Abnormal prediction error is associated with negative and depressive symptoms in schizophrenia.

Prediction error in learning is where learning occurs to the degree to which an outcome consequent to a stimulus is surprising. It has been suggested that abnormal use of prediction error in schizophrenia may underlie the formation of inappropriate associations giving rise to psychotic symptoms. Kamin blocking is a phenomenon that demonstrates prediction error. Kamin blocking is shown where prior learning about a stimulus A paired with an outcome retards learning about a stimulus B when presented subsequently as part of a stimulus compound AB paired with the same outcome. Prior studies have indicated reduced Kamin blocking in schizophrenia specifically in non-paranoid patients. It is however unclear how reduced Kamin blocking is associated with specific symptoms in schizophrenia. The present study examined Kamin blocking performance in a high functioning community-based sample of 34 people with schizophrenia and 48 controls closely matched for pre-morbid IQ. In these patients we measured Kamin blocking and symptoms using positive and negative symptom scales (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS). Results confirmed that people with schizophrenia had significantly reduced Kamin blocking. Kamin blocking performance was associated with negative and depressive symptoms. These associations with symptoms were crucially not found with baseline associative learning or unblocking measures, confirming specificity to the Kamin blocking effect. These data demonstrate first that abnormal prediction error as assessed in the Kamin blocking task is associated with negative and depressive symptoms rather than positive symptoms in high functioning schizophrenia patients. Second this strongly suggests that reduced Kamin blocking may be useful as an animal model of specific relevance to negative and depressive symptoms in schizophrenia.

Appetitive overshadowing is disrupted by systemic amphetamine but not by electrolytic lesions to the nucleus accumbens shell.

There is evidence that the indirect dopamine (DA) agonist amphetamine (AMP) can disrupt selective learning in an aversive overshadowing task, consistent with a role for the DA system in this form of salience manipulation. In the following experiments we assessed in the male Wistar rat: (1) whether amphetamine disruption of overshadowing extends to an appetitively motivated overshadowing task; and (2) whether selective electrolytic lesions to the n.acc (shell versus core subfields) disrupt appetitively motivated overshadowing. The experiments used sucrose reward pellets as the unconditioned stimulus (UCS). In each case, a conditioned stimulus (CS, light) was either conditioned alone or in compound together with a more intense CS (noise or tone). The presence of overshadowing was demonstrated as reduced conditioning to the light when it had been previously conditioned in compound compared to when it had been conditioned alone. It was predicted that AMP and lesions to the n.acc shell would disrupt overshadowing. AMP was found to abolish overshadowing at 0.5 mg/kg, but not at 1 mg/kg. Contrary to prediction, the shell lesioned animals did not differ from shams. The results of Experiment 1 add to the evidence that the DA system can moderate salience processing of weaker predictors, also in cases where CS salience is manipulated directly via the physical intensities of the stimuli, as here. However, in terms of the brain structures involved, Experiment 2 suggests that, overshadowing is moderated by projections of the DA system without n.acc.

The childhood experience of care and abuse questionnaire (CECA.Q): validation in a community series.

