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Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (r20.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (P=0.027, n=69). These observations were marginal after correction for multiple testing. We performed in vitro electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings. [ABSTRACT FROM AUTHOR]

We examined the influence of the genome-wide significant schizophrenia risk variant rs1625579 near the microRNA (miRNA)-137 (MIR137) gene on well-established sources of phenotypic variability in schizophrenia: age-at-onset of psychosis and brain structure. We found that the MIR137 risk genotype strongly predicts an earlier age-at-onset of psychosis across four independently collected samples of patients with schizophrenia (n=510; F1,506=17.7, P=3.1 × 10−5). In an imaging-genetics subsample that included additional matched controls (n=213), patients with schizophrenia who had the MIR137 risk genotype had reduced white matter integrity (F3,209=13.6, P=3.88 × 10−8) throughout the brain as well as smaller hippocampi and larger lateral ventricles; the brain structure of patients who were carriers of the protective allele was no different from healthy control subjects on these neuroimaging measures. Our findings suggest that MIR137 substantially influences variation in phenotypes that are thought to have an important role in clinical outcome and treatment response. Finally, the possible consequences of genetic risk factors may be distinct in patients with schizophrenia compared with healthy controls. [ABSTRACT FROM AUTHOR]

Background/Objectives:Dietary factors have been hypothesized to influence the risk of preeclampsia. The aim of this study was to investigate the association between maternal intake of sugar and foods with a high content of added or natural sugars and preeclampsia.Subjects/Methods:A prospective study of 32 933 nulliparous women in the Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health. Participants answered a general health questionnaire and a validated food frequency questionnaire during pregnancy. Information about preeclampsia was obtained from the Medical Birth Registry of Norway. The relative risk of preeclampsia was estimated as odds ratios (OR) and 95% confidence intervals (CIs) and adjusted for known confounders.Results:The intake of added sugar was higher in women who developed preeclampsia than in healthy women in the unadjusted analysis, but not in the adjusted model. Of food items with a high content of added sugar, sugar-sweetened carbonated and non-carbonated beverages were significantly associated with increased risk of preeclampsia, both independently and combined, with OR for the combined beverages 1.27 (95% CIs: 1.05, 1.54) for high intake (>=125ml/day) compared with no intake. Contrary to this, intakes of foods high in natural sugars, such as fresh and dried fruits, were associated with decreased risk of preeclampsia.Conclusions:These results suggest that foods with a high content of added sugar and foods with naturally occurring sugars are differently associated with preeclampsia. The findings support the overall dietary advice to include fruits and reduce the intake of sugar-sweetened beverages during pregnancy. [ABSTRACT FROM AUTHOR]

Tardive dyskinesia (TD) is a severe, debilitating movement disorder observed in 25-30% of the patients treated with typical antipsychotics. Cannabinoid receptor 1 (CNR1) activators tend to inhibit movement, an effect prevented by rimonabant and other selective CNR1 antagonists. Furthermore, CNR1 receptor is downregulated in Huntington's disease and upregulated in Parkinson's disease. Twenty tagSNPs spanning the CNR1 gene were analyzed in schizophrenia patients of European ancestry (n=191; 74 with TD). Significant genotypic (P=0.012) and allelic (P=0.012) association was observed with rs806374 (T>C). Carriers of the CC genotype were more likely to be TD positive (CC vs TT+TC, odds ratio=3.4 (1.5-7.8), P=0.003) and had more severe TD (CC vs TT+TC; 9.52±9.2 vs 5.62±6.9, P=0.046). These results indicate a possible role of CNR1 in the development of TD in our patient population. However, these observations are marginal after correcting for multiple testing and need to be replicated in a larger patient population. [ABSTRACT FROM AUTHOR]

