Marc Branchey

Cerebral perfusion in early and late opiate withdrawal: a technetium-99m-HMPAO SPECT study

The purpose of this study was to determine if cerebral blood flow (CBF) alterations are associated with discontinuation of heroin in chronic heroin users, and whether these alterations are reversible during abstinence. Ten physically healthy opioid-dependent males, hospitalized on an inpatient drug rehabilitation unit, were studied. Each patient had an initial single photon emission computed tomographic (SPECT) scan with the radiotracer technetium-99m-d,l-hexamethylpropyleneamine oxime (99mTc-HMPAO) 1 week after opiate discontinuation and a repeat scan 2 weeks later. The initial scans in 9 of the 10 subjects demonstrated significant, often discrete, perfusion defects, especially in the frontal, parietal, and temporal cortices. Two weeks later, repeat brain perfusion SPECT scans showed improvement in all nine subjects who had abnormal scans. Comparisons of the first scan with the second scan showed an increase in cortical uptake on the repeat SPECT study. All subjects had normal computed tomographic or magnetic resonance imaging scans. The results of this preliminary study suggest that the chronic use of opiates, like chronic use of cocaine, results in perfusion abnormalities without corresponding abnormalities on imaging studies of cerebral anatomy and morphology. This study also documents that these perfusion defects are partially reversible with short-term abstinence.

Depression, suicide, and aggression in alcoholics and their relationship to plasma amino acids

In an earlier study we found an association in alcoholic patients between depression and low ratios of tryptophan over amino acids sharing with it the same transport carrier into the brain. A decreased tryptophan ratio has been shown to be correlated with lower brain tryptophan and serotonin. Because it has been postulated that altered serotonin metabolism may be a highly significant contributing factor not only to depression but also to aggressive and suicidal behavior, we decided to assess the existence of possible associations between amino acid abnormalities and these behaviors in a population of alcoholics. We observed a significant association between histories of aggression and depression. In addition, depressed patients with a history of aggression were found to have the lowest tryptophan ratio values. These values differed significantly from those found in depressed patients with no aggression history and from those observed in patients with no history of aggression and depression. Two of the three suicide attempters in the study fell also in the group of patients with an aggression history. Our data suggest the existence of a subgroup of alcoholics with marked amino acid abnormalities at risk for manifestations of depression, suicide, and aggression.

Effects of estrogen and progesterone on sleep patterns of female rats

Abstract Sleep-wakefulness cycles were recorded in ovariectomized female rats that were injected with estrogen plus progesterone and estrogen alone. Two daily injections with estrogen followed by progesterone resulted in significant reductions in the percentages of time spent in both REM and NREM stages of sleep during the night following the injection of progesterone. Treatment with estrogen alone for six consecutive days resulted in a reduction in REM sleep but did not appear to influence NREM sleep. Thus both hormone treatments modified sleep, but the combined action of estrogen and progesterone more closely duplicated the sleep patterns observed in the intact animal on the night of behavioral estrus.

Effects of sex hormones on sleep patterns of male rats gonadectomized in adulthood and in the neonatal period

Abstract Sleep-wakefulness cycles were recorded following the administration of estrogen and progesterone to adult male rats castrated at birth or in adulthood. For the neonatal male castrates, two daily injections of estrogen followed by progesterone resulted in significant reductions in the percentages of time spent in both REM and NREM stages of sleep during the night following the progesterone injection. That response to female hormones was similar to the response previously reported for similarly treated gonadectomized female rats. The adult male castrates did not show the modification of sleep patterns in response to hormone treatment. The data represent evidence of sexual differentiation of the brain mechanisms regulating sleep that is comparable in certain respects to the differentiation of mechanisms regulating sexual behavior in rats.

n-3 Polyunsaturated Fatty Acids Decrease Anxiety Feelings in a Population of Substance Abusers

There is mounting evidence that low levels of n-3 polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology of a number of psychiatric disorders. Preclinical studies have shown that n-3 PUFAs decrease anxietylike behaviors, but there is a paucity of information about their effects on anxiety in humans. In light of our observation that substance abusers have poor dietary habits and the strong association between anxiety disorders and substance use disorders, the possibility that the administration of supplements of n-3 PUFAs would decrease the anxiety level of a group of substance abusers was explored. Thirteen patients were given on a daily basis capsules containing 3 g of n-3 PUFAS (eicosapentaenoic acid + docosahexaenoic acid). Eleven patients received similarly looking placebo capsules containing vegetable oil. The trial was double-blind, randomized, and lasted 3 months. A scale assessing anxiety feelings was administered at baseline and on a monthly basis thereafter. Six PUFA group patients and 8 placebo group patients were followed for an additional 3 months after treatment discontinuation and administered the same questionnaire monthly. Patients who received n-3 PUFAs for 3 months showed a progressive decline in anxiety scores. This was not the case for patients who received placebos. A comparison of the 2 groups was significant (P = 0.010). Anxiety scores remained significantly decreased in the PUFA group for 3 months after treatment discontinuation. A comparison of the 2 groups followed for 6 months was also significant (P = 0.042). In conclusion, these preliminary data indicate that n-3 PUFA supplementation could be beneficial in the treatment of some patients with anxiety disorders.

Effects of ethanol on evoked potentials in the rat

Visual-evoked potentials were recorded from the visual cortex and reticular formation of chronically implanted rats. Recordings were obtained at fixed time intervals after an intraperitoneal injection of saline, 0.5, and 1.5 g/kg of ethyl alcohol. A significant depression in the evoked potentials was obtained with the high dose of alcohol, and was found to be even more striking at the visual cortex than at the reticular formation. However, no significant effect was observed with the low dosage of alcohol at either site.