BACKGROUND: Childhood neglect and abuse, as measured by retrospective interview, is highly predictive of psychiatric disorder in adult life and has an important role in aetiological models. However, such measures are labour-intensive, costly, and thus restricted to relatively modest sample sizes. A compact self-report assessment of childhood experience is invaluable for research screening purposes and large-scale survey investigation. METHOD: A self-report questionnaire (CECA.Q) was developed to mirror an existing validated interview measure: the childhood experience of care and abuse (CECA). The questionnaire assessed lack of parental care (neglect and antipathy), parental physical abuse, and sexual abuse from any adult before age 17. A high-risk series of 179 London women were interviewed using the CECA together with the PSE psychiatric assessment, and completed the CECA.Q at later follow-up. Repeat CECA.Qs were returned for 111 women and 99 women additionally completed the parental bonding instrument (PBI; Parker, Tupling, & Brown, 1979). RESULTS: Satisfactory internal scale consistency was achieved on the CECA.Q for antipathy (alpha = .81) and neglect (alpha = .80) scales. There was satisfactory test-retest for both care and abuse scales. Significant associations were found between CECA.Q scales and the parallel interview scales with cut-offs determined for high sensitivity and specificity. CECA.Q neglect and antipathy scales were also significantly related to PBI parental care. CECA.Q scales were significantly related to lifetime history of depression. Optimal cut-off scores revealed significant odds ratios (average of 2) for individual scales and depression. When indices were compiled to reflect peak severity of each type of adversity across perpetrator, odds-ratios increased (average 3). A dose-response effect was evident with the number of types of neglect/abuse and rate of lifetime depression. CONCLUSION: The CECA.Q shows satisfactory reliability and validity as a self-report measure for adverse childhood experience. The merits of having parallel questionnaire and interview instruments for both research and clinical work are discussed.

Modulation of latent inhibition in the rat by altered dopamine transmission in the nucleus accumbens at the time of conditioning.

Latent inhibition describes a process by which pre-exposure of a stimulus without consequence retards the learning of subsequent conditioned associations with that stimulus. It is well established that latent inhibition in rats is impaired by increased dopamine function and potentiated by reduced dopamine function. Previous evidence has suggested that these effects are modulated via the meso-accumbens dopamine projections. We have now undertaken three experiments to examine this issue directly, especially in the light of one study in which latent inhibition was reported to be unaffected by direct injection of amphetamine into the accumbens. Latent inhibition was studied using the effect of pre-exposure of a tone stimulus on the subsequent formation of a conditioned emotional response to the tone. 6-Hydroxydopamine-induced lesions of dopamine terminals in the nucleus accumbens resulted in potentiation of latent inhibition. Bilateral local injections of the dopamine antagonist haloperidol into the nucleus accumbens (0.5 microg/side) before conditioning also potentiated latent inhibition. Moreover, such injections were able to reverse the disruptive effect of systemic amphetamine (1mg/kg, i.p.) on latent inhibition. Bilateral local injection of amphetamine (5 microg/side) into the nucleus accumbens before conditioning was able to disrupt latent inhibition, provided that it was preceded by a systemic injection of amphetamine (1mg/kg) 24h earlier.We conclude that the attenuation of latent inhibition by increased dopamine function in the nucleus accumbens is brought about by impulse-dependent release of the neurotransmitter occurring at the time of conditioning. The previously reported failure to disrupt latent inhibition with intra-accumbens amphetamine is probably due to impulse-independent release of dopamine. The implications of these conclusions for theories linking disrupted latent inhibition to the attentional deficits in schizophrenia, and to the dopamine theory of this disorder, are discussed.

Evidence for dopamine D(1) receptor involvement in the stimulus selection task: overshadowing in the rat.

RATIONALE: A number of lines of evidence suggest that dopamine might play a role in stimulus selection, the process whereby specific cues are selected to guide action. OBJECTIVES: In order further to define the potential role for dopamine in stimulus selection, the present series of studies examined whether dopaminergic drugs modulate overshadowing, a paradigm that involves stimulus selection in rats. Overshadowing is where preferential learning occurs to one (usually the more salient) element of a stimulus compound. METHODS: Overshadowing was measured in rats using a thirst motivated conditioned emotional response paradigm (CER). Two simultaneously presented stimuli (light and tone) were paired with an aversive unconditioned stimulus (mild footshock); overshadowing is observed when learning to the less salient stimulus is weaker than learning to the same stimulus when it is conditioned alone. RESULTS: d-Amphetamine sulphate (1 mg/kg, IP) was found selectively to disrupt overshadowing, without affecting the CER in control animals. The dopamine (DA) D(2) receptor antagonists, haloperidol (0.2 mg/kg, IP) or raclopride (0.5 mg/kg, IP), failed to reverse amphetamine-induced disruption of overshadowing. In contrast, the selective DA D(1) antagonist SCH 23390 (0.05 mg/kg, IP) reversed amphetamine-induced disruption of overshadowing. The partial DA D(1) agonist SKF 38393 (5 mg/kg, IP) was found to abolish overshadowing when given alone. CONCLUSION: These data indicate a modulatory role for the DA D(1) receptor in the expression of stimulus selection and suggest that the DA D(1) receptor might play a role in salience allocation aspects of learning.

