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S Kapur

Publications and source records attributed to S Kapur.

At least 73 records · Page 4Linked to original sources
PubMed2000

The effect of divided attention on encoding and retrieval in episodic memory revealed by positron emission tomography.

The effects of divided attention (DA) on episodic memory encoding and retrieval were investigated in 12 normal young subjects by positron emission tomography (PET). Cerebral blood flow was measured while subjects were concurrently performing a memory task (encoding and retrieval of visually presented word pairs) and an auditory tone-discrimination task. The PET data were analyzed using multivariate Partial Least Squares (PLS), and the results revealed three sets of neural correlates related to specific task contrasts. Brain activity, relatively greater under conditions of full attention (FA) than DA, was identified in the occipital-temporal, medial, and ventral-frontal areas, whereas areas showing relatively more activity under DA than FA were found in the cerebellum, temporo-parietal, left anterior-cingulate gyrus, and bilateral dorsolateral-prefrontal areas. Regions more active during encoding than during retrieval were located in the hippocampus, temporal and the prefrontal cortex of the left hemisphere, and regions more active during retrieval than during encoding included areas in the medial and right-prefrontal cortex, basal ganglia, thalamus, and cuneus. DA at encoding was associated with specific decreases in rCBF in the left-prefrontal areas, whereas DA at retrieval was associated with decreased rCBF in a relatively small region in the right-prefrontal cortex. These different patterns of activity are related to the behavioral results, which showed a substantial decrease in memory performance when the DA task was performed at encoding, but no change in memory levels when the DA task was performed at retrieval.

Acoustic Stimulation↗
PubMed2000

The effects of divided attention on encoding- and retrieval-related brain activity: A PET study of younger and older adults.

Divided attention (DA) disrupts episodic encoding, but has little effect on episodic retrieval. Furthermore, normal aging is associated with episodic memory impairments, and when young adults are made to encode information under DA conditions, their memory performance is reduced and resembles that of old adults working under full attention (FA) conditions. Together, these results suggest a common neurocognitive mechanism by which aging and DA during encoding disrupt memory performance. In the current study, we used PET to investigate younger and older adults' brain activity during encoding and retrieval under FA and DA conditions. In FA conditions, the old adults showed reduced activity in prefrontal regions that younger adults activated preferentially during encoding or retrieval, as well as increased activity in prefrontal regions young adults did not activate. These results indicate that prefrontal functional specificity of episodic memory is reduced by aging. During encoding, DA reduced memory performance, and reduced brain activity in left-prefrontal and medial-temporal lobe regions for both age groups, indicating that DA during encoding interferes with encoding processes that lead to better memory performance. During retrieval, memory performance and retrieval-related brain activity were relatively immune to DA for both age groups, suggesting that DA during retrieval does not interfere with the brain systems necessary for successful retrieval. Finally, left inferior prefrontal activity was reduced similarly by aging and by DA during encoding, suggesting that the behavioral correspondence between these effects is the result of a reduced ability to engage in elaborate encoding operations.

Adult↗
PubMed2000

Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia.

OBJECTIVE: Since all antipsychotics block dopamine D(2) receptors, the authors investigated how well D(2) receptor occupancy in vivo predicts clinical response, extrapyramidal side effects, and hyperprolactinemia. METHOD: In a double-blind study, 22 patients with first-episode schizophrenia were randomly assigned to 1.0 or 2. 5 mg/day of haloperidol. After 2 weeks of treatment, D(2) receptor occupancy was determined with [(11)C]raclopride and positron emission tomography, and clinical response, extrapyramidal side effects, and prolactin levels were measured. Patients who showed adequate responses continued taking their initial doses, those who did not respond had their doses increased to 5.0 mg/day, and evaluations were repeated at 4 weeks for all patients. RESULTS: The patients showed a wide range of D(2) occupancy (38%-87%). The degree of receptor occupancy predicted clinical improvement, hyperprolactinemia, and extrapyramidal side effects. The likelihood of clinical response, hyperprolactinemia, and extrapyramidal side effects increased significantly as D(2) occupancy exceeded 65%, 72%, and 78%, respectively. CONCLUSIONS: The study confirms that D(2) occupancy is an important mediator of response and side effects in antipsychotic treatment. The data are consistent with a "target and trigger" hypothesis of antipsychotic action, i.e., that the D(2) receptor specificity of antipsychotics permits them to target discrete neurons and that their antagonist properties trigger within those neurons intracellular changes that ultimately beget antipsychotic response. While limited to haloperidol, the relationship between D(2) occupancy and side effects in this study helps explain many of the observed clinical differences between typical and atypical antipsychotics.