Rationale: Atypical antipsychotic drugs (APDs), many of which are direct or indirect serotonin (5-HT) agonists, and tandospirone, a 5-HT partial agonist, have been reported to improve cognition in schizophrenia. Objectives and methods: We tested the effect of 5-HT agonism, alone, and in combination with other psychotropic agents, including the atypical APD, lurasidone, in reversing the deficit in novel object recognition (NOR) induced by subchronic treatment with the non-competitive NMDA receptor antagonist, phencyclidine (PCP) (2 mg/kg, b.i.d., for 7 days). Results: Subchronic treatment with PCP induced a persistent NOR deficit. Lurasidone (0.1 mg/kg), a potent 5-HT partial agonist, 5-HT antagonist, and weaker D antagonist, tandospirone (0.6 mg/kg), and the selective post-synaptic 5-HT agonist, F15599 (0.16 mg/kg), ameliorated the subchronic PCP-induced-NOR deficit. The 5-HT antagonist, WAY100635 (0.6 mg/kg), blocked the ameliorating effects of tandospirone and lurasidone. The combination of sub-effective doses of tandospirone (0.2 mg/kg) and lurasidone (0.03 mg/kg) also reversed the PCP-induced NOR-deficit. Buspirone, a less potent partial 5-HT agonist than tandospirone, was less effective. Co-administration of tandospirone (0.2 mg/kg) and pimavanserin (3 mg/kg), a relatively selective 5-HT receptor inverse agonist, did not reverse the effect of sub-chronic PCP on NOR. The D antagonist, haloperidol, blocked the ameliorating effect of tandospirone on the PCP-induced deficit in NOR. Conclusions: These results indicate that 5-HT agonism is adequate to ameliorate the PCP-induced impairment in NOR and suggest further study of utilizing the combination of a 5-HT agonist and an atypical APD to ameliorate some types of cognitive impairment in schizophrenia. [ABSTRACT FROM AUTHOR]

Antipsychotic-induced weight gain has emerged as a serious complication in the treatment of patients with most antipsychotics. We have conducted the first in-depth examination of dopamine receptor genes in antipsychotic-induced weight gain. A total of 206 patients (139 of European descent and 56 African Americans) who underwent treatment for chronic schizophrenia or schizoaffective disorder were evaluated after on average over 6 weeks of treatment. Thirty-six tag single nucleotide polymorphisms (SNPs) and one variable-number tandem repeat, spanning the five dopamine receptor genes (DRD1-DRD5) were analyzed. In the total sample, we found a nominally significant association between the DRD2 rs1079598 marker and weight change using a cutoff of 7% gain (P=0.03). When stratifying the sample according to ethnicity and antipsychotics with highest risk for weight gain, we found significant associations in three DRD2 SNPs: rs6277 (C957T), rs1079598 and rs1800497 (TaqIA). The other genes were primarily negative. We provide evidence that dopamine receptor DRD2 gene variants might be associated with antipsychotic-induced weight gain in chronic schizophrenia patients. [ABSTRACT FROM AUTHOR]

