Search

Heath et al. (1989) reported that serum from 96% of unmedicated schizophrenic patients contained IgG autoantibodies specific for the septal region of rhesus monkey brain, compared with 0% of nonschizophrenic control subjects and 6% of schizophrenic patients who were on neuroleptic medication. Using the same technique of crossed immunoelectrophoresis, we have tried to replicate this finding. In contrast to the original report, we observed “positive” precipitin arcs with IgG concentrates from all 14 serum samples tested. The failure of immunoelectrophoretic methods to provide convincing evidence of pathogenic autoantibodies in schizophrenia in no way detracts from the hypothesis that autoimmune processes are involved in some forms of schizophrenia. Such methods have not proved useful in established autoimmune diseases such as Graves' disease and myasthenia gravis in which the pathogenic autoantibodies against cell-surface receptors can only be detected by assays which measure functional interactions with such receptors.

Background Tricyclic antidepressants sometimes trigger mania in bipolar patients, but little is known about their potential for abuse in this regard. Case description We describe a man with bipolar disorder and alcohol dependency who abused dosulepin repeatedly in order to induce manic episodes. This caused serious problems for treatment and long-term outcome. We mention two further cases in which dosulepin or clomipramine was used deliberately to induce bipolar mania. Conclusions Tricyclic antidepressants can be abused to induce mood elevation in bipolar patients. This should be considered in cases of treatment-resistant mania.

Schizophrenia is a debilitating, costly, socially disruptive, life-threatening disease in which available treatments are largely palliative and empirical, and produce significant short- and long-term side effects. Therefore, a strong case can made for exploring alternative treatments with a rational basis for use in this disease. Considerable evidence indicates that autoimmune processes may be involved in some forms of schizophrenia, including altered risk of certain autoimmune diseases in patients and their relatives, shared epidemiological features, and apparent involvement of genes known to influence the immune response repertoire. Attempts to provide direct evidence for autoimmune processes have proven elusive, possibly due to the technical difficulty inherent in accessing autoantibodies with high affinity for brain cell-surface receptors. In view of this impasse, we argue for a well-designed trial in schizophrenia of immunosuppressive therapy, which is now the mainstay of therapy for many autoimmune diseases. Analysis of disease states in which immunosuppression has been effectively used over many decades provides guidelines necessary for a meaningful trial.

Day and colleagues draw attention to the prevalence of serious alcohol problems and discuss useful guidance from the National Institute for Health and Care Excellence (NICE) on improving the assessment and management of this …

The comedic range of medical transcription errors is vast indeed.1 My personal favourite reflects, I fancy, healthy scepticism on the part of the typist who indicated a recalcitrant patient to be invested in “homeopathetic” …

Recent regulatory warnings about adverse behavioural effects of antidepressants in susceptible individuals have raised the profile of these issues with clinicians, patients, and the public. We review available clinical trial data on paroxetine and sertraline and pharmacovigilance studies of paroxetine and fluoxetine, and outline a series of medico-legal cases involving antidepressants and violence. Both clinical trial and pharmacovigilance data point to possible links between these drugs and violent behaviours. The legal cases outlined returned a variety of verdicts that may in part have stemmed from different judicial processes. Many jurisdictions appear not to have considered the possibility that a prescription drug may induce violence. The association of antidepressant treatment with aggression and violence reported here calls for more clinical trial and epidemiological data to be made available and for good clinical descriptions of the adverse outcomes of treatment. Legal systems are likely to continue to be faced with cases of violence associated with the use of psychotropic drugs, and it may fall to the courts to demand access to currently unavailable data. The problem is international and calls for an international response.

Following a telephonic deposition, the author discovered that a psychiatrist expert witness for the other side had electronically eavesdropped on the entire six-hour proceedings. Under cross-examination the expert admitted eavesdropping on instruction of state's attorneys, and directing their deposition of the author, but denied wrongdoing. The ethical implications of such deceptive behavior and its rationalization are discussed.

