as a consequence of the therapeutic activity on positive, negative, behavioural, affective and cognitive symptoms. It should have few secondary effects, both in the short and long term, thus assuring a good life-quality, the fundamental condition for the patient's compliance and adherence. Currently only few studies have been published evaluating atypical antipsychotic effects vs. typical ones in the first psychotic episode, particularly studying different profile evaluations and different molecule rating standards. Our aim has been the therapeutic profile evaluation of atypical anti-psychotic molecules vs. typical ones, using "Liège's star" parameters (anti- manic, anti-autistic, anti-delusional, extra-pyramidal, ataraxic-sedative and adrenolitic). We added 2 complex scales, the first for loss in affectiveness, the second for cognitive and behavioural disorganization. We utilized Aosta's Psychiatric Service data-base, evaluating patients in their first psychotic episode diagnosed with various schizophrenic disorders per DSM IV criteria. We considered everyone who received, as monotherapy, or a typical molecule or an atypical one and who had been tested, at the beginning and at the end of the psychotic episode, with MMPI and PANSS Rating Scale. We evaluated 107 patients, 68 men and 39 women, whose mean age was 25,04 years (SD=3,789): 21 schizo-affective, 27 schizophreniform, 23 brief reactive psychosis and 36 paranoid- type schizophrenic disorders. The mean observation time was 117,18 days. Monotherapy was with olanzapine (23), quetiapine (8), risperidon (19), haloperidol (20), clopentixol (9), chlorpromazine (10), pimozide (8) and sulpiride (10). For the evaluation of adrenolitic, sedative and extrapyramidal effects we utilized clinical data and specific drugs administrations. We based our estimate for anti-delusional activity on P1, p3, p4, p5, p6, p7, g9 and g12 PANSS items score, correlated with Se and Pa MMPI results; for anti- autistic activity 2,3 and 4 PANSS items score related with MMPI Si Scale; for activity on behavioural and cognitive symptoms p2, n5, n6, n7 PANSS items score; for activity on negative symptoms PANSS negative global score. From the MMPI score we evaluated aggressiveness, hypochondria, negative symptoms, depression and psychasthenia. Our trial results hypothesise that neuroleptic anti-deficitary activity develops itself on different, qualitative and chronological levels: a continuous pathway from the original stimulus, through a dis-inhibiting effect to a final anti-autistic effect it would cause a deficit reduction. We haven't seen considerable differences between typical or atypical molecules perform inhibiting activity on D2 receptors. It seems that atypical molecules specific activity on D1, D3 and D4 receptors (affinity) and on 5HT2 receptors (inhibition) comes out as negative symptoms improve. We can say, too, that, according to compliance, adherence and concordance parameters, atypical molecules improve patient's life-quality through a good treatment and a real therapeutic alliance. Finally, we have seen that therapies with atypical molecules increase the family's satisfaction and compliance.

Lymphocyte peripheral benzodiazepine receptor mRNA decreases in obsessive-compulsive disorder.

The relative content of peripheral benzodiazepine receptor (pBR) mRNA was examined by reverse transcriptase-polymerase chain reaction in lymphocytes of obsessive-compulsive disorder (OCD) patients, according to their clinical course of illness. pBR mRNA significantly decreased only in chronic OCD patients (n=8) as compared to controls (n=10), whereas no significant changes were observed in episodic OCD patients (n=7). We suggest that modulation of pBR gene expression might delineate a clinical heterogeneity in OCD.

Peripheral benzodiazepine receptor messenger RNA is decreased in lymphocytes of generalized anxiety disorder patients.

BACKGROUND: The aim of this study was to assess whether the decrease of peripheral benzodiazepine receptor (pBR) number in peripheral blood mononuclear cells (PBMC), previously observed in patients with generalized anxiety disorder, is paralleled by changes in the relative content of messenger RNA (mRNA) encoding pBR. METHODS: Eight patients with a DSM-III-R diagnosis of generalized anxiety disorder were examined before, during, and after 2'-chloro-N-desmethyl-diazepam treatment. Eight healthy subjects were analyzed in parallel. The relative content of pBR mRNA was determined by reverse-transcriptase-polymerase chain reaction, using beta-actin as internal standard. Kinetic binding properties of pBR were measured using 3H-PK11195 as a ligand. RESULTS: pBR and pBR mRNA were significantly decreased in untreated generalized anxiety disorder patients as compared to controls (by 45% and 70%, respectively). Both pBR density and mRNA levels returned to control values during treatment or after withdrawal, which also coincided with recovery from anxiety. CONCLUSIONS: These results suggest that the turnover rate of pBR is reduced in PBMC of generalized anxiety disorder patients, and that this change occurs at the transcriptional level.