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Biomedical subjects

P C Whybrow

Publications and source records attributed to P C Whybrow.

At least 19 recordsLinked to original sources
PubMed1995

Evidence of chaotic mood variation in bipolar disorder.

BACKGROUND: Using long-term daily mood records obtained from patients with bipolar disorder and normal subjects, we sought to determine the temporal pattern of mood in bipolar disorder. METHODS: Time series of 1.0 to 2.5 years from seven rapid-cycling patients with bipolar disorder and 28 normal controls were obtained. These were evaluated with several techniques to identify whether the temporal pattern of mood originates from a periodic, a random, or a deterministic source. RESULTS: True cyclicity was not apparent in the power spectra of either the normal subjects or the patients with bipolar disorder. Instead, spectra with a broadband "l/f" shape were observed in both groups, and these spectra were significantly flatter in normal subjects (P = .02). Correlation dimension estimates are a measure of nonlinear deterministic structure, and convergent estimates could be obtained for six of the seven patients with bipolar disorder and none of the normal subjects (P < .001). Additional findings are consistent with these results. CONCLUSIONS: These studies indicate that mood in patients with bipolar disorder is not truly cyclic for extended periods. Nonetheless, self-rated mood in bipolar disorder is significantly more organized than self-rated mood in normal subjects and can be characterized as a low-dimensional chaotic process. This characterization of the dynamics of bipolar disorder provides a unitary theoretical framework that can accommodate neurobiologic and psychosocial data and can reconcile existing models for the pathogenesis of the disorder. Furthermore, consideration of the dynamical structure of bipolar disorder may lead to new methods for predicting and controlling pathologic mood.

Adult↗
PubMed1994

Testing definitions of dysphoric mania and hypomania: prevalence, clinical characteristics and inter-episode stability.

37 outpatients with at least one prospectively observed manic or hypomanic episode comprised a sample for comparison of five definitions of dysphoric (hypo)mania. Dysphoric symptoms were continuously rather than bimodally distributed. Prevalence of dysphoria varied from 5 to 73% depending on the definition used. Female gender was associated with dysphoria under two of the five definitions. Inter-episode stability in patients with at least two prospectively observed episodes (n = 15) was not significantly different from chance. These data do not indicate that (hypo)mania can be dichotomized on the basis of dysphoria. Advantages and disadvantages of dimensional and categorical approaches to specifying mood in mania or hypomania are discussed.

Adult↗
PubMed1994

The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members.

Members of the National Depressive and Manic-Depressive Association who have bipolar disorder were surveyed. 59% of respondents had their first symptoms during childhood or adolescence. Long delays between symptom onset, treatment-seeking, and receipt of a bipolar diagnosis were common. 45% of respondents currently experience frequent recurrences. Child/adolescent onset was associated with a positive family history, depressive or mixed initial symptoms, and frequent recurrence, with predominantly depressive symptoms. Frequent recurrences were associated with depressive or mixed initial symptoms and depressive episodes, but not with medication non-compliance. Both child/adolescent onset and frequent recurrence were associated with increased social morbidity, which was diminished by effective treatment. Respondents with frequent recurrences were less likely to be treated with mood-stabilizers, more likely to be treated with anti-depressants, or anxiolytics, and more likely to report past anxiety symptoms and diagnoses. 13% of respondents had no medical insurance, and 15% had failed to take medicine for financial reasons. The treatment of bipolar illness could be enhanced by (a) public health efforts to promote early diagnosis and treatment; (b) ensuring adequate trials of mood-stabilizers for patients with frequent recurrences; (c) further research on bipolar disorder with prominent anxiety symptoms; and (c) improved access to mental health care.

Adolescent↗
PubMed1994

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↗
PubMed1994

The therapeutic use of triiodothyronine and high dose thyroxine in psychiatric disorder.

An intimate association between disturbances of thyroid hormone homeostasis and behavior has been recognized for a long time already: Hyper- and hypothyroidism can induce disturbances of mood and intellectual function (in severe cases even psychosis can be mimicked). Reciprocally many psychiatric disturbances, such as major depression and manic depressive disease have associated with them disturbances of peripheral thyroid hormone metabolism. Approximately 10% of depressed persons seem to have subclinical hypothyroidism and another approximately 35% have a blunted TSH response to TRH. The use of lithium clearly increases these numbers. In some cases a positive correlation between elevated T4 and the speed of response to antidepressant drugs has been reported. Patients with manic depressive disease respond less well to treatment with lithium when they have a so called "rapid cycling disorder" (defined as more than 4 episodes of disturbed behavior a year). These patients were shown to have a comparably high incidence (up to 50%) of mild subclinical hypothyroidism. In an open study of 11 patients (10 females--9 of them premenopausal--1 male) with rapid cycling disorder adjunctive treatment with TSH suppressive doses of T4 (T4 levels at approximately 150% of normal) reduced the manic and depressive phases in both amplitude and frequency and even led to remittance in some patients. T4 treatment was begun only after stable "therapeutic" blood levels of lithium carbonate and/or anticonvulsants have been reached, since it has been shown that T4 therapy alone can precipitate dysphoric manic like symptoms which require treatment with neuroleptics. Careful evaluation of possible side effects like osteoporosis revealed surprisingly an even higher bone density in treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Bipolar Disorder↗
PubMed1993

A family history study of rapid-cycling bipolar disorder.

