Higher Orexin A levels in lumbar compared to ventricular CSF: a study in idiopathic normal pressure hydrocephalus.

Orexin A (ORX-A) is implicated in the regulation of various physiological processes, including sleep/wake cycles and reward/motivation. The hypothalamic ORX-A neurons project throughout the brain and spinal cord. In the present study we established and compared ORX-A levels in lumbar and ventricular cerebrospinal fluid (CSF) samples, drawn from idiopathic normal pressure hydrocephalus (INPH) patients, during respectively, lumbar puncture and shunt placement. Ventricular and lumbar CSF levels of total protein and of the dopamine, serotonin and norepinephrine metabolites HVA, 5-HIAA and MHPG respectively, were also estimated. ORX-A was quantified using a commercially available radioimmunoassay kit. Neurotransmitter metabolites were quantified by high performance liquid chromatography. Expectedly, HVA and 5-HIAA levels were significantly higher and total protein levels lower in ventricular compared to lumbar CSF while there were no differences in MHPG levels. However, in contrast to HVA and 5-HIAA and similar to total protein, lumbar ORX-A levels were significantly higher than ventricular levels. The higher lumbar compared to ventricular ORX-A levels may reflect elevated contributions from the spinal cord. The finding of a ventriculo-lumbar difference for ORX-A should be considered in studies utilizing its CSF levels in assessing Orexin system status.

Elevated CSF serotonin and dopamine metabolite levels in overweight subjects.

OBJECTIVE: Neurotransmitter systems participate in the regulation of food intake, and their activities are expected to influence eating behavior. DESIGN AND METHODS: We investigated possible associations between body mass index (BMI) and central noradrenaline, serotonin, and dopamine activities, as reflected by the cerebrospinal fluid levels of their main metabolites methoxyhydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA), respectively. We studied 192 subjects (111 males, 81 females) admitted to neurologic clinic for diagnostic investigations that included CSF analysis, and were found not to suffer from any major neurological disease. Subjects were categorized in three groups, namely in lower, in the two middle, and in upper BMI quartiles, the limits calculated separately for males and females. RESULTS: No differences were found in MHPG levels between groups, while subjects in the upper BMI quartile showed significantly elevated levels of 5-HIAA and HVA compared to the levels of subjects in lower and middle quartiles. CONCLUSIONS: The results provide evidence that in overweight subjects there are enhanced demands in serotoninergic and dopaminergic signaling for their reward system that may lead to increased motivation for food consumption. The implication of reward centers in eating behavior supports the hypothesis of common mechanisms in obesity and drug addiction.

Prolactin and cortisol responses to acute intravenous clomipramine challenge in patients with mania, depression and healthy controls: evidence for reduced serotonergic responsivity.

Serotonergic dysregulation has been shown to be involved in the pathophysiology of unipolar and bipolar depression. Neuroendocrine challenge tests have been extensively used to investigate serotonin functioning in the brain. Although the role of serotonin has received a great deal of attention using neuroendocrine challenge paradigms, little effort has been made to explore the role of serotonin in mania. We assessed serotonergic neuroendocrine responsivity in patients with depression (n = 22), mania (n = 11) and 15 healthy controls by measuring the prolactin (PRL) and cortisol responses to i.v. clomipramine (CMI) and searched for possible differences among the groups. Blunted PRL responses to CMI in manic and depressed patients compared to healthy controls were found. The response to CMI disclosed similar results for the 2 patient groups. No significant differences were found among the 3 subject groups in the cortisol response to CMI. The blunted PRL responses to CMI in patients with mania and depression suggest that serotonergic functioning in mania and depression is similarly impaired, at least at the level of hypothalamus-hypophysis.

Serum and cerebrospinal fluid prolactin levels in male and female patients with clinically-isolated syndrome or relapsing-remitting multiple sclerosis.