Enhancement of latent inhibition by two 5-HT2A receptor antagonists only when given at both pre-exposure and conditioning.

RATIONALE: Clozapine-like atypical antipsychotic drugs, such as olanzapine, risperidone and sertindole, bind most strongly to 5-HT(2A) receptors, which may contribute to their antipsychotic effects. Antipsychotic drugs, such as clozapine and haloperidol, have been found to enhance latent inhibition (LI) in humans and rats. LI is a process of learning to ignore irrelevant stimuli that is disrupted in acute, positive-symptom schizophrenia, and can be modelled in animals. OBJECTIVES: The aim of this study was to determine the effects of two selective 5-HT(2A) receptor antagonists, SR 46,349B and ICI 169,369, on LI, as a test of their antipsychotic potential. METHODS: Doses of the 5-HT(2A) receptor antagonists that were sufficient for receptor blockade were determined in 5-HT behavioural syndrome tests. SR 46,349B and ICI 169,369 were then tested for enhancement of LI and reversal of amphetamine-induced attenuation of LI in a conditioned suppression paradigm. RESULTS: SR 46,349B (0.6-2.4 mg kg(-1) i.p.) and ICI 169,369 (10-40 mg kg(-1) i.p.) antagonised 5-hydroxytryptophan (5-HTP)-induced head twitches and wet dog shakes, which are mediated by 5-HT(2A) receptors, but had no effect on mCPP-induced hypolocomotion, which is mediated by 5-HT(2C) receptors. Neither SR 46,349B (1.2 mg kg(-1) i.p.) nor ICI 169,369 (40 mg kg(-1) i.p) affected 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT)-induced forepaw treading, suggesting that they were not in vivo 5-HT(1A) receptor antagonists. SR 46,349B (2.4 mg kg(-1) i.p.) and ICI 169,369 (40 mg kg(-1) i.p.) enhanced LI when given at both the pre-exposure and conditioning stages of the paradigm, but not when given at either pre-exposure or conditioning only. Both drugs also reversed the disruption of LI induced by D-amphetamine (1 mg kg(-1) i.p.). CONCLUSIONS: The profile of SR 46,349B and ICI 169,369 in LI differs from that of clozapine and haloperidol in LI, which both enhance LI when given only at the conditioning stage of the paradigm.

Reduced Kamin blocking in non paranoid schizophrenia: associations with schizotypy.

Kamin blocking (KB) is an attentional phenomenon whereby prior learning about a stimulus (A) retards learning about a new stimulus (B) when later presented in compound (AB) with the original stimulus A. KB has been shown to be reduced in patients with schizophrenia. Using Oades' KB paradigm it has been suggested that drug treatment may influence the expression of KB abnormalities in patients. It is therefore unclear whether Reduced KB are due to drug treatment or to the illness itself. One experimental approach that circumvents drug treatment confounds is to study schizotypal traits in healthy volunteers. In the present study we investigated KB using the Oades paradigm in 27 healthy volunteers and 21 schizophrenic patients. We additionally investigated the relationship between KB performance and measures of schizotypal traits and a number of factors relevant to the experience of schizophrenia using the O-LIFE questionnaire. Our results indicate first a clear negative relationship between general schizotypy and more specifically, Unusual experiences (UNEX) and cognitive disorganisation (COGDIS) and KB performance. This relationship was qualitatively and quantitatively similar in both healthy volunteers and schizophrenic patients. Second we have independently replicated reduced KB in non-paranoid patients and no change in KB in paranoid patients using the Oades KB task. This study also confirms that reduced KB in non-paranoid patients is confined to early test trials (3-4) while the negative relationships with schizotypy scales UNEX and COGDIS that we have found are also confined to these early test trials confirming the psychological relevance of this specificity.

