William E. Fann

Association study of schizophrenia and the dopamine D3 receptor gene locus in two independent samples

Using a case-control design, an association of schizophrenia with the dopamine D3 receptor gene (D3RG) locus was investigated. Initial analysis of pooled results from published studies revealed a significant excess of individuals homozygous for either allele among the patients. The association was next tested in two cohorts ascertained independently at Pittsburgh, Pennsylvania and at Houston, Texas. The Pittsburgh sample was comprised of patients with schizophrenia (DSM-III-R) (n = 130). The controls belonged to two groups: adults screened for the absence of substance abuse or major psychiatric illness (n = 128), and neonates (n = 160). Multivariate analysis suggested an association with allele 1 of the biallelic D3RG polymorphism in comparison with the adult, but not the neonatal, controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.69, confidence intervals 1.80, 104.30). Survival analysis suggested an earlier age of onset among male patients homozygous for allele 2. The Houston cohort included Caucasian patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria, n = 50), and normal controls matched for gender (n = 51). In this group, no significant associations were noted among all the patients or among subgroups of patients based on family history or age of onset. Possible reasons for the discordant results are discussed.

Deanol in tardive dyskinesia: A preliminary report

Deanol, a CNS stimulant and putative precursor of choline, has been given to 10 subjects with tardive dyskinesia. All subjects showed relief of symptoms of TD, possibly through enhancing CNS cholinergic mechanisms.

Association between genetic variation at the porphobilinogen deaminase gene and schizophrenia.

There is growing evidence that some genetic predisposition is important in the etiology of schizophrenia. We have sought to implicate a major gene by performing a candidate gene association study comparing the allele frequencies of seven restriction fragment length polymorphisms (RFLPs) at six loci in both a psychiatrically normal control group (N = 51) and an affected (schizophrenia or schizoaffective disorder) group (N = 55). Each group comprised Caucasians of northern European origin. The candidate areas (D5S39, D5S78, dopamine receptor D2 (DRD2), D11S29, porphobilinogen deaminase (PBGD), and D11S84) were selected on the basis of prior cytogenetic findings in schizophrenics, linkage studies, and/or implicated gene products. The presence of a polymorphic ApaLI site within the PBGD gene showed a significant association with the presence of illness (P = 0.02). The relative risk of possessing the allele with the ApaLI site was 2.10. No significant association was found with any of the six other RFLPs. Our data suggests that either the PBGD gene itself or an unknown gene linked to and/or in linkage disequilibrium with the PBGD locus predisposes some individuals to schizophrenia. Independent replication of these findings will be required to determine their relevance to schizophrenia.

High‐Dose Benzodiazepine Therapy in Hospitalized Anxious Patients

Abstract: Severely anxious hospitalized patients were treated with rapidly increasing doses of two benzodiazepine compounds to test the feasibility of rapid pharmacotherapy of the condition. Twenty‐one subjects completing the study all obtained substantial relief from symptoms; in only three subjects were symptoms completely eliminated. No serious side effects were encountered.

Neuroleptic-Induced Movement Disorders: Pharmacology and Treatment

Since 1952, when Delay & Deniker introduced chlorpromazine (Thorazine), the prototype of the group of major tranquilizers known as neuroleptics, psychiatrists and neurologists have been aware that patients sometimes develop aderse neurological conditions as side effects of these drugs. It is our purpose in this discussion to examine some current theories concerning the pharmacology of neuroleptic-induced movement disorders — primarily parkinsonism, and the dyskinesias — and to consider some of the recent thinking regarding their treatment. We have conducted in our laboratory a series of studies testing the clinical efficacy of adrenergic and cholinergic compounds in relieving symptoms of various drug-induced movement disorders. We will here report on some of these investigations and subsequently consider them in the wider context of work done throughout the field of drug-related extrapyramidal disorders.

Psychotropic Drug Interactions

Publisher Summary This chapter provides an overview of psychotropic drug interactions. Psychotropic polypharmacy has developed and continued largely out of clinical experience. Physicians have prescribed combinations of drugs in the hope of alleviating clinical symptoms resistant to single medications. Although some drug combinations are desirable and efficacious, most are of limited usefulness and are potentially hazardous. Drug interactions can occur by changes in absorption, excretion, metabolism, or plasma protein-binding effects, and by blocked transport and changes in drug mediator activity. Some drug interactions produce clinical responses directly contrary to those intended; consequently, it is vital that physicians understand pharmacologic principles when prescribing more than one drug. As interactions among most drugs are unknown or only partially known, polypharmacy should be regarded primarily as investigational. Despite the fact that current evidence indicates that most drug combinations are no more effective than drugs used singly, many physicians continue to prescribe polydrug regimens. The rationale behind this practice is that lower doses of two drugs may be more potent therapeutically and may cause fewer side effects than higher doses of one drug. Surveys of prescribing trends, however, indicate that doses of drugs used in combination tend to be higher than doses of the same drugs used individually. Furthermore, two drugs, even at lower doses, appear to cause more side effects than a higher dose of a single drug. Until further research clarifies possible drug interactions, physicians should limit the number of psychotropic drugs administered simultaneously.

Psychopharmacology and Psychophysiological Disorders

Many patients who consult a primary-care care physician suffer from anxiety and/or depression to some degree, and these emotional disturbances generally play an important role in the patient’s physical complaints. Based on the relationship of emotions to somatic condition, patients can be categorized into three groups. In one group of patients, anxiety/depression contributes entirely to the presenting complaints (1). When anxiety is prominent, the patient may complain of such symptoms as palpitations, breathlessness, vocal tremors, tremors of the extremities, gastrointestinal hyperactivity, excessive sweating, diarrhea, muscular tension, urinary frequency. The depressed patient may present with symptoms of excessive fatigue, lack of energy, loss of appetite, loss of libido, insomnia, chronic headache or backache, constipation, or other vegetative signs. Symptoms of anxiety and depression may also occur simultaneously. ‘‘Masked depression” is very common; hypochondriacal complaints, psychosomatic disorders, and acting-out behavior frequently are depressive equivalents and may be precursors of true depressive reactions (2, 3). Supportive psychotherapy, with or without the use of psychotropic drugs, usually alleviates the anxiety and/or depression, along with their physical concomitants.