Mark S. Gold

Relationship of Thyrotropin-releasing hormone test and dexamethasone suppression test abnormalities in unipolar depression

The thyrotropin-releasing hormone (TRH) test and the dexamethasone suppression test (DST) were administered to 50 inpatients with unipolar depression. Of the patients tested, 64% had a blunted thyroid-stimulating hormone (TSH) response to TRH and 50% failed to suppress on the DST. There was no significant association between these two abnormalities by chi-square test. This lack of association suggests that the blunted TSH response to TRH is not an artifact of hypothalamic-pituitary-adrenal hyperactivation. The TRH test and the DST complemented each other as biological markers for active unipolar depression: 30% of the patients were identified by both tests, 34% by the TRH test only, 20% by the DST only, and 16% by neither test. The two tests may be useful in developing a nosology for major unipolar depression that is based on both descriptive and neurobiological information.

A rationale for opiate withdrawal symptomatology

The discovery of opioid peptide transmitters and the delineation of their interactions with the noradrenergic locus ceruleus (LC) has led to our proposing that opiate effects on mood and physiological responses result from the opiate-induced inhibition of the LC. Withdrawal of opiates removes this tonic inhibition of the LC and could readily result in a piperoxane-like release from inhibition. The hypothesis that noradrenergic hyperactivity underlies the physiologic and affective changes seen in opiate withdrawal and spontaneous panic seen in man can be readily tested in man by evaluating the efficacy of drugs which inhibit the LC and block piperoxane- and LC-elicited increases in specific behaviors for the treatment of opiate withdrawal and naturally occurring panic-anxiety states in man.

USE OF PSYCHOTROPIC DRUGS IN TREATMENT OF METHADONE MAINTAINED NARCOTIC ADDICTS

I t is not surprising that individuals addicted to drugs have come to ascribe to chemicals a wide variety of powers including being able to produce euphoria, banish despair, abolish fatigue, and provide oblivion. Drugs are not only a way of life but a way of coping with life. Because of this reliance on a chemical connection, therapists have been ambivalent about continuing the connection during treatment. At the poles of the ambivalence are, on the one hand, those programs, usually residential therapeutic communities, which prohibit the use not only of methadone but often of any tranquilizers or other psychotropic drugs. At the other pole are those programs, often found in prisons, where control of the population is deemed of first importance and the prisoner addicts are often dosed with two or three different sedating drugs simultaneously. Physicians in methadone programs, not uncommonly, find themselves in the middle of this continuum. They have already accepted the principle, by use of methadone, that it is appropriate to prescribe some drugs in treatment of the narcotic addict. In carrying out the remainder of treatment, however, they wish to de-emphasize the use for drugs to solve all of life’s problems. However, doctors are either besieged by patients wanting drugs, especially the minor tranquilizers, or they feel that patients could benefit from use of a particular drug such as an antidepressant. Their dilemma is compounded by the paucity of controlled studies about the use of psychotropic drugs in treating narcotic addicts, inadequate tools for accurate diagnostic assessment, the pressure of time and too many patients, plus the subtle pressure of other staff either in the direction of not wanting the physician to prescribe any other drugs or of wanting the physician to act as a control agent to sedate troublesome patients. Since it is quite possible that some or most drug addicts are self-medicators, i t may be important to understand what underlying condition is being treated by the illicit drug. There has been, however, a striking lack of unanimity concerning the incidence and prevalence of specific psychiatric disorders or symptom clusters of drug addicts. Even less understood is the effect of methadone on any underlying emotional problem. Does methadone lead to depres’sion or improve it? Does it suppress the symptoms of schizophrenia or mania to some degree? In some cases, patients had previous admissions to psychiatric fac es, trials of antipsychotic medications and then found heroin. In other cases, patients with a family history of bipolar Type One illness and siblings with hospitalizations for mania are maintained on methadone and appear to have only mild recurrent depressive episodes which may not require hospitalizations or medication. These and other

The thyrotropin-releasing hormone test in the diagnosis of unipolar depression

The establishment of criteria for a blunted thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) may prove useful in distinguishing patients with major unipolar depression from patients with nonmajor depressions and controls. To this end, we administered the TRH test to a group of depressed, euthyroid inpatients diagnosed by Research Diagnostic Criteria and 20 normal volunteer controls. The mean maximal TSH response (delta TSH) to infusion of 500 micrograms of TRH of 7.3 +/- SD 4.6 microIU/ml in the 105 patients with major depressive disorder, primary unipolar subtype was significantly lower than that of 13.4 +/- SD 4.4 in the 20 controls and 10.9 +/- SD 4.4 in the 40 patients with nonmajor depressions. The differences were not explainable by differences in baseline thyroid function, age, or sex. When a delta TSH less than or equal to 7.0 microIU/ml was used as a diagnostic test for unipolar depression, the sensitivity of the TRH test was 56%, the specificity 93%, and the predictive value 91%. These results suggest that the TRH test may be useful in confirming the diagnosis of major unipolar depression and hence identifying patients likely to respond to antidepressant medications or electroconvulsive therapy.