Scopolamine deficits in negative patterning discrimination: evidence for a role of the central cholinergic system in retention but not acquisition of non-spatial configural association learning.

The effects of scopolamine (0.1 mg/kg s.c. and 0.6 mg/kg s.c.) were assessed on the acquisition and retention of a negative patterning discrimination task in rats. At 0.1 mg/kg scopolamine did not affect either acquisition or retention of the task. At 0.6 mg/kg scopolamine did not affect acquisition but did impair retention of the task. This impairment is likely to be centrally mediated as N-methyl scopolamine (0.6 mg/kg s.c.) did not affect retention. Lack of effect of scopolamine on acquisition of the task indicates that the central cholinergic system is not a necessary substrate of the acquisition of non-spatial configural associations. The scopolamine-induced deficit in retention of the task, suggests that there may, however, be a central cholinergic involvement in the retention/retrieval of this type of learning.

Reversal of amphetamine-induced behaviours by MDL 100,907, a selective 5-HT2A antagonist.

MDL 100,907 is a potent and selective antagonist of the 5-HT2A receptor which, unlike other antagonists at this receptor, has little affinity for the 5-HT2C receptor. We have investigated the antipsychotic potential of MDL 100,907 by examining its ability to antagonise different behavioural effects of amphetamine in rats. MDL 100,907 reversed the locomotor stimulant effects of amphetamine in rats without itself having any effect on locomotor activity. It also antagonised the disruptive effects of amphetamine on the development of latent inhibition. In contrast, MDL 100,907 had no effect on the discriminative stimulus properties of amphetamine, nor did it affect the ability of amphetamine to reduce the threshold required to sustain rewarding brain stimulation in the ventral tegmental area. This profile is different from that of typical and atypical neuroleptics, and also from other 5-HT2 receptor antagonists, which lack the selectivity of MDL 100,907. These results suggest that MDL 100,907 may have a unique interaction with dopaminergic systems and support the further development of selective 5-HT2 receptor antagonists as a novel therapeutic strategy for schizophrenia.

Latent inhibition: the nucleus accumbens connection revisited.

It has been proposed that dopaminergic transmission in the nucleus accumbens plays a key role in regulating latent inhibition (LI), i.e. the retardation of conditioning that occurs if a to-be-conditioned stimulus is first presented a number of times ('preexposure') without other consequence. New evidence in support of this hypothesis is presented or reviewed here, showing that: (1) intra-accumbens injection of haloperidol at the time of conditioning potentiates LI; (2) destruction of dopaminergic terminals in the nucleus accumbens potentiates LI; (3) intra-accumbens haloperidol reverses the blockade of LI caused by systemic nicotine; (4) intra-accumbens haloperidol reverses the blockade of LI caused by systemic amphetamine; (5) after a single systemic injection of amphetamine (insufficient on its own to block LI), a subsequent intra-accumbens injection of amphetamine at the time of conditioning blocks LI; and (6) intra-accumbens (like systemic) amphetamine administered 15 min before conditioning, without prior systemic amphetamine, failed to block LI. The difference between the effects on LI of one and two administrations of amphetamine, respectively, is interpreted in terms of the need for sensitisation of the response to amphetamine, with the result that the response to the second administration includes a component of impulse-dependent dopamine release in the nucleus accumbens that is otherwise lacking. Data from dialysis experiments suggest that such impulse-dependent accumbens dopamine release also occurs at relatively long delays after a single systemic administration of amphetamine. It was accordingly predicted, and found, that, although LI is intact 15 min after an i.p. injection (confirming previous results), it is abolished at 90 min after the injection of amphetamine. This finding is consistent with the effects of amphetamine in human subjects, in whom LI is blocked 90 min after a single oral administration. Overall, these results strengthen the case that the blockade of LI by elevated, and potentiation of LI by decreased, dopaminergic transmission are both due specifically to actions in the nucleus accumbens; and also add to the similarities between LI studied in animal and human subjects, respectively.