Adolescent↗
PubMed2000

Are animal studies of antipsychotics appropriately dosed? Lessons from the bedside to the bench.

Animal models are crucial for understanding the mechanism of action of antipsychotics. However, the dose of an antipsychotic in animal studies is often arbitrarily chosen, with haloperidol 1 mg/kg being a rather common standard. Recent clinical positron emission tomography (PET) studies in patients show all antipsychotics to block dopamine D2 receptors, and most are effective at doses that lead to 60% to 80% D2 occupancy. When occupancy exceeds 80%, the incidence of side effects rises sharply. To use this "bedside" information to inform the "bench," we measured D2 occupancy in rats using a method similar in principle to the [11C]-raclopride PET method in humans. We found that: 1) as in humans, haloperidol is effective in animal models of antipsychotic action when D2 occupancy > 70% and leads to effects in models of extrapyramidal side effects when D2 occupancy is > 80%; 2) very low doses, 0.06 mg/kg/sc, cause acute D2 occupancy of 75%; 3) and even doses that acutely saturate D2 receptors give little D2 occupancy after 24 hours due to the very short half-life of haloperidol in rats (2.5 hours versus 24 hours in humans). We conclude that most previous animal studies of antipsychotics have used doses giving rise to inappropriately high acute D2 occupancy and inappropriately low D2 occupancy between doses. We exemplify how this dosing confounder could lead to inappropriate conclusions. Data from the bedside translated to the bench--using D2 occupancy as a mediating variable--will lead to more valid animal models.

Animals↗
PubMed2000

Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport.

The stress-activated p38 mitogen-activated protein kinase (MAPK) was recently shown to be activated by insulin in muscle and adipose cells in culture. Here, we explore whether such stimulation is observed in rat skeletal muscle and whether muscle contraction can also affect the enzyme. Insulin injection (2 U over 3.5 min) resulted in increases in p38 MAPK phosphorylation measured in soleus (3.2-fold) and quadriceps (2.2-fold) muscles. Increased phosphorylation (3.5-fold) of an endogenous substrate of p38 MAPK, cAMP response element binder (CREB), was also observed. After in vivo insulin treatment, p38 MAPKalpha and p38 MAPKbeta isoforms were found to be activated (2.1- and 2.4-fold, respectively), using an in vitro kinase assay, in immunoprecipitates from quadriceps muscle extracts. In vitro insulin treatment (1 nmol/l over 4 min) and electrically-induced contraction of isolated extensor digitorum longus (EDL) muscle also doubled the kinase activity of p38 MAPKalpha and p38 MAPKbeta. The activity of both isoforms was inhibited in vitro by 10 micromol/l SB203580 in all muscles. To explore the possible participation of p38 MAPK in the stimulation of glucose uptake, EDL and soleus muscles were exposed to increasing doses of SB203580 before and during stimulation by insulin or contraction. SB203580 caused a significant reduction in the insulin- or contraction-stimulated 2-deoxyglucose uptake. Maximal inhibition (50-60%) occurred with 10 micromol/l SB203580. These results show that p38 MAPKalpha and -beta isoforms are activated by insulin and contraction in skeletal muscle. The data further suggest that activation of p38 MAPK may participate in the stimulation of glucose uptake by both stimuli in rat skeletal muscle.

Animals↗
PubMed2000

A medical hypothesis: phosphorus balance and prostate cancer.