Background: Prolongation of the corrected QT interval (QTc) is understood to be a predictor of risk for ventricular arrhythmia; consequently, data on QTc effects of drugs are used by regulatory bodies to evaluate potential safety risks. Clinical pharmacology studies in adults receiving oral ziprasidone demonstrated a dose-dependent mean increase (4.5-19.5 milliseconds [ms]) in QTc over the range of 40-160 mg/d with a small incremental increase (22.5 ms) at 320 mg/d. In a comparative study of ziprasidone versus five antipsychotics, the mean QTc increase at steady state maximum concentration (C(max)) for ziprasidone was 15.9 ms. Accordingly, the effects of ziprasidone on QTc were studied in phase II-IV randomized controlled trials (RCTs).Objective: The objective of this study was to provide clinicians and clinical researchers with a comprehensive analysis of QTc changes associated with ziprasidone based on data from Pfizer-sponsored phase II-IV RCTs in schizophrenia or bipolar disorder patients, safety reports and post-marketing surveillance.Methods: The following analyses of data were conducted to obtain a comprehensive summary of QTc data on ziprasidone: (i) post hoc analyses (using primarily descriptive statistics) of pooled QTc data (Fridericia correction) from more than 40 phase II-IV adult ziprasidone RCTs organized according to the following subgroups: all monotherapy studies in schizophrenia and bipolar disorder, all intramuscular (IM) studies, adjunctive studies in bipolar disorder and fixed-dose oral studies; (ii) post hoc analyses from 36 phase II-IV adult ziprasidone RCTs exploring the relationship between QTc change from baseline and baseline QTc in adults; (iii) post hoc analyses from phase II-IV adult ziprasidone RCTs modelling QTc change as a function of ziprasidone concentration in both adult (17 studies) and paediatric (5 studies) subjects; (iv) cardiac adverse event (AE) reports from all phase II-IV adult ziprasidone RCTs in schizophrenia; (v) a large simple trial entitled Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC) in 18 154 subjects with schizophrenia (the only previously reported results included here); and (vi) cardiac-related AEs presented in a ziprasidone post-marketing surveillance report created in 2007.Results: A total of 4306 adults received ziprasidone in placebo- and active-comparator phase II-IV RCTs and had evaluable QTc data. One subject reached a QTc ≥480 ms; 33 (0.8%) had a QTc ≥450 ms. QTc prolongation ≥30 ms was observed in 389 subjects (9.0%); ≥60 ms in 30 (0.7%); and ≥75 ms in 12 (0.3%). In the placebo-controlled studies, mean change in QTc from baseline to end of study was 3.6 (± 20.8) ms in the ziprasidone group; the corresponding QTc change in the pooled placebo group was -0.3 (± 20.6) ms. Data from IM studies, and bipolar studies in which ziprasidone was used adjunctively with lithium, valproate or lamotrigine, demonstrated similar QTc effects. A scatter-plot of QTc prolongation against baseline QTc showed QTc prolongation ≥60 ms exclusively in adult subjects with a baseline QTc ≤400 ms. The final concentration-response analysis model, comprising 2966 data points from 1040 subjects, estimates an increase in QTc of 6 ms for each 100 ng/mL increase in ziprasidone concentration. The large simple trial (ZODIAC) failed to show that ziprasidone is associated with an elevated risk of non-suicidal mortality relative to olanzapine in real-world use. Post-marketing data over a 5-year period did not show a signal of increased cardiac AEs.Conclusions: These analyses provide the first comprehensive summary of QTc changes associated with ziprasidone based on Pfizer-sponsored phase II-IV RCTs, safety reports and post-marketing surveillance. The results of the analyses of pooled data from phase II-IV RCTs in adults demonstrate a modest mean increase in QTc, infrequent QTc prolongation ≥60 ms (<1.0%) and rare observation of QTc ≥480 ms. These data are consistent with results from ziprasidone clinical pharmacology studies, safety reports and post-marketing surveillance. Taken together, they provide the most comprehensive evidence published to date that ziprasidone appears to be safe when used as indicated in patients with schizophrenia or bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: Assertive community treatment for the severely mentally ill is being implemented increasingly internationally. It is unclear whether recommended characteristics of assertive outreach (AO) teams influence care and outcomes. We hypothesised that recommended characteristics of AO teams such as joint health and social care management would predict reduced hospitalisation in the first year of an AO client programme and related outcomes throughout England. Methods: A two-stage design was used: a stratified sample of 100 of the 186 'stand-alone' AO teams in England and a systematic sample of clients from each team with stratification for black and ethnic minority patients. Team characteristics, treatment and outcomes were collected from teams. Analyses took account of patients' histories, clustering and ethnic minority over-sampling. Results: Under AO the proportion of time spent in hospital following admission decreased. Only 3/1,096 patients went missing in 9 months. Although patient' histories significantly predicted outcomes almost no team characteristics predicted re-admission or other patient outcomes after 1 and 3 years. Ethnic minority clients were more likely to be on compulsory orders only on jointly managed teams ( P = 0.030). Multidisciplinary teams and teams not working out of hours significantly predicted that patients received psychological interventions, but only 17% of sampled patients received such treatments. Conclusions: Characteristics of AO teams do not explain long-term patient outcomes. Since recommended team characteristics are not effective new models of care should be developed and the process of care tested. Managing teams to implement evidence-based psychological interventions might improve outcomes. [ABSTRACT FROM AUTHOR]

im: The 2007 adult psychiatric morbidity survey in England provides detailed information of high quality about sexual abuse. Given the major psychiatric implications of child sexual abuse (CSA), we aimed to establish its sociodemographic distribution in the general population. Method: The experience of sexual abuse was elicited in a random sample of the English household population ( N = 7,353), using computer assisted self-completion interviewing. Respondents were handed a laptop, and entered their responses to detailed questions. The interviewer was blind to their responses. CSA was defined as occurring before the age of 16. Results: 2.9% of women and 0.8% of men reported CSA involving non-consensual intercourse, figures that rose to 11.1 and 5.3% if experiences involving sexual touching were included. CSA was common before puberty, but peaked in adolescence. CSA greatly increased the chance in adulthood both of further sexual abuse (OR 10.6; CI 8.9-12.6), and of prostitution (OR 3.3; CI 1.9-5.5). There was no association with ethnicity or social class, but people over 65 were less likely to report CSA. The odds of CSA were doubled in those not brought up with both biological parents until the age of 16. Conclusion: CSA is common, particularly in women, and is not the preserve of any particular social group. Its frequency and its association with psychiatric consequences render it a major public health issue. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to analyze whether maternal negative affectivity assessed in pregnancy is related with subsequent infant food choices.Design: The study design was a cohort study.Subjects: The subjects were mothers (N=37 919) and their infants participating in the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health.Measurements: Maternal negative affectivity assessed prepartum (Hopkins Symptom Checklist 5 (SCL-5) at weeks 17 and 30 of pregnancy), introduction of solid foods by month 3 and feeding of sweet drinks by month 6 (by the reports of the mothers) were analyzed.Results: Mothers with higher negative affectivity were 64% more likely (95% confidence interval 1.5-1.8) to feed sweet drinks by month 6, and 79% more likely (95% confidence interval 1.6-2.0) to introduce solid foods by month 3. These odds decreased to 41 and 30%, respectively, after adjusting for mother's age, body mass index (BMI) and education.Conclusion: The maternal trait of negative affectivity is an independent predictor of infant feeding practices that may be related with childhood weight gain, overweight and obesity. [ABSTRACT FROM AUTHOR]

