Drug-treated Patients Research Articles

Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

Regulatory T cell (Treg) subsets return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are associated with immunological remission of lupus.

Compared with conventional drug therapy, autologous hemopoietic stem cell transplantation (HSCT) can induce very-long-term remission in refractory lupus patients. Herein, we show that in posttransplant patients, both CD4(+)CD25(high)FoxP3(+) and an unusual CD8(+)FoxP3(+) Treg subset return to levels seen in normal subjects; accompanied by almost complete inhibition of pathogenic T cell response to critical peptide autoepitopes from histones in nucleosomes, the major lupus autoantigen from apoptotic cells. In addition to a stably sustained elevation of FoxP3, posttransplant CD8 T cells also maintained markedly higher expression levels of latency-associated peptide (LAP), CD103, PD-1, PD-L1, and CTLA-4, as compared with pretransplant CD8 T cells that were identically treated by a one-time activation and rest in short-term culture. The posttransplant CD8 regulatory T cells (Treg) have autoantigen-specific and nonspecific suppressive activity, which is contact independent and predominantly TGF-beta dependent. By contrast, the pretransplant CD8 T cells have helper activity, which is cell contact dependent. Although CD4(+)CD25(high) Treg cells return during clinical remission of conventional drug-treated lupus, the posttransplant patient's CD8 Treg cells are considerably more potent, and they are absent in drug-treated patients in whom CD4 T cell autoreactivity to nucleosomal epitopes persists even during clinical remission. Therefore, unlike conventional drug therapy, hemopoietic stem cell transplantation generates a newly differentiated population of LAP(high)CD103(high) CD8(TGF-beta) Treg cells, which repairs the Treg deficiency in human lupus to maintain patients in true immunological remission.

Weight loss and changes in use of antidiabetic medication in obese type 2 diabetics after laparoscopic gastric banding

Background Interest in bariatric surgery is growing as an effective method for long-term metabolic control in morbidly obese patients with type 2 diabetes. We analyzed the weight loss and changes in use of diabetic medication in obese patients with type 2 diabetes treated with laparoscopic adjustable gastric banding (LAGB). Methods From 1993 to 2005, 1791 morbid obese patients underwent LAGB at our institution. Of the 1791 patients, 394 (22%) had type 2 diabetes mellitus at baseline. Of the 394 patients with diabetes, 52 were receiving diabetic medication. The median follow-up period for the drug-treated diabetic patients was 3 years (range .25–9). Results The drug-treated diabetic patients were older (age 47.6 ± 7.5 versus 37.5 ± 10.7 years, P <.001), weighed more (body mass index 49.1 ± 9.5 versus 45.6 ± 7.5 kg/m 2, P 0.001), and were more frequently affected by co-morbidities than the nondiabetic patients at surgery. The percentage of excess weight loss 1 year after surgery was less (32.4% ± 14.1% versus 41.1% ± 19.9%, P <.01) for the drug-treated diabetic patients than for the nondiabetic patients. This difference was maintained for 5 years of follow-up. A significant decline occurred in the use of both oral diabetic medication and insulin after surgery. Of the 52 patients treated with oral antidiabetic medication at baseline, 33 required oral antidiabetic medication at the end of follow-up. Of the 6 patients who also required insulin at baseline, 2 did so at the end of follow-up. The use of diabetic medication had increased in 4 patients (7.7%), was unchanged in 12 (23.1%), had decreased in 17 (32.7%), and was suspended in 19 (36.5%) of 52 patients. Conclusion The amount of weight loss after LAGB was less in drug-treated diabetic patients than in nondiabetic patients. However, LAGB was associated with a sustained reduction in the use of diabetic medication.

Experiences of Telemedicine-Aided Hypertension Control in the Follow-Up of Finnish Hypertensive Patients

The prevalence of hypertension is high in Finland. Only one fourth of the drug-treated hypertensive patients reach their target pressure. We evaluated a commercially available telemedicine system for impact in reaching better blood pressure control among Finnish hypertensive patients. A telemedicine system, the Doc@home, was used to assist blood pressure treatment in 19 Finnish hypertensive patients. Blood pressure control improved during the 3-month follow-up. Patient-to-Doc@home compliance was good, but study physicians found the system time consuming in the beginning. According to our results, the Doc@home telemedicine system showed a promising approach in hypertension treatment but needs some further development and trained staff to become a still more practical alternative.