Objective: To review the production of cardiac arrhythmia by thioridazine, and consider the role of government regulation in light of antipsychotic prescribing trends in New Zealand. Methods: We conducted a focused literature review on psychotropic-induced cardiotoxicity, including mechanisms and incidence. In addition, we considered trends in antipsychotic prescription in New Zealand and decisions made by regulatory bodies in Australia, North America and the United Kingdom regarding restrictions on the prescription of thioridazine. Results: In general, the cardiotoxicity of antipsychotics, including thioridazine, relates to the ability of these drugs to antagonize voltage-sensitive potassium channels, and thereby prolong the QT interval. This action can lead to malignant arrhythmias in a very small proportion (< < 1%) of patients; the risk may be increased by other drugs or factors which prolong QT or inhibit the metabolism of thioridazine. A review of prescription doses and volumes in New Zealand indicates that thioridazine is prescribed mainly in low doses by nonspecialists, and its use has been waning significantly over the past 2 years. These trends predate recent publicity regarding cardiotoxicity. Conclusions: Recommendations regarding thioridazine use are presented. Although new patients should not receive this drug, existing patients benefiting from modest doses should not be denied access unless clear-cut risk factors for cardiotoxicity are evident.

The international pharmaceutical market shows substantial regional differences in availability and promotion of drugs.1 This variation depends on affluence, health requirements, capacity for local manufacture, and the restrictions which countries may impose to control dangerous or inappropriate use of drugs.2 3 Because of their limited industrial base, most developing countries import most of their drugs, and transnational corporations are adept at exploiting variations in such markets.1 Commercial interests may conflict with public health needs in developing countries,4 5 6 particularly when people are poisoned due to inadequate restriction of pharmaceutical use, misleading advertising or labelling, or frankly bogus products. Promotion of unsafe drugs in the developing world has long attracted criticism, particularly when products have been banned or restricted in the country of manufacture.3 5 Pharmaceutical adverts, labelling, and package inserts in developing countries often show the twin problems of exaggerated indications and minimised adverse effects.1 5 6 Drug exports from the United States to developing …

Richards and colleagues make an impassioned plea for a “patient revolution” on the basis of several recognised and correctable deficits in paternalistic Western healthcare.1 A sudden vast change (http://en.wiktionary.org/wiki/revolution) is neither desirable nor likely, given the variability in patients’ motivation and capacity to participate in …

The aim of this pilot project was to explore the extent to which judgments made by psychiatrist examiners accord with those of patients in postgraduate clinical examinations, so as to inform further consideration of the role of patients in such assessments. Senior psychiatrist examiners (N=8) and patients (N=30) rated 16 aspects of trainee psychiatrist interviewing style and performance during 30 observed clinical interviews (OCIs) conducted in the format of official examinations. Significant differences were apparent in the judgments of examiners and patients regarding 7 of 16 rated aspects of trainee performance. Differences were evident largely in domains in which patients could be expected to be “expert,” reflecting their subjective experience of the interviewer. By contrast, there was little difference in the judgments of patients and examiners on the more technical criteria. These preliminary findings provide some challenge to the assumption that psychiatrists are the best judges of the “technical” skills and knowledge required by the profession. They support previous findings, with simulated patients, of the discrepancy between patient and examiner judgments of the more subjective elements of the examination. Psychiatric patients could contribute to clinical examinations as co-examiners, rather than merely constituting the substrate for the examination.

In pointing out that claims for vitamin D exceed available evidence, Harvey and Cooper do not mention psychiatric disorders.1 In this domain, too, enthusiasts tend to overinterpret deficiency and …

Blood viscosity (η B) at shear rates 10 and 100s-1, plasma viscosity (η P), hematocrit (Hct), and whole blood cholesterol (Chol) were measured in 50 patients with a history of myocardial infarction or unstable angina pectoris. Erythrocyte morphology was also studied by scanning electron microscopy to determine the proportion of nondiscocytic erythrocytes (NDE). There was a significant positive correlation between Chol and ηP ( r = 0.41, P < 0.004) and a highly significant negative correlation ( r = -0.69, P < 0.001) between Chol and Tk, a viscometric index of erythrocyte rigidity based on relative blood viscosity at high shear (ηB/ηP) corrected for Hct. This latter result indicates Chol reduction in this population may increase erythrocyte rigidity Twenty-five patients with Chol values in the range 4.0-8.0 mmol/L were commenced on a standard lipid-lowering diet and after eight weeks half were also given pravastatin (40 mg daily). After thirty-two weeks Chol had fallen significantly more in the pravastatin group (28%) than in the diet only group (11%, P = 0.005). There was no change in ηP for either group but a signifi cant increase in Tk for the pravastatin group only ( P = 0.011). The change in total choles terol (ΔChol) for each patient over thirty-two weeks was negatively correlated with both the change in the index of erythrocyte rigidity (ΔTk) ( r = -0.40, P = 0.044) and the change in the proportion of nondiscocytic erythrocytes (ΔNDE) ( r = -0.47, P = 0.026). These data suggest that cholesterol reduction within the normolipemic range may be associated with unfavorable changes in blood rheology