Tardive dyskinesia (TD) is a side effect of chronic antipsychotic medication exposure. Abnormalities in dopaminergic activity in the nigro-striatal system have been most often suggested to be involved because the agents that cause TD share in common potent antagonism of dopamine D2 receptors (DRD2). Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD, with the most consistent findings being an association between TD and the Ser9Gly polymorphism of the DRD3 gene and the TaqIA site 3′ of the DRD2 gene. The DRD4 gene codes for the third member of the D2-like dopamine receptor family, and the variable number tandem-repeat polymorphism in exon 3 of DRD4 has been associated with TD. However, other polymorphisms have not been thoroughly examined. In this study, we investigated five polymorphisms spanning the DRD4 gene and their association with TD in our European Caucasian sample (N=171). Although the exon 3 variable number tandem repeat was not associated with TD, haplotypes consisting of four tag polymorphisms were associated with TD in males. This study suggests that DRD4 may be involved in TD in the Caucasian population, although further replication studies are needed.The Pharmacogenomics Journal (2009) 9, 168–174; doi:10.1038/tpj.2009.2; published online 24 February 2009 [ABSTRACT FROM AUTHOR]

Background/Objectives:Milk and dairy products are the main sources of iodine in the Norwegian diet. This is due to a high consumption of milk and dairy products combined with a relatively high concentration of iodine in milk because of mandatory iodine fortification of cow fodder. The aim of the present study was to investigate the relation between 24-h urinary iodine excretion and estimated dietary intake, and to explore the use of 24-h urinary iodine excretion as a possible biomarker for the intake of milk and dairy products when assessing the validity of a new food frequency questionnaire for pregnant women participating the Norwegian Mother and Child Cohort Study (MoBa).Subject/Methods119 women participated in a validation study. Iodine was analyzed in 24-h urine. Dietary intakes were estimated by a food frequency questionnaire (FFQ) and a 4-day weighed food diary (FD). Using linear regression, predictors of urinary iodine excretion were identified. The triangular method was applied to calculate validity coefficients.Results:Significant predictors of 24-h urinary iodine excretion were: intake of dairy products, iodine-containing supplements and intake of fruit/vegetables. Fish/seafood intake and time of the year influenced 24-h urinary iodine excretion, although not significantly. The validity coefficients observed for total intake of dairy products were 0.65, 0.94 and 0.52 for the FFQ, the FD and the 24-h urinary iodine excretion, respectively.Conclusions:The present study showed that 24-h urinary iodine excretion may be a useful biomarker for validating the intake of milk and dairy products in pregnant Norwegian women.European Journal of Clinical Nutrition (2009) 63, 347–354; doi:10.1038/sj.ejcn.1602952; published online 5 December 2007 [ABSTRACT FROM AUTHOR]

Rationale: Clozapine is a unique antipsychotic, with efficacy against positive symptoms in treatment-resistant schizophrenic patients, and the ability to improve cognition and treat the negative symptoms characteristic of this disease. Despite its unique clinical actions, no specific molecular mechanism responsible for these actions has yet been described. Objectives and methods: To comprehensively profile a large library of neuropsychiatric drugs, including most antipsychotics, at human monoamine receptors using R-SAT, an in vitro functional assay. Results: Profiling revealed that N-desmethylclozapine (NDMC), the principal metabolite of clozapine, but not clozapine itself, is a potent and efficacious muscarinic receptor agonist, a molecular property not shared by any other antipsychotic. To further explore the role of NDMC muscarinic receptor agonist properties in mediating the physiological actions of clozapine, systemically administered NDMC was found to stimulate the phosphorylation of mitogen-activated protein kinase (MAP kinase) in mouse CA1 hippocampal neurons, an effect that was blocked by scopolamine, confirming central M1 muscarinic receptor agonist activity in vivo. Lastly, an analysis of clozapine and NDMC serum levels in schizophrenic patients indicated that high NDMC/clozapine ratios better predicted improvement in cognitive functioning and quality of life than the levels of either compound alone. Conclusions: The muscarinic receptor agonist activities of NDMC are unique among antipsychotics, and provide a possible molecular basis for the superior clinical effects of clozapine pharmacotherapy. [ABSTRACT FROM AUTHOR]