There is considerable evidence that prolactin (PRL) exerts immunomodulatory actions, thus being involved in the processes of autoimmune diseases. Animal studies suggest that elevated serum PRL levels may be related to neuroprotection or participate in remyelination after brain injury. To address this question, we estimated PRL levels in both serum and cerebrospinal fluid (CSF) in drug-free male and female patients with clinically-isolated syndrome (CIS) suggestive of MS (i.e. after the first episode) as well as in patients with relapsing-remitting (RR) MS after two or more relapses, and related them to clinical, paraclinical and laboratory data. Seventy two patients with RR MS and 80 patients with CIS in the age range 17-61 years were studied. PRL levels of patients were compared with 74 control subjects, separately for males and females. Significantly higher PRL levels in serum and CSF were found in female RRMS patients but not in males. Patients with CIS had normal PRL levels. No associations were found with disease activity, duration of illness, presence of active lesions or the presence of oligoclonal bands in CSF. The elevated PRL levels observed in female but not in male RRMS patients, or in patients with CIS, could be suggestive of a sexually dimorphic response to central nervous system injury as a result of an increased proneness of females to synthesise and release PRL, which is possibly linked to the relatively more favourable prognosis of MS in women.

The notion of "Sisyphus task" in medicine: A reconstruction.

In medicine, along with the other domains of our life, the myth of Sisyphus is frequently evoked upon confronting a task conceived as laborious, endless and for some futile or even purposeless and meaningless. In this paper, we explore the origin of the myth of Sisyphus so that its connotations and symbolizations will hopefully emerge clearer. It is suggested that the natural background of the myth might be related to the seismologic history of Greece, and Corinth in particular, a city ruined and rebuilt several times. The natural component might symbolically echo in the personified myth of Sisyphus, Corinth's founder and might explain the peculiar labor he was condemned to execute eternally, as well as the meanings the myth carries. Like his own city, Sisyphus also suffered the same "ups and downs" of fate, either as a public figure -patron of several big achievements- or as a punished hero condemned to role a stone in the underworld. His persistent efforts led to temporary successes, even though he could not find permanent solutions to the labors he undertook alive or dead. Thus, the myth of Sisyphus is related to human efforts and its limitations, the feasible and infeasible the two main poles between which the myth functions. Conceptualizing with Sisyphean terms their function, physicians can celebrate their transient victories, and by realizing their limitations, reconstruct their aspirations without decreasing their efforts.

Platelet monoamine oxidase activity in subjects tested for Huntington's disease gene mutation.

Monoamine oxidase activity (MAO) has been related to neuronal damage, since the oxidative deamination of biogenic amines produces free radicals that may enhance oxidative stress. Elevated enzyme activities in brain (MAO-A and MAO-B forms) and in platelets (MAO-B form) have been reported in several degenerative diseases, indicating that MAO activity may be involved in the disease progression. We estimated platelet MAO activity in a group of 59 patients (34 males) with HD, 20 subjects (7 males) at risk, and 29 (14 males) healthy subjects with positive family history for HD, categorized according to clinical features and the number of CAG repeat units (CAG-RN) at the Huntington gene. A group of 64 subjects (36 males) with negative family history for HD served as controls. In contrast to some previous studies, platelet MAO activities in both male and female patients (CAG-RN 40 to 62) with overt symptomatology, were not different compared to same sex control subjects. Subjects at risk (CAG-RN 39 to 52), though, showed significantly lower activities compared to same sex patients or controls. MAO activities seem to increase with disease progression, and tend to be higher in patients with dementia. The increases may be an epiphenomenon of disease pathology, but the possibility that an increase in the expression of the enzyme precedes the onset of the disease and contributes to enhanced oxidative stress should be considered in future longitudinal studies as a possible mechanism that accelerates disease progression.

Head-up tilt test with clomipramine challenge in vasovagal syndrome--a new tilt testing protocol.

