Hypothesized neurochemical models for psychiatric syndromes in alcohol and drug dependence.

Exploration of the neurochemistry of psychiatric and substance use disorders in dual diagnosis patients may help explain the greater than chance comorbidity of these disorders and lead to advances in treatment. This paper will focus on the hypothesized neurochemical changes associated with primary substance use disorders which might lead to secondary psychiatric disorders by mimicking the hypothesized neurochemical changes of primary psychiatric disorders. For example, hypothesized serotonergic deficits in alcoholism, endorphin deficits in opioid dependence, and dopamine depletion in cocaine dependence all might predispose to depression. A vicious cycle of cocaine dependence and depression and a vicious cycle of alcohol and drug dependence and panic anxiety are reviewed as models for hypothesized alcohol or drug withdrawal related neurochemical changes predisposing to continued chemical dependency. Exploration of the neurochemistry of dual diagnosis patients reinforces the need for treatment approaches that take into account both aspects of illness.

Hepatitis in 101 consecutive suburban cocaine and opiate users.

The records of 101 cocaine and/or heroin drug abusing patients admitted consecutively to Fair Oaks Hospital were evaluated for history of IV drug abuse, antigen and serum antibody evidence of hepatitis A and B infection, and elevation of serum SGPT. One patient, an IV user, had hepatitis B antigen present in his blood. No patient had acute hepatitis A (IgM) antibody present. Forty-five out of fifty-three (84.9%) IV abusers were Hep B Ab positive, while two out of twenty-nine non-IV abusers (6.9%) were positive. Twenty of fifty-three (43.4%) IV users had positive hepatitis A Ab while one of twenty-nine (3.4%) of non-IV users were positive. Thirty-five of fifty-five (63.6%) IV users had elevated SGPT compared to five of forty-one (12.2%) in non-IV users. IV users tended to be older than non-IV users. The data presented in this article indicate that there is a greatly increased incidence of both hepatitis A and B in IV drug users compared to non-IV users and that the hepatitis B incidence is increased in a far greater amount than could be expected in a normal population. The type of drug injected (heroin, other opiates, or cocaine) was not an important determinant. The presence of hepatitis B antibodies in any drug abusing patient who denies IV use is a strong indication that they may not be telling the truth about their past drug abuse. It makes little difference whether drug abusing patients live in the inner city or the suburbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Psychiatric applications of thyroid tests.

Thyroid tests, especially the TRH test, can aid psychiatrists in the same way that laboratory tests are used in other medical specialties. Such tests augment clinical judgment and provide information about possible primary thyroid disturbances. The TRH test has the added value of prognostic significance when repeated after a course of treatment. Thyroid tests may also identify subgroups of depressed patients who can benefit from thyroid hormone replacement or who require T3 potentiation of tricyclics, as well as those patients with bipolar illness who are hypothyroid and may be at risk for rapid cycling.

Cocaine update: from bench to bedside.

The aim of this paper is to review and explore the psychopharmacology of cocaine from two divergent points of view--the chronic user and the laboratory. Cocaine's behavioral effects will be correlated with neurophysiological, neurochemical events, and reports by users of consequences of chronic use. These studies and reports when pieced together offer considerable promise in the development of a natural history of compulsive cocaine use. Additional neurochemical and neurophysiological research investigations are needed to allow for the development of non-addicting treatments for detoxification (à la clonidine) and prophylaxis (à la naltrexone). In the absence of these data cocaine treatment programs have been developed borrowing heavily from self help, contingency contracting and inpatient programs for working addicts.

Number of cortisol time-points and dexamethasone suppression test sensitivity for major depression.

Failure to suppress cortisol secretion after administration of dexamethasone has been reported to be a diagnostic marker for major depression and to have prognostic implications when repeated after antidepressant treatment. The pulsatile pattern of cortisol secretion suggested to us that increasing the number of post-dexamethasone cortisol determinations might significantly increase the sensitivity of the dexamethasone suppression test (DST) for major depression. With a conventional two-point DST (1600 h and midnight), 5% of 20 normal volunteers, 8% of 13 inpatients with non-major depressions, and 31% of 65 inpatients with primary major depression failed to suppress. With six post-dexamethasone points (0800 h, 1200 h, 1600 h, 2000 h, 2200 h, midnight), the respective percentages were 10, 15 and 44%. The additional points increased the sensitivity from 31 to 44%, mostly by identifying more major depressives with a "late escape" pattern. If a clinician is using the DST to establish a marker for major depression that can be repeated to monitor response to treatment and the likelihood of relapse, then perhaps the increased sensitivity of the six-point DST would be helpful, despite a modest decrease in specificity from 94 to 88%.

Psychopharmacologic treatment of depression.

The authors emphasize the favorable response of most patients with major depression to appropriate pharmacotherapy, and present a decision-tree approach to the pharmacotherapy of major depression. Also discussed are use of contemporary clinical nosology and neuroendocrine diagnostic tests to identify candidates for pharmacotherapy and/or ECT, use of secondary tricyclics because of their lower incidence of side-effects, monitoring plasma levels of antidepressants to achieve therapeutic levels, and potentiating tricyclic nonresponders with T3 or lithium.

Plasma cortisol and beta-endorphin immunoreactivity in nonmajor and major depression.

Plasma cortisol levels of 28 hospitalized patients meeting Research Diagnostic Criteria for major or nonmajor (minor or intermittent) depression were significantly higher than those of eight normal subjects. In contrast, plasma beta-endorphin immunoreactivity was significantly lower in patients with nonmajor depression than in those with major depression or in normal subjects. A low ratio of plasma beta-endorphin to cortisol immunoreactivity was found to characterize patients in both groups. Through the use of only this ratio, a post-hoc analysis identified 25 depressed patients and seven controls. These findings have implications for psychiatric diagnosis and the involvement of the endogenous opioid system in the pathogenesis of depression.

Specificity of the DST and the TRH test for major depression in alcoholics.

The authors examined dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) test results in 32 chronic alcoholics without depression or hepatic disease to see if alcoholism alone might lead to positive test results. After 3 weeks of sobriety there were no DST abnormalities, but blunted TRH test results were observed in eight of the 32 alcoholics. More of the 15 patients also tested during alcohol withdrawal than of the 20 normal subjects or the 32 alcoholics without alcohol withdrawal had DST and TRH test abnormalities. When performed after 3 weeks of sobriety, the DST but not the TRH test has potential as a specific laboratory adjunct in the diagnosis of depression in alcoholics.

The TRH test and urinary MHPG in unipolar depression.

Twenty-five men and 26 women with major unipolar depression were evaluated by the TRH test and urinary MHPG excretion. A significant positive correlation between TSH response to TRH and urinary MHPG was found in the men, though not in the women. These findings suggest that at least for depressed men, central norepinephrine deficiency may be the neurobiological substrate of blunted TSH responses to TRH.

The thyrotropin-releasing hormone and dexamethasone suppression tests in the familial classification of depression.

Eighty-eight depressed patients who had received a dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) test were divided into four subgroups based on family history of psychiatric illness. Nonsuppression on the DST was found in 46% of familial pure depressive disease (FPDD) patients, 38% of sporadic depressive disease (SDD) patients, 38% of depressive spectrum disease (DSD) patients, and 50% of mixed depressive disease patients (patients with both a first degree relative with alcoholism and one with depression). A blunted thyroid-stimulating hormone response to TRH was found in 50% of FPDD patients, 56% of SDD patients, 47% of DSD patients, and 56% of mixed depressive disease patients. Neither the DST nor TRH test was found to distinguish significantly among the four familial subgroups of depression.