Bunney We

Psychological Factors in the Prognosis of Malignant Melanoma: A Prospective Study*

&NA; Sixty‐four patients with Stage I or II malignant melanoma who were apparently disease free rated the amount of adjustment needed to cope with their illness on a scale of 1 to 100. The resultant figure was called the melanoma adjustment score. Twenty‐nine patients who relapsed within 1 year of surgery reported a score of 53 ± 31 (mean ± SD); 35 nonrelapsers reported a score of 80 ± 20, p < 0.001. Based upon analysis of indivual melanoma adjustment scores in the first 31 patients, we predicted that subjects scoring ≥ 65 would stay in remission, whereas those scoring < 65 would relapse. Applying this prospectively to the next 33 patients we correctly identified 25 of 33 outcomes (76%), p < 0.03. This psychological variable was independent of known biological prognostic factors, which did not predict 1 year survival. The melanoma adjustment score was also independent of the number of positive lymph nodes, which did correlate with outcome in these patients. The results suggest a role for psychological factors in the one year prognosis of this malignancy.

Naloxone decreases diurnal variation in pain sensitivity and somatosensory evoked potentials.

Abstract A group of 35 normal subjects had somatosensory evoked potentials (EPs) recorded and were tested on a psychophysical pain judgment task in morning and afternoon sessions. Subjects tested in the morning were found to be significantly less pain sensitive than those tested in the afternoon on psychophysical judgments. EP measures were consistent with decreased sensitivity in the morning. In a second experiment, a group of 12 normal subjects also received naloxone (2 mg, iv) in a double blind trial, 6 in the morning and 6 in the afternoon. Naloxone hyperalgesia effects on the EP were present in the morning and absent in the afternoon. It has been recently demonstrated that beta-lipotropin, a possible precursor of the endogenous opiate beta-endorphin shares with ACTH a diurnal rhythm. Our results are consistent with the hypothesis that endorphins at least partially mediate diurnal variations in pain appreciation.

Peptides in the cerebrospinal fluid of neuropsychiatric patients: an approach to central nervous system peptide function.

This review highlights that essentially all of the recently discovered putative central nervous system (CNS) peptides and other peptide substances are measurable in human cerebrospinal fluid (CSF). Preliminary evidence also suggests that peptides in CSF may have an active regulatory role in relation to CNS function and behavior. Even if this is not the case, CSF peptides may prove to be a useful indirect marker of CNS peptide function and metabolism. Alterations in peptides have been reported in neurological and psychiatric illness, pain symptoms and their treatment, symptoms such as anxiety, and following treatment with CNS active drugs such as carbamazepine. CSF methodologies provide a strategy for the study of the interaction of classical neurotransmitters and peptide substances and their relationship to neural function and behavior in man. Assessment of peptides in CSF may supplement post mortem studies of peptide levels and receptor distribution and help lead to new diagnostic and treatment approaches in neuropsychiatric disorders.

The switch process in manic‐depressive illness

Research data collected on 75 Bipolar I patients, hospitalized at the NIMH between 1963 and 1975, were reviewed to identify “switches” into and out of mania. There were 27 “slow” switches (i.e. occurring over a period of 2–6 days) in 14 patients and 89 “rapid” switches (i.e. occurring in 24 hours or less) in 35 patients. No patient showed both “rapid” and “slow” switches during his hospitalization. Among the 89 rapid switches, 52 switches were into mania and 37 were out of mania. Rapid switches into and out of mania occurred significantly more often in the morning (7 a.m. to 3 p.m.) than at night (11 p.m. to 7 a.m.) or in the evening (3 p.m. to 11 p.m.). Estimated average sleep time on the night prior to switch into mania showed a significant drop as compared to sleep time on the second, third and fourth nights prior to switch. Patients who switched into mania at night were rated as significantly more manic during the 4 days following the switch than patients who switched in the morning or evening. Patients who switched into mania at night and evening were rated as sleeping significantly less during the 4 days following the switch than patients who switched in the morning.

