Akathisia, dystonia, dyskinesia and parkinsonism, the four main categories of neuroleptic-induced extrapyramidal syndromes (EPS), represent major disadvantages in antipsychotic therapy. In vulnerable patients, acute EPS may progress into potentially irreversible forms such as tardive dystonia and tardive dyskinesia. In the psychiatric clinic, these EPS are often insufficiently recognised or permitted to exist without treatment. In order to ensure a better EPS diagnosis, a simple examination procedure is described. EPS rating scales may serve as an aid in this process. Guidelines are given to prevent and treat EPS. Thus, EPS are best prevented by a course of neuroleptic medication involving as little antidopaminergic D2 effect as possible, including the use of the lowest effective dose (sometimes obtained by addition of a benzodiazepine or carbamazepine) and with antipsychotic drugs which produce low D2 receptor blockade. Treating EPS also consists of using the lowest effective dose and antipsychotics with a low D2 dopamine receptor occupancy. At present, clozapine is the only drug that produces antipsychotic benefits at doses that cause far less D2 receptor antagonism in the basal ganglia of the brain than that seen with standard neuroleptics; however, newer drugs, such as olanzepine, seroquel and sertindole, are on the way.

Within the NIMH Research Domain Criteria (RDoC) framework, dimensions of behavior are investigated across diagnoses with the goal of developing a better understanding of their underlying neural substrates. Currently, this framework includes five domains: cognitive, social, arousal/regulatory, negative, and positive valence systems. We argue that the inclusion of a motor systems domain is sorely needed as well. Independent of medication, distinct areas of motor dysfunction (e.g. motor planning/inhibition/learning/coordination, involuntary movements) commonly appear across a number of mental disorders (e.g. schizophrenia, bipolar disorder, autism, attention deficit hyperactivity disorder, Alzheimer's disease, depression) as well as neurological disorders accompanied by significant psychological symptoms (e.g. Parkinson's disease). In addition, motor systems are amenable to study across multiple levels of analysis from the cellular molecular level focusing on cytoarchitechtonics and neurotransmitter systems, to networks and circuits measured using neuroimaging, and finally at the level of overt behavioral performance. Critically, the neural systems associated with motor performance have been relatively well defined, and different circuits have been linked to distinct aspects of motor behavior. As such, they may also be differentially associated with symptoms and motor dysfunction across diagnoses, and be uniquely informative about underlying etiology. Importantly, motor signs can change across stages of illness; they are also often present in the prodromal phases of disease and closely linked with course, suggesting that these behaviors represent a core feature reflective of pathogenic processes. The inclusion of a motor domain would allow researchers to better understand psychopathology more broadly, and may also reveal important contributions to disease processes across diagnoses.

Dyskinesia is an extrapyramidal movement disorder characterized by involuntary, repetitive, irregular motions that affect the mouth and face and/or the limbs and trunk. Tardive dyskinesia (TD) is a well-known complication of long-term treatment with antipsychotic drugs. Dyskinesia is also induced with levodopa, a treatment for Parkinson's disease, and it occurs spontaneously as a symptom of Huntington's disease. Research on the pathogenesis of TD has focused on a dysfunction of either the dopaminergic or serotonergic system. However, recent evidence has suggested that we should focus on the possible damage of GABAergic medium spiny neurons (MSNs). MSNs are the first station in the cortico-striato-thalamo-cortical circuit that regulates the amplitude and velocity of movements. Two pathways can be distinguished in this circuit: a direct pathway, which increases movements (hyperkinesia), and an indirect pathway, which decreases movements (hypokinesia). Both pathways are activated by glutamatergic corticostriatal neurons. Here, we discuss some evidence that supports the hypothesis that indirect pathway MSNs are damaged in dyskinesia.

Considerable evidence from preclinical and clinical investigations implicates disturbances of brain dopamine (DA) function in the pathophysiology of several psychiatric and neurologic disorders. We describe a neural model that may help organize theseindependent experimental observations. Cortical regions classically associated with the limbic system interact with infracortical structures, including the nucleus accumbens, ventral pallidum, and dorsomedial nucleus of the thalamus. In our model, overactivity in forebrain DA systems results in the loss of lateral inhibitory interactions in the nucleus accumbens, causing disinhibition of pallidothalamic efferents; this in turn causes rapid changes and a loss of focused corticothalamic activity in cortical regions controlling cognitive and emotional processes. These effects might be manifested clinically by some symptoms of psychoses. Underactivity of forebrain DA results in excess lateral inhibition in the nucleus accumbens, causing tonic inhibition of pallidothalamic efferents; this perpetuates tonic corticothalamic activity and prevents the initiation of new activity in other critical cortical regions. These effects might be manifested clinically by some symptoms of depression. This model parallels existing explanations for the etiology of several movement disorders, and may lead to testable inferences regarding the neural substrates of specific psychopathologies.

We report a 45 year old man with neuroleptic-induced dyskinesia for whom deep brain stimulators (DBS) were implanted in the globus pallidus internus (GPi). We describe a significant improvement in his symptoms. Lastly, we review briefly the success of deep brain stimulation to date, and discuss the clinical implications for individuals who develop movement disorders during neuroleptic use.

Functional laryngeal dyskinesia is a disorder that presents with stridor. Failure to recognize its features can result in inappropriate investigation and treatment for a condition that has a psychogenic origin. The key feature in diagnosis is paradoxical vocal fold adduction on inspiration, as seen on fibre-optic nasendoscopy. This phenomenon together with the associated stridor may disappear after distraction techniques or when the patient is asleep. We present five such cases which presented to hospitals in south west London over a 12 month period.

The treatment of psychosis in patients with Parkinson's disease (PD) is one of the most difficult problems in clinical psychiatry. Clozapine's low propensity to induce extrapyramidal side effects makes it an attractive treatment for psychotic patients with PD. A number of published uncontrolled studies suggest that low-dose clozapine is effective in these patients. However, the dose range, side effect profiles and length of treatment have varied in these reports. In this article, the authors review the literature and report on the effects of clozapine in a patient with Parkinson's disease and psychosis. Clozapine (50mg per day) resulted in a complete resolution of psychosis, improvement of motor function, reduction of “off” time and a major improvement in levodopa-induced dystonic dyskinesias. The only adverse effect was mild sedation during the first two weeks of clozapine treatment. The lack of acute blockade of striatal D2 receptors by clozapine and the failure of chronic clozapine treatment to suppress striatal dopamine release may account for its beneficial effect in Parkinson's disease. Additionally, an ameliorating effect of clozapine on parkinsonism might be due to its action on serotonergic systems leading to release of striatal dopamine.