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Chronic fatigue syndrome is characterised by severe physical and mental fatigue associated with disability, which by definition markedly affects people's lives. At one end of the spectrum, newspaper headlines imply [...]

Antipsychotic-induced weight gain (AIWG) is a common side effect with a high genetic contribution. We reanalyzed genome-wide association study (GWAS) data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) selecting a refined subset of patients most suitable for AIWG studies. The final GWAS was conducted in N=189 individuals. The top polymorphisms were analyzed in a second cohort of N=86 patients. None of the single-nucleotide polymorphisms was significant at the genome-wide threshold of 5x10-8. We observed interesting trends for rs9346455 (P=6.49x10-6) upstream of OGFRL1, the intergenic variants rs7336345 (P=1.31 × 10-5) and rs1012650 (P=1.47 × 10-5), and rs1059778 (P=1.49x10-5) in IBA57. In the second cohort, rs9346455 showed significant association with AIWG (P=0.005). The combined meta-analysis P-value for rs9346455 was 1.09 × 10-7. Our reanalysis of the CATIE GWAS data revealed interesting new variants associated with AIWG. As the functional relevance of these polymorphisms is yet to be determined, further studies are needed.

Aims.To assess the extent to which being a victim of intimate partner violence (IPV) is associated with psychiatric disorders in men and women.Methods.A stratified multistage random sample was used in the third English psychiatric morbidity survey. Psychiatric disorders were measured by the Clinical Interview Schedule (Revised) and screening questionnaires. IPV was measured using British Crime Survey questions.Results.18.7% (95% CI 17.1–20.4; n= 595 of 3197) of men had experienced some form of IPV compared with 27.8% of women (95% CI 26.2–29.4; n= 1227 of 4206; p< 0.001). IPV was associated with all disorders measured (except eating disorders in men). Physical IPV was significantly linked to psychosis and with substance and alcohol disorders in men and women, but significant associations with common mental disorders (CMDs), post-traumatic stress disorder (PTSD) and eating disorders were restricted to women. Emotional IPV was associated with CMDs in men and women.Conclusions.The high prevalence of experiences of partner violence, and strength of the association with every disorder assessed, suggests enquiry about partner violence is important in identifying a potential risk and maintenance factor for psychiatric disorders, and to ascertain safety, particularly in women as they are at greatest risk of being victims of violence.

The concept that the efficacy of all antipsychotic drugs (APDs) can be explained by their action on dopamine (DA) D2 receptors is most challenged by drugs such as clozapine which target serotonin (5-HT)2A receptors as an essential component of their efficacy and tolerability. The 5-HT2A receptor, along with 5-HT1A, 5-HT 2C, 5-HT 6 or 5-HT 7 receptors, all of which are components of the mechanism of action of clozapine, represent important targets for treating multiple aspects of schizophrenia, especially psychosis and cognitive impairment. The class of atypical antipsychotic drugs (APDs), of which clozapine is the prototype, share in common more effective 5-HT 2A receptor inverse agonism and weaker interference with D2 receptor stimulation, either through D2 receptor blockade or partial D2 receptor agonism. This has led to development of a selective 5-HT2A antagonist, ACP-103 (pimavanserin), which has been found to be effective as monotherapy in L-DOPA psychosis and has promise as an add-on agent for sub-effective doses of atypical APDs. We review here the extensive preclinical evidence to support the importance of 5-HT2A receptor inverse agonism to the action of clozapine and related atypical APDs, and evidence supporting the potential of selective 5-HT2A, 5-HT 6 , and 5-HT 7, antagonists, 5-HT1A partial agonists and 5-HT2C agonists for development of drugs which ameliorate psychosis or cognitive impairment.

