Claire Rascle

Clinical features of latent inhibition in schizophrenia

Paradigms of Latent Inhibition (LI) are inter-species and derived from learning theories. They are considered as tools which allow the attentional processes to be studied. The absence of LI is interpreted as difficulty in discriminating relevant and irrelevant stimuli. Abolition of LI has been shown in acute schizophrenics. The objectives of our study were partly to validate an LI paradigm, based on a contingency detection between two stimuli, in healthy subjects, and partly to analyse LI in schizophrenics. The study included 105 subjects (65 patients and 40 controls). Patients fulfilled the DSM IV diagnosis of schizophrenia. 35 in the acute phase and 30 in the chronic phase. We observed a loss of LI for acute schizophrenics, and an enhancement of LI for chronic schizophrenics. The variations in LI are interpreted from the perspective of a disturbance in the attentional processes. The LI status in acute schizophrenics appears to correlate with the clinical criteria with a prognostic value (low intensity of the negative dimension, late age at the first hospitalization). Moreover, the enhancement of LI correlates with the negative dimension of schizophrenic disease. This correlation is found in acute and chronic schizophrenics. It suggests that the variations of LI may be an indicator of adaptive strategies to a cognitive dysfunction specific to schizophrenia.

Low posttrauma GABA plasma levels as a predictive factor in the development of acute posttraumatic stress disorder

BACKGROUND Gamma amino-butyric acid (GABA) regulates the intensity and the duration of the central hyperadrenergic response in times of high stress and has been negatively associated with anxiety, depression, and sleep problems. We hypothesized that individuals with low plasma GABA levels may be more prone to develop posttraumatic stress disorder (PTSD) in the aftermath of trauma exposure. METHODS To test this hypothesis, we measured plasma GABA levels in a population of 108 road traffic accident victims on arrival at a traumatology department and assessed them for PTSD 6 weeks later. RESULTS The mean GABA level (nmol/mL) in the PTSD group (n = 55; M =.20; SD =.08) was significantly lower compared with members of the trauma-exposed group who did not develop PTSD [n = 17; M =.30; SD =.09), t(70) = 3.94, p =.0002]. CONCLUSIONS Provided that GABA levels in the brain are genetically predetermined, our results would suggest that individuals with low plasma GABA levels are premorbidly more vulnerable to stress-related disorders such as acute PTSD. If replicated, plasma GABA levels measured in the aftermath of trauma exposure might help to identify individuals at high risk for developing PTSD.

Test for Catatonia with zolpidem

Catatonia is associated with severe motor and behavioural signs and has psychiatric and other general medical aetiologies. The effectiveness of benzodiazepines for catatonia has been shown. Mastain et al described a case of reproducible relief of a catatonic syndrome with zolpidem, a selective -aminobutyric acid A (GABA-A) agonist with a hypnoselective profile. GABA-A agonists enhance GABA activity that may reverse abnormal basal ganglia dopaminergic activity which has been postulated to explain the motor abnormalities of catatonia. We report clinical changes in relation to zolpidem plasma concentrations that confirm the improvements of catatonia syndrome with zolpidem. A 21-year-old woman with a first episode of schizoaffective disorder was treated with haloperidol 4 weeks after onset of the episode. Since her condition deteriorated haloperidol was discontinued. She met the criteria for diagnosis of catatonia according to DSM-IV. She displayed severe oppositional behaviour, mutism, staring, posturing, and food and drink refusal. 1 month after haloperidol withdrawal she was given zolpidem 10 mg orally with informed consent from her father. Zolpidem plasma concentrations were monitored every 15 min with concomitant rating assessments of the catatonic symptoms with the scale proposed by Rosebush et al. All her motor and behavioural signs resolved. The improvement occurred 15 min after administration of zolpidem as the plasma concentration reached 90 ng/mL and lasted 4 h. Relapse occurred when plasma concentrations fell below 90 ng/mL (see figure). The trial was replicated 24 h later with an identical threshold effect. She was then placed on alprazolam 2 mg three times daily and the catatonia resolved. Response to zolpidem is consistent with the effectiveness of GABA-A agonists in catatonia. Zolpidem may be an effective and prompt pharmacological test for catatonia.

SPECT imaging, clinical features, and cognition before and after low doses of amisulpride in schizophrenic patients with the deficit syndrome

The aim of the study was to examine the action of low-dose amisulpride (100 mg/d), an atypical antipsychotic from the benzamide class with a high affinity for the D2 and D3 dopamine receptors, given for 4 weeks in 19 schizophrenic patients with the deficit syndrome, in terms of clinical response, modifications in their cognitive performance and changes in brain perfusion values. A secondary objective was to distinguish between primary and secondary deficit, according to Carpenters definition. Both efficacy and a relatively low rate of side effects of low-dose amisulpride in the deficit forms of schizophrenia were found as expected from earlier placebo-controlled studies. Our study found significant changes in the cerebral blood flow, before and after treatment, more marked in the frontal area and particularly in the dorso-lateral frontal area. A significant improvement of cognitive function was found after treatment, without a link to any particular changes in a loco-regional perfusion value. Finally, a distinction between primary and secondary deficit showed a higher percentage of clinical improvement in the patients with a secondary deficit. The psychometric and cerebral perfusion changes were no different in the two groups.

Carbamazepine in the treatment of neuroleptic malignant syndrome

BACKGROUND Neuroleptic malignant syndrome (NMS) is a potentially lethal adverse effect to neuroleptic drugs. METHODS We report on 2 cases where NMS dramatically improved with carbamazepine. Incidental removal and reapplication of carbamazepine attests to its effectiveness for this condition. RESULTS A 34-year-old woman treated for a major depressive disorder experienced NMS with a phenothiazine. Her condition dramatically improved in 8 hours after she was administered carbamazepine. Since carbamazepine was discontinued, NMS recurred in 10 hours and remitted anew within less than 24 hours after reintroduction. A 31-year-old woman experiencing a schizoaffective disorder displayed NMS with aphenothiazine and a butyrophenone. NMS completely resolved within 8 hours after she was administered carbamazepine. NMS recurred within 12 hours after carbamazepine discontinuation. CONCLUSIONS These data thus account for a cause-effect relationship between carbamazepine administration and NMS relief, and argue against the neuroleptic withdrawal to be responsible by itself for NMS relief.