Prevalence, awareness and treatment of hypertension in Finland during 1982–2007

To assess the trends in prevalence and in control of hypertension in various parts of Finland during 1982-2007. Three independent cross-sectional population surveys were conducted in 1982, 2002 and 2007 with age-stratified samples of men and women aged 25-64 years from the national population register. The total number of participants with complete blood pressure (BP) measurements was 16 775. Overall, during 1982-2007, the prevalence of hypertension (systolic BP > or = 140 mmHg and/or diastolic BP > or = 90 mmHg and/or current use of antihypertensive drug treatment) fell significantly in both sexes. In men, it fell from 63.3 to 52.1%; in women, from 48.1 to 33.6% (P < 0.001 for both sexes). However, during the past 5-year period, a decline was observed only in women in south-western Finland (P = 0.003). Furthermore, previously observed significant increases in the proportions of treated and controlled hypertensive individuals did not continue among men during 2002-2007. Despite the evident progress in all aspects of hypertension care since 1982, still in 2007, only 68% of all hypertensive individuals were aware of their condition, 52% of those who were aware were treated with antihypertensive drugs and 37% of the drug-treated patients had normal BP. Steady progress has been made in the prevention and treatment of hypertension in Finland. However, further improvements are clearly needed.

Effectiveness of benzodiazepines: do they work or not?

Evaluation of: Martin JLR, Sainz-Pardo M, Furukawa TA et al. Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials. J. Psychopharmacol. 21, 774–782 (2007). The benzodiazepines have been extensively prescribed for decades for vague indications such as anxiety, sleeplessness and muscle tension. Despite increasing knowledge of their adverse effects, such as sedation, psychomotor and cognitive impairment, and dependence on long-term use, and the recent advent of better alternatives, their use continues largely unabated. The paper under review assesses the sparse high-quality data related to efficacy (denoted by the dropout rate for failure to respond), effectiveness (dropout rate for any reason) and dropout for adverse effects. The conclusion is that efficacy was significantly higher for the drugs as compared with placebo; by contrast, no convincing evidence was found of any short-term effectiveness: and adverse effects were 1.5-times more frequent in the drug-treated patients. Various reasons for these results are discussed. I point out the changes in diagnostic criteria over the years and the lack of accepted methods of assessing estimates of effectiveness in clinical practice. Excessive prescribing of these controversial drugs is likely to continue.

Diffusion‐weighted imaging and magnetization transfer imaging of tardive and edentulous orodyskinesia

Oral dyskinesias occur in elderly individuals in relation to drug use (tardive dyskinesia, TD) or edentulousness (edentulous orodyskinesia, EOD) but their characterization remains incomplete. Our aim was to investigate whether magnetic resonance techniques such as diffusion-weighted imaging (DWI) and magnetization transfer imaging (MTI) of the brain could be used to differentiate dyskinetic patients from control subjects. Eight drug-treated patients with TD, 12 EOD patients, 8 drug-treated patients without TD, and 10 control subjects were recruited and examined by DWI and MTI. Measurements in the caudate nucleus, putamen, and globus pallidus yielded globally different apparent diffusion coefficient (ADC) values between drug treated patients with TD and control subjects but the magnetization transfer ratios showed no significant variations. The discrimination between dyskinetic patients and control subjects offered by ADC values was however slightly poorer than the discrimination offered by the previously published choline/creatine ratios measured by MR spectroscopy in the basal ganglia. The results are consistent with the pathophysiological hypothesis of damage to cholinergic interneurons.