The role of 5-hydroxytryptamine (serotonin) (5-HT)(7) receptor antagonism in the actions of atypical antipsychotic drugs (APDs), e.g., amisulpride, clozapine, and lurasidone, if any, is uncertain. We examined the ability of 5-HT(7) receptor antagonism alone and as a component of amisulpride and lurasidone to reverse deficits in rat novel object recognition (NOR) produced by subchronic treatment with the N-methyl-D-aspartate receptor antagonist phencyclidine (PCP), and we examined the ability of supplemental 5-HT(7) antagonism to augment the inability of sulpiride, haloperidol, and (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY379268), a metabotropic glutamate receptor (mGluR) 2/3 agonist, which lack 5-HT(7) antagonism, to reverse the NOR deficit. The 5-HT(7) receptor antagonist, (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine (SB269970) (0.1-1 mg/kg) dose-dependently reversed PCP-induced NOR deficits. In addition, the ability of lurasidone (0.1 mg/kg) and amisulpride (3 mg/kg) to reverse this deficit was blocked by cotreatment with the 5-HT(7) receptor agonist (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin (AS19) (5-10 mg/kg), which did not affect NOR in naive rats. Sulpiride, a less potent 5-HT(7) antagonist than amisulpride, did not itself improve the PCP-induced NOR deficit. However, a subeffective dose of SB269970 (0.1 mg/kg) in combination with subeffective doses of lurasidone (0.03 mg/kg), amisulpride (1 mg/kg), or sulpiride (20 mg/kg), also reversed the PCP-induced NOR deficit. Pimavanserin, a 5-HT(2A) inverse agonist, LY379268, and haloperidol did not potentiate the ability of subeffective SB269970 to improve the NOR deficit. Furthermore, the mGluR2/3 antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid (LY341495), which blocks the effect of clozapine to reverse the NOR deficit, did not block the SB269970-induced amelioration of the NOR deficit. These results suggest 5-HT(7) antagonism may contribute to the efficacy of some atypical APDs in the treatment of cognitive impairment in schizophrenia and may itself have some benefit in this regard.

Subchronic administration of the N-methyl-d-aspartate receptor antagonist, phencyclidine (PCP), in rodents has been shown to produce impairment in novel object recognition (NOR), a model of visual learning and memory. We tested the hypothesis that the selective 5-HT(2A) inverse agonists, pimavanserin and (R)-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl]-4-piperidinemethanol (M100907), would potentiate subeffective doses of atypical antipsychotic drugs (APDs) to reverse the NOR deficits. Female rats received vehicle or PCP (2 mg/kg b.i.d.) for 7 days, followed by a 7-day washout. Pimavanserin (3 mg/kg) or M100907 (1 mg/kg) alone, or four atypicial APDs, risperidone (0.05-0.1 mg/kg), melperone (1-3 mg/kg), olanzapine (1-2 mg/kg), or N-desmethylclozapine (1-2 mg/kg), and the typical APD, haloperidol (0.05-0.1 mg/kg), were administered alone, or in combination with pimavanserin or M100907, before NOR testing. The exploration times of objects during 3-min acquisition and retention trials, separated by a 1-min interval, were compared by analysis of variance. Vehicle-, but not PCP-treated, animals, explored the novel object significantly more than the familiar in the retention trial (p < 0.05-0.01). Pretreatment with the higher doses of the atypical APDs, but not pimavanserin, M100907, or haloperidol alone, reversed the effects of PCP. The effect of risperidone was blocked by haloperidol pretreatment. Coadministration of pimavanserin or M100907, with ineffective doses of the atypical APDs, but not haloperidol, also reversed the PCP-induced deficit in NOR. These results support the importance of 5-hydroxytryptamine(2A) receptor blockade relative to D(2) receptor blockade in the ability of atypicals to ameliorate the effect of subchronic PCP, a putative measure of cognitive dysfunction in schizophrenia.

Observational studies point to a positive association between fish consumption and both birth weight and prolonged gestation. Prolonged gestation has been associated with marine n-3 fatty acids, in particular, eicosapentaenoic acid and docosahexaenoic acid, in several—but not all—randomized controlled trials. The present study examined the relationship between fetal growth and fish consumption during pregnancy in 44,824 women from the Danish National Birth Cohort, enrolled during the years 1996–2002. The cohort included about 30% of all deliveries taking place in Denmark during this period. Consumption of total, fatty, and lean fish was estimated by a food frequency questionnaire in mid-pregnancy.