Promoting access to unbiased, expert drug information has been the mission of the International Society of Drug Bulletins since 1986. Because member bulletins refuse money from the pharmaceutical industry, they typically run on tight budgets. Like the US Food …

This study extends our previous report of the efficacy and tolerability of fluoxetine in severe premenstrual syndrome (PMS), describes which aspects of the disorder are responsive to such treatment, and assesses the relationship between steady-state drug level and clinical outcome. Twenty-one women with documented PMS satisfied criteria for late luteal phase dysphoric disorder (DSM-III-R) and accepted the offer of a double-blind, randomized crossover trial of fluoxetine hydrochloride 20 mg/day vs placebo. Symptom severity was measured with daily self-rating, monthly premenstrual assessment forms and psychiatric interviews after 3 months each of baseline, placebo and fluoxetine treatment. Compared with an inconsistent placebo response, fluoxetine produced marked improvement in 15 of 16 women completing the trial, eight showing virtually complete remission of PMS symptoms. Fluoxetine's efficacy extended over a range of affective, physical and behavioural symptoms; its superiority obtained whether it preceded or followed placebo. Three women withdrew due to adverse effects of fluoxetine, and 10 of 16 completing the trial reported at least one adverse effect of this agent. Compared with placebo, fluoxetine produced more (but usually transient) insomnia, sweating, gastrointestinal and menstrual disturbance. Plasma levels of fluoxetine and its active metabolite were not reliably associated with efficacy nor with side effects. Serotonergic agents appear to have considerable promise in treating a range of symptoms in women with severe PMS.

Moclobemide and fluoxetine were tested in a six-week trial involving 122 patients with major depressive illness. Patients initially received moclobemide, 150 mg three times daily, or fluoxetine 20 mg/day, but during weeks 3, 4, 5 and 6 the doses could be altered, giving a range of 300-600 mg/day for moclobemide or 20-40 mg/day for fluoxetine. No dietary restrictions were imposed on the patients. The trial was completed by 49 patients receiving moclobemide, and 43 patients receiving fluoxetine. The efficacies of these two agents, as determined on the Hamilton Depression Rating Scale and from Clinical Global Assessments, were found not to differ significantly. The frequencies of occurrence of adverse reactions were also similar, but sedation, nausea and vomiting were reported more frequently with fluoxetine, and insomnia was experienced with moclobemide. Tolerance of both drugs was judged to be high.

A combination of behavioural and cognitive adverse effects is illustrated in this case report of a recurrent triazolam-induced eating disorder. The co-occurrence of bingeing, irritability and anterograde amnesia is suggestive of a drug-induced Kleine-Levin Syndrome.

Four cases of self-poisoning with 'Roundup' herbicide are described, one of them fatal. One of the survivors had a protracted hospital stay and considerable clinical and laboratory detail is presented. Serious self-poisoning is associated with massive gastrointestinal fluid loss and renal failure. The management of such cases and the role of surfactant toxicity are discussed.

A cannabis smoking trial was conducted using paid volunteers. Subjective intoxication, measured using a visual analogue scale, was compared with heart rate and with salivary delta-9-tetrahydrocannabinol (THC) levels at various times after smoking a cigarette containing 11 mg THC. Subjective intoxication and heart rate elevation were significantly correlated with the log of salivary THC. Salivary THC levels are a sensitive index of recent cannabis smoking, and appear more closely linked with the effects of intoxication than do either blood or urine cannabinoid levels.

During Our Medical School years we roughly double our vocabulary and by graduation have learnt a new language. While we may try to revert to our mother tongue with patients, communication problems abound [1–3] often because patients do not understand the technical language of medicine. Australian writers have n called attention to the serious misunderstandings produced by the use of medical lingo across the Tasman [4,5]. Such problems of comprehension are likely to be aggravated, for patients j and doctors alike, by the current proliferation of medical acronyms [6] and euphemisms [7,8].

