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Biomedical subjects

R Post

Publications and source records attributed to R Post.

At least 19 recordsLinked to original sources

Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders.

Until recently it was believed that no more than 1% of the general population has bipolar disorder. Emerging transatlantic data are beginning to provide converging evidence for a higher prevalence of up to at least 5%. Manic states, even those with mood-incongruent features, as well as mixed (dysphoric) mania, are now formally included in both ICD-10 and DSM-IV. Mixed states occur in an average of 40% of bipolar patients over a lifetime; current evidence supports a broader definition of mixed states consisting of full-blown mania with two or more concomitant depressive symptoms. The largest increase in prevalence rates, however, is accounted for by 'softer' clinical expressions of bipolarity situated between the extremes of full-blown bipolar disorder where the person has at least one manic episode (bipolar I) and strictly defined unipolar major depressive disorder without personal or family history for excited periods. Bipolar II is the prototype for these intermediary conditions with major depressions and history of spontaneous hypomanic episodes; current evidence indicates that most hypomanias pursue a recurrent course and that their usual duration is 1-3 days, falling below the arbitrary 4-day cutoff required in DSM-IV. Depressions with antidepressant-associated hypomania (sometimes referred to as bipolar III) also appear, on the basis of extensive international research neglected by both ICD-10 and DSM-IV, to belong to the clinical spectrum of bipolar disorders. Broadly defined, the bipolar spectrum in studies conducted during the last decade accounts for 30-55% of all major depressions. Rapid-cycling, defined as alternation of depressive and excited (at least four per year), more often arise from a bipolar II than a bipolar I baseline; such cycling does not in the main appear to be a distinct clinical subtype - but rather a transient complication in 20% in the long-term course of bipolar disorder. Major depressions superimposed on cyclothymic oscillations represent a more severe variant of bipolar II, often mistaken for borderline or other personality disorders in the dramatic cluster. Moreover, atypical depressive features with reversed vegetative signs, anxiety states, as well as alcohol and substance abuse comorbidity, is common in these and other bipolar patients. The proper recognition of the entire clinical spectrum of bipolarity behind such 'masks' has important implications for psychiatric research and practice. Conditions which require further investigation include: (1) major depressive episodes where hyperthymic traits - lifelong hypomanic features without discrete hypomanic episodes - dominate the intermorbid or premorbid phases; and (2) depressive mixed states consisting of few hypomanic symptoms (i.e., racing thoughts, sexual arousal) during full-blown major depressive episodes - included in Kraepelin's schema of mixed states, but excluded by DSM-IV. These do not exhaust all potential diagnostic entities for possible inclusion in the clinical spectrum of bipolar disorders: the present review did not consider cyclic, seasonal, irritable-dysphoric or otherwise impulse-ridden, intermittently explosive or agitated psychiatric conditions for which the bipolar connection is less established. The concept of bipolar spectrum as used herein denotes overlapping clinical expressions, without necessarily implying underlying genetic homogeneity. In the course of the illness of the same patient, one often observes the varied manifestations described above - whether they be formal diagnostic categories or those which have remained outside the official nosology. Some form of life charting of illness with colored graphic representation of episodes, stressors, and treatments received can be used to document the uniquely varied course characteristic of each patient, thereby greatly enhancing clinical evaluation.

Antidepressive Agents↗

Gabapentin in the acute treatment of refractory bipolar disorder.

BACKGROUND: Gabapentin, a new anti-epileptic agent, has been anecdotally reported to be effective in the treatment of mania. We systematically assessed the response rate in bipolar patients being treated adjunctively with gabapentin for manic symptoms, depressive symptoms, or rapid cycling not responsive to standard treatments. METHOD: Twenty-eight bipolar patients experiencing manic (n = 18), depressive (n = 5), or rapid-cycling (n = 5) symptoms inadequately responsive to at least one mood stabilizer were treated in an open fashion with adjunctive gabapentin. Illness response was assessed using the Clinical Global Impression Scale modified for bipolar disorder (CGI-BP). A 'positive response' was operationalized as a CGI response of much or very much improved. RESULTS: Fourteen of the 18 (78%) treated for hypomania or mania had a positive response to a dosage range of 600-3,600 mg/day. Patients with hypomania responded fastest, with a positive response achieved in 12.7 +/- 7.2 days. Patients with classic mania had a mean time to positive response of 25 +/- 12 days, and in patients with mixed mania it was 31.8 +/- 20.9 days. All of the five patients treated for depression had a positive response within 21 +/- 13.9 days. Only one of five patients with rapid cycling had a positive response. Gabapentin was well tolerated by all patients, with the most common side-effect being sedation. CONCLUSIONS: Gabapentin appears to have acute anti-manic and anti-depressant properties as an adjunctive agent for refractory bipolar illness. Prospective double-blind studies are needed to further delineate its acute efficacy when used as monotherapy and its prophylactic efficacy as monotherapy or in conjuction with other mood stabilizers.

Acetates↗

Folk remedy use in the inner city.