Atypical antipsychotic drugs, which are distinguished from typical antipsychotic drugs by a lower incidence of extra-pyramidal side effects and less propensity to elevate serum prolactin levels (e.g., clozapine, olanzapine, risperidone, quetiapine, ziprasidone), have become the most widely used treatments for schizophrenia, although their precise mechanism of action remains controversial. It has been suggested that this group of atypical antipsychotic drugs is characterized by preferentially high affinities for 5-hydroxytryptamine (5-HT)2A serotonin receptors and relatively low affinities for D2-dopamine receptors. It has recently been proposed that these atypical antipsychotic drugs may also be distinguished from typical antipsychotic drugs (e.g., haloperidol, fluphenazine, chlorpromazine, and so on) by inverse agonist actions at the 5-HT2C-INI RNA edited isoform of the human 5-HT2C receptor transiently expressed in COS-7 cells. We have examined the relationship among 5-HT2C inverse agonist potency, efficacy, and atypical antipsychotic drug status in HEK-293 cells of a large number of typical and atypical antipsychotic drugs using human embryonic kidney (HEK)-293 cells stably transfected with the h5-HT2C-INI receptor. Inverse agonist actions at h5-HT2C-INI receptors were measured for both typical and atypical antipsychotic drugs. Thus, some typical antipsychotic drugs (chlorpromazine, mesoridazine, fluphenazine, and loxapine) were efficient inverse agonists, whereas several clinically effective atypical antipsychotic drugs (remoxapride, quetiapine, sulpiride, melperone, amperozide) were not. Additionally, several drugs without significant antipsychotic actions (M100907, ketanserin, mianserin, ritanserin, and amitriptyline) were potent inverse agonists at the 5-HT2C-INI isoform expressed in HEK-293 cells. Taken together, these results demonstrate that both typical and atypical antipsychotic drugs may exhibit inverse agonist effects at the 5-HT2C-INI isoform of the human 5-HT2C receptor and that no relationship exists between inverse agonist actions and atypicality.

The serotonin (5-HT)(2A/2C) receptor antagonist ritanserin has been reported to potentiate the dopamine (DA) D(2/3) receptor antagonist raclopride-induced DA release in medial prefrontal cortex (mPFC) and nucleus accumbens (NAC) but not striatum (STR). Because of reciprocal interactions between 5-HT(2A) and 5-HT(1A) receptors, we tested the hypothesis that 5-HT(1A) receptor agonism also potentiates D(2/3) receptor antagonist-induced DA release using a combination of the 5-HT(1A) receptor agonist R(+)-8-hydroxy-2-(di-n-propylamino)-tetralin [R(+)-8-OH-DPAT] and the D(2/3) receptor antagonist S(-)-sulpiride (SUL). R(+)-8-OH-DPAT (0.05 mg/kg s.c.) potentiated low but not high dose SUL (1, 3 but not 10 or 25 mg/kg s.c.)-induced DA release in NAC, but had no effect in STR at all doses tested (1, 3, 10, and 25 mg/kg s.c.). However, R(+)-8-OH-DPAT (0.05 mg/kg s.c.) alone had no effect on basal, potentiated SUL (10 and 25 mg/kg s.c.)-induced DA release in mPFC; the effect of low dose SUL (1 and 3 mg/kg s.c.) was not tested because it alone had no effect on DA release. This potentiation was abolished by pretreatment with the 5-HT(1A) receptor antagonist WAY100635 (0.05 mg/kg s.c.), which alone had no effect on DA release. These results suggest that 5-HT(1A) receptor agonism facilitates DA release in mPFC and NAC but not STR in combination with D(2) receptor antagonism.

The present study was designed to compare the effects of typical and atypical antipsychotic drugs on extracellular dopamine (DA) levels in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), using in vivo microdialysis with dual probe implantation in awake, freely moving rats. Amperozide (2 and 10 mg/kg), clozapine (5 and 20 mg/kg), and olanzapine (10 mg/kg), all of which are atypical antipsychotics, produced greater increases in extracellular DA levels in the mPFC than in the NAC. Olanzapine (1 mg/kg), risperidone (0.1 and 1 mg/kg), also an atypical antipsychotic, and S-(-)-sulpiride (25 mg/kg), a typical antipsychotic, produced comparable increases in extracellular DA levels in the mPFC and the NAC. S-(-)-sulpiride (10 mg/kg) and haloperidol (0.1 and 1 mg/kg), another typical antipsychotic, significantly increased extracellular DA levels in the NAC but not in the mPFC. The effects of the six antipsychotic drugs to increase extracellular DA levels in the mPFC relative to those in the NAC was positively correlated with the difference between their pKi values for serotonin (5-hydroxytryptamine, 5-HT2A) and DA-D2 receptors and was inversely correlated to their pKi values for D2 or D3 receptors, but was not for 5-HT2A receptors alone. These results are consistent with the hypothesis that the ability of antipsychotic drugs to produce a greater increase in prefrontal compared with NAC extracellular DA levels may be related, in part, to weak D2 and D3 receptor affinity relative to 5-HT2A receptor antagonism.