Background There is controversial evidence that a low serum cholesterol level is associated with an increased risk of depression, suicide, and violence. The aim of this study was to identify or exclude any small or infrequent adverse effect of long-term reduction of serum cholesterol with pravastatin sodium on psychological well-being. Methods The study population consisted of 1130 respondents from a representative sample of 1222 patients with stable coronary artery disease participating in the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study. Subjects were randomized in a double-blind manner to treatment with pravastatin sodium, 40 mg/d (n = 559), or placebo (n = 571) for at least 4 years. Psychological well-being was assessed with a standard self-administered questionnaire at baseline and after 6 months, 1 year, 2 years, and 4 years. The questionnaire assessed anxiety and depression, anger, impulsiveness, alcohol consumption, and adverse life events. Results Serum cholesterol levels decreased by an average of 1.3 mmol/L (50 mg/dL) with pravastatin therapy and did not change with placebo. During follow-up there was no significant difference by treatment group in measures of anxiety and depression, anger expression, or impulsiveness (95% confidence interval excluded differences of >0.2 SD) and no difference in the proportion of subjects with excessive alcohol consumption or adverse life events (odds ratio, 1.0; 95% confidence interval, 0.8-1.2). There was no evidence of a treatment effect for persons whose baseline serum cholesterol level was in the lowest 10% ( Conclusion Long-term reduction of serum cholesterol with pravastatin has no adverse effect on psychological well-being.

In 1935 Barany serendipitously discovered the temporary relief of tinnitus after lignocaine injection of nasal turbinates.1 Since that time, other agents known to suppress the activity of excitable membranes have been tried, including antiarrhythmic and anti-convulsant drugs. Among such drugs, carbamazepine has the best documented efficacy in patients with a …

To the Editor.— Gross-Isseroff and colleagues1 report reduced binding of tritiated prazosin in brain sections of suicide victims compared with those of matched control subjects. This observation suggests a functional noradrenergic abnormality in the central nervous system of suicidal individuals. However, several issues are unclear. First, did the rater score autoradiograms without knowing from which experimental group the sections came? It is difficult to exclude bias otherwise. Second, no data are Presented on tricyclic antidepressant levels in the samples, even though the authors' method implies that they were measured. These drugs are variably potent α1-antagonists, as shown by their ability to displace tritiated prazosin from specific binding sites in the human brain. 2 Were the authors able to ensure that residual tricyclic levels did not inhibit tritiated prazosin binding in some of the suicide cases? Finally, the authors present 84 suicide vs control t tests in the statistical analysis without

240 mg daily) and report no side effects from the medication. Both report also that their speech continues to be better than it has been for as long as they can remember. They report also that failure to take the verapamil for a day or so (e.g., forgetting to do so, temporarily running out of the medication) is followed by a return of more stuttering. Their rates of dysfluency while reading a 1000 syllable story (RD) and speaking extemporaneously for 3 min (SD) are given in Table 1 along with the corresponding dysfluency rates on initial (baseline) testing and at the 6-month follow-up. The results we published in 1989 are more modest

1 Clonidine inhibition of the acoustic startle reflex in the rat was used as a behavioural measure of alpha 2-adrenoceptor sensitivity following acute or chronic administration of tricyclic antidepressants. 2 Chronic (14 day) administration of desipramine (10 mg/kg, i.p.) attenuated the depressant effect of clonidine (20 or 40 microgram/kg) on the startle reflex. 3 No change in response to clonidine was obtained after chronic treatment with two other tricyclic antidepressants, amitriptyline (10 mg/kg) or iprindole (5 mg/kg). 4 Acute administration of these tricyclics (1 h) did not modify the effect of clonidine on startle. 5 It is suggested that the development of alpha 2-adrenoceptor subsensitivity produced by chronic tricyclics may be unique to those compounds, such as desipramine, which are active in blocking the uptake of noradrenaline.

Electrophysiological and radioligand binding methods were used to characterize noradrenergic denervation supersensitivity at alpha 1-adrenoceptors in rat thalamus. Denervation was accomplished either by intraventricular or intracerebral injection of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA). In the physiological studies, the sensitivity of single lateral geniculate neurons to norepinephrine, carbachol, and serotonin was compared in sham and lesioned animals various times after 6-OHDA. Conducted in parallel were radioligand binding studies in which the density and affinity of thalamic alpha 1-adrenoceptors were measured with the specific antagonist [3H]prazosin. The results indicate that denervation produces a selective increase in the sensitivity of geniculate neurons to alpha 1-adrenergic stimulation and a concomitant increase in alpha 1-adrenoceptor density and agonist affinity.