PURPOSE: The aim of the study was to randomly compare clomipramine, used as a challenge-agent during head-up tilt test, with isoproterenol, used in the conventional test, in patients with vasovagal syndrome. SUBJECTS AND METHODS: The serotonergic re-uptake inhibitor clomipramine was infused (5mg in 5min) at the start of head-up tilt test (Clom-HUT) in 126 patients (mean age 41+/-16 years) with positive history of recurrent neurocardiogenic syncope, and in 54 healthy control subjects (mean age 46+/-15 years). All subjects had also been tested with a conventional 60 degrees head-up tilt test (Con-HUT) for 30 min and, if negative, isoproterenol infusion was performed at the end of the test. The two tests were performed in a random order with a 24-h interval between them. RESULTS: Fifty-two of the 126 patients (41%) and two of the 54 controls had a positive response to Con-HUT. In the Clom-HUT the proportion of patients who experienced a positive response increased to 83% (105 subjects), while this happened only to four control subjects. The predictive accuracy of Clom-HUT increased compared to Con-HUT from 58 to 86%, respectively. CONCLUSION: The results indicate an increased responsiveness of central serotonergic neural system in subjects with vasovagal syndrome, the activation of which leads to sympathetic withdrawal. The use of clomipramine infusion during tilt test seems to improve considerably its diagnostic value.

Prolactin responses to acute clomipramine and haloperidol of male schizophrenic patients in a drug-free state and after treatment with clozapine or with olanzapine.

Atypical neuroleptics share a common feature, showing higher affinity for 5-HT2 receptors than for D2 dopamine receptors, but show considerable differences in their clinical and pharmacological properties. In clinical doses, they occupy serotonergic receptors near saturation, but show considerable differences regarding the D2 receptor occupancies, with clozapine showing the lowest degree of occupation. We assessed serotonergic and dopaminergic receptor responsiveness in two groups of male schizophrenic patients, one treated with the atypical neuroleptic clozapine (14 patients, doses 200-600 mg/d) and the other treated with olanzapine (11 patients, doses 10-30 mg/d). We measured the prolactin responses to the acute administration of a serotonergic drug, clomipramine, and a dopaminergic one, haloperidol. Tests were first performed in the drug-free state, and were repeated after the patients had been treated with stable doses of either drug for six weeks. Clomipramine administration induced significant increases of prolactin in the drug-free state. These responses were eliminated after treatment of the patients with either drug, thereby indicating a high 5-HT receptor occupancy by both clozapine and olanzapine. The prolactin responses to haloperidol were not altered after treatment with clozapine, but were significantly reduced after the olanzapine treatment. The baseline prolactin levels were not influenced by clozapine treatment, and were moderately but significantly increased after treatment with olanzapine. The results indicate that there is a difference between the two drugs in their capacity to block dopamine receptors at the hypothalamus-pituitary level, and match the results obtained by SPECT receptor binding studies for striatal dopamine receptors.

Neuroendocrine responsivities of the pituitary dopamine system in male schizophrenic patients during treatment with clozapine, olanzapine, risperidone, sulpiride, or haloperidol.

BACKGROUND: Atypical antipsychotic drugs, in clinical doses, occupy 5-HT2 receptors near saturation, while D2 dopamine receptors, assessed usually in striatum by SPECT or PET methods, are occupied to different degrees.We hypothesized that these differences in D2 receptor occupancies may also be evaluated by a neuroendocrine approach, namely by measuring the plasma prolactin responses to i. m. administered haloperidol, since the expected elevations depend mainly on the free remaining D2 receptors in the tuberoinfundibular tract. METHODS: We measured the plasma prolactin levels at 0,30, 60, 90, and 120 minutes after administration of 5 mg haloperidol i. m. in six groups of male patients with schizophrenia: a). 33 patients in a drug-free state,b). 15 patients on treatment with clozapine (range 200-600 mg/day), c). 15 patients on olanzapine (10-30mg/day), d). 14 patients on risperidone (8-16mg/day), e). 23 patients on haloperidol (10-40mg/day), f) 14 patients on sulpiride (600-1600mg/day). Data were also obtained from a group of 14 healthy male control subjects. The differences in baseline prolactin levels and in the responses to acute haloperidol of the seven groups were compared. RESULTS: The baseline prolactin levels did not differ significantly in the groups of controls (8.3+/-.8 ng/ml), drug-free patients (8.0+/-.6) and patients treated with clozapine (7.7+/-.8), they were moderately elevated in patients treated with olanzapine (16.8+/-.9), elevated in patients on haloperidol (34.4+/-7.3),and theyw ere even higher in the groups of patients treated with risperidone (54.9+/-2.4) or sulpiride (58.8+/-7.0). All groups of patients gave attenuated prolactin responses to i. m. haloperidol compared to healthy controls. During treatment with haloperidol, risperidone, or sulpiride, no significant prolactin increases after i. m. haloperidol were observed. The group treated with olanzapine gave significant prolactin increases, which were lower than those obtained in the group of patients treated with clozapine, who gave responses similar to that of the drug-free patients. CONCLUSIONS: lasma prolactin levels and responses to i. m. haloperidol of patients on treatment with antipsychotic drugs, reflect the prolactin release potencies of the drugs, which are related, but not restricted, to their affinities to D2 dopamine receptors. According to the prolactin baseline levels and responses to i. m. haloperidol, the drugs of this study can be categorized for their potency to the pituitary dopamine system that controls prolactin release, as follows: sulpiride > risperidone > haloperidol > olanzapine > clozapine. This categorization is similar to that obtained by binding studies in striatal D2 dopamine receptors using brain imaging techniques.