Stress-induced plasma beta-endorphin immunoreactivity may predict postoperative morphine usage

The relationship between stress and human behavior is studied using general surgery as a stress paradigm. As indices of arousal, presurgery and surgery plasma beta-endorphin and cortisol immunoreactivity are assessed. Behavioral analysis is restricted to the measurement of total morphine usage during the first 24 postoperative hours under standard PRN (as needed) clinical orders. Individual patient morphine requirements vary widely (12-56 mg). Both presurgery and mean surgery plasma beta-endorphin levels significantly predict morphine requirement, and similar, although not so strong, correlations are found for cortisol. Patient age is also found to be negatively correlated with morphine requirement. When multiple regression analysis is used, the variables of plasma beta-endorphin and age predict 70% of the variance in individual morphine requirements.

A collaborative study of genetic linkage of bipolar manic‐depressive illness and red/green colorblindness : A PROJECT OF THE BIOLOGICAL PSYCHIATRY COLLABORATIVE PROGRAM OF THE WORLD HEALTH ORGANIZATION

A study of linkage of bipolar manic‐depressive illness to the protan/deutan colorblindness region of the X‐chromosome was performed on 16 informative families, in a WHO collaborative study (eight families from Brussels, six from Bethesda, one each from Basel and Copenhagen). Overall, the series did not support close linkage, but is possibly suggestive of loose linkage. but is possibly suggestive of loose linkage. The possibility of genetic heterogeneity of bipolar manic‐depressive illness, with one form linked to colorblindness, is considered.

Slow and rapid psychobiological alterations in a manic-depressive patient: clinical phenomenology.

A distinctive pattern of clinical change during eight affective episodes is reported in a rapidly cycling manic-depressive patient. After a rapid switch to near maximal intensity of affective symptoms, slow changes in symptomatology were documented by significant slopes and correlation coefficients over the course of each episode. Decreases in depression, anxiety, drowsiness, helplessness/hopelessness, anger, and sadness preceded the switches into mania; decreases in mania, euphoria, seeking others, and talking preceded the switches into depression. Psychologically important events appeared to regularly precede rapid mood switches. It is suggested that the consistent, slow clinical changes which occur during affective episodes may reflect part of an underlying rhthmic biological process and that environment events may be capable of triggering a final common pathway for the mood switch during a vulnerable period.

Use of narcotic antagonists to study the role of endorphins in normal and psychiatric patients

This chapter reviews our studies of the effects of narcotic antagonists on sleep, respiration and pain, and on the symptoms of certain psychiatric illnesses. The recent discoveries of endogenous polypeptides that bind to opiate receptors in brain (Hughes et al. 1975; Teschemacher et al. 1975) have stimulated a search for the physiological role of these opioid substances. The pharmacological effects of opiate alkaloids provide the best available model for the effects of endorphins. Thus, since morphine and its congeners affect mood, pain appreciation, sleep, respiration, and release of pituitary hormones, these physiological functions are prime candidates for endorphin activity.

Prolactin response to beta-endorphin in man

Abstract Beta endorphin was administered intravenously to six medication-free schizophrenic patients under placebo-controlled conditions. Serum prolactin (PRL) and growth hormone (GH) concentrations were measured for 90 minutes after infusion. Prolactin was significantly increased following beta-endorphin infusion compared to placebo infusions. Growth hormone levels were not affected by beta-endorphin. The implications of the PRL response in schizophrenic patients await further study.

Catecholamines and Affective Illness: Studies with L-DOPA and Alpha-Methyl-Para-Tyrosine

In this paper we will review previous data and present new data on the clinical effects of L-dihydroxyphenylalanine (L-DOPA) and alpha-methyl-para- tyrosine (α-MPT) in the affective disorders and on the biochemical pharmacology of these agents in man and in the laboratory animal. These studies were prompted by the catecholamine hypothesis, which remains of central importance in current research in the affective disorders (Bunney and Davis 1965; Schildkraut 1965). This hypothesis proposes that some, if not all, depressions are associated with a deficiency of catecholamines at functionally important adrenergic sites in brain, and that mania may be associated with an excess of these amines (Schildkraut 1965). Pharmacologic agents that cause an increase in active catecholamines released by appropriate neurons should be associated with alleviation of depression or production of mania, and pharmacologic agents that cause a decrease in the amount of catecholamines available to the receptor should be associated with worsening of depression or improvement of mania.