The tendency of antipsychotics to produce extrapyramidal side-effects varies inversely with their antimuscarinic activity. This paper reviews the antipsychotic and antimuscarinic potency of these drugs and compares the total antimuscarinic activity in standard daily doses of antipsychotics, antiparkinson agents and antidepressants. The authors examine factors associated with tolerance of benztropine withdrawal in 39 inpatients. Patients with serious EPS relapse after benztropine withdrawal had an excess of antipsychotic over antimuscarinic activity in their remaining medications. The results suggest an optimal ratio between total antipsychotic and anticholinergic doses, and a simple model for predicting antiparkinson drug requirements.

Rat startle responses to air puffs were monitored in a stabilimeter during the intraventricular infusion of various doses of 5-hydroxytryptamine (5-HT) or the putative hallucinogenic congener of 5-HT, 5-hydroxy-N, N-dimethyltryptamine (5-HDMT) or saline. Qualitatively opposite effects were observed, with 5-HT producing a dose-dependent decrease in responsivity and 5-HDMT increasing the magnitude of startle responses. No specific effects of either compound could be demonstrated on the presumably separable processes of sensitization and habituation. The results are discussed in the context of a central serotonergic system which facilitates behavioral inhibition and which antagonized by indoleamine hallucinogens.

Concern about the risk of nuclear war has sparked interest in the psychology of the nuclear arms race. This paper reviews recent work in this area and develops a model linking the threat of nuclear weaponry, resultant anxiety, and psychological defence mechanisms employed by the managers of the arms race. The role of psychological defences implicit in military and political social systems is emphasized. Primitive or narcissistic defences found at both individual and group levels are maladaptive as they increase rather than decrease the risk of nuclear conflict. Psychological approaches to crisis management and conflict resolution require development and application to this problem.

The ability of systemically and locally administered prazosin to block alpha 1-adrenoceptors was examined in two brain areas in the rat. Using single unit recording of neurons in the lateral geniculate and dorsal raphe nuclei, evidence was obtained for the selective blockade of alpha 1-adrenoceptors by both intravenous and iontophoretic prazosin. Since effective systemic doses of prazosin were within the clinical range, it appears likely that brain alpha 1-adrenoceptors would be blocked during prazosin therapy in humans.

Binding of [3H]prazosin, a selective alpha 1-adrenoceptor antagonist, to thalamic membranes was studied following chronic treatment of rats with tricyclic antidepressants. Rosenthal analysis showed no change in the number or affinity of antagonist binding sites; however, the ability of the alpha 1-agonist phenylephrine to compete for these sites was significantly enhanced after chronic tricyclic treatment. This result is consistent with previous studies showing physiological alpha 1-supersensitivity in thalamus after chronic antidepressant administration.

Responses of single dorsal lateral geniculate neurons to iontophoretic noradrenaline, serotonin, and carbachol were studied following acute or chronic administration of tricyclic antidepressants. Long-term (15-20 day) treatment of rats with a variety of clinically effective tricyclics, including the atypical iprindole, significantly enhanced alpha 1-adrenoceptor mediated activations induced by noradrenaline. This change appears to require chronic treatment, since acute and short term (6-8 day) tricyclic regimens fail to consistently affect noradrenaline's action. Long term antidepressant treatment was also effective in enhancing geniculate neuron sensitivity to serotonin, in accord with previous studies, but failed to modify responses to the cholinergic agonist carbachol. It is suggested that the modulation of noradrenaline and serotonin receptor activity may represent a slowly developing action of tricyclic antidepressants which correlates with their delayed clinical effects.