Stromal-mediated protection of tyrosine kinase inhibitor-treated BCR-ABL-expressing leukemia cells

Clinical studies of patients with chronic myeloid leukemia revealed that a common pattern of response is a dramatic fall in the circulating population of blast cells, with a minimal or delayed decrease in marrow blasts, suggesting a protective environment. These observations suggest that a greater understanding of the interaction of stromal cells with leukemic cells is essential. Here, we present an in vivo system for monitoring relative tumor accumulation in leukemic mice and residual disease in leukemic mice treated with a tyrosine kinase inhibitor and an in vitro system for identifying integral factors involved in stromal-mediated cytoprotection. Using the in vivo model, we observed high tumor burden/residual disease in tissues characterized as significant sources of hematopoiesis-promoting stroma, with bone marrow stroma most frequently showing the highest accumulation of leukemia in untreated and nilotinib-treated mice as well as partial protection of leukemic cells from the inhibitory effects of nilotinib. These studies, which showed a pattern of leukemia distribution consistent with what is observed in imatinib- and nilotinib-treated chronic myeloid leukemia patients, were followed by a more in-depth analysis of stroma-leukemia cell interactions that lead to protection of leukemia cells from nilotinib-induced cytotoxicity. For the latter, we used the human BCR-ABL-positive cell line, KU812F, and the human bone marrow stroma cell line, HS-5, to more closely approximate the bone marrow-associated cytoprotection observed in drug-treated leukemia patients. This in vitro system helped to elucidate stromal-secreted viability factors that may play a role in stromal-mediated cytoprotection of tyrosine kinase inhibitor-treated leukemia cells.

Influence of Elevated Cardiometabolic Risk Factor Levels on Treatment Changes in Type 2 Diabetes

Undertreatment of risk factors in patients with type 2 diabetes is common. We assessed the influence of elevated levels of blood pressure, total cholesterol, and A1C on decisions of Dutch general practitioners to change drug treatment in a cohort of 3,029 patients during a 1-year period. Respectively, 58, 71, and 21% of patients remained untreated despite poor blood pressure, lipid levels, and glycemic control. Of poorly controlled but already drug-treated patients, 52% did not receive intensification for antihypertensive medication, 81% not for lipid-lowering medication, and 43% not for glucose-lowering medication. We observed a significantly lower treatment intervention rate in moderately than in poorly controlled patients for blood pressure. This was not seen for decisions on cholesterol or A1C results. The low overall action rates observed for blood pressure and especially lipid management cannot sufficiently be explained by the use of treatment thresholds higher than those indicated by guidelines.

Proton magnetic resonance spectroscopy study of dyskinesia patients

Oral dyskinesias may occur spontaneously or be induced by medications such as antipsychotics and antidepressants. In this study, single voxel proton magnetic resonance spectroscopy was used to compare metabolite levels in the striatum for (1) 12 patients with drug-induced tardive dyskinesia (TD), (2) 12 patients with spontaneous oral dyskinesia (SOD), (3) 8 antidepressant-treated patients without TD, and (4) 8 control subjects. Statistically significant reductions in the choline/creatine (Cho/Cr) ratio were measured for the drug-treated patients with TD (-13%, P = 0.020) and SOD patients (-12%, P = 0.034) relative to control subjects. In comparison with antidepressant-treated patients without TD, drug-treated patients with TD showed a non statistically significant reduction in Cho/Cr (-11%, P = 0.079). All other metabolite ratios (N-acetylaspartate (NAA)/Cr, myo-inositol (mI)/Cr, glutamine + glutamate (Glx)/Cr, macromolecule + lipid (MM+Lip)/Cr, NAA/Cho) were unaffected by either type of dyskinesia. The observed Cho/Cr reduction in dyskinesia patients suggests decreased membrane phosphatidylcholine turnover, which provides free choline as precursor of molecules responsible for cellular signal transduction.

CS1 Is Expressed on Myeloma Cells from Early Stage, Late Stage, and Drug-Treated Multiple Myeloma Patients, and Is Selectively Targeted by the HuLuc63 Antibody.