Rationale: Cognitive dysfunction in schizophrenia has been demonstrated to be dependent, in part, on dopaminergic activity. Clozapine has been found to improve some domains of cognition, including verbal memory, in patients with schizophrenia. Objectives: This study tested the hypothesis that plasma homovanillic acid (pHVA) levels, a peripheral measure of central dopaminergic activity, would predict the change in memory performance in patients with schizophrenia treated with clozapine. Methods: Twenty-seven male patients with schizophrenia received clozapine treatment for 6 weeks. Verbal list learning (VLL)-Delayed Recall (VLL-DR), a test of secondary verbal memory, was administered before and after clozapine treatment. Blood samples to measure pHVA levels were collected at baseline. Results: Baseline pHVA levels were negatively correlated with change in performance on VLL-DR; the lower baseline pHVA level was associated with greater improvement in performance on VLL-DR during treatment with clozapine. Baseline pHVA levels in subjects who showed improvement in verbal memory during clozapine treatment (n=13) were significantly lower than those in subjects whose memory performance did not improve (n=14). Conclusions: The results of this study indicate that baseline pHVA levels predict the ability of clozapine to improve memory performance in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

We show that the operation of the braid group on the set of complete exceptional sequences in the category of coherent sheaves on an exceptional curve $ \mathbb{X} $ over a field k is transitive. As a consequence the list of endomorphism skew-fields of the indecomposable direct summands of a tilting complex is a derived invariant. Furthermore, we apply the result in order to establish a bijection (which is compatible with the K-theory) between the sets of translation classes of exceptional objects in the derived categories of two derived-canonical algebras with the same Cartan matrix, but which are defined over possibly distinct fields. [ABSTRACT FROM AUTHOR]

Background: "Saving lives: our healthier nation" includes a target to reduce the death rate from suicide. Thoughts of suicide and feeling life is not worth living might be the first step in a pathway that can end in completed suicide. This study aims to identify factors associated with feeling life is not worth living amongst the household population of Great Britain, and to assess the strength of these associations after taking account of an individual's level of psychiatric morbidity. Methods: The 1993 OPCS National Psychiatric Morbidity Surveys of Great Britain assessed psychiatric morbidity using the Revised Clinical Interview Schedule amongst a stratified, clustered probability sample of 9830 subjects representative of the British private household population aged 16-64. Results: Of the sample 0.8 % (95 % CI 0.6 %-1 %) had thoughts of suicide in the week before interview and 3.1 % (95 % CI 2.7 %-3.5 %) reported thoughts of life not worth living in the week before interview. Psychiatric morbidity was most strongly associated with such thoughts. Ethnicity, marital status and low social support were strongly associated with such thoughts after adjusting for age, sex and psychiatric morbidity. Conclusions: Reducing psychiatric morbidity in the population as a whole might also decrease the frequency of suicidal thoughts. Policies which improve social support at a population level might also have a large impact on prevalence of suicidal thoughts. [ABSTRACT FROM AUTHOR]

We have shown that treatment with interleukin-2 (IL-2) or interferon-α (IFNα) may induce depressive symptoms and activation of the cytokine network and that IL-2 treatment may diminish serum dipeptidyl pepdidase IV (DPP IV) activity. DPP IV (EC 3.4.14.5) is a membrane bound serine protease which catalyzes the cleavage of some cytokines and neuroactive peptides which modulate T cell activity. The aims of the present study were to examine the effects of IFNα-based immunotherapy on serum DPP IV activity in relation to induction of the inflammatory response system. In 18 patients with chronic active hepatitis C, we determined the Montgomery and Asberg Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAM-A), serum DPP IV activity, the kynurenine/tryptophan (K/T) quotient, which is an indicator of cytokine (in particular IFN)-induced catabolism of tryptophan, and serum interleukin-8 (IL-8) before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFNα. IFNα-immunotherapy significantly suppressed serum DPP IV 2-4 weeks and 1624 weeks after starting IFNα-based immunotherapy. The reduction in serum DPP IV activity was more pronounced 16-24 weeks after starting immunotherapy than after 2-4 weeks. The IFNα-induced suppression of serum DPP IV activity was significantly correlated to IFNα-induced increases in the MADRS and HAM-A and increases in the K/T quotient and serum IL-8. In conclusion, long-term immunotherapy with IFNα suppresses serum DPP IV activity and the immunotherapyinduced changes in DPP IV are related to increases in severity of depression, anxiety and activation of the inflammatory response system. [ABSTRACT FROM AUTHOR]