Changes in dopamine receptor responsivity during alcohol detoxification may predict relapse.

In the search for clinical and biological variables that may predict relapse of alcohol dependent patients after detoxification, we followed up for 1 year male patients that had undergone successful detoxification. The patients had been tested earlier during their usual alcohol consumption and immediately after detoxification for the responsivity of D2 dopamine receptors (as measured by the increases in prolactin plasma levels caused by intramuscular administration of 5 mg of the dopamine receptor blocker haloperidol). Of the 18 patients, eight had not consumed alcohol for more than 6 months, and ten had relapsed within 6 months. Comparison of the clinical and neuroendocrine data for the two subgroups revealed no significant differences in age, amount of alcohol consumed during alcohol abuse, score in the Beck Depression Inventory, score in the Brief Michigan Alcoholism Screening Test, or prolactin responses to haloperidol before detoxification. In patients who relapsed, the duration of alcoholism was marginally shorter (P=0.055). Patients who did not relapse had significantly higher (P=0.003) prolactin responses to haloperidol in the test performed after detoxification as compared with patients who did relapse, and their responses were similar to those of a group of healthy male subjects. The results show that the increase in dopamine receptor responsivity that occurs after detoxification is a favourable factor for non-relapse; it may reflect recovery from down-regulation of the dopaminergic reward system caused by alcohol consumption.

Neuroendocrine serotonergic and dopaminergic responsivity in male schizophrenic patients during treatment with neuroleptics and after switch to risperidone.

RATIONALE: The pharmacological profile of risperidone is that of an atypical neuroleptic regarding its serotonin 5-HT2A and dopamine D2 receptor blocking properties. Treatment with risperidone, though, results in considerably elevated plasma prolactin (PRL) levels which are not observed with other atypical neuroleptics, such as clozapine, indicating a differentiated action on receptors that are involved in PRL release, mainly dopaminergic and serotonergic. OBJECTIVE: To assess the responsivity of serotonergic and dopaminergic receptors during treatment with neuroleptics and after switch to risperidone, using neuroendocrine paradigms. METHODS: Two neuroendocrine challenge tests, measuring the PRL increases induced by acute administration of serotonergic (clomipramine, 25 mg i.v.) and dopaminergic (haloperidol, 5 mg i.m.) drugs were performed in 13 male schizophrenic patients during treatment with typical neuroleptics and, later, after 6 weeks of treatment with risperidone. The tests were also performed in a group of nine healthy male volunteers. PRL was estimated in blood samples taken every 15 min for 1 h for clomipramine and every 30 min for 2 h for haloperidol. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS). RESULTS: During treatment with neuroleptics (mean dose 1354 mg chlorpromazine equivalents, range 300-2400 mg), i.m. haloperidol caused significant elevations in plasma PRL, which were totally abolished after 6 weeks treatment with risperidone (mean dose 12.1 mg/day, range 8-16 mg/day), indicating complete D2 receptor blockade. In contrast, the PRL increases obtained after clomipramine administration during neuroleptic treatment were preserved after treatment with risperidone. Both PRL response patterns to clomipramine were similar to that of healthy controls. BPRS score was 50.2+/-9.3 points during neuroleptic treatment and was reduced after risperidone to 30.1+/-6.6 points, i.e., 40% in the mean. CONCLUSIONS: During treatment with typical neuroleptics, the PRL responses to clomipramine are normal, and they are preserved after switch to risperidone in doses that cause complete dopamine receptor blockade. Risperidone, a dopamine and 5-HT receptor blocker, does not affect 5-HT receptors that are involved in the PRL release by the 5-HT uptake blocker clomipramine, indicating a different behavior than other atypical neuroleptics such as clozapine or olanzapine, for which a reduction of the PRL release induced by serotonergic agents like fenfluramine or mCPP has been reported. A conclusive identification of the 5-HT receptor subtypes that are involved in this different action cannot be identified at present, but it should be taken into account that risperidone differs from clozapine, showing higher affinity for 5-HT2A than 5-HT2C receptors and lacking the marked affinity of clozapine to 5-HT1A receptors.