Introduction: One-third of multiple myeloma (MM) patients exhibit high-risk features such as abnormal cytogenetics, high LDH, amplification of CKS1-B or spiked expression of MAF, MAF-B or FGFR3. While not affecting complete response rates, median durations of event-free and overall survival, even with high-dose melphalan-based tandem autotransplants of such patients, do not exceed 24 mo and 36 mo, compared to 60 mo and ≥ 90 mo for the remainder. Monoclonal antibody (mAb)-mediated therapy may target a chemotherapy-resistant myeloma cell pool. CS1 (CD2 subset 1, CRACC, SLAMF7), a member of the CD2 family of cell surface glycoproteins, exhibits high-level expression on primary myeloma cells, indicating that CS1 is a potential target for treatment in MM.Methods: Gene expression was assessed using an Affymetrix GeneChip array. Protein expression was measured by flow cytometry, and immunohistochemistry (IHC), using HuLuc63, a novel humanized anti-CS1 mAb. HuLuc63-mediated lysis of myeloma cells via antibody dependent cellular cytotoxicity (ADCC) was measured by 51Cr-release.Results: CS1 mRNA was detected in >95% of CD138+ purified plasma cells from >95% of healthy donors, newly diagnosed myeloma patients, and those with relapsed myeloma (Fig. 1a). CS1 remained highly expressed in patients following VDTPACE treatment, albeit at a reduced level. CS1 expression was also high following bortezomib (Velcade®) treatment, with a subset of patients showing increased expression post-treatment. CS1 protein expression on primary myeloma cells was confirmed by flow cytometry, while IHC analysis of normal tissues revealed anti-CS1 staining primarily on CD138+ tissue plasma cells. Finally, we determined that HuLuc63 could induce killing of myeloma cells using purified allogeneic NK cells (Fig. 1b). Blocking the Fc receptor greatly reduced this activity indicating an ADCC mechanism. Killing of myeloma targets was also observed in autologous systems suggesting that HuLuc63 can overcome KIR-mediated NK cell inhibition of autologous NK cells. In summary, we observed high mRNA and protein expression of CS1 in myeloma from early stage, late stage, and treated patients, and showed enhanced lysis of myeloma cells in vitro with HuLuc63. Our data support the potential clinical utility of CS1-targeted therapy. HuLuc63 will be entering a phase I clinical trial for advanced myeloma patients. [Display omitted] [Display omitted]

A Combined Empirical and Mechanistic Codon Model

The evolutionary selection forces acting on a protein are commonly inferred using evolutionary codon models by contrasting the rate of synonymous to nonsynonymous substitutions. Most widely used models are based on theoretical assumptions and ignore the empirical observation that distinct amino acids differ in their replacement rates. In this paper, we develop a general method that allows assimilation of empirical amino acid replacement probabilities into a codon-substitution matrix. In this way, the resulting codon model takes into account not only the transition-transversion bias and the nonsynonymous/synonymous ratio, but also the different amino acid replacement probabilities as specified in empirical amino acid matrices. Different empirical amino acid replacement matrices, such as secondary structure-specific matrices or organelle-specific matrices (e.g., mitochondria and chloroplasts), can be incorporated into the model, making it context dependent. Using a diverse set of coding DNA sequences, we show that the novel model better fits biological data as compared with either mechanistic or empirical codon models. Using the suggested model, we further analyze human immunodeficiency virus type 1 protease sequences obtained from drug-treated patients and reveal positive selection in sites that are known to confer drug resistance to the virus.

Dysregulation of Retinoid Transporters Expression in Body Fluids of Schizophrenia Patients

This study aims to find the biomarkers or associated proteins in body fluids of schizophrenia patients so that we can further understand the etiology of schizophrenia. We applied proteomic technologies combining two-dimensional electrophoresis with Coomassie blue staining and mass spectrometry and identified a procedure for the clinical screening of disease-influenced body fluid proteins in two sets of samples, plasma from 19 schizophrenia patients and cerebrospinal fluid (CSF) from 35 drug-treated schizophrenic patients and 36 healthy controls. The expression of transthyretin (TTR) tetramer increased significantly in plasma of schizophrenic patients after a valid 2 months in-hospital antipsychotic treatment. Conversely, the expression of the TTR tetramer and apolipoprotein E (ApoE) was down-regulated by up to 1.68 and 3.62 times, respectively, in the CSF of schizophrenia patients compared to that of normal controls, which has not been reported previously. Considering that the TTR tetramer and ApoE are both retinoid transporters, retinoid dysfunction might be involved in the pathology of schizophrenia.

