Neuroleptics

In this study we have investigated the pathophysiology of two idiopathic focal dystonias: hand cramp with excessive cocontractions of agonist and antagonist hand or forearm muscles during specific tasks, such as writing, and facial dystonia manifested by involuntary eyelid spasms (blepharospasm) and lower facial and jaw spasms (oromandibular dystonia). We used positron emission tomography (PET) to measure the in vivo binding of the dopaminergic radioligand [ 18 F]spiperone in putamen in 21 patients with these two focal dystonias and compared the findings with those from 13 normals. We measured regional cerebral blood flow and blood volume in each subject as well as the radiolabeled metabolites of [ 18 F]spiperone in arterial blood. A stereotactic method of localization, independent of the appearance of the images, was used to identify the putamen in all of the PET images. We analyzed the PET and arterial blood data with a validated nonsteady-state tracer kinetic model representing the in vivo behavior of the radioligand. An index of binding called the combined forward rate constant was decreased by 29% in dystonics, as compared with normals ( p Ͻ 0.05). There were no significant differences between dystonics and normals in regional blood flow, blood volume, nonspecific binding, permeability-surface area product of [ 18 F]spiperone or the dissociation rate constant. These findings are consistent with a decrease of dopamine D 2 -like binding in putamen and are the first demonstration of a receptor abnormality in idiopathic dystonia. These results have important implications for the pathophysiology of dystonia as well as for function of the basal ganglia.

The dopamine partial agonist aripiprazole is increasingly used to treat pathologies for which other antipsychotics are indicated because it displays fewer side effects, such as sedation and depression-like symptoms, than other dopamine receptor antagonists. Previously, we showed that aripiprazole may protect motivational function by preserving reinforcement-related signals used to sustain reward-maximization. However, the effect of aripiprazole on more cognitive facets of human reinforcement learning, such as learning from the forgone outcomes of alternative courses of action (i.e., counterfactual learning), is unknown. To test the influence of aripiprazole on counterfactual learning, we administered a reinforcement learning task that involves both direct learning from obtained outcomes and indirect learning from forgone outcomes to two groups of Gilles de la Tourette (GTS) patients, one consisting of patients who were completely unmedicated and the other consisting of patients who were receiving aripiprazole monotherapy, and to healthy subjects. We found that whereas learning performance improved in the presence of counterfactual feedback in both healthy controls and unmedicated GTS patients, this was not the case in aripiprazole-medicated GTS patients. Our results suggest that whereas aripiprazole preserves direct learning of action-outcome associations, it may impair more complex inferential processes, such as counterfactual learning from forgone outcomes, in GTS patients treated with this medication. Aripiprazole is a recently introduced antipsychotic medication with dopamine receptor partial agonist mechanisms 1. In schizophrenia patients, aripiprazole exhibited efficacy comparable to that of typical and atypical antip-sychotics in the treatment of positive and negative symptoms as well as in the prevention of relapse 2, 3. Its efficacy has also been demonstrated in other neurological disorders for which antipsychotics are indicated, such as Gilles de la Tourette syndrome (GTS) 4, 5. Its tolerability is often considered superior to that of typical antipsychotics, and it is associated with fewer adverse side effects, such as extrapyramidal and metabolic syndromes 6, 7. In GTS, arip-iprazole is effective for suppressing tics while displaying a less severe side effect profile than dopamine receptor antagonists with regard to motivational deficits such as sedation and depressive reactions 8. Due to this advantageous cost-benefit trade-off, aripiprazole has become a widely prescribed treatment for schizophrenia and GTS. Pharmacological studies in humans suggest that dopamine receptor antagonist-induced sedation and depres-sive states may be the consequence of blunting of reward-related signals 9, 10. For instance, reward-seeking behaviour and reward prediction errors encoded in the ventral striatum were reduced by haloperidol administration in healthy volunteers 11. In contrast, both functions were preserved in GTS patients medicated with aripiprazole 12 .

This study was designed to validate an in vivo measurement of the functional sensitivity of basal ganglia neuronal circuits containing dopamine D 2 receptors. We hypothesized that a D 2 agonist would decrease striatopallidal neuronal activity, and hence regional cerebral blood flow (rCBF) over the axon terminals in the globus pallidus. Quantitative pallidal blood flow was measured using positron emission tomography (PET) with bolus injections of H 2 15 O and arterial sampling in six baboons before and after intravenous administration of the selective D 2 agonist U91356a. We also tested whether the response to U91356a was modified by previous acute administration of various antagonists. Another baboon had serial measurements of blood flow under identical conditions, but received no dopaminergic drugs. In all animals that received U91356a, pallidal flow decreased in a dose-related manner. Global CBF had a similar response, but the decline in pallidal flow was greater in magnitude and remained significant after accounting for the global effect. A D 2 antagonist, but not antagonists of D 1 , serotonin-2, or peripheral D 2 receptors, prevented this decrease. This work demonstrates and validates an in vivo measure of the sensitivity of D 2 -mediated basal ganglia pathways. It also supports the hypothesis that activation of the indirect striatopallidal pathway, previously demonstrated using nonselective D 2 -like agonists, can be mediated specifically by D 2 receptors. We speculate that the U91356a-PET technique may prove useful in detecting functional abnormalities of D 2mediated dopaminergic function in diseases such as parkinsonism, dystonia, Tourette syndrome, or schizophrenia.