Over the last three decades the mortality rate for prostatic carcinoma has steadily increased. Carcinoma of prostate (CaP), the most common malignancy in men, is also the second most common cause of cancer deaths in men. However, few epidemiologic studies have been done, and there are scant clues to the etiology/pathogenesis of CaP. As treatment failures for advanced carcinoma continue to frustrate clinicians, more emphasis has recently been focused on strategies to prevent invasive CaP. Prostatic hyperplasia is a universal phenomenon in aging men. Mechanism and signals causing this growth are not understood. Thus, prostatic diseases affect men over the age of 45 and increase in frequency with age so that by the eighth decade more than 90% of men have benign prostatic hyperplasia, of which some progress to CaP. Data from several studies support that higher levels of active metabolite of vitamin D, 1,25-(OH)2-D, reduce the risk of prostatic hyperplasia and CaP. Men with high serum levels of 1,25-(OH)2-D have a reduced risk of poorly differentiated and clinically advanced CaP. Receptor for vitamin D has been reported in both normal and cancer prostate cells. 1,25-(OH)2-D inhibits proliferation and induces differentiation of normal and neoplastic cells. Hypercalcemic activity of 1,25-(OH)2-D or its analogues, however, thwart their use for therapy in humans. 1,25-(OH)2-D also has an established role in phosphorus homeostasis. Low dietary intake of phosphorus leads to an increase in serum concentration of 1,25-(OH)2-D. In addition, dietary fructose reduces plasma phosphate levels by 30 to 50% for more than 3 hr due to a rapid shift of phosphate from extracellular to intracellular compartment. Fruit intake has been shown to be associated with reduced risk of CaP, particularly the advanced type. Put together, these observations support that dietary determinants of hypophosphatemia, leading to increased plasma levels of 1,25-(OH)2-D, could reduce the risk of aging men to develop prostatic diseases, both benign prostatic hyperplasia and CaP.

Calcitriol↗
PubMed2000

Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action.

RATIONALE AND OBJECTIVE: While the blockade of dopamine D2 receptors are necessary for antipsychotic action, antipsychotic agents differ nearly a thousand-fold in their affinity for the D2 receptor. This affinity is determined by the rate at which the antipsychotic agent binds to (kon) and the rate at which it dissociates from (koff) the D2 receptors. The objective of this study was to determine the relationship between kon, koff and the affinity (Ki) of antipsychotic agents for the D2 receptors, with particular reference to typical and atypical antipsychotic agents. DESIGN: The koff of several typical as well as atypical antipsychotic agents (nemonapride, spiperone, haloperidol, chlorpromazine, raclopride, olanzapine, sertindole, clozapine and quetiapine) was measured in vitro using the 3H-radiolabelled analogues of these drugs. The affinity of these drugs for the D2 receptor was determined by competition with 3H-raclopride in vitro. The kon was derived from values of affinity and ++koff. MAIN OUTCOME MEASURES: kon, koff, and the Ki of antipsychotic drugs. RESULTS: The range of affinity values was similar to that conventionally accepted (0.025-155 nmol/L). The koff values varied a thousand-fold from 0.002 to 3.013 min-1, with relatively little variation in kon. The rate at which antipsychotic agents come off the receptor (koff) accounted for 99% of the variation in their affinity for the D2 receptor; differences in kon did not account for differences in affinity. CONCLUSIONS: The differences in the affinity of antipsychotic agents are entirely determined by how fast they come off the D2 receptor. These differences in koff may lead to functionally different kinds of dopamine blockade. Drugs with a higher koff will be faster in blocking receptors, and once blocked, will provide more access to surges in dopamine transmission. Since atypical drugs show a lower affinity and a faster dissociation, a higher koff for the D2 receptor is proposed as a mechanism for "atypical" antipsychotic effect.

Animals↗
PubMed2000

Glyceryl trinitrate treatment of chronic fissure in ano: one year's experience with 0.5% GTN paste.

OBJECTIVE: Assessment of the efficacy of topical 0.5% glyceryl trinitrate (GTN) paste in the treatment of chronic fissures in ano. PATIENTS AND METHODS: Forty-five patients were treated with 0.5% GTN paste and reviewed at 3, 6 and 12 weeks to assess symptoms, side effects and fissure healing. RESULTS: At 6 weeks, 73% of patients had no fissures. In 27% of cases treatment was unsuccessful. At three month follow up there was no early recurrence. The prevalence of headaches was 84% with 11% headache related non-compliance. CONCLUSIONS: The use of 0.5% GTN induces rapid healing of chronic anal fissures with a 73% healing rate in this study. Successful treatment may come at the expense of a high incidence of headaches and a lower compliance than found in studies involving a lower concentration of GTN. A balance is required between fissure healing and headache intolerance.

Administration, Topical↗
PubMed1999

Is amoxapine an atypical antipsychotic? Positron-emission tomography investigation of its dopamine2 and serotonin2 occupancy.