Effects of amphetamine and/or l-dopa and physiotherapy after stroke ? a blinded randomized study

Major therapeutic advances in the rehabilitation of subacute stroke are lacking. A promising approach is treatment with facilitating drugs like amphetamine or levodopa in combination with physiotherapy. In a randomized, double-blind, placebo-controlled clinical trail, the effect of 10 sessions with either 20 mg of D-amphetamine, 100 mg of L-dopa or 10 mg of D-amphetamine + 50 mg of L-dopa combined with physiotherapy during a 2-week period was investigated in 25 patients admitted to a stroke rehabilitation unit. Motor function (Fugl-Meyer score) and activities of daily living (Barthel's index) were assessed. All patients improved significantly over the intervention period. Drug-treated patients did not show any additional increase in motor function or ADL. It is feasible and safe to perform larger clinical trials with this type of four-arm design. However, the lack of significant effects could be because of type, dosage, and time of drugs as well as the physical intervention strategy.

Increased Neuroactive Steroid Concentrations in Women With Bipolar Disorder or Major Depressive Disorder

Changes in the plasma concentrations of neuroactive steroids have been associated with various neuropsychiatric disorders. However, the possible role of neuroactive steroids in bipolar disorder (BD) has remained unknown. We therefore determined the plasma levels of neuroactive steroids during the luteal phase of the menstrual cycle in women with BD or major depressive disorder (MDD). The plasma concentrations of 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THPROG), 3alpha,21-dihydroxy-5alpha-pregnan-20-one, progesterone, and cortisol were determined in 17 outpatients with BD, 14 outpatients with MDD, and 16 healthy control subjects. All patients were in a state of well-being and without relapse or recurrence for at least 3 months. Plasma concentrations of progesterone and 3alpha,5alpha-THPROG were significantly greater in patients than in controls, also being higher in BD patients than in MDD patients. Drug-free patients with BD or MDD showed similar differences in steroid concentrations relative to controls, as did drug-treated patients. Comorbidity with panic disorder, obsessive-compulsive disorder, or eating disorder had no effect on the association of mood disorders with steroid concentrations. Women with BD or MDD in a state of well-being showed higher plasma concentrations of progesterone and 3alpha,5alpha-THPROG in the luteal phase than did healthy controls. These differences did not seem to be attributable simply to drug treatment or to comorbidity with other psychiatric conditions in the patients.

Optimal design of clinical trials for drugs designed to slow the course of Alzheimer’s disease

Compounds now in clinical development are hypothesized to slow the clinical progression and pathogenesis of Alzheimer’s disease (AD) by their effects to diminish production, increase clearance, or decrease aggregation of amyloid β protein. Options for investigating the effects of these and other drugs on clinical progression and pathogenesis of AD were examined at a conference that included: (1) a review of experimental methods used to investigate disease-modifying drugs for multiple sclerosis, rheumatoid arthritis, cardiovascular disease, and osteoporosis; (2) discussion of possible study designs and outcome measures for trials in patients with AD; and (3) discussion of biomarkers available for AD. There is no uniformly best way to investigate a drug’s impact on AD progression but characteristics of studies supportive of a disease-slowing effect can be specified. Relevant clinical outcomes in drug-treated patients versus placebo-treated patients should be compared over at least 1 and possibly as long as 2 years with biomarkers reflective of pathogenesis and of the drug’s mechanistic effects measured concurrently.

Basal Ganglia Shape Alterations in Bipolar Disorder

Shape differences in the caudate heads and putamen were compared between drug-naive and drug-treated patients with bipolar disorder and healthy comparison subjects by using spherical harmonic (SPHARM) techniques. On the basis of previous studies, the authors hypothesized that the drug-naive patients would exhibit shape differences of the caudate heads and putamen, especially on the right side, relative to the healthy comparison subjects, and that shape differences, relative to healthy comparison subjects, would differ between drug-naive and drug-treated patients. Brain magnetic resonance images were acquired from 49 bipolar disorder patients (21 drug-naive and 28 drug-treated patients) and 37 healthy comparison subjects. Volumetric measurements were obtained, and SPHARM descriptions were used to measure between-group radius differences in the surfaces of the caudate heads and putamen. Although no significant between-group volume differences were found in the striatal structures, significant shape differences in the anterior and ventral surfaces of the striatum were observed. Specifically, shape differences, more prominent for the right side, were found for drug-naive bipolar disorder patients, relative to the healthy comparison subjects, but not for drug-treated bipolar disorder subjects. The findings suggest that drug-naive bipolar disorder patients have shape differences of the striatum, relative to healthy comparison subjects, and that these differences may be modulated by treatment. The findings more generally demonstrate the sensitivity of the SPHARM analytic technique for detecting subtle anatomical shape differences in small brain regions in the absence of volume differences.