Dopamine receptor responsivity in schizophrenic patients in a drug-free state and after treatment with olanzapine.

1. Olanzapine is a novel atypical antipsychotic with affinity for a number of neurotransmitter receptors including dopamine D1, D2, D4, serotonin 5HT2A, 5HT2C, histamine H1, a1-adrenergic, and muscarinic receptors. 2. A neuroendocrinological method to check the degree of dopamine receptor blocking is by measuring the prolactin (PRL) responses to acute (i.m.) administration of haloperidol (HAL). The authors applied this test in a group of male patients with DSM-IV schizophrenia in the drug-free state. The patients were subsequently treated with olanzapine (OLZ) (mean daily dose: 22.5+/-5.8) and the test was repeated six weeks later. For the HAL-test, 5mg HAL were injected i.m. and blood samples were taken at times 0, 30, 60, 90 and 120 minutes. Fourteen patients enrolled in the study. Psychopathology was assessed by means of the Brief Psychiatric Rating Scale (BPRS). 3. Six weeks treatment with OLZ resulted in significant decreases in the total BPRS score and on the score of its subscales for positive, negative, and general psychopathology. Comparison of the PRL response patterns, after HAL administration by analysis of variance for repeated measures (ANOVAR) for drug treatment and time, revealed a highly significant time effect (F=28.98, p=0.000) and a significant treatment by time interaction (F=8.27, p=0.000008). Namely, in the drug-free state significant increases were found in the PRL levels after i.m. HAL administration which were significantly reduced during treatment with OLZ, indicating moderate receptor blockade.

Neurochemical variables in subjects with adjustment disorder after suicide attempts.

The investigation of biological correlates of suicidal behavior is important for identifying high-risk subjects. The objective of this study was to examine the neurochemical variables' platelet MAO activity and urinary MHPG, 5HIAA and HVA, the main metabolites of noradrenaline, serotonin and dopamine, neurotransmitters that are considered to be involved in the pathophysiology of suicidal behavior, as well as plasma cortisol, in a group of subjects with adjustment disorder after a suicide attempt. Fifty-three patients, 42 females and 11 males, were included in the study and were compared to a group of 50 healthy controls, 25 females and 25 males. Platelet MAO activity was found to be significantly lower in both male and female patients compared to controls of the same sex (P < 0. 001 for both comparisons). 5HIAA and HVA were not different between patients and controls, but MHPG was significantly higher in the patients group (P = 0.008). Moreover, plasma levels of cortisol were significantly higher in the patients compared to the controls (P < 0. 001). Our results confirm the hypothesis of low platelet MAO activity as a biological characteristic of patients who attempt suicide. They also point to a possible parallel activation of the noradrenergic system.

Provocation of neurocardiogenic syncope by clomipramine administration during the head-up tilt test in vasovagal syndrome.