Studies on the withdrawal of anticholinergics from patients on antipsychotics have produced conflicting results. This 12-week study employed a double-blind crossover design on 39 adult in-patients selected from a total hospital population of 620. The Colombia Scale was used to determine extrapyramidal side effects (EPS). All patients were stabilised prior to the study on benztropine mesylate 2 mg b.i.d., and gradual withdrawal was employed. Benztropine withdrawal produced a significant increase in overall EPS scores. Ten patients (26%) required reinstatement of benztropine while on placebo. Sialorrhoea, rigidity and postural instability were the most prominent changes. Neither age, sex, nor diagnosis were significantly predictive of EPS. Depot medications and doses greater than 1000 mg/day chlorpromazine-equivalent were related to significant EPS increase. The intrinsic anticholinergic properties of the antipsychotics themselves and concomitant medications, such as antidepressants, appeared protective against development of EPS. Most patients on a combination of antipsychotics and anticholinergics can safely be withdrawn from the latter.

In addition to their well recognized activity in blocking uptake of biogenic amines, tricyclic antidepressants have recently been shown, with chronic treatment, to alter neurotransmitter receptor sensitivity. In this study, the responsiveness of facial motoneurons to norepinephrine (NE) and serotonin (5-HT) was assessed with single unit recording and microiontophoretic techniques. Treatment of rats with daily intraperitoneal injections of several clinically effective tricyclics for 14–20 days was found to enhance responses to NE, 5-HT, and to an intravenously administered 5-HT agonist, 5-MeODMT. These changes in sensitivity were not seen in animals chronically treated with saline, chlorpromazine, or fluoxetine, and thus appear specific to antidepressants. Acute effects of tricyclics on NE and 5-HT responses were variable, dependent on the specific drug tested, and appear to have no necessary relation to the pronounced sensitization produced by chronic treatment.

Chronic but not acute administration (21 days) of desipramine (10 mg/kg), amitriptyline (10 mg/kg) or iprindole (5 mg/kg) enhanced the stimulatory effect of the α1-adrenergic agonist phenylephrine on the acoustic startle reflex when phenylephrine was infused into the subarachnoid space of the spinal cord. Comparable supersensitivity to phenylephrine also occurred 1 week after selective depletion of norepinephrine in the spinal cord via intrathecal administration of 6-hydroxydopamine. Behavioral supersensitivity to phenylephrine was associated with an increase in the number of 3H-prazosin binding sites following denervation but not following chronic antidepressant treatments. The results indicate that chronic antidepressant treatments may enhance functional α1-adrenergic transmission through mechanisms different than those following denervation.

Summary The behavior of rats with selective lesions of either the dorsal (B7), median (B8), or lateral (B9) raphe nuclei was compared to that of sham-lesioned controls in a variety of experimental situations. As described previously 17 , the extent of damage to the midbrain raphe nuclei was determined by fluorescence histochemistry, and the tryptophan hydroxylase and tyrosine hydroxylase activities of 6 forebrain regions were measured for each rat. None of the lesions affected tyrosine hydroxylase activity. Lesions of B7, which reduced tryptophan hydroxylase in the striatum, thalamus, cortex, and hypothalamus, had no significant effect on any of the behavioral measures. Lesions of B9, although twice as large, neither reduced forebrain tryptophan hydroxylase significantly nor affected any of the behavioral variables. However, B8 lesions, which reduced hippocampal, septal, cortical, and hypothalamic tryptophan hydroxylase, had behavioral effects similar to those reported after combined raphe lesions or parachlorophenylalanine. Median raphe-lesioned rats were hyperactive when placed in a novel environment and throughout the dark phase of the light/dark cycle. With respect to locomotor activity, B8-lesioned rats were also hyper-responsive to amphetamine. When placed in a stabilimeter and subjected to repeated air puff stimuli, rats with B8 lesions exhibited larger startle responses. Furthermore, only B8-lesioned animals perseverated when given two unreinforced trials in a Y-maze. All these histologic, biochemical, and behavioral variables were assessed individually for all 39 animals, and a multivariate correlational analysis incorporating the data of this and the preceding paper 17 is presented here. These experiments suggest that the mesolimbic serotonergic pathway originating in B8 subserves some of the inhibition necessary to dampen behavioral responsivity.

Activation of adenylate cyclase by a stable guanosine 5'-triphosphate analog was augmented in brain membrane preparations from rats treated on a long-term basis with tricyclic antidepressants or electroconvulsive shock. These treatments may facilitate cyclase activation by promoting the interaction of the regulatory and catalytic subunits of the enzyme. This finding suggests a possible mechanism for the changes in sensitivity to various neurotransmitters seen after antidepressant administration.