Childhood abuse and psychotic experiences - evidence for mediation by adulthood adverse life events.

AIMS: We have previously reported an association between childhood abuse and psychotic experiences (PEs) in survey data from South East London. Childhood abuse is related to subsequent adulthood adversity, which could form one pathway to PEs. We aimed to investigate evidence of mediation of the association between childhood abuse and PEs by adverse life events. METHODS: Data were analysed from the South East London Community Health Study (SELCoH, n = 1698). Estimates of the total effects on PEs of any physical or sexual abuse while growing up were partitioned into direct (i.e. unmediated) and indirect (total and specific) effects, mediated via violent and non-violent life events. RESULTS: There was strong statistical evidence for direct (OR 1.58, 95% CI: 1.19-2.1) and indirect (OR 1.51, 95% CI: 1.32-1.72) effects of childhood abuse on PEs after adjustment for potential confounders, indicating partial mediation of this effect via violent and non-violent life events. An estimated 47% of the total effect of abuse on PEs was mediated via adulthood adverse life events, of which violent life events made up 33% and non-violent life events the remaining 14%. CONCLUSIONS: The association between childhood abuse and PEs is partly mediated through the experience of adverse life events in adulthood. There is some evidence that a larger proportion of this effect was mediated through violent life events than non-violent life events.

Psychiatric symptoms and risk of victimisation: a population-based study from Southeast London.

AimsAlthough violence is a vital public health problem, no prospective studies have tested for subsequent vulnerability to violence, as a victim or witness, in members of the general population with a range of psychiatric symptoms, or evaluated the importance of higher symptom burden on this vulnerability. METHODS: We used successive waves of a household survey of Southeast London, taken 2 years apart, to test if association exists between psychiatric symptoms (symptoms of psychosis, common mental disorders, post-traumatic stress disorder and personality disorder) and later victimisation, in the form of either witnessing violence or being physically victimised, in weighted logistic regression models. Statistical adjustment was made for prior violence exposure, sociodemographic confounders, substance/alcohol use and violence perpetration. Sensitivity analyses were stratified by violence perpetration, sex and history of mental health service use. RESULTS: After adjustments, psychiatric symptoms were prospectively associated with reporting any subsequent victimisation (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.25-2.83), a two times greater odds of reporting witnessed violence (OR 2.24, 95% CI 1.33-3.76) and reporting physical victimisation (OR 1.76, 95% CI 1.01-3.06). One more symptom endorsed was accompanied by 47% greater odds of subsequent victimisation (OR 1.47, 95% CI 1.16-1.86). In stratified analyses, statistical associations remained evident in non-perpetrators, and among those without a history of using mental health services, and were similar in magnitude in both men and women. CONCLUSIONS: Psychiatric symptoms increase liability to victimisation compared with those without psychiatric symptoms, independently of a prior history of violence exposure and irrespective of whether they themselves are perpetrators of violence. Clinicians should be mindful of the impact of psychiatric symptoms on vulnerability to victimisation, including among those with common psychiatric symptoms and among those who are not considered at risk of perpetrating violence.

Neighbourhood deprivation is positively associated with detection of the ultra-high risk (UHR) state for psychosis in South East London.

BACKGROUND: Individuals are defined as being at ultra-high risk (UHR) for psychosis based on a combination of attenuated psychotic symptoms, help-seeking behaviour, genetic risk, and social/occupational deterioration. Limited evidence is available on whether UHR detection differs by neighbourhood, and potential explanations. AIMS: To examine neighbourhood distribution of detected UHR using cases from the OASIS service in South East London, investigating neighbourhood deprivation as an explanatory variable. METHODS: Geographic data were collected on patients who met UHR criteria over a fourteen-year period, at the neighbourhood (lower super output area, LSOA) level. Rates were calculated based on cases and age-specific population estimates. Poisson regression assessed associations between UHR rate and neighbourhood deprivation, and with particular deprivation domains, adjusting for referrals for UHR assessment, population density, and proportions of non-White people, and young single people. RESULTS: Rate of UHR detection was statistically related to neighbourhood deprivation, but referral rate was not: compared to the least deprived neighbourhoods, the most deprived neighbourhoods had a greater than two-fold increase in incidence rate of detected UHR (adjusted incidence rate ratio (IRR): 2.11, 95% confidence interval (CI): 1.21,3.67). In contrast, a small, imprecise association was observed for referral for assessment for UHR (adjusted IRR: 1.26 (95%CI: 0.84,1.89)). Evidence was also found for associations of UHR detection rate with domains of deprivation pertaining to health and barriers to services. CONCLUSIONS: The distribution of UHR detection rates by neighbourhood is not random and may be explained in part by differences in the social environment between neighbourhoods.