OBJECTIVES: We sought to test the hypothesis that activation of the serotonergic system in patients with vasovagal syndrome during the head-up tilt test provokes syncope. BACKGROUND: Central serotonergic activation participates in the pathogenesis of neurocardiogenic syncope. Drugs increasing serotonin (5-HT) in the central nervous system have not been tested as drug challenges during the head-up tilt test with clomipramine (Clom-HUT). METHODS: The serotonergic re-uptake inhibitor clomipramine was infused (5 mg in 5 min) at the start of Clom-HUT in 55 patients (mean age 40 +/- 17 years) with a positive history of recurrent neurocardiogenic syncope and in 22 healthy control subjects (mean age 46 +/- 15 years). Blood samples were taken at 0, 5, 10 and 20 min for estimation of plasma prolactin and cortisol as neuroendocrine indicators of central serotonergic responsivity. All subjects had been previously tested with a basic 60 degrees head-up tilt test (B-HUT) for 30 min, and if negative, isoproterenol infusion was given at the end of the test. RESULTS: Twenty-nine (53%) of the 55 patients and none of the 22 control subjects had a positive result in the B-HUT. With Clom-HUT, the proportion of patients who experienced a positive response increased to 80% (n = 44), although this happened to only one control subject. Prolactin and cortisol plasma levels increased significantly in the positive Clom-HUT patient group only. CONCLUSIONS: The results indicate an increased responsivity of the central serotonergic neural system in subjects with vasovagal syndrome, the activation of which leads to sympathetic withdrawal. The use of clomipramine infusion with the tilt test seems to considerably improve its diagnostic value.

Brain natriuretic peptide increases acutely and much more prominently than atrial natriuretic peptide during coronary angioplasty.

BACKGROUND: Increased levels of plasma brain natriuretic peptide (BNP) are observed in patients with congestive heart failure, hypertension, left ventricular hypertrophy, and acute myocardial infarction. However, there are no data on serial changes in plasma levels of BNP in patients undergoing coronary angioplasty. HYPOTHESIS: The study was undertaken to examine plasma concentrations of BNP together with those of atrial natriuretic peptide (ANP) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). METHODS: Plasma concentrations of BNP and ANP were examined in 13 patients with stable angina pectoris and good left ventricular function undergoing PTCA. Blood samples were taken from the femoral vein at baseline, after the first balloon inflation, after the end of the procedure, and 4 h thereafter. RESULTS: Plasma BNP levels were 14 +/- 4 at baseline, 22 +/- 10 after the first balloon inflation, 28 +/- 12 at the end of the procedure, and 15 +/- 4 pgr/ml 4 h thereafter (F = 13.05, p < 0.00001). Plasma ANP levels were 80 +/- 15, 86 +/- 14, 90 +/- 24, and 75 +/- 6 fmol/l (F = 5.95, p = 0.002), respectively. The increase of BNP at the end of the procedure was related to the increase of ANP (r = 0.78, p = 0.002). CONCLUSION: Plasma BNP levels increase acutely and much more prominently than those of plasma ANP during coronary angioplasty; however, plasma BNP levels return to baseline values shortly after the end of the procedure.

Dopamine receptor responsivity in alcoholic patients before and after detoxification.

OBJECTIVE: To assess central dopamine receptor responsivity in alcoholic patients during their usual alcohol consumption and after detoxification. METHOD: Plasma prolactin levels were measured at 0, 30, 60, and 90 min after administration of 5 mg haloperidol i.m. in 21 hospitalized male alcoholic patients during usual alcohol consumption, and 13 days later (mean, range 7-17 days), after detoxification. The test was also performed in seven healthy male volunteers. The patterns of prolactin responses were compared using repeated measures analysis of variance. RESULTS: The prolactin responses to haloperidol increased significantly after detoxification compared to those during usual alcohol consumption (state x time interaction P < 0.01; planned comparisons for times 0 and 90 min between states P = 0.03). Compared to controls, the responses of the patients before detoxification were lower (group-time interaction P = 0.001), and the difference was not significant after detoxification (P = 0.19). The magnitude of plasma prolactin (PRL) responses were not related to duration of alcohol abuse, score in the Brief Michigan Alcoholism Screening Test (BMAST) scale, or family history of alcoholism. CONCLUSIONS: Alcohol detoxification is accompanied by a normalization of the low responsivity of central dopaminergic receptors during alcohol abuse. The data support the hypothesis of a participation of the central dopaminergic system in alcohol dependence.