The purpose of the present investigation was to study the nature and development of the scope of industrial psychology as indicated in the contributions to the Annual Reviewfrom the time of its inception in 1950 until 1978. All the contributions in the 1950's were called Industrial Psychology. From 1961 on, Industrial Psychology was never again used as a main caption. In the 1970's there were more contributions than in previous decades: new captions, new themes, and new topics. There were three contributions, for example, on Personnel Attitudes and Motivation, two on Organizational Development; there were also contributions on Personnel and Human Resources, and for the first time contributions on Training and Development and Career Planning as well as continuing Consumer and Engineering Psychology which first appeared in the 1960's. There were substantial decreases in the use of the two major reference sources. Instead there were substantial gains in such sources as the Journal of Personality and Social Psychology, Organizational Behavior and Human Performance, the Training Development Journal, and the Journal of Applied Behavioral Science. In the 1970's there is also a publication explosion. Not only has the field expanded, but it is still expanding and growing away from what in the 1950's was industrial to organizational behavior and development. The nature and extent of the changes are considered in all dimensions of organizational behavior contributions. Topics still not systematically considered are industrial-labor management relations and power and leadership.

The authors examined the affinities of 36 typical and atypical antipsychotic agents for the cloned rat 5-hydroxytryptamine-6 (5-HT6) and rat 5-hydroxytryptamine-7 (5-HT7) receptors in transiently expressed COS-7 cells (5-HT7) or stably transfected HEK-293 cells (5-HT6 receptors). Clozapine and several related atypical antipsychotic agents (rilapine, olanzepine, tiospirone, fluperlapine, clorotepine and zotepine) had high affinities for the newly discovered 5-HT6 receptor (Kis < 20 nM). The 5-HT7 receptor bound clozapine, rilapine, fluperlapine, clorotepine, zotepine and risperidone but not tiospirone and olanzepine, with affinities less than 15 nM. In addition, several typical antipsychotic agents (chloroprothixene, chlorpromazine, clothiapine and fluphenazine) had high affinities for both the 5-HT6 and 5-HT7 receptors. Pimozide, a diphenylbutylpiperidine, had the highest affinity of all the typical antipsychotic agents tested for the 5-HT7 receptor (Ki = 0.5 nM). Three putative atypical antipsychotic agents melperone, amperozide and MDL 100907 did not bind with high affinities to either the 5-HT6 or 5-HT7 receptors (Kis > 50 nM). Several dopamine-selective antipsychotic agents (raclopride, rimcazole and penfluridol) had essentially no affinity for either the 5-HT6 or 5-HT7 receptors (Ki values > 5000 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

The extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum and the nucleus accumbens were measured in awake, freely-moving rats. Clozapine (20 mg/kg, i.p.) increased extracellular DA and HVA in both regions but increased DOPAC only in the striatum. Scopolamine (1 mg/kg), although it had no effect by itself in the striatum or nucleus accumbens, inhibited the ability of clozapine to increase extracellular DA, DOPAC and HVA concentrations in the striatum. The clozapine-induced increase in DA in the frontal cortex was not blocked by scopolamine. Haloperidol (1 mg/kg, i.p.) and thioridazine (10 mg/kg, i.p.) also increased extracellular DA, DOPAC and HVA in the striatum, but scopolamine pretreatment did not inhibit these increases. The results suggest that clozapine differs from haloperidol and thioridazine in that the effect of clozapine, but not that of the two neuroleptic drugs, to increase DA release in the striatum acutely depends on muscarinic receptor stimulation. These results suggest that clozapine, despite its strong muscarinic antagonist properties, does not produce full blockade of muscarinic receptors in vivo in the striatum. The interaction of clozapine with the cholinergic system in the striatum could be relevant to its lack of ability to produce extrapyramidal symptoms or tardive dyskinesia.