Tobacco smoking is associated with psychotic experiences in the general population of South London.

BACKGROUND: The association between cigarette smoking and psychosis remains unexplained, but could relate to causal effects in both directions, confounding by socioeconomic factors, such as ethnicity, or use of other substances, including cannabis. Few studies have evaluated the association between cigarettes and psychotic experiences (PEs) in diverse, inner-city populations, or relationships with number of cigarettes consumed. METHODS: We assessed associations and dose-response relationships between cigarette smoking and PEs in a cross-sectional survey of household residents (n = 1680) in South East London, using logistic regression to adjust for cannabis use, other illicit substances, and socioeconomic factors, including ethnicity. RESULTS: We found association between any PEs and daily cigarette smoking, which remained following adjustment for age, gender, ethnicity, cannabis and use of illicit stimulant drugs (fully adjusted odds ratio 1.47, 95% confidence interval 1.01-2.15). Fully adjusted estimates for the association, and with number of PEs, increased with number of cigarettes smoked daily, implying a dose-response effect (p = 0.001 and <0.001, respectively). Odds of reporting any PEs in ex-smokers were similar to never-smokers. CONCLUSIONS: In this diverse epidemiological sample, association between smoking and PEs was not explained by confounders such as cannabis or illicit drugs. Daily cigarette consumption showed a dose-response relationship with the odds of reporting PEs, and of reporting a greater number of PEs. There was no difference in odds of reporting PEs between ex-smokers and never-smokers, raising the possibility that the increase in PEs associated with smoking may be reversible.

Minority status and mental distress: a comparison of group density effects.

BACKGROUND: It has been observed that mental disorders, such as psychosis, are more common for people in some ethnic groups in areas where their ethnic group is less common. We set out to test whether this ethnic density effect reflects minority status in general, by looking at three situations where individual characteristics differ from what is usual in a locality. METHOD: Using data from the South East London Community Health study (n = 1698) we investigated associations between minority status (defined by: ethnicity, household status and occupational social class) and risk of psychotic experiences, common mental disorders and parasuicide. We used a multilevel logistic model to examine cross-level interactions between minority status at individual and neighbourhood levels. RESULTS: Being Black in an area where this was less common (10%) was associated with higher odds of psychotic experiences [odds ratio (OR) 1.34 95% confidence interval (CI) 1.07-1.67], and attempted suicide (OR 1.84 95% CI 1.19-2.85). Living alone where this was less usual (10% less) was associated with increased odds of psychotic experiences (OR 2.18 95% CI 0.91-5.26), while being in a disadvantaged social class where this was less usual (10% less) was associated with increased odds of attempted suicide (OR 1.33 95% CI 1.03-1.71). We found no evidence for an association with common mental disorders. CONCLUSIONS: The relationship between minority status and mental distress was most apparent when defined in terms of broad ethnic group but was also observed for individual household status and occupational social class.

Towards a Standard Psychometric Diagnostic Interview for Subjects at Ultra High Risk of Psychosis: CAARMS versus SIPS.

Background. Several psychometric instruments are available for the diagnostic interview of subjects at ultra high risk (UHR) of psychosis. Their diagnostic comparability is unknown. Methods. All referrals to the OASIS (London) or CAMEO (Cambridgeshire) UHR services from May 13 to Dec 14 were interviewed for a UHR state using both the CAARMS 12/2006 and the SIPS 5.0. Percent overall agreement, kappa, the McNemar-Bowker χ (2) test, equipercentile methods, and residual analyses were used to investigate diagnostic outcomes and symptoms severity or frequency. A conversion algorithm (CONVERT) was validated in an independent UHR sample from the Seoul Youth Clinic (Seoul). Results. There was overall substantial CAARMS-versus-SIPS agreement in the identification of UHR subjects (n = 212, percent overall agreement = 86%; kappa = 0.781, 95% CI from 0.684 to 0.878; McNemar-Bowker test = 0.069), with the exception of the brief limited intermittent psychotic symptoms (BLIPS) subgroup. Equipercentile-linking table linked symptoms severity and frequency across the CAARMS and SIPS. The conversion algorithm was validated in 93 UHR subjects, showing excellent diagnostic accuracy (CAARMS to SIPS: ROC area 0.929; SIPS to CAARMS: ROC area 0.903). Conclusions. This study provides initial comparability data between CAARMS and SIPS and will inform ongoing multicentre studies and clinical guidelines for the UHR psychometric diagnostic interview.