Previous studies have yielded mixed evidence as to whether rapid-cycling bipolar disorder (four or more episodes per year) is associated with a distinctive pattern of patient characteristics and familial aggregation of affective disorder. In this study, Family History Research Diagnostic Criteria (FH-RDC) were used to interview 165 patients with rapid-cycling bipolar disorder, non-rapid-cycling bipolar disorder, or recurrent unipolar depressive disorder about the psychiatric history of 812 adult first-degree relatives. In a validity study, FH-RDC diagnoses were demonstrated to agree reasonably well with best-estimate diagnoses by two psychiatrists/psychologists, based on direct interviews with the Structured Clinical Interview for DSM-III-R. Relatives of patients with recurrent unipolar depression were less likely to have bipolar disorder and more likely to have unipolar depression than were relatives of rapid-cycling or non-rapid-cycling bipolar patients. Rapid-cycling patients were younger and more likely to be female than non-rapid-cycling patients. The relatives of rapid cyclers did not differ significantly from those of non-rapid cyclers in the prevalence of bipolar disorder, unipolar disorder, rapid-cycling bipolar disorder, or substance abuse. However, there were nonsignificant trends for the relatives of rapid-cycling bipolar patients, compared with those of non-rapid-cycling bipolar patients, to have more substance abuse and less bipolar disorder given the presence of affective disorder.

Adult↗
PubMed1991

Measurement of tissue lithium concentration by lithium magnetic resonance spectroscopy in patients with bipolar disorder.

Measurements of the lithium concentration in the occipital pole of the head and calf muscle of nine patients with bipolar disorder in remission were performed using in vivo lithium-7 nuclear magnetic resonance spectroscopy (7Li NMR). 7Li NMR measurements were performed on a 1-m-bore, 1.85-T, superconducting magnet supplemented with a multinuclear spectrometer, using 11.5-cm-diameter surface coils. The average lithium concentration in the occipital pole was 0.36 +/- 0.10 mEq/L, whereas in the muscle it was 0.50 +/- 0.17 mEq/L, both lower than the average serum lithium concentration (0.79 +/- 0.23 mEq/L). The average brain/serum lithium concentration ratio was 0.47 +/- 0.12 whereas the average muscle/serum lithium concentration ratio was 0.66 +/- 0.20. There was a positive correlation between the brain versus serum and brain versus muscle lithium concentrations. The hypothesis is advanced that the minimal effective concentration of brain lithium concentration for maintenance treatment of bipolar disorder is around 0.2-0.3 mEq/L.

Adult↗
PubMed1991

Independent assessment of manic and depressive symptoms by self-rating. Scale characteristics and implications for the study of mania.

We report the reliability and validity of the Internal State Scale, a self-report instrument for the simultaneous assessment of severity of manic and depressive symptoms. The Internal State Scale consists of four empirically derived subscales: Activation, Well-Being, Perceived Conflict, and the Depression Index. All subscales had good internal consistency reliability. Activation subscale scores were significantly higher in manic patients than in depressed patients or control subjects, while Well-Being subscale scores were significantly lower and the Depression Index subscale scores were significantly higher in depressed patients than in the other two groups. Activation subscale scores were correlated specifically with clinician ratings of mania. Depression Index subscale scores were correlated specifically with clinician ratings of depression. Further evidence for the validity of the subscales of the Internal State Scale in reflecting manic or depressive symptoms came from discriminant function analysis in which these subscales assigned 88% of subjects to the correct diagnostic groups. In affectively ill patients who were studied in two or more mood states, Activation, Depression Index, and Well-Being subscale scores changed significantly in the predicted directions, while the same discriminant algorithm assigned 79% of mood states to the correct diagnostic category. Bimodal distribution of scores of manic patients on the Well-Being and Depression Index subscales substantiated earlier findings that euphoric mood is not an essential feature of mania. Based on findings from this and previous studies, the hypothesis is proposed that variables related to activation level, and not to mood state, constitute the core characteristics of the manic syndrome.

Bipolar Disorder↗
PubMed1990

Rapid cycling bipolar affective disorder. I. Association with grade I hypothyroidism.

Thirty patients with rapid cycling bipolar affective disorder were studied prospectively to assess presence and severity of thyroid hypofunction. Seven (23%) were classified as having grade I hypothyroidism, while 8 (27%) had grade II and 3 (10%) had grade III abnormalities. This prevalence of grade I hypothyroidism is significantly greater than that reported in studies of unselected bipolar patients during long-term treatment with lithium carbonate, although only 63% of this sample of rapid cycling patients was taking lithium carbonate or carbamazepine. The association of rapid cycling with grade I hypothyroidism cannot be accounted for by lithium carbonate use or by the preponderance of women among rapid cycling patients. These findings (1) indicate that hypothyroidism during bipolar illness is a risk factor for the development of rapid cycling, and (2) leads to the hypothesis that a relative central thyroid hormone deficit occurring in bipolar patients predisposes to a rapid cycling course.