The racemic mixture of 3,4-methylenedioxymethamphetamine (MDMA), which has been reported to produce selective destruction of serotonergic neurons in the central nervous system, was studied to determine its neuroendocrine and temperature effects and mechanism of action. MDMA elevated serum concentrations of corticosterone in doses ranging from 3 to 20 mg/kg administered i.p. Serum corticosterone concentrations were elevated 30 min after the administration of MDMA (10 mg/kg i.p.) and remained elevated 4 hr later. Serum prolactin (PRL) concentrations were elevated by administration of MDMA in doses ranging from 1 to 20 mg/kg i.p., and were maximal 60 min after the injection of 10 mg/kg i.p., declining rapidly over the next 4 hr. MDMA also significantly elevated the body temperature of rats maintained at ambient (23 degrees C) temperature. MDMA-induced corticosterone secretion and hyperthermia were blocked by the 5-hydroxytryptamine (5-HT) antagonists, ketanserin and mianserin, which have a high affinity for 5-HT2 binding sites. Conversely, neither (-)-pindolol, a beta antagonist that also blocks 5-HT1A-mediated responses, nor the nonspecific 5-HT antagonists, cyproheptadine and metergoline, had an effect on MDMA-induced corticosterone secretion. None of the 5-HT antagonists blocked MDMA-induced PRL secretion. Pretreatment with fluoxetine (10 mg/kg i.p.) 16 hr before MDMA administration significantly blunted the effect of MDMA on corticosterone but not PRL secretion. Pretreatment with p-chlorophenylalanine (150 mg/kg i.p.) for 3 days depleted cortical and hypothalamic 5-HT and 5-hydroxyindoleacetic acid by approximately 80% and significantly attenuated MDMA-induced corticosterone and PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary Pindolol has been shown to be a partial agonist at 5-HT1a receptors in preclinical studies. It has also been reported to inhibit the effects of other 5-HT1a partial agonists such as ipsapirone and buspirone on hormone secretion and body temperature in man, indicating its antagonist action at 5-HT1a receptors in man. To determine if pindolol has 5-HT1a agonist as well as antagonist effects in man, pindolol, 30 mg, p.o. and placebo, were given single blind in random order to 23 normal men with indwelling venous catheters and its effects on hormone secretion and body temperature noted. Pindolol significantly increased basal plasma cortisol concentrations, whereas it decreased plasma prolactin (PRL) concentrations and body temperature. The increase in plasma cortisol due to pindolol suggests a 5-HT1a agonist action and is consistent with a 5-HT1a partial agonist mechanism in man whereas the PRL effects are consistent with an antagonist action at 5-HT1a receptors. The effects of pindolol on plasma cortisol concentration and body temperature were significantly negatively correlated. Furthermore, these results indicate significant differences in the 5-HT1a-dependent regulation of PRL and the hypothalamo-pituitary-adrenal (HPA) axis and body temperature, and suggest that human basal PRL secretion is tonically stimulated by a 5-HT1a mechanism whereas the HPA axis and body temperature are not. Since rodent studies suggest differences in 5-HT1a receptor sensitivity between males and females, the results reported here need to be replicated in females. These differences in the effect of pindolol are discussed in terms of receptor reserve theory.

Recently, some investigators have established a seasonal pattern in normal human psychology, physiology and behaviour, and in the incidence of psychiatric psychopathology. In an attempt to elucidate the chronopsy and meteotropism in the latter, we have examined the chronograms of, and the biometeorological relationships to bed occupancy of the psychiatric ward of the Antwerp University Hospital during three consecutive calendar years (1987–1989). Weather data for the vicinity were provided by a local meteorological station and comprise mean atmospheric pressure, air temperature, relative humidity, wind speed and minutes of sunlight and precipitation/day. The number of psychiatric beds occupied during the study period exhibited a significant seasonal variation. Peaks in bed occupancy were observed in March and November, with lows in August. An important part of the variability in the number of beds occupied could be explained by the composite effects of weather variables of the preceding weeks. Our results suggest that short-term fluctuations in atmospheric activity may dictate some of the periodicities in psychiatric psychopathology.