Unemployment, ethnicity and psychosis.

OBJECTIVE: This study describes the incidence of psychosis in unemployed people and determines whether unemployment has a greater impact on the development of psychosis amongst Black minority groups than White groups. METHOD: Patients with a first diagnosis of Research Diagnostic Criteria psychosis, in a defined area of London from 1998 to 2004, were identified. Crude and standardised incidence rates of psychosis amongst unemployed people for each ethnic group were calculated. Poisson regression modelling tested for interactions between unemployment and ethnicity. RESULTS: Hundred cases occurred amongst employed people and 78 cases occurred amongst the unemployed people. When standardised to the employed White population of the area, White unemployed people had a standardised incidence ratio (SIR) of 11.7 (95% CI 6.4-19.7), Black Caribbean people had a SIR of 60.1(95% CI 39.3-88) and Black African people had a SIR of 40.7 (95% CI 25.8-61.1). There was no interaction however between ethnicity and unemployment (Likelihood ratio test P = 0.54). CONCLUSION: Rates of psychosis are high amongst unemployed people in south London and extremely high amongst Black Caribbean and Black African unemployed people. There was no evidence however that the minority groups were particularly sensitive to the stresses, limitations or meaning of unemployment.

Effect of antihypertensive therapy on cognitive functions of patients with hypertension.

OBJECTIVES: Hypertension is known to be associated with cognitive decline. Many studies revealed that control of hypertension with antihypertensive therapy controls the cognitive decline associated with hypertension. While there are reports that suggest that antihypertensive drugs do not provide protection from cognitive decline, the present study is designed to evaluate the cognitive status of patients recently diagnosed as hypertensive and effect of 3 month long antihypertensive therapy on cognitive functions. MATERIALS AND METHODS: A predesigned pretested questionnaire was used to collect the information. The PGI memory scale (PGIMS) was employed to assess memory function of patients. Baseline memory functions were evaluated before starting the treatment with antihypertensive and compared with the cognitive function scores of healthy volunteers. After the 3 months of treatment, cognitive functions were evaluated again by the same scale. The unpaired t-test was used to compare the cognitive functions between case and control and the paired t-test was used to compare pre- and post-treatment score. RESULTS: This study revealed that mean scores of six subtests of cognitive functions were less in cases as compared to subjects in comparison group. After 3 months of antihypertensive therapy, scores of five sub-tests were found to be increased. Among these five subtests, four were those which were found declined at the baseline. CONCLUSION: This suggests that antihypertensive therapy given for 3 months improved the score of those cognitive function tests in which hypertensive patients perform poorly during recruitment and there was no deterioration of any test after 3 months of antihypertensive therapy.

Incremental communication for multilayer neural networks: error analysis.

Artificial neural networks (ANNs) involve a large amount of internode communications. To reduce the communication cost as well as the time of learning process in ANNs, we earlier proposed (1995) an incremental internode communication method. In the incremental communication method, instead of communicating the full magnitude of the output value of a node, only the increment or decrement to its previous value is sent to a communication link. In this paper, the effects of the limited precision incremental communication method on the convergence behavior and performance of multilayer neural networks are investigated. The nonlinear aspects of representing the incremental values with reduced (limited) precision for the commonly used error backpropagation training algorithm are analyzed. It is shown that the nonlinear effect of small perturbations in the input(s)/output of a node does not cause instability. The analysis is supported by simulation studies of two problems. The simulation results demonstrate that the limited precision errors are bounded and do not seriously affect the convergence of multilayer neural networks.

Incremental communication for multilayer neural networks.

A new method of inter-neuron communication called incremental communication is presented. In the incremental communication method, instead of communicating the whole value of a variable, only the increment or decrement of its previous value is sent on a communication link. The incremental value may be either a fixed-point or a floating-point value. Multilayer feedforward network architecture is used to illustrate the effectiveness of the proposed communication scheme. The method is applied to three different learning problems and the effect of the precision of incremental input-output values of the neurons on the convergence behavior is examined. It is shown through simulation that for some problems even four-bit precision in fixed- and/or floating-point representations is sufficient for the network to converge. With 8-12 bit precisions almost the same results are obtained as that with the conventional communication using 32-bit precision. The proposed method of communication can lead to significant savings in the intercommunication cost for implementations of artificial neural networks on parallel computers as well as the interconnection cost of direct hardware realizations. The method can be incorporated into most of the current learning algorithms in which inter-neuron communications are required. Moreover, it can be used along with the other limited precision strategies for representation of variables suggested in literature.

