Biomedical subjects
Publications and source records attributed to G D Tollefson.
Current knowledge about monoamine oxidase (MAO) inhibitors is reviewed, with particular attention to the mode of action, prognostic indicators, treatment protocol, response prediction, toxicity, and untoward drug interactions. The MAO inhibitors are often effective in the treatment of affective disorders, anxiety states, and phobias.
Personality disorders are characterized by inflexible maladaptive traits that cause significant impairment in social and occupational functioning. Categories of personality disorders include paranoid, schizoid, histrionic, narcissistic, antisocial, borderline, avoidant, dependent, compulsive and passive-aggressive. The inflexible nature of these disorders and the lack of an alternative behavioral repertoire result in an inability to cope with environmental pressure. The goal of management is the development of healthier behavioral responses to stress. A personality change in older patients suggests organic disease.
A variety of psychologic disorders may present as physical complaints without organic basis. As characterized by Sydenham over 300 years ago, such disorders "mimic all the physical disease to which man is heir." The case here presents the evolution of a conversion disorder (urinary retention) in response to a decision to terminate pregnancy. The predominant disturbance in a conversion disorder is an involuntary loss or alteration in somatic function that is temporally related with an environmental stressor. Conversion, as a defense mechanism, provides primary gain by keeping the conflict from the patient's awareness and secondary gains by generating environmental support and avoidance of undesired activities. Awareness of a patient's current life events, past responses to stress, and support systems is essential in order to recognize and manage this array of physical complaints of functional origin.
Based on evidence that mania may include an alteration of cholinergic function, we have previously investigated the effects of various monovalent ions on the muscarinic cholinergic receptor from human caudate nucleus utilizing the radio-labeled antagonist (3H)quinuclidinyl benzilate (QNB). In this study we observed that Li+ at 1 mM was unique in its ability to specifically reduce the affinity of 3H-QNB for the muscarinic receptor (increasing the QNB dissociation constant from 35.9 pM to 72.4 pM). The sodium-specific induction of positive cooperativity (nHill) at the muscarinic cholinergic receptor was inhibited in the presence of Li+. Both observations achieved statistical significance at p less than 0.05. A Li+-related decrease in specific QNB binding sites (Bmax) by 23% (from 2480 to 1900 pmole/g protein) was additionally manifest, albeit only achieving a statistical trend (p less than 0.10). The exact mode of Li+ action in the management of major affective illnesses remains speculative. The observations that this cation specifically mediates a reduction of muscarinic receptor affinity and number of binding sites within the human caudate suggests further consideration of the association between muscarinic cholinergic activity and mania as it relates to Li+.
Neuropsychiatric impairment during senescence and consequent to alcohol abuse demonstrates several parallels in the areas of short-term memory and sensorimotor skills. In this study high-affinity binding of the muscarinic cholinergic antagonist quinuclidinyl benzilate (QNB) was determined with post-mortem human brain tissue from normal young adults, age-matched ethanol abusers, and nondemented senior adults without histories of substance abuse. Hippocampus was chosen because of its high-density cholinergic innervation and probable role in the mnemonic process. A statistical significance emerged between nonalcoholic young adults and both ethanol abusers and seniors in reference to cooperative binding interactions (Hill coefficient, nH) amongst the latter two groups. Analysis of the respective receptor affinities (KD) revealed a significant difference between each group. A trend toward an increased KD occurred from nonalcoholic young adults to alcoholic young adults to nonalcoholic seniors. Concerning the density of receptor sites (Bmax) no difference emerged between alcoholic or nonalcoholic young adults. However nonalcoholic seniors manifest a statistically significant reduction in Bmax; this feature is consistent with the reports of several other investigators. Amongst subjects with a pathologic history of ethanol abuse, a premature senescence along parameters of nH and KD emerged, albeit not including the apparent age-dependent decline in Bmax.
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A peripheral model offers a valuable research tool for the investigation of central cholinopathic disorders. The in vitro affinities of several psychotropic drugs for the muscarinic cholinergic binding sites of human caudate and erythrocyte were compared in competition with a tritiated antagonist (quinuclidinyl benzilate). The relative affinities of the drugs for both tissues were strikingly similar. Thus, the erythrocyte muscarinic receptor may represent an accessible in vitro assay for the characterization of central cholinopathic states.
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Psychomotor agitation, a common clinical feature of major depression, may first emerge or intensify during pharmacotherapy. Whether agitation is part of the underlying course of depression or iatrogenic complicates treatment planning. We analyzed data from blinded clinical trials involving 4,737 patients with major depression assigned to a selective serotonin reuptake inhibitor (fluoxetine), a comparator antidepressant (usually a tricyclic antidepressant [TCA]), or placebo. Item 9 of the Hamilton Depression Rating Scale was used to assess the degree of psychomotor agitation. The vast majority of depressed patients exhibited baseline psychomotor agitation. The rate of increased agitation from baseline during acute pharmacotherapy was comparable between fluoxetine and either placebo or TCAs. Substantial emergence of psychomotor agitation also occurred at a similar incidence across the three treatment groups and typically appeared within the first 3 wk. Improvement in agitation was significantly more prominent (P < 0.001) among fluoxetine-treated than among placebo-treated patients. Fluoxetine-treated patients demonstrated numerically superior improvement rates compared with TCA-treated patients; however, this difference was not significant. Data derived from this large series of clinical trials suggested no evidence that either fluoxetine or TCAs induced psychomotor agitation at rates exceeding the natural course of the disorder over time (placebo cohort). On the contrary, pharmacotherapy with either fluoxetine or TCAs was typically associated with diminished agitation, probably as part of the response pattern of depression.
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Treatment response to antidepressant medication was examined in 59 patients with nonchronic major depression and 35 patients with chronic major depression. Patients with chronic major depression had a poorer response to imipramine or desipramine than nonchronic patients.