This chapter describes the recent developments in the field of psychiatric pharmacogenetics. Most pharmacogenetic studies of antidepressants have focused predominantly on treatment response, perhaps also due to the fact that most current antidepressants are well tolerated and fairly safe. Pharmacotherapy is the treatment of choice for psychotic symptoms of mental conditions such as schizophrenia, bipolar disorder, and psychotic depression. Antipsychotic drugs are traditionally divided into two groups: typical (first-generation) antipsychotics, with strong affinity for the dopamine receptor, and atypical (second-generation) antipsychotics, with multiple receptor targets. Anticonvulsant drugs are widely used in the management of behavioral disorders, including bipolar disorder, mood disorders, and impulse control disorders. While psychiatry has entered the new area of pharmacogenetics, it is important to remember that this new technology will only provide additional information on one aspect of the complex and personal history of psychiatric patients.

This introduction presents an overview of the concepts discussed in this book The Neuropsychiatry of Epilepsy. In the intervening years, there has been a clear appreciation in biological psychiatry of the neurobiological bases of psychopathologies as major depressive disorder, obsessive-compulsive disorder and other anxiety-related conditions, and there has been further development of psychotropic and anticonvulsant drugs (AEDs). The second edition starts with epidemiology, which has become a prominent discipline in research attempting to disentangle the extent and variety of psychiatric comorbidities in epilepsy. The clinical presentations and the wide spectrum of peri-ictal disorders are then discussed. Depression in epilepsy may not be quite like depression in the absence of epilepsy, the neuroanatomy giving a special stamp on the phenomenology. The book concludes with a discussion on the brain mechanisms of consciousness as may be revealed through investigations of patients with seizure disorders.

Epilepsy is a disease of the brain characterized by recurring unprovoked epileptic seizures, caused by a transient abnormality of neuronal activity which results in synchronized electrical discharges of neurons within the central nervous system (CNS). This chapter focuses on the most important characteristics of voltage- and ligand-gated ion channels, their role in determining neuronal excitability, and the impact of some reported mutations on epileptogenesis in idiopathic epilepsies. It describes the importance of the thalamocortical loop and thalamic ion channels for the generation of generalized seizures. The binding of transmitters and the coupling to channel opening are complex processes which can consequently be influenced by amino acid changes in many different regions of these channels. Most anticonvulsant drugs that are in clinical use today act by modulating the function of ion channels and the chapter describes how ion channel function can be altered by genetic defects associated with idiopathic epilepsies.

Paroxysmal dyskinesias are a heterogeneous group of disorders characterized by intermittent attacks of hyperkinetic involuntary movements without loss of consciousness. The paroxysmal movements may affect the arm or leg on one or both sides of the body, or all extremities. All kinds of paroxysmal dyskinesias may be symptomatic in origin. Twenty-two percent of one series of patients with paroxysmal movement disorders had underlying causative diseases. History and neurologic examination are the cornerstones on the way to the diagnosis of paroxysmal dyskinesias. The paroxysmal nature and predominantly short duration of the attacks, the aura symptoms and the response to even low doses of anticonvulsant drugs suggest that paroxysmal dyskinesias closely resemble epilepsy. Sandifer syndrome is a rare movement disorder in toddlers. During or immediately after feeding, affected children exhibit severe dystonic movements or postures of the head and neck. They often vomit and are malnourished.

This chapter addresses pharmacogenetic issues associated with the clinical use of anticonvulsant drugs (ACDs). There are a number of different kinds of natural genetic variation that result in functional protein differences and affect drug responsiveness. The type of variation that is most prevalent in the genome and, arguably, the most relevant to common diseases and complex traits is represented by single nucleotide polymorphisms (SNPs). The chapter presents general comments relevant to the mechanisms of action of conventional classes of ACD. It then addresses how these mechanisms are potentially influenced by genetic variation. Subsequently, commonly used drugs are discussed individually in some depth relative to genes that may affect various aspects of their pharmacology, including metabolism. Among the nonsedating standard ACDs, those most frequently prescribed are phenytoin, carbamazepine, and valproic acid with the depressant drugs phenobarbital and clonazepam also being in common use.