Prolactin secretion in response to haloperidol challenge in delusional (psychotic) and non-delusional depression.

Certain studies on measures related to central neurotransmitter activity have demonstrated that in delusional (psychotic) depression there is a dopaminergic dysregulation which distinguishes it from non-psychotic depression. A neuroendocrinologic method to check the degree of DA receptor responsivity is by measuring the prolactin responses to acute intramuscular administration of haloperidol. We studied this possibility by applying the haloperidol test in seven delusional and ten non-delusional depressed patients. All patients met DSM-IV criteria for a major depressive episode, single or recurrent, with or without psychotic features. After a three-week washout period, 5 mg of haloperidol were injected i.m. and blood samples were taken at 0, 30, 60, 90 and 120 minutes. In both trials, significant time effects were observed (elevated prolactin levels, F = 11.36, P = 0.000). However, the prolactin responses to haloperidol did not differ significantly between the two patient groups (F = 0.12, P = 0.97). These data do not show a difference in D(2) receptor responsivity, at least at the hypothalamus-pituitary level, between psychotic and non-psychotic depression.

Administration of citalopram before ECT: seizure duration and hormone responses.

From theoretical and clinical perspectives, it is important to know if selected serotonin-reuptake inhibitors (SSRIs), often administered concurrently with electroconvulsive therapy (ECT), modify seizure duration. In a study with a double-blind, cross-over design, the authors evaluated the effect of citalopram, the most selective SSRI available, on the length of electrically induced seizures and on hormone secretion during ECT. Ten depressed women were given either 20 mg citalopram or placebo orally 2 hours before the third and fourth ECT sessions. Seizure duration was assessed by the cuff technique and from electroencephalographic recordings, whereas blood for prolactin, thyrotropin, and cortisol assessment was sampled before ECT and 5, 10, 20, 30, 40, and 60 minutes after ECT. No adverse effects after the administration of citalopram were recorded. The length of seizures was not statistically different in the citalopram (29.3+/-8.4 seconds) and placebo sessions (28.2+/-9.4 seconds). Neither pre-ECT plasma hormone levels measured 2 hours after citalopram or placebo administration nor the patterns of ECT-induced hormone secretions differed between the two drug and placebo conditions. The lack of effect of citalopram on hormones in this study may be a result of possible deficiencies of the monoaminergic (i.e., serotoninergic) systems in depression. Although safety and efficacy issues were not fully addressed by coadministering citalopram for the long term and throughout the course of ECT, these findings support the view that challenges the typical clinical practice of discontinuing SSRIs before ECT.

Gonadal axis hormones in male schizophrenic patients during treatment with haloperidol and after switch to risperidone.

RATIONALE: The atypical neuroleptic risperidone, in addition to its dopamine receptor blocking activity, has a high affinity for serotonergic receptors. Since both dopaminergic and serotonergic neuronal activities participate in regulation of the pituitary gonadal axis (PGA), it is expected that a switch from treatment with haloperidol to treatment with risperidone should influence plasma levels of PGA hormones. OBJECTIVE: To study the effects of a drug with dopamine and serotonin receptor blocking activity on PGA hormones in patients who were on treatment with a dopamine receptor blocker. METHODS: Plasma levels of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), as well as prolactin and cortisol, were measured in 16 male schizophrenic patients during treatment with haloperidol (mean dose 23.3 mg daily, SD = 16.9) and 6 weeks later after switching to treatment with risperidone (mean dose 11.8 mg daily, SD = 2.9). Psychopathology was assessed by BPRS. RESULTS: After switching to risperidone, total BPRS score and the scores in its subscales for positive, negative, and general symptoms were all significantly reduced in the order of 35-45%. Prolactin levels were significantly increased from 39.5+/-22.3 to 58.9+/-28.5 ng/ml (F= 4.61, P = 0.04), while cortisol, testosterone, LH, and FSH remained unchanged. No significant correlations between prolactin increases and reduction in BPRS or in its subscale scores were found. CONCLUSIONS: The results show that blocking of both dopamine and serotonin receptors does not influence the pituitary gonadal axis but considerably increases prolactin release.