BACKGROUND: Folk remedies (FRs) are common in some minority communities within the United States. However, little information is available about the use of FRs in the inner city. The objectives of this study were to identify the prevalence and types of FRs used in the inner city, to characterize the population using FRs, and to study patient attitudes toward discussing FRs with physicians. METHODS: We interviewed 71 patients over the age of 18 who visited an inner city ambulatory clinic. RESULTS: The rate of FR use ranged from 10% to 50% among common medical conditions, with most patients (59%) using at least one remedy. Folk remedy use did not correlate with patient age. Most patients used FRs because they believed them to be efficacious, and most felt comfortable discussing FRs with their physicians. CONCLUSIONS: Inner city residents of all ages use FRs to treat illness. These FRs are benign and consist of common household items. Health care workers should feel comfortable discussing FRs with their patients since their patients are comfortable with the topic.

Adolescent↗

Attentional effects of single dose triazolam.

1. While the effects of benzodiazepines on human memory have been extensively studied little is known about the effects of these agents on attentional processes. The authors studied the effects of a single dose of triazolam on selective visual-spatial attention using a double blind, placebo controlled design. 2. In each of 2 sessions 12 normal volunteers ingested either 0.25 mg of triazolam or placebo. Attentional performance was evaluated using two versions of the covert orienting paradigm which measured automatic (exogenous) and controlled (endogenous) aspects of attentional orienting, respectively. 3. Triazolam selectively modified performance on automatic orienting to exogenous cues. Specifically, triazolam increased the facilitation of target detection seen at shorter (150 msec) SOA's. This may indicate an increase in facilitation and a reduction in inhibition or a slowing of the time course of the biphasic attentional effect normally resulting from exogenous cuing. 4. These results indicate the importance of using experimental paradigms which effectively dissociate endogenous and exogenous mechanisms of spatial orienting in studies evaluating the effects of pharmacological agents on visual-spatial attention.

Adolescent↗

T2 hyperintensities in bipolar disorder: magnetic resonance imaging comparison and literature meta-analysis.

OBJECTIVE: Accumulating evidence suggests a greater number of T2 abnormalities in the brains of patients with bipolar I disorder. The authors sought to evaluate the presence of signal "hyperintensities" in both bipolar I and II subjects and systematically review the existing literature. METHOD: Magnetic resonance images of the brain were obtained prospectively for 29 patients with bipolar I disorder, 26 patients with bipolar II disorder, and 20 normal comparison subjects. The presence and location of signal hyperintensities in three brain regions (periventricular white matter, subcortical gray matter, and deep white matter) were evaluated. RESULTS: No significant differences were found between groups for the presence of subcortical gray or deep white matter hyperintensities. Periventricular hyperintensities were more common in bipolar I patients (62%) than in bipolar II patients (38%) and normal comparison subjects (30%). Within patient groups, medication use was not significantly different for those with or without the presence of white matter hyperintensities. The literature on bipolar disorder and signal hyperintensities is reviewed. A meta-analysis of the pooled data in the literature on bipolar illness and signal hyperintensities revealed that the odds of having a T2 hyperintensity are significantly greater for bipolar I than for normal comparison subjects. CONCLUSIONS: Having bipolar I disorder significantly increases the chance of having white matter changes in the brain. This study suggests that bipolar II patients may be more similar than bipolar I patients to comparison subjects on T2 measures. The possible pathophysiological significance of hyperintensities is discussed.

Adult↗

Electrical kindling is associated with increases in amygdala acetylcholine levels: an in vivo microdialysis study.

Using brain microdialysis, acetylcholine (Ach) levels were assessed in the nucleus amygdaloideus lateralis of electrically kindled rats using a cholinesterase inhibitor in the perfusion fluid to prevent Ach breakdown. During kindling development, when the animals displayed afterdischarges lasting more than 30 s but no seizures, a significant increase in Ach levels (+66%) was observed after electrical stimulation. Ach levels were also elevated after a stage 5 kindled seizure (+48%), with no additional increment compared to rats experiencing only afterdischarges. Chronic diazepam administration prevented kindling development and the increment in Ach overflow; however, diazepam itself (following acute administration) tended to decrease Ach levels in the amygdala. These findings are convergent with pharmacological data suggesting that changes in the cholinergic function may be important especially during amygdaloid kindling development.

Acetylcholine↗

Multisite data reanalysis of the validity of rapid cycling as a course modifier for bipolar disorder in DSM-IV.