Die vorliegende Publikation ging aus dem yom Schweizerischen N ationalfonds finanzierten Nationalen Forschungsprogramm (NFP) 5l zum Thema «Integration und Ausgrenzung» hervor und befasst sich mit der Entwicklung der Zürcher Psychiatrie zwischen 1870 und 1970. Sie versteht sich in einem doppelten Sinn aIs paradigmatisch: zum einen lassen sich am Fall Zürich Überlegungen zur Entwicklung der Psychiatrie in modernen Gesellschaften generell anstellen, zum andern ermoglicht die Geschichte der «psychiatrischen Ordnung» Einblicke in gesellschaftliche Strukturen und die diskontinuierlicheDynamik des soziokulturellen Wandels. lm Foigenden wird versucht, den psychiatriegeschichtlichen Kontext, in dem die Studie entstand, zu skizzieren und einige Entwicklungen im sakularen Untersuchungszeitraum nachzuzeichnen. Ziel ist nicht eine Zusammenfassung der Resultate, sondern es wird exemplarisch auf einige Aspekte der Studie hingewiesen. Da gerade innovative Problemstellungen neue und weiterführende Fragen aufwerfen, werden abschliessend einige analytische Perspektiven benannt, mit denen sich eine wissenschaftsund kulturhistorisch sensibilisierte Psychiatriegeschichte künftig verstarkt auseinandersetzen konnte.

We report a case of conversion disorder (partial aphonia) that was successfully treated with speech therapy. During the one year duration of this illness, the patient regained transiently (minutes) her normal speech on a few occasions, independently of concomitant pharmacological interventions. One year after recovery she developed aphonia for the second time, which responded again to speech therapy, although the response rate was slower. Several mechanisms of conversion disorder are reviewed as specifically applied to this case. The possible role of pertinent shame mechanisms in the conversion pathology is discussed.

Remusatia vivipara (RV) found throughout in hilly region and used in folk medicine to treat whooping cough and used for wound to dispel any worms and germs. The present study was undertaken to investigate effect of RV on haloperidol induced catalepsy in mice. The effect of deferent doses (100 and 200 mg/kg) of various extract i.e. Ethanolic, Chloroform and ether extract of leaves of RV was studied on haloperidol (1 mg/kg, i.p.) induced catalepsy using bar test. The result indicated that haloperidol induced catalepsy was significantly for ethanolic and chloroform extract.

Tardive dyskinesia (TD) is one of the most significant sideeffects of classical antipsychotics (CAPs). Patient-related factors associated with TD include age, sex, psychiatric diag-nosis, extrapyramidal symptoms (EPS), cognitive deficits, and structural brain damage (1,2). Diabetes mellitus (DM) may also be a risk factor for TD (1,2). Mukherjee and colleagues suggested a possible association between TD and impaired glucose metabolism (3,4). Other studies report a higher incidence of DM in relatives of patients with TD, sug-gesting a genetic link between dopamine mechanisms and 398 Can J Psychiatry, Vol 49, No 6, June 2004 Background: This study examines the links among diabetes, tardive dyskinesia (TD), and other extrapyramidal symptoms (EPS) in schizophrenia outpatients treated with typical and atypical antipsychotics. Objectives: Using a retrospective chart review, we compared 30 schizophrenia patients with diabetes mellitus (DM) with 30 schizophrenia patients, matched for age and...

This open cross-sectional questionnaire study investigated subjective oral symptoms in hospitalized psychiatric patients,
comparing those taking typical vs. atypical neuroleptic drugs. The present study included 170 hospitalized patients who
were taking psychiatric medications. We observed a significantly higher prevalence of xerostomia in the typical neuroleptic
group (66%) compared with the atypical neuroleptic group (53%, p<0.01). In our study, 28% of women and 17% of men
received professional consultations for dry mouth. Persistent oral pain lasting throughout the day was reported by 46% and
5% of patients in the typical and atypical neuroleptic groups, respectively. The oral pain was predominantly located in the
tongue and buccal mucosa; it was described as a burning sensation by patients in both medication groups. These results
emphasize the need for awareness of oral discomfort and its subsequent effects on quality of life in this challenging patient
group