Enhancement of working memory performance in the rat by MDL 26,479, a novel compound with activity at the GABAA receptor complex.

MDL 26,479, a novel triazole compound with action at the GABAA receptor complex, was examined in 2 models of working memory deficit in the rat. MDL 26,479 attenuated a scopolamine-induced acquisition deficit in a T-maze reinforced alternation task. MDL 26,479 also reversed a performance deficit induced by increased delay between sample and choice trials in the same task, suggesting that the compound may have memory enhancing potential. This finding further supports claims that drugs acting at the GABAA receptor complex are of potential use in the treatment of memory disorder.

Reversal of learning and memory impairments following lesion of the nucleus basalis magnocellularis (NBM) by concurrent noradrenergic depletion using DSP4 in the rat.

In the following study the behavioural effects of simultaneous lesion of the nucleus basalis magnocellularis (NBM) using ibotenic acid and noradrenergic depletion following a single i.p. administration of DSP4 (50 mg/kg) were examined in the rat. NBM lesion induced a deficit in acquisition of a reinforced T-maze alternation task, a working memory adaptation of a spatial navigation task in a water maze and 24 h retention in a passive avoidance task compared to sham controls. No effect of the lesion on a reference memory version of spatial navigation in a water maze task was found. Animals that received a combination of NBM lesion and DSP4 treatment showed no impairment on any of the tasks that were impaired by NBM lesion alone. This indicates a reversal of the learning and memory deficits consequent to NBM lesion by simultaneous noradrenergic depletion. NBM lesion induced a significant reduction in choline-acetyltransferase activity in the frontal cortex, and DSP4 induced a significant decrease in noradrenaline concentration in occipital cortex and hippocampus, confirming the effects of these treatments. These results suggest an interaction between central noradrenergic and cholinergic systems in learning and memory processes.

Effects of clozapine on latent inhibition in the rat.

In the present study we have examined the effect of clozapine, an atypical antipsychotic drug, on latent inhibition (LI) using the conditioned emotional response (CER) procedure. In this procedure, ten pre-exposures to the to-be-conditioned stimulus result in weak or no LI whereas 30 pre-exposures produce robust LI. Three different experimental protocols were used to study the effects of clozapine: facilitation of LI in animals subjected to ten pre-exposures to the to-be-conditioned stimulus; antagonism of the disruptive effect of amphetamine (1mg/kg, s.c.) on LI in animals receiving 30 pre-exposures; antagonism of the disruptive effect of nicotine (0.6mg/kg, s.c.) on LI in animals receiving 30 pre-exposures. High doses of clozapine (3 and 10mg/kg, s.c.) disrupted the CER in non pre-exposed animals. Despite this, clozapine significantly facilitated the development of LI at 1 and 10mg/kg and significantly attenuated the disruptive effects of nicotine at 0.3 and 1mg/kg and of amphetamine at 2 and 5mg/kg. These results demonstrate that clozapine is active in the LI model and further support the utility of this model in the study of mechanisms of action of antipsychotic drugs.

An investigation into age and gender differences in human Kamin blocking, using a computerized task.