Background: Psychiatric symptoms are wide-spread in the general population, but have little effect on performance. Deficits in performance and psychiatric symptoms may be the end point of processes common to both, or they may be caused by quite different factors. In this paper we examine the epidemiological distribution of psychiatric symptoms and performance deficits, as indicated by difficulties in activities of daily living (ADL). We hypothesised that ADL difficulties are partly independent of psychiatric symptoms, and that this is reflected in a different demographic distribution.Method: The household component of the National Surveys of Psychiatric Morbidity was based on a sample of around ten thousand subjects selected at random from the population of Great Britain. Psychiatric symptoms were elicited by lay interviewers using the revised Clinical Interview Schedule. Performance was assessed by asking about difficulties experienced in performing seven types of everyday activity. In this paper, our chosen variables were overall symptom and ADL deficit scores, and these were related to standard demographic variables.Results: There were significant differences in the epidemiological distribution of psychiatric symptoms and ADL difficulties. In particular, men experienced more ADL difficulties at a given symptom level than women. There were also differences in relation to social class, employment status, marital status, ethnic group and age.Conclusions: ADL deficits and psychiatric symptoms are related in the general population, and this probably represents common factors in their origin. However, discrepancies in the social distribution of these phenomena suggest there are also aetiological differences. These do not appear to be the result of the impact of physical illness on activities of daily living. Our results emphasise that ADL difficulties should be studied separately, particularly in investigations of treatment seeking. [ABSTRACT FROM AUTHOR]

Scrutinizes an atypical antipsychotic drug. Characteristics of clozapine; Difference between clozapine and typical neuroleptic drugs; Explanation of the atypical features of clozapine using the serotonin/ dopamine model.

Provides information on a study which investigated the potential of near-infrared reflectance spectroscopy as a rapid and nondestructive method to determine total fat and protein in mixed, homogenized and freeze-dried human diets. Materials and methods; Results and discussion.

Abstract The self-report version of the Strengths and Difficulties Questionnaire (SDQ) was administered to two samples of 11 16 year olds: 83 young people in the community and 116 young people attending a mental health clinic. The questionnaire discriminated satisfactorily between the two samples. For example, the clinic mean for the total difficulties score was 1.4 standard deviations above the community mean, with clinic cases being over six times more likely to have a score in the abnormal range. The correlations between self-report SDQ scores and teacher- or parentrated SDQ scores compared favourably with the average crossinformant correlations in previous studies of a range of measures. The self-report SDQ appears promising and warrants further evaluation. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Maintenance of rats on a lithium-containing diet for 3-21 days resulted in a suppression of prolactin (PRL) secretion in vivo and in vitro. Lithium treatment also resulted in an increase in the activity of tuberoinfundibular dopaminergic neurons, as evidenced by an increased accumulation of dihydroxyphenylalanine (DOPA) in the median eminence after inhibition of DOPA decarboxylase and an increased concentration of dopamine in the anterior pituitary gland. The accumulation of DOPA in the neurointer-mediate lobe of the pituitary gland, the prefrontal cortex, the striatum and the nucleus accumbens was also enhanced by lithium treatment. It is concluded that lithium treatment enhances the synthesis of dopamine in many brain regions and that an increased activity of tuberoinfundibular dopaminergic neurons results in an enhanced inhibitory control of PRL secretion. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 α-methyl-p-tyrosine (AMPT) or γ-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Perlapine is a dibenzohetereopine compound chemically related to clothiapine, loxapine, and clozapine. Although the latter three compounds are antipsychotic, perlapine has not been reported to be antipsychotic. Nevertheless, all four drugs increase rat plasma prolactin levels. The order of potency is loxapine, perlapine, clothiapine, and clozapine. These results suggest that either perlapine should be reexamined for antipsychotic properties or there are hitherto unsuspected discrepancies between the dopamine receptors relevant to antipsychotic activity in man and those that regulate prolactin secretion in the rat. [ABSTRACT FROM AUTHOR]