Efficacy of clonidine in opiate withdrawal: A study of thirty patients

In a placebo-controlled, double-blind crossover trial, clonidine caused a marked and significant reduction of objective signs and subjective symptoms of opiate withdrawal in thirty hospitalized opiate addicts. In an open trial of clonidine in opiate withdrawal, clonidine was found to suppress opiate withdrawal signs and symptoms, allowing all of the patients to detoxify successfully from chronic opiate addiction. Clonidine was demonstrated to reverse and suppress the signs, symptoms, and effects associated with opiate withdrawal. These data support a release from chronic opiate-induced noradrenergic inhibition producing noradrenergic hyperactivity as the pathophysiological substrate for opiate withdrawal. Clonidine replaces opiate-mediated inhibition with alpha-2 mediated inhibition of noradrenergic nuclei.

The thyroid-stimulating hormone response to thyrotropin-releasing hormone in mania and bipolar depression

The release of thyroid-stimulating hormone (TSH) from the pituitary after infusion of 500 microgram of thyrotropin-releasing hormone (TRH) was decreased (p < 0.01) in manic patients and increased (p < 0.01) in bipolar depressed patients compared to a control group of patients with personality disorders. These results suggest that the TRH test may be useful in the diagnosis of psychiatric disorders and in the prediction of response to pharmacotherapy. We discuss the role of central monoaminergic systems in changes in the TSH response to TRH.

Autism and attention: Theoretical considerations and a pilot study using set reaction time

SummaryWe have presented an attentional model that may have value in the pathophysiology of autism. We have presented data that suggest attentional dysfunction and an attentional hypothesis that may explain autisms multisensory clinical appearance and natural history. Only further studies will be able to evaluate this hypothesis and hopefully provide us with something more promising to offer parent and child in the way of therapy.

Thyroid-stimulating hormone response to thyrotropin-releasing hormone in unipolar depression before and after clinical improvement

Fourteen patients with unipolar depression who had a blunted thyroid-stimulating hormone (TSH) response to infusion of 500 micrograms of thyrotropin-releasing hormone (TRH) and who showed marked clinical improvement after pharmacotherapy and/or electroconvulsive therapy had the TRH test repeated after improvement. The mean (+/- SD) maximal TSH response to TRH (delta TSH) increased significantly from 4.0 +/- 1.9 to 9.1 3.5 micro IU/ml. The number of patients with delta TSH less than 7.0 micro IU/ml increased significantly from 0 to 9 of 14 after improvement. Eleven of the patients were followed for 5 to 19 months, and none showed clear relapse. The results suggest that the blunted TSH response to TRH has features of both a state marker for active unipolar depression and a trait marker for vulnerability to this illness, and support the suggestion that the TRH test may be useful in diagnosis and treatment planning.

Evidence for an endorphin dysfunction in methadone addicts: Lack of ACTH response to naloxone

Chronic exogenous opiate administration might be responsible for the acute and protracted abstinence syndrome by producing a prolonged decrease in the availability of endogenous opioids (endorphins). However, the hypothesis that potent exogenous opiates may have anti-endorphin effects has been difficult to test. We have been investigating this hypothesis with neuroendocrine test paradigms which have provided preliminary evidence of anti-endorphin effects for chronic methadone. Naloxone-induced ACTH response data from chronic methadone addicts offers preliminary support for the hypothesis that chronic exogenous opiate administration has anti-endorphin effects. The subjects were 7 male methadone addicts who had been addicted to greater than or equal to 40 mg of methadone and 7 male healthy opiate-naive volunteers. Naloxone failed to produce a significant increase in ACTH in methadone addicts while opiate-naive normal volunteers demonstrated a significant naloxone-induced release of ACTH. Five of the seven methadone addicts ahd no demonstrable ACTH response to naloxone. These impaired naloxone response data reported here for recently detoxified addicts suggest that chronic methadone administration comprises the functional integrity of the endorphin system. Prolonged abstinence, post-detoxification depression and other affective symptoms which contribute to relapse may result from a prolonged endorphin derangement.

Thyroid Stimulating Hormone and Growth Hormone Responses to Thyrotropin Releasing Hormone in Anorexia Nervosa

Ten female patients who satisfied objective criteria for the diagnosis of anorexia nervosa were given 500 ug of thyrotropin releasing hormone. Thyroid stimulating hormone and growth hormone responses were measured in duplicate by radioimmunoassay. These patients had a low normal Δ thyroid stimulating hormone but a delayed peak response. In addition, these patients had pathological growth hormone release in response to thyrotropin releasing hormone infusion. Both delayed peak thyroid stimulating hormone and growth hormone response to thyrotropin releasing hormone have been reported for patients with hypothalamic disorders.