[Prevention and treatment of tardive dyskinesia caused by antipsychotic drugs]. / Dyskinésies tardives induites par les antipsychotiques : données actuelles sur leur prévention et prise en charge.

INTRODUCTION: Tardive dyskinesia (TD) is a movement disorder of tongue, jawbone, trunk and/or limbs that may appear after a prolonged use of dopamine receptor blocking agents (after 3 months of treatment or after 1 month for patients over 60), and that are present during at least four consecutive weeks. TD is a frequent side effect of both classical neuroleptics and new generation antipsychotic drugs. The prevalence of iatrogenic TD is between 24 and 32 % after treatment with classical neuroleptics and about 13 % after treatment with a new generation antipsychotic. OBJECTIVE: This paper presents an updated literature review of data on diagnosis, prevention and treatment of TD. METHODS: We conducted a review of literature using the Medline Browser tool, screening studies from 1950 to 2013 in English or French with keywords « tardive dyskinesia ¼, « tardive dystonia ¼, and « abnormal movements caused by antipsychotic drugs ¼. RESULTS: We first describe and define semeiological features of TD: dystonia, tremor, myoclonus, acathisie, chorea, ballism and athetosia. Secondarily, we resume the main differential diagnoses to exclude when confronted with this kind of movement disorders. Differential diagnoses for dyskinesia can be classified between primary (Parkinson and Huntington diseases) and secondary (Wilson disease, intoxication, metabolic abnormality, cerebrovascular accident) abnormal movements. Psychogenic TD can be evocated if previous pathologies are excluded in case of atypical clinical presentation. We detail the risk factors for TD. Endogenous risk factors are related to the patient's age, underlying psychiatric disease (bipolar disorder or Alzheimer dementia), addiction to alcohol or cocaine, female gender, or neurodevelopmental vulnerability. Iatrogenic risk factors are high doses of antipsychotics, long or intermittent administration, and particular pharmaceutical classes or associations of antipsychotics. As a comprehensive tool, we review the main physiopathological hypotheses to explain the occurrence of TD in some patients: hypersensitivity of D2 neuronal receptor or neurotoxicity associated with oxidative stress mechanisms. We also summarize the current guidelines for prevention and treatment of TD. Three successive curative strategies are suggested in the literature. First, the clinician can adapt the current antipsychotic treatment (switch to a new generation antipsychotic, diminution or cessation of antipsychotic drugs). If this first intervention is not pertinent or ineffective, the clinician can prescribe an antikinetic therapeutic agent, such as tetrabenazine, or an antioxidant. Review of the published studies does not show proof of efficacy of cholinergic or anticholinergic drugs, benzodiazepine or other GABAergic drugs, nor for amantadine. Non-medication therapeutics such as ECT and TMS are discussed, but the level of proof is insufficient to promote them as a curative treatment for TD. In case of high resistance and discomfort for the patient, a neurosurgical intervention should be discussed. These curative interventions are limited, emphasising the importance of TD prevention, by limiting the prescription and doses of antipsychotics, regularly evaluating their side effects and informing the patient of TD's risk. CONCLUSION: We propose to practitioners a synthesised update of literature concerning a frequent iatrogenic effect of antipsychotics. Nevertheless, no solid guidelines have as yet been established, and further clinical studies are expected in order to better understand this frequent and discomforting side effect.

[Cognitive vulnerability to alcohol dependence: related neuroanatomic endophenotypes]. / Vulnérabilité cognitive à l'alcoolo-dépendance : identification d'endophénotypes morphologiques cérébraux.

INTRODUCTION: Executive function impairments and high level of impulsivity may constitute heritable endophenotypes that confer predisposition for alcohol dependence. Brain volume abnormalities have also been reported in young, alcohol-naïve subjects at high risk (HR) for alcohol dependence, and linked to cognitive dysfunction. METHODS: This paper presents a literature review of magnetic resonance imaging (MRI) studies that examined brain volumes in adolescent/young adult HR offspring from families with multiple cases of alcohol dependence compared to low risk controls with no family history of alcohol or drug misuse. In some of these studies, executive functioning and externalizing symptoms were also assessed. RESULTS: In HR subjects, local white matter volume deficits were found in the corpus callosum and in the right orbito-frontal cortex, and lower fractional anisotropy in the left inferior longitudinal fasciculus and in the right optic radiation. Altered fronto-cerebellar connectivity has also been reported. Diminished gray matter volume of the cerebellar cortex was found in HR subjects, in the frontal, cyngulate and para-hippocampal gyri, and also in the amygdala, the thalamus and the cerebellum. These structural abnormalities have been associated with higher impulsivity level and executive function impairments, themselves markers of vulnerability to alcoholism. These premorbid cerebral abnormalities may increase the risk for developing an alcohol use disorder in HR subjects through atypical control processing. CONCLUSION: Brain abnormalities may potentially constitute an abnormal neural network that might underlie the risk towards alcohol dependence. These circuitry abnormalities might contribute to the reward deficiency, as well as impaired response inhibition that predict impulsive spectrum behavior, which are thought to represent the inherited vulnerability to alcohol dependence in HR individuals.

[Denial of pregnancy and neonaticide: psychopathological and clinical features]. / Déni de grossesse et néonaticide : aspects cliniques et psychopathologiques.

Pregnancy denial and neonaticide have recently received media coverage following a series of French cases of neonatal killing. Although it has been known for a long time that some women deny their pregnancy and may kill their newborns, there is still no consensus on the etiopathogenic factors involved in the denial of pregnancy occurrence. Even though neonaticide is often committed by young, poor, unmarried women with little or no prenatal care, it appears that denial of pregnancy is a heterogeneous condition associated with different psychological features. Societies are ambivalent with regard to mothers who killed their children and tend to lay the entire blame on them. Furthermore, there is a widespread lack of understanding among the public on these affairs, when birth control techniques and methods are widely available. The purpose of this article is to describe the different types of pregnancy denial and neonaticide and to review the still debated etiopathogenic hypotheses. The absence of the physical changes of pregnancy at the time of the denial such as cessation of menstruation, abdominal swelling or perception of foetal movements is also discussed.