Beginning one day after receiving fluphenazine enanthate (Prolixin Enanthate®), 25 mg, subcutaneously, an acute schizophrenic girl with mixed schizoaffective and excited catatonic symptomatology became mute and withdrawn, then developed severe muscular rigidity and hyperpyrexia, and finally became comatose. The patient developed large increases in serum creatine phosphokinase (CPK) activity by the third day of this syndrome. The previously described symptoms, which have been labeled the neuroloptic 'malignant' syndrome (Delay and Deniker, 1968), diminished with supportive treatment and intravenous benztropine mesylate (Cogentin®). Because of renewed psychotic behavior, phenothiazine treatment was eventually restarted, including treatment with fluphenazine enanthate, without recurrence of the extrapyramidal or hypothalamic symptoms. The difficulty in distinguishing between the neuroleptic 'malignant' syndrome and Stauder's 'acute lethal catatonia' is emphasized. The relationship between these syndromes and malignant hyperpyrexia is discussed. Possible causes of the increased serum CPK activity are discussed. [ABSTRACT FROM AUTHOR]

Copyright of Potato Research is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Potato Research is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study was carried out to examine some components of in vivo immune function in major depression and schizophrenia. Toward this end, plasma concentrations of interleukin-1β (IL-1β) and IL-6, soluble IL-2 receptor (sIL-2R), and transferrin receptor (TfR) were measured in 28 normal controls, 11 schizophrenics and 13 major-depressed patients. Schizophrenic and major-depressed patients showed significantly higher plasma sIL-2R and TfR than normal controls. There was a trend toward higher plasma IL-6 in the psychiatric patients, and particularly in schizophrenic patients, than in normal volunteers. In normal controls and in the total study group, there were highly significant and positive correlations between plasma TfR and sIL-2R concentrations. It is suggested that schizophrenia and major depression are characterized by immune disorders that may indicate activation of cell-mediated immunity such as T-cell activation. [ABSTRACT FROM AUTHOR]

Pindolol has been shown to be a partial agonist at 5-HT receptors in preclinical studies. It has also been reported to inhibit the effects of other 5-HT partial agonists such as ipsapirone and buspirone on hormone secretion and body temperature in man, indicating its antagonist action at 5-HT receptors in man. To determine if pindolol has 5-HT 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-HT agonist action and is consistent with a 5-HT partial agonist mechanism in man whereas the PRL effects are consistent with an antagonist action at 5-HT 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-HT-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-HT mechanism whereas the HPA axis and body temperature are not. Since rodent studies suggest differences in 5-HT 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. [ABSTRACT FROM AUTHOR]

Buspirone, a putative serotonin (5-HT) partial agonist, did not produce hypothermia in 17 normal volunteers in a placebo controlled, single blind study. Thus, buspirone may be a weaker agonist at those 5-HT receptors which mediate hypothermia compared to ipsapirone or gepirone, two other 5-HT partial agonists which have been reported to produce hypothermia by a 5-HT-mediated mechanism. [ABSTRACT FROM AUTHOR]

The density of 5-HT binding usingH-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) as binding ligand, was studied in human frontal cortex of suicide victims and normal controls who died due to medical disease or accidentally. There was no difference in the maximum number of binding site (B) or K (an inverse measure of affinity) of 5-HT receptor binding sites between normal controls and the entire group of suicide victims. However, nonviolent suicides had significantly higher B (22-25%) compared to both controls and violent suicides. A negative correlation between age and B of 5-HT binding sites was found in male controls but not in female controls or suicide victims. This relationship was less apparent among the male controls over age 60. [ABSTRACT FROM AUTHOR]

Serotonin (5-HT) receptor binding was studied, usingH-spiperone as the ligand, in post-mortem brain specimens obtained from schizophrenic patients (N=11) and non-psychiatric controls (N=11). The maximum number of binding sites (B) was significantly decreased in schizophrenic patients as compared to normal controls. This difference did not appear to be due to neuroleptic treatment. No difference in K (an inverse measure of the affinity ofH-spiperone to its binding sites) was observed between the two groups. However, studies with unmedicated schizophrenic patients are needed to draw any definite conclusion. The role of serotonergic processes in the psychobiology of schizophrenia is discussed. [ABSTRACT FROM AUTHOR]

Two atypical neuroleptic agents, clozapine and fluperlapine, produced rapid elevations in plasma PRL concentrations that were similar in magnitude to those produced by haloperidol. However, the PRL response to clozapine or fluperlapine was of much shorter duration than that elicited by haloperidol. Clozapine, but neither fluperlapine nor haloperidol, produced a rapid increase in the activity of tuberoinfundibular dopamine (TIDA) neurons, as evidenced by an enhanced accumulation of dihydroxyphenylalanine (DOPA) in the median eminence after the inhibition of DOPA decarboxylase. The clozapine-induced increase in DOPA accumulation was evident within 30 minutes after its administration and persisted for at least 4 hours. The clozapine-induced increase in the activity of TIDA neurons may account, in part, for the abbreviated PRL response to this neuroleptic. In addition, ability to produce a short-lived increase in PRL secretion in the rat appears to be common to the atypicl neuroleptic drugs. [ABSTRACT FROM AUTHOR]