BACKGROUND: All currently available atypical antipsychotics have, at clinically relevant doses: i) high serotonin (5-HT)2 occupancy; ii) greater 5-HT2 than dopamine (D)2 occupancy; and iii) a higher incidence of extrapyramidal side effects when their D2 occupancy exceeds 80%. A review of pharmacologic and behavioral data suggested that amoxapine should also conform to this profile; therefore, we undertook a positron-emission tomography (PET) study of its 5-HT2 and D2 occupancy. METHODS: Seven healthy volunteers received 50-250 mg/day of amoxapine for 5 days and then had [11C]-raclopride and [18F]-setoperone PET scans. RESULTS: 5-HT2 receptors showed near saturation at doses of 100 mg/day and above. The D2 receptor occupancies showed a dose-dependent increase, never exceeding 80%; at all doses 5-HT2 occupancy exceeded D2 occupancy. CONCLUSIONS: PET data show that amoxapine's profile is very similar to that of the established atypical antipsychotics. These data, together with amoxapine's in vitro pharmacologic profile, effectiveness in animal models, and efficacy in psychotic depression raise the possibility of amoxapine as an "atypical" antipsychotic agent in the treatment of schizophrenia.

Adult↗
PubMed1999

Relationship between central and peripheral serotonin 5-HT2A receptors: a positron emission tomography study in healthy individuals.

5-HT2A receptors on platelet membranes are often measured as indirect markers of the central 5-HT2A receptors. However, the 5-HT2A receptors on the platelets and those in the brain have never been assessed simultaneously in humans. The purpose of this study was to evaluate the relationship between platelet membrane and neocortical 5-HT2A receptors measured simultaneously in normal healthy volunteers. Twelve healthy volunteers had the 5-HT2A receptors on their platelet membranes assessed in vitro using [3H]lysergic acid diethylamide ([3H]LSD) and their central 5-HT2A receptors measured in vivo using [18F]setoperone and positron emission tomography (PET) imaging. We find no significant correlation between the binding potential (Bmax/Kd) of 5-HT2A receptors on platelets and in brain in the same individual (F1,10 = 0.7, P = 0.42). The study was limited by a small sample and the fact the two different ligands were used (i.e. LSD for platelets and setoperone for brain); nonetheless, the findings suggest that changes in platelet 5-HT2A receptors may not indicate similar changes in central 5-HT2A receptors.

Adult↗
PubMed1999

Strategies to expand the donor pool for pancreas transplantation.

BACKGROUND: Our organ procurement organization has been forced to liberalize the donor criteria in order to expand the donor pool for pancreas transplantation. In this report, we describe our experience using whole organ pancreatic grafts from "marginal" donors, which include grafts obtained from donors over 45 years of age and from donors who were identified to be hemodynamically unstable at the time of organ retrieval. METHODS: A prospective study was performed between July 1994 and March 1998, during which time 137 pancreas transplants were performed at our center using organs procured by our own surgeons (organs sent by other teams were excluded). The rapid en bloc technique was used exclusively. The use of pancreatic grafts from marginal donors was analyzed for short-term and overall graft survival, and for delayed graft function and complications. RESULTS: Overall pancreas graft survival for our series was 83%, with a mean follow-up of 23 months. There were 22 pancreas grafts from donors over 45 years of age, 13 of whom were greater than 50 years of age. The actual graft survival rate of the over-45 donor group was 86%. Fifty-one grafts were removed from hemodynamically unstable donors on high-dose vasopressors. The actual graft survival in this group was 86%. There was no significant difference found in graft survival between recipients of pancreatic grafts from marginal and nonmarginal donors. Delayed graft function was exhibited by more recipients of grafts from donors on high-dose vasopressors (P<0.05), but this had no effect on long-term graft survival and endocrine function. Recipients of marginal donor grafts did not have higher rates of complication compared to recipients of nonmarginal grafts. CONCLUSIONS: Based on our results, we currently employ a graft selection strategy not limited by donor age or hemodynamic stability. Our selection of pancreas organs for transplantation is based on careful inspection of the pancreas and determination of the adequacy of the ex vivo flush. Our results suggest that the current pancreas donor pool may be expanded substantially.

Adolescent↗
PubMed1999

Prostaglandin E1 influences pulsatile preservation characteristics and early graft function in expanded criteria donor kidneys.