Polyunsaturated fatty acid status and relapse vulnerability in cocaine addicts

There is mounting evidence that low levels of some polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology of depressive and aggressive disorders, including homicides. There is also evidence derived mostly from the animal literature that PUFAs could play a role in the abuse of substances through their action on central serotonergic and dopaminergic systems that are both known to play a role in reward mechanisms. In this study, we explored the possibility that the relapse rates of cocaine addicts discharged after a period of detoxification on an inpatient unit would be associated with their PUFA status. Thirty-eight patients were enrolled in the study. PUFA status was assessed only at baseline, shortly after admission. Resumption of substance use was assessed 3 months, 6 months and 1 year following discharge. Thirty-two patients remained available for follow-up for the duration of the study. Subjects who relapsed at 3 months had significantly lower baseline levels of total n-6 PUFAs, linoleic acid (LA, 18:2n-6), arachidonic acid (AA, 20:4n-6) and total n-3 PUFAs when compared to non-relapsers by ANCOVAs with age and weight as covariates. Lower baseline total n-6 PUFAs, LA and AA continued to predict relapse 6 months and 12 months following discharge. Age, marital status, educational level, cocaine use parameters or psychopathology did not differ between relapsers and non-relapsers. In conclusion, low PUFA status at baseline was a better predictor of relapse than cocaine use, sociodemographic or clinical parameters. These data suggest, but do not prove, the existence of a causal relationship between n-6 or n-3 status and relapse vulnerability in cocaine addicts, and provide a rationale for the exploration of possible relationships between relapse to addictive disorders and PUFA status in observational and interventional trials.

Long-chain n-3 polyunsaturated fatty acids decrease feelings of anger in substance abusers

It has been suggested that low levels of n-3 polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology of some psychiatric disorders. In light of the existence of strong associations between high-frequency and high-severity aggressive behaviors and substance use disorders and of our observation that substance abusers have poor dietary habits, the possibility that the administration of supplements of n-3 PUFAs would decrease their anger levels was explored. A lifelong history of aggressive behaviors and problems with the law was obtained in 24 patients. Thirteen patients received on a daily basis capsules containing 3 g of n-3 PUFAs (EPA+DHA). Eleven patients received placebo capsules. The trial was double-blind, randomized, and lasted 3 months. An anger scale was administered at baseline and every month thereafter. Six PUFA group patients and eight placebo group patients were followed for an additional 3 months after treatment discontinuation. Four patients in each group had a history of assaultive behavior. The baseline fish and n-3 PUFA intakes of these eight patients were significantly lower than those of the non-aggressive patients. When given for 3 months, n-3 PUFAs were superior to placebo in diminishing anger scores. Scores remained decreased for 3 months following treatment discontinuation. These data provide further support for emerging evidence indicating that supplementation with long-chain n-3 PUFAs could be beneficial in the treatment of some individuals with aggressive tendencies.

Cocaine Addicts with Conduct Disorder Are Typified by Decreased Cortisol Responsivity and High Plasma Levels of DHEA-S

There is evidence that children with antisocial behaviors have increased plasma levels of the adrenal androgen dehydroepiandrosterone sulfate (DHEA-S) and either a decreased level of another adrenal steroid, cortisol, or a decreased cortisol responsivity to stress. Low levels of cortisol have also been reported in antisocial adults but their levels of DHEA-S have not been studied. The present study was designed to perform in adult cocaine addicts simultaneous assessments of DHEA-S and cortisol as a function of a diagnosis of antisocial personality disorder (adult symptoms) and of a retrospective diagnosis of conduct disorder (CD). Basal cortisol and DHEA-S were determined in the plasma samples of 40 hospitalized men. The patients’ cortisol responsivity was also assessed while they were being exposed to a stressful situation. Patients who had a retrospective CD diagnosis had significantly increased DHEA-S levels and secreted less cortisol when stressed. Comparisons between patients who did and did not meet the antisocial personality disorder adult criteria did not reveal any significant difference in DHEA-S or in cortisol responsivity. This could be attributed to the nature of the criteria used to define the adult disorder, which focus mostly on a failure to conform to social norms, whereas a number of CD criteria involve displays of some degree of violence. In conclusion, adults who retrospectively qualified for a CD diagnosis had increased DHEA-S levels and a decreased cortisol reactivity, confirming observations made in children and indicating that mechanisms underlying adrenal steroid alterations in childhood could still be at play in adulthood.

Patterns of Psychotropic Drug Use and Tardive Dyskinesia

The possible association between demographic and drug history variables and tardive dyskinesia was explored in patients hospitalized at a facility where computerized records giving complete and detailed information on drug use were available. The variables studied included age, sex, diagnosis, time since first neuroleptic intake, and frequency of drug-free episodes. In addition, total intake, number of treatment days, average daily dose, and current intake were assessed for all neuroleptics, high potency and low potency neuroleptics, and antiparkinsonian and antidepressant medication. There was no significant relationship between most of the variables under investigation and tardive dyskinesia. Only three variables appeared to be significant risk factors: increasing age, time since first neuroleptic intake, and frequency of drug-free episodes. The finding of a correlation between the frequency of drug-free episodes and tardive dyskinesia is of particular interest and may have implications for our approach to the use of drug holidays.