Adult↗
PubMed1990

Rapid cycling bipolar affective disorder. II. Treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study.

Eleven patients with rapid cycling bipolar affective disorder whose symptoms were refractory to their current medication regimen were entered into an open trial of high-dose levothyroxine sodium added to a stable regimen of those medications. At baseline, all patients exhibited a rapid cycling pattern and were evaluated prospectively through at least one affective episode. Levothyroxine was added to the baseline medication regimen, and the dosage was increased until clinical response occurred or until side effects precluded further increase. While patients were taking levothyroxine, scores on both depressive and manic symptom rating scales decreased significantly compared with baseline. This improvement was due to the clear-cut response of depressive symptoms in 10 of 11 patients, with manic symptoms responding in five of the seven patients who exhibited them during baseline evaluation. Four patients then underwent single- or double-blind placebo substitution; three patients relapsed into either depression or cycling. Treatment response did not depend on previous thyroid status. In 9 of 10 responsive patients, supranormal circulating levels of free thyroxine were necessary to induce clinical response. Side effects were minimal, and there were no signs or symptoms of levothyroxine-induced hypermetabolism.

Adult↗
PubMed1989

Pituitary-adrenal and thyroid effects on melatonin content of the rat pineal gland.

Based on clinical findings of diminished nocturnal serum melatonin levels in affective illness, we hypothesized that alterations in the pituitary-adrenal or thyroid axes of the rat might alter the nocturnal rise of melatonin content of the pineal gland in that species. Two experiments were conducted to investigate these issues. In the first, rats were injected for nine days with adrenocorticotropic hormone (ACTH) or corticosterone, timed to accentuate and prolong the normal circadian corticosterone rise. Although both these treatments produced significant elevations of serum corticosterone, there was no difference in pineal melatonin content during the day or night from that measured in control rats. In the second experiment, hypothyroidism was induced in rats by thyroid-parathyroidectomy, and hyperthyroidism was produced by injection of triiodothyronine (T3) for nine days. Despite clear evidence of metabolic and endocrine effects of these thyroid manipulations, pineal melatonin content was not altered during the day or night. The nocturnal increase of melatonin may have been phase-advanced in the hypothyroid group, although the experiment was not designed to detect such a shift. There thus is no evidence from this study in the rat to suggest that diminished nocturnal melatonin production in affective illness might be due to associated alterations in the pituitary-adrenal or thyroid systems.

Adrenocorticotropic Hormone↗
PubMed1986

The effect of changing thyroid function on cyclic affective illness in a human subject.

Thyroid function abnormalities are common in persons with rapid-cycling bipolar affective illness. Some women who cycle rapidly respond to thyroxine, but there is scant evidence that the people who have thyroid abnormalities are the ones who respond to thyroid treatment. The authors report successful thyroxine treatment of a man whose rapid cycling began and resolved after changes in his thyroid status. The period of his affective cycle was altered by both lithium and thyroxine. The authors suggest that CNS thyroid status may determine the clinical course of some persons with a fixed cycle of affective episodes.

Adult↗
PubMed1984

Financial aid for medical students: a review and a proposal.

By making it possible for all students admitted to medical school to finance their education, the federal government has been a dominant variable in medical education for over two decades. Financial aid programs during the 1960s were directed at increasing the number of applicants, medical school places, and, ultimately, the number of physicians. With these goals largely achieved, a trimming of the federal systems of financial aid seems probable. Unless accommodations can be made, such changes will have broad financial implications for both students and medical schools and could threaten the diversity, stability, and quality of the applicant pool. The authors in this article review the history of medical school financial aid and describe the development of an institutionally based, privately financed loan program. The authors propose that such programs can help preserve adequate financial aid for medical students as federal programs decline.

Education, Medical↗
PubMed1981

A hypothesis of thyroid-catecholamine-receptor interaction. Its relevance to affective illness.

Recent prospective studies suggest that thyroid state plays a role in affective disorders. A lack of thyroid hormones can lower the threshold for depression; an excess can contribute to a state of tense dysphoria. Thyroid function in some persons also appears to influence the course of affective disorders. Adequate mobilization of thyroid hormones favors recovery from depression; excess mobilization increases the risk of mania in vulnerable individuals. Although other mechanisms may be involved, evidence suggests that the modulation by thyroid hormones of the beta-adrenergic receptor response to catecholamines may contribute to these effects. Norepinephrine stimulates such receptors; thyroid hormones increase their ability to receive stimulation. The plausibility of such interactions between catecholamines and thyroid hormones occurring in the CNS is strengthened by their common origin in the amino acid tyrosine and by their synergism in many metabolic processes.

Adenosine Monophosphate↗