8-OH-DPAT (8-hydroxy-2-[di-n-propylamino] tetralin) is a novel aminotetralin derivative which has been proposed to be a serotonin (5-HT) agonist devoid of dopamine agonist effects. We now report that the administration of 8-OH-DPAT, like known 5-HT agonists, produced a rapid elevation of serum prolactin concentrations in male rats. The prolactin response to 8-OH-DPAT, like that induced by other 5-HT agonists, was greatly potentiated in animals pretreated with the tryptophan hydroxylase inhibitor, para-chlorophenylalanine. However, the 8-OH-DPAT-induced elevation of serum prolactin cocentrations in untreated rats was not dose-dependent and was modest in magnitude compared to that produced by known 5-HT agonists. In contrast to the stimulatory effects of 8-OH-DPAT on prolactin secretion in vivo 8-OH-DPAT suppressed the secretion of prolactin from anterior pituitary tissue in vitro, and this effect was blocked by haloperidol. The results of the present study are supportive of the view that 8-OH-DPAT has dopamine agonist, as well as 5-HT agonist, properties. [ABSTRACT FROM AUTHOR]

Fluoxetine (Lilly 110140) is a potent, specific serotonin (5-HT) uptake blocker which is being tested in man for antidepressant activity. One of 9 depressed patients receiving this drug developed a dystonic reaction, parkinsonian rigidity, and increased serum prolactin levels, all signs of decreased dopaminergic activity. Homovanillic acid levels also decreased in the cerebrospinal fluid of this subject. We postulate that fluoxetine, via the increase in 5-HT activity resulting from 5-HT uptake blockade, inhibited both the nigro-striatal and tubero-infundibular dopaminergic neurons. These results provide additional evidence for a linkage between serotonergic and dopaminergic neurons in man. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The affinities of 13 atypical and 12 typical antipsychotic drugs for the cloned rat D dopamine receptor and the D/D 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 D 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 D receptor, with Ks less than 20 nM (loxapine, chlorpromazine, fluphenazine, mesoridazine, thioridazine and trifluoroperazine). The ratios of D/D affinities did not differentiate between these two types of antipsychotic drugs. Thus, D dopamine receptor affinity, used as a single measure, does not distinguish between the group of typical and atypical antipsychotic drugs analyzed. [ABSTRACT FROM AUTHOR]

A letter to the editor discussing risk factors for agranulocytosis is presented.

Phencyclidine (Sernyl, Phen) is a potent psychotomimetic drug in man. In conjunction with restraint stress, Phen produces increased plasma creatine phosphokinase (CPK) and aldolase (Ald) activities and skeletal muscle pathology in rats. Increased plasma CPK and Ald activities and skeletal muscle pathology are found in some acutely psychotic patients. It was therefore of interest to determine if Phen increased plasma CPK or Ald levels in man. Four of seven subjects had no elevations of plasma CPK or Ald activity either before or after Phen, 0.1 mg/kg, i.v. One subject had increased CPK levels which began 1 h after Phen. Two subjects had increased Ald and/or CPK levels which began within 24 h before Phen administration and which persisted or increased for at least 24 h after Phen. The plasma enzyme changes occurred in those subjects who showed the most pronounced cognitive disruption after Phen. The effects of stress and Phen on plasma CPK and Ald levels and its implications for the study of muscle abnormalities in psychotic patients are discussed. [ABSTRACT FROM AUTHOR]

Serum creatine phosphokinase (CPK) and aldolase activities were determined in thirty-six subjects following the administration of LSD-25 or N,N-dipropyltryptamine in varying doses. No significant increase in the mean activity of either enzyme was found at the times blood samples were obtained after drug administration. The results are discussed with reference to the increases in CPK and aldolase activity which occur in the acute psychoses. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about dopamine receptor D3 (DRD3) genes' multiple variants influence age-at-onset of schizophrenia.

Copyright of Experientia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Creatine phosphokinase activity was found in human lymphocytes. Only MM type of the enzyme was detected in lymphocytes and polymorphonuclear leukocytes. [ABSTRACT FROM AUTHOR]