Sub-chronic antipsychotic drug treatment does not alter brain phospholipid fatty acid composition in rats

Altered membrane phospholipid fatty acid composition is reported in schizophrenia and appears to be reduced by antipsychotic drug treatment. To determine whether antipsychotic drugs have a direct effect on brain phospholipid fatty acid composition, the effects of sub-chronic treatment with a “typical” and an “atypical” antipsychotic drug were determined in adult male Sprague–Dawley rats. Rats were treated with haloperidol (1 mg/kg), clozapine (20 mg/kg) or vehicle daily for 21 days. Whole brain total phospholipid composition was determined by gas chromatography. No alterations in brain phospholipid composition were produced by either drug. This suggests that the apparent normalization of membrane phospholipids observed in drug-treated schizophrenic patients is not due to a direct pharmacological effect of these drugs nor can the pharmacological effects of these drugs occurring in this time frame be attributed to alterations in neuronal membrane fatty acid composition.

Differences by Age and Race/Ethnicity in Knowledge About Hypercholesterolemia

This investigation sought to identify gaps in patients' knowledge about hypercholesterolemia and lipid-lowering therapy in an inner-city US population. Chart reviews and interviews were conducted for drug-treated hypercholesterolemic patients at 3 hospital-based cardiology practices in Bronx, NY. Univariate and multivariate analyses were used to assess whether race/ethnicity, sex, and age were predictors of knowledge. Subjects (n = 467, age 65.3 years) were 55% female, 38% Hispanic, 32% black, and 25% white. Most recognized hypercholesterolemia as a cause of heart disease (88%) and stroke (76%), although older subjects (>70 years) and Hispanic subjects, particularly non-English speakers, were significantly less likely to know about cardiovascular disease risks associated with hypercholesterolemia. Only 14% recalled their recent cholesterol levels, and recall was significantly lower among black, Hispanic, and older subjects. Overall, 31% expected to require lipid-lowering medications indefinitely in the future, while 66% did not know how long they would need to continue using medications. Blacks and Hispanics were significantly less likely to believe that they would need to continue taking medications indefinitely. Achieved lipid levels and self-reported medication adherence were relatively favorable although were unrelated to knowledge levels. In summary, among hypercholesterolemic patients in an urban population, relatively few knew their own cholesterol levels or expected to require medications indefinitely in the future. Older patients, black and Hispanic patients, and non-English speakers were significantly less likely to have accurate knowledge about hypercholesterolemia. Therefore, patient and community education efforts targeted to specific populations may lead to improved management of hypercholesterolemia in inner-city regions.

Subjective and neurovegetative changes in healthy volunteers and panic patients performing simulated public speaking

Drug-free symptomatic panic patients, drug-treated nonsymptomatic patients and healthy controls were submitted to simulated public speaking. Subjective anxiety, cognitive impairment and discomfort measured by the visual analog mood scale as well as skin conductance level were higher in symptomatic patients than in controls at the beginning of the experimental session, nonsymptomatic patients lying in between. Subjective sedation, spontaneous fluctuations of skin conductance, heart rate and blood pressure were similar in the three groups. Preparation and performance of speech decreased sedation while increasing anxiety, cognitive impairment, level and fluctuations of skin conductance, heart rate and blood pressure. Anxiety, cognitive impairment and conductance level were less increased in symptomatic patients than in controls. Electrodermal activity, but not cardiovascular measures of sympathetic arousal correlated with anticipatory anxiety. Chronic treatment with serotonin uptake inhibitors attenuated the differences between panic patients and controls, supporting the participation of serotonin in panic disorder.