OBJECTIVE: The validity of rapid cycling as a distinct course modifier for bipolar disorder was assessed by comparing patients with and without a history of rapid cycling (4 or more affective episodes in 12 months) on demographic, clinical, family history, and outcome variables. These data were also used to formulate operational criteria for the modifier. METHOD: Data on subjects with rapid-cycling (N = 120) and nonrapid-cycling (N = 119) bipolar disorder from four sites were pooled and analyzed by using case-control and historical cohort methods. RESULTS: The rapid-cycling group contained more women and more subjects from higher social classes than the nonrapid-cycling group. Family history did not differ between the groups. The diagnosis had predictive validity in that the rapid-cycling patients had more episodes than the nonrapid-cycling patients during prospective follow-up. The relationship between gender and episode frequency supported the validity of the cutoff point of 4-8 episodes per year. The data regarding whether patients with rapid cycling based on truncated episodes more closely resembled rapid-cycling or nonrapid-cycling patients were equivocal. Patients whose only rapid cycling was associated with antidepressants resembled spontaneously rapid-cycling patients, while the majority of spontaneously rapid-cycling patients also had periods of antidepressant-associated rapid cycling. CONCLUSIONS: The validity of rapid cycling as a distinct course modifier for bipolar disorder is supported by differences in gender, prospectively assessed outcome, and perhaps social class between rapid-cycling and nonrapid-cycling patients. The relationship of gender to episode frequency supports the cutoff of 4 or more episodes per year.

Adult↗

Conditioning as a critical determinant of sensitization induced by psychomotor stimulants.

It is apparent that stimuli associated with psychomotor stimulants as well as opiates acquire the ability to elicit motor behaviors that probably reflect the acquisition and operation of incentive motivational processes. Such conditioning also appears to be a critical determinant of behavioral sensitization seen with repetitive administration of these agents. The conditioning of motor excitation to stimuli associated with psychomotor stimulants follows the principles of classical conditioning and is relatively long lasting. Dopaminergic mechanisms appear to be involved in the acquisition of such conditioned behaviors, since neuroleptics are effective blockers of the process. Dopaminergic blockade probably disrupts conditioning through several different mechanisms including attenuation of the conditioned and unconditioned excitatory properties of the CS and blockade of the US. DA blockade prevents stimuli associated with psychomotor stimulants from acquiring and subsequently generating positive affective motivational states that are reflected by increases in motoric output. While dopamine appears to be necessary for the formation of conditioned motor excitation, it is not critically involved in the expression of the conditioned effects. This seems to suggest that DA may serve only to modulate the formation of motivationally significant associations but is not involved in the expression of conditioned drug effects that may be mediated through DA-independent pathways. The amygdala and nucleus accumbens are two structures in the CNS involved in the acquisition of conditioned motor excitation. Interestingly, both of these brain regions are the recipients of mesolimbic DA input. Dopamine probably plays different roles in each region during the conditioning process. In the amygdala, mesolimbic DA may serve to modulate processes that attach emotional significance to environmental stimuli; further, DA may play a role in determining which stimuli gain access to structures afferent to the amygdala, including the nucleus accumbens. Dopamine in the nucleus accumbens, on the other hand, serves to determine which limbic inputs gain access to the motor pathways. In this way, DA in the nucleus accumbens may translate the motivational determinants of behavior that are mediated by limbic structures into biologically relevant actions. Understanding the mechanisms that determine the conditioning of drug effects to associated stimuli also has possible relevance for elucidating processes underlying addictive behaviors. For example, it has been proposed (Stewart et al. 1984) that the acquisition of incentive motivational properties by stimuli associated with drugs determines the craving in addicts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Factors predicting mortality in rural elderly hospitalized for pneumonia.

To identify predictors of mortality, the records of 133 elderly patients with pneumonia admitted to a small rural midwestern hospital were examined using a retrospective cohort design. All recorded clinical information available to the patient's physician within the first hours of admission was reviewed. Twenty-one (15.8%) patients died during the hospitalization. Patients with preexisting coronary heart disease, dementia, urinary incontinence, and impaired mobility were more likely to die. Impaired mental status, absence of fever, rapid respiratory rate, hypotension, cyanosis, and diffuse abnormalities on chest examination were also associated with mortality. Logistic regression analysis revealed five predictive indicators of mortality: impaired level of consciousness (odds ratio [OR] = 11.3), tachypnea (OR = 10.8), temperature lower than normal (OR = 14.2), white cell count higher than 20 X 10(9)/L (20,000 mm-3) (OR = 12.2), and cyanosis (OR = 8.6). A risk score based on this regression model demonstrated that 1 of 95 patients with a score lower than 3 (1%), 7 of 22 with a score of 3 (32%), and 13 of 15 patients with a score higher than 3 (87%) died during their hospitalization. The validity of this risk-scoring system was confirmed in another sample of 40 patients. Studies such as this may be useful in identifying information of important prognostic value that enables physicians, patients, and family members to make more effective decisions.

Aged↗

Psychiatric implications of basic and clinical studies with corticotropin-releasing factor.

Corticotropin-releasing factor (CRF) is a newly sequenced neuropeptide thought to be a principal stimulus to pituitary corticotropin (ACTH) secretion. Evidence obtained from laboratory animals and primates is reviewed which indicates that CRF not only stimulates the pituitary-adrenal axis but also influences several aspects of CNS function which may be of relevance to psychiatric illness. Clinically, experience in administering ovine CRF to more than 150 individuals shows that CRF can be helpful in resolving differential diagnostic dilemmas in patients with various disorders of the hypothalamic-pituitary-adrenal axis and in furthering an understanding of the pathophysiology of conditions such as Cushing's disease and depression.

Adrenocorticotropic Hormone↗