INTRODUCTION: Unlike simple cold storage, machine preservation allows dynamic assessment and manipulation of the donor organ prior to transplantation. We prospectively compared the effects of five pharmacological agents added to the perfusate during machine preservation of expanded criteria donor (ECD) kidneys in order to (1) describe their influence on perfusion parameters and (2) determine their influence on early graft outcome. METHODS: Two hundred seventy-five consecutive ECD kidneys were preserved in our laboratory between 1/1/94 and 12/31/97 by either machine perfusion (MP) or cold storage (CS). ECD kidneys were defined as those requiring pretransplant biopsy. ECD kidneys were divided by method of preservation and MP kidneys were randomized to receive prostaglandin E1 (MP+PGE1), trifluoperazine (TFP), verapamil (VER), papaverine (PAP), mannitol (MAN), or no intervention during the period of machine perfusion. CS kidneys were randomized to receive PGE1 (CS+PGE1), TFP, VER, PAP, or no intervention. All MP kidneys were preserved by continuous hypothermic pulsatile perfusion using Belzer II solution and perfusion parameters were measured every hour during pulsatile perfusion. All CS kidneys were stored in 1.0 L of University of Wisconsin (UW) solution. RESULTS: The addition of PGE1 to machine perfusate increased renal flow and decreased renal resistance. Moreover, the MP+PGE1-treated group was associated with improved early graft function compared to all other groups. The addition of VER, TFP, PAP, or MAN influenced neither the perfusion characteristics nor the incidence of early graft function in MP kidneys. Similarly, the addition of VER, TFP, or PAP did not influence early graft function in the CS kidneys. The CS+PGE1 group exhibited a significantly lower incidence of early graft function than did the MP+PGE1 group. CONCLUSIONS: PGE1 treatment during machine preservation improves hydrostatic perfusion parameters and reduces the incidence of delayed graft function in ECD kidneys. Moreover, the addition of PGE1, TFP, VER, or PAP to UW does not influence early graft function in the CS kidney.

Alprostadil↗
PubMed1999

Calcium ion concentration of machine perfusate predicts early graft function in expanded criteria donor kidneys.

Pulsatile preservation offers the advantage of pretransplant assessment of donor kidneys. Selected electrolyte concentrations of machine perfusate were measured over time in order to: (1) describe electrolyte changes in perfusate during the pulsatile preservation of expanded-criteria donor (ECD) kidneys, and (2) to assess the prognostic significance of these characteristics to early graft function. One hundred and fifty ECD kidneys were preserved in our laboratory between 1 January 1995 and 11 January 1997. ECD kidneys were defined as those requiring pretransplant biopsy. Kidneys were grouped by the presence or absence of delayed graft function (DGF), and perfusion parameters were measured every hour during pulsatile perfusion. All kidneys were preserved by continuous hypothermic pulsatile perfusion using Belzer II solution. Renal flow is decreased and renal resistance is increased in the presence of DGF in machine-preserved ECD kidneys. In addition, ionized calcium concentration of the machine perfusate is significantly elevated in the DGF group compared with the No DGF group (0.091 vs 0.054, P = 0.0016). The incidence of DGF is significantly lower in the ECD kidney. Among the pretransplant variables of donor characteristics, perfusion parameters and histology, perfusion parameters are highly predictive of early graft function. In addition, we found that ionized calcium concentration in the perfusate is significantly elevated in kidneys exhibiting DGF, which may have implications for assessing the suitability of donor kidneys for transplantation.

Calcium↗
PubMed1999

The effects of single dose nefazodone and paroxetine upon 5-HT2A binding potential in humans using [18F]-setoperone PET.

RATIONALE: Alterations in 5-HT2A receptor binding are implicated in suicidality and depression. 5-HT2A receptors may also be involved in the therapeutic effects of antidepressants. OBJECTIVES: The purpose of this study was to assess the effect of paroxetine and nefazodone on 5-HT2A receptors after a single dose. METHODS: Seven subjects received a single dose of nefazodone 200 mg and five subjects received a single dose of paroxetine 20 mg. Before and after the dose, 5-HT2A binding potentials (Bmax/Kd) were determined in each subject using [18F]-setoperone PET. RESULTS: Nefazodone induced a significant change in 5-HT2A binding potential (-39+/-17%,, P = 0.003) while paroxetine showed no significant alteration of 5-HT2A binding potential (+3+/-13%, P = 0.73). CONCLUSIONS: The change in 5-HT2A binding potential seen with nefazodone represents blockade of 5-HT2A receptors by the drug. We do not find evidence for acute downregulation of 5-HT2A receptors with paroxetine within 9 h.