The search for an improved clozapine-like compound has resulted in the selection of a new molecule: JL13 (5-(4-methylpiperazin-1-yl)-8-ch loro-pyrido[2,3-b][1,5]benzoxazepine fumarate). Like clozapine, JL13 did not antagonize apomorphine-induced stereotypy and did not produce catalepsy but antagonized apomorphine-induced climbing in rodents (ID50=3.9 mg kg-1s.c.). It was inactive againstd-amphetamine-induced stereotypy but antagonizedd-amphetamine-induced hyperactivity in the mouse (ID50=4.4 mg kg-1i.p.). JL13, like clozapine, was able to antagonize (∓)-DOI-induced head-twitches in the mouse (ID50=2.0 mg kg-1i.p.). In the open-field test in the rat and forced swimming test in the mouse a high similarity was noted between the two drugs in the same range of doses. In a complex temporal regulation schedule in the dog, JL13 showed a high resemblance with clozapine without inducing sialorrhea, palpebral ptosis or any significant motor side effects. In rats trained to discriminate clozapine, JL13 (10 mg kg-1i.p.) induced a high level of generalization (70%) to clozapine. In a drug discrimination procedure in the squirrel monkey, JL13 (3–10 mg kg-1i.m.) produced a full substitution of clozapine. On the basis of these preclinical data, it is thus predicted that JL13 would be a promising atypical antipsychotic drug.

Mean plasma prolactin levels obtained from male rats following anesthesia with ketamine, decapitation or via indwelling venous catheters were not significantly different although a larger variance was found in the samples obtained via catheters. Ketamine, at anesthetic doses, did not affect the increases in prolactin produced by reserpine or α-methylparatyrosine. Ketamine, at various doses, did not potentiate the effect of subthreshold doses of 5-hydroxytryptophan on prolactin secretion. Thus, ketamine would appear to be a suitable anesthetic for use in studies of prolactin secretion in male rats. Further studies in female rats are required.Supported in part by grant nos. USPHS MH 30938, 29206, and RCSA MH 47808 to HYM.

The objective of this study was to report the effect of the slow withdrawal of clozapine from 19 patients withneuroleptic-responsive schizophrenia at the end of a 2-year clinical trial of clozapine and to compare this with the results of naturalistic discontinuation of clozapine treatment in 64neuroleptic-resistant schizophrenic patients. Nineteen neuroleptic-responsive schizophrenic patients who received clozapine were withdrawn from clozapine by tapering it over 3-week period with and without the addition of a typical neuroleptic. Fifteen of the 19 neuroleptic-responsive patients experienced the return of psychotic symptoms during or after the clozapine taper, which were most severe in the ten patients in whom the withdrawal of clozapine was carried out without prior addition of neuroleptic treatment. Addition of a neuroleptic prior to clozapine withdrawal prevented the emergence of positive symptoms during clozapine withdrawal in each of eight patients. Nevertheless, psychotic symptoms emerged, usually within a week after discontinuing clozapine, in six of the eight patients. Neuroleptic treatment, with or without an anticholingergic drug, was much less effective in treating positive symptoms in these patients immediately after the clozapine withdrawal than it had been 2 years previously. Cyproheptadine, a non-selective serotonin receptor antagonist, augmented the antipsychotic effect of neuroleptics in each of four patients who relapsed following withdrawal from clozapine and relieved extrapyramidal symptoms in a fifth patient. The frequency of relapse following withdrawal of clozapine in 64 neuroleptic-resistant patients was significantly lower (25/64, 39.1%) than in the neuroleptic-responsive patients.

Abstract: The affinities of 13 atypical and 12 typical antipsychotic drugs for the cloned rat D4 dopamine receptor and the D4/D2 ratios were examined. Of the atypical antipsychotic drugs tested, only clozapine, risperidone, olanzapine, zotepine and tiospirone had affinities less than 20 nM. In fact, many atypical antipsychotic drugs had relatively low affinities for the cloned rat D4 receptor, with Ki values greater than 100 nM (Seroquel, fluperlapine, tenilapine, FG5803 and melperone). Additionally, several typical antipsychotic drugs had high affinities for the cloned rat D4 receptor, with Kis less than 20 nM (loxapine, chlorpromazine, fluphenazine, mesoridazine, thioridazine and trifluoroperazine). The ratios of D2/D4 affinities did not differentiate between these two types of antipsychotic drugs. Thus, D4 dopamine receptor affinity, used as a single measure, does not distinguish between the group of typical and atypical antipsychotic drugs analyzed.