Attrition of the Zeigarnik effect: role of subjects' expectancy aroused by placebos.

The present paper describes the effect for 45 medical students and interns of "placebo" treatment on the Zeigarnik effect. Attrition of the Zeigarnik effect caused by placebo was resistant to caffeine and diazepam (ns = 58 and 28).

Age-related decrease in omega conotoxin binding to rat cardiac synaptosomes.

A cardiac synaptosomal preparation developed by this laboratory was used to study neuronal calcium channels in aging rat heart. Ca2+ channels were quantified by measuring binding of iodinated omega conotoxin, which is reported to specifically block neuronal Ca2+ channels. We determined the binding of [125I]-omega conotoxin GVIA to a synaptosomal preparation from the hearts of 6- and 24-month-old male Fisher 344 rats. The maximum number of binding sites (Bmax +/- SD, fmol/mg protein) is lower in preparations from 24-month (2.2 +/- 0.6) than from 6-month (3.4 +/- 0.7)-old rats. This decrease in number of binding sites suggests an age-related reduction in the number of neuronal calcium channels. Since calcium is essential for exocytotic release of norepinephrine and is made available intracellularly through neuronal calcium channels, the reduction in neuronal calcium channel number may explain, in part, our previous observations of diminished release of norepinephrine in senescent hearts.

Characterization of norepinephrine accumulation by a crude synaptosomal-mitochondrial fraction isolated from rat heart.

Norepinephrine (NE) uptake into a heart synaptosomal-mitochondrial fraction was assessed under conditions where neuronal uptake (type 1) was linear with respect to both time and protein concentration. The NE accumulation process was sensitive to incubation temperature, sodium ion concentration and medium osmolality. Furthermore, NE uptake was attenuated by the neuronal uptake inhibitor desmethylimipramine (DMI) in a concentration dependent manner; the IC50 value was approximately 10 nM and maximum inhibition was obtained at 100 nM. In contrast, the extraneuronal uptake inhibitor, metanephrine did not significantly attenuate NE uptake. Kinetic analysis demonstrated that the DMI sensitive NE accumulation is saturable with a KM of approximately 400 nM and that NE uptake occurs via a single uptake process. This demonstration of neuronal type NE uptake by a synaptosomal-mitochondrial fraction constitutes a successful demonstration of the preparation of a rat heart subcellular fraction containing functional synaptosomes.

Some aspects of activity profile of sodium lawsonate in mice and rats.

Sodium lawsonate (SL: derivative of lawsone, hydroxy-1,4-naphthaquinone) was studied for its activity profile in mice and rats, with emphasis on actions on the central nervous system. The drug produced a cataleptic state, hypothermia and loss of active avoidance behaviour, but it did not augment barbiturate sleep. The catalepsy was prevented by hyoscine (mice) or by sodium salicylate (rats). SL did not affect apomorphine-sterotypy (a dopamine-mediated behaviour) but blocked the lithium-induced head twitches (a serotonin-mediated behavioural response). SL did not produce excitation, analgesia or exhibit anti-MES activity. All actions of SL were rapid in onset and brief in duration. In view of effective dose range (40-80 mg/kg, i.p.) and MLD 50 values (76 mg/kg, i.p., in mice; 122 mg/kg, i.p., in rats), safety index of SL appears to be low.

The effect of centrophenoxine at the skeletal neuromuscular junction.

Centrophenoxine exhibited some interesting actions at the neuromuscular junction. The drug was ineffective in rat or chick preparations, but blocked neuromuscular transmission in frog preparations. The blockade was reversed by adrenaline, potassium, choline and physostigmine. The drug had no effect on muscle contractility or endplate cholinoceptor. Hemicholinium 3 induced a neuromuscular blockade in rat (in vivo) which was reversed by choline but not by centrophenoxine. Neither of these two drugs could reverse the blocking effect of hemicholinium in frog preparations. It is concluded that centrophenoxine acts only in frog and the blockade involves a presynaptic mechanism. The work further suggests that choline uptake systems in the rat and the frog may not be identical, since choline competed with hemicholinium for the uptake system in rat and with centrophenoxine (but not with hemicholinium) in the frog.