Adult↗
PubMed1999

The clinical pharmacology of brompheniramine in children.

BACKGROUND: Brompheniramine has been widely used in the treatment of allergic rhinitis and other disorders during the past 4 decades. There are no published studies of its clinical pharmacology in children. OBJECTIVES: This study was performed to test the hypothesis that brompheniramine would have a prompt onset of action and a 24-hour duration of action in children. METHODS: Before brompheniramine 4 mg was ingested, and at intervals from 0.5 to 30 hours thereafter, blood samples were obtained for quantitation of plasma brompheniramine concentrations by means of HPLC. Concurrently, epicutaneous tests with histamine phosphate were performed; wheals and flares were traced at 10 minutes, and the areas were measured by using a computerized digitizing system. RESULTS: In 14 children, mean age 9.5 +/- 0.4 years (SEM), the peak brompheniramine concentration was 7.7 +/- 0.7 ng/mL, and the time at which peak concentrations occurred was 3.2 +/- 0.3 hours. The terminal elimination half-life was 12.4 +/- 1.1 hours, and the oral clearance was 20.2 +/- 2.1 mL/min/kg. Compared with predose areas, the wheals and flares produced by histamine phosphate 1 mg/mL were significantly decreased from 0.5 to 30 hours and from 1 to 30 hours, respectively (P <.05), with mean maximum inhibition at 12 (52% +/- 9%) and 6 hours (72% +/- 10%), respectively. CONCLUSIONS: In children a single dose of brompheniramine produces prompt, long-lasting peripheral H1 -blockade. Revised dosage regimens may be needed in this population.

Adolescent↗
PubMed1999

Mechanism of adipose tissue iNOS induction in endotoxemia.

The aim of the present study was to investigate the mechanism of adipose tissue inducible nitric oxide synthase (iNOS) induction in endotoxemia. Systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) to rats for </=8 h markedly increased iNOS mRNA and protein levels in white and brown adipose tissues. This effect was comparable to or greater than the induction of iNOS in liver, kidney, or skeletal muscle. iNOS activity was also found to be greatly enhanced in both white and brown adipose tissues of LPS-treated rats (an approximately 12- to 20-fold increase). Treatment of cultured 3T3-L1 adipocytes with LPS, tumor necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN-gamma) alone failed to induce iNOS activity. However, when used in combination, TNF-alpha, IFN-gamma, and LPS markedly and synergistically increased iNOS activity in these cells. In conclusion, these results suggest that adipose tissue is a major site of iNOS expression in endotoxemia. Our data further indicate that iNOS induction can be reproduced in vitro in cultured adipocytes and that a concerted action of cytokines and endotoxin is needed for maximal activation of the enzyme.

3T3 Cells↗
PubMed1999

Serotonin 5-HT2 receptors in schizophrenia: a PET study using [18F]setoperone in neuroleptic-naive patients and normal subjects.

OBJECTIVE: Several postmortem studies have reported a decreased density of serotonin 5-HT2 receptors in the prefrontal cortex in schizophrenia. The purpose of this study was to investigate this in patients with schizophrenia by means of [18F]setoperone and positron emission tomography (PET) imaging. METHOD: Thirteen neuroleptic-free patients with schizophrenia, 10 of whom were also neuroleptic-naive, were compared with a group of 26 normal subjects in the same age range. The density of 5-HT2 receptors was assessed with the use of [18F]setoperone and PET in standardized cortical regions of interest. RESULTS: Increasing age was associated with similar declines in 5-HT2 receptors in all cortical regions in the patient group and in the normal comparison group. After control for the effect of age, there was no statistically significant difference between the patients and the comparison subjects in 5-HT2 receptor density in any of the cortical regions. CONCLUSIONS: This study failed to find the decrease in 5-HT2 receptors reported in postmortem studies of schizophrenia. The study had the power to detect a decrease of 25% or more in 5-HT2 receptors, which was anticipated on the basis of the previous postmortem studies. Thus, a primary serotonergic abnormality in schizophrenia, if one exists, is either small or unlikely to be at the level of the 5-HT2 receptors. This finding does not rule out a therapeutic role for 5-HT2 antagonists in schizophrenia, but it does suggest that the therapeutic contribution is likely to be an indirect one.

Antipsychotic Agents↗