Bromocriptine (0.5–6.0 mg/day) was administered to seven unmedicated chronic schizophrenic and two schizoaffective patients. Transient slight improvement was noted in four patients and marked improvement in one other. Clinical improvement was associated with nausea and drowsiness. These doses of bromocriptine stimulated serum growth hormone and inhibited serum prolactin levels in some subjects. These results suggest that bromocriptine may stimulate dopamine autoreceptors and, through this mechanism, attenuate symptoms in a small proportion of psychiatric patients.

Buspirone, an effective antianxiety compound, produced a dose-dependent, relatively prolonged increase in rat plasma prolactin (PRL) levels. The stimulation of PRL secretion by buspirone was additive with the effect of a-methyl-p-tyrosine (AMPT) or ?-butyrolactone. In vitro, buspirone itself had no effect on the release of PRL from rat pituitary glands but it blocked the inhibitory action of dopamine (DA). Buspirone also increased DA turnover in the striatum as measured by the AMPT-induced depletion of striatal DA levels. These results demonstrate the ability of buspirone to block pituitary and striatal DA receptors.

Although d- and l-amphetamine had no effect on plasma prolactin levels in untreated male rats, both d- and l-amphetamine reversed the increase in plasma prolactin levels produced by reserpine and 5-hydroxytryptophan (5-HTP). Only d-amphetamine significantly reversed the effect of alpha-methylparatyrosine (AMPT) on plasma prolactin levels. This reversal is probably due to a direct or indirect dopamine agonist effect of amphetamine, rather than to an effect on norepinephrine. This conclusion is based on the finding that apomorphine, a direct-acting dopamine agonist, reversed the reserpine-induced increase in prolactin secretion, while clonidine, a direct-acting alpha-adrenergic agonist, potentiated the reserpine-induced stimulation of prolactin secretion. The effect of d-amphetamine on the increase in plasma prolactin levels produced by reserpine, 5-HTP, or AMPT was always greater than that of the l-isomer, suggesting that the d-isomer has a more profound effect on dopaminerelease or neuronal reuptake, or both, than l-amphetamine. Chronic administration of d-amphetamine prior to reserpine did not inhibit the ability of d-amphetamine to reverse the reserpine-induced increase in plasma prolactin. Chronic administration of AMPT did not enhance the ability of d-amphetamine to reverse the AMPT-induced increase in plasma prolactin.

We have given a brief overview of the focus, objectives and methodology of the national psychiatric comorbidity survey of Great Britain, and the first reports of the results will follow shortly. The survey data will have considerable national value in providing information on mental health policy and implementation at both national and local levels, and they will also have international value, linking up with other surveys elsewhere in the world to demonstrate the heavy public health impact of mental disorders in terms of their high prevalence, associated social disability and comorbidity, and use of services (World Bank 1993).

In this study are presented the results of an investigation of the scope of personality psychology as indicated by the contributions in the Annual Review of Psychologyfrom 1950 to 1975 inclusive. To make possible a more comprehensive comparison by decades as well as to depict the facts concerning trends and changes, the tabulated data for the 50's, 60's and 70's are presented separately. The findings show growth in increased frequency of both book and general references, increased knowledge as indicated by more topics covered in the field, increased complexity of issues considered, and greater diversity. In the 50's all contributions were under one caption—Personality. The 60's were characterized by conflicting consideration of personality structure versus personality dynamics. In the 70's attention was given to measurement and assessment and also emphasis on clinical approach. Some but not sufficient attention is given by a few of the contributors to economics, political and social determinants. Attitudes expressed by the contributors range from extreme pessimism to eternal optimism. Considering the increased resourcefulness in the selection of themes, increased rigor in methodology, the attitude warranted is one of skeptical optimism.

Skeletal muscle tissue was obtained from the vastus lateralis or peroneus brevis muscles of 34 healthy volunteers. Focal and extensive areas of Z band streaming and disruption of myofibrillar architecture without Z band streaming were quantified in Araldite-embedded specimens examined in the phase microscope. Extensive areas of Z band streaming in more than 2.0 percent of fibers was present in only two of the 34 volunteers. Myofibrillar disruptions without Z band streaming was much less common than Z band streaming. The size of extensive areas of Z band streaming or myofibrillar disruptions was quantified by counting the number of adjacent fibrils and contiguous sarcomeres occupied by either type of lesion. These data should be of use in determining if such lesions are present in excessive amounts in suspected pathologic material.