Kamin blocking (KB) is a function within selective attention found to be deficient in schizophrenia. Disparate results in the KB literature, specifically regarding age and gender effects, suggest that we do not yet have a comprehensive understanding of KB in normal human development. The aim of this study is to provide a thorough investigation into the development and occurrence of KB in a normal population. The design replicated and extended a study by Oades, Roepcke, and Schepker (1996). KB is measured using a computer game called the "mouse in the house." Participants must use a joystick to move an icon around a set floor plan, to find a hidden location. These locations are cued by sets of colors, which denote the KB paradigm. Data was collected on 222 participants across 5 age groups (6-8 years; 9-12 years; 13-17 years; 18-21 years; 22+ years). Comparisons were carried out for age and gender effects. KB was observed in all age groups, but there was no significant effect of age on mean KB score. A measure of frequency of participants who showed KB did show a significant increase with age. A significant difference was found between males and females, with females having higher KB score than males. The gender difference was present from the earliest age tested. Our findings suggest significant age and gender differences in the manifestation of selective attention and information processing abilities. This has implications for understanding the development of attention and the understanding of the age and gender dependence of the development of schizophrenia.

Differential effects of scopolamine and mecamylamine on working and reference memory in the rat.

The effects of the muscarinic antagonist scopolamine (0.1-0.6 mg/kg, IP) and the nicotinic antagonist mecamylamine (1-10 mg/kg) were compared in T-maze alternation and discrimination tasks in the rat. Scopolamine dose dependently disrupted performance on the alternation task and potentiated the increase in errors made in controls when the delay between forced and choice runs was increased from 0 to 30 s. Mecamylamine disrupted performance at the 10-mg/kg dose only and dose dependently inhibited the increase in errors made in controls when the delay between forced and choice runs was increased to 30 s. In simple T-maze discrimination, only the 0.6-mg/kg dose of scopolamine disrupted performance of the task, while mecamylamine at both 5 and 10 mg/kg disrupted task performance. These results confirm that working memory tasks are more sensitive to central muscarinic blockade than reference memory tasks. They also demonstrate that in delay conditions working memory performance is enhanced following central nicotinic blockade while reference memory performance is disrupted. This suggests that centrally active muscarinic and nicotinic antagonists have dissociable effects on memory processes in the rat.

MDL 73,147EF, a 5-HT3 antagonist, facilitates latent inhibition in the rat.

Latent inhibition (LI) is a behavioral model of selective attention that has been used to study the attentional deficits seen in schizophrenia. In the present study, we examined the effect of 5-hydroxytryptamine3 (5-HT3) receptor blockade on LI using the conditioned emotional response (CER) procedure. Prior exposure to 20, 30, or 40 stimulus presentations significantly, and almost completely, inhibited the CER to that stimulus. This LI effect was much weaker when only 10 preexposures were given. 1H-indole-3-carboxylic acid, trans-octahydro-3-oxo-2,6-methano-2H-quinolizin-8-yl ester methanesulfonate (MDL 73,147EF), a selective 5-HT3 receptor antagonist, significantly facilitated the LI effect observed after 10 preexposures at 0.1 mg/kg but not at 0.01 mg/kg. The magnitude of this effect was comparable to that observed with the classical neuroleptic haloperidol (0.1 mg/kg). Neither MDL 73,147EF nor haloperidol affected the CER in animals not preexposed to the stimulus. These results strongly corroborate suggestions that 5-HT3 receptor antagonists will be of use in the treatment of schizophrenia.

Predicting onset of depression: the Vulnerability to Depression Questionnaire.

OBJECTIVES: The development of a self-report questionnaire capable of assessing cognitive and interpersonal vulnerability factors for clinical depression is described. The Vulnerability to Depression Questionnaire (VDQ) was developed to provide a brief, economical alternative to the Self-Evaluation and Social Support interview (SESS; O'Connor & Brown, 1984), assessing negative evaluation of self, negative interaction with partner or child and lack of a support figure. DESIGN: The VDQ was tested in a prospective study of community-based women who were contacted on three occasions over the course of approximately 1 year, to: (i) compare the VDQ's capacity to categorize vulnerability compared with the SESS interview, and (ii) to test the VDQ's prediction of onset of clinical depression during the follow-up. METHOD: Selected nondepressed respondents completed the VDQ and were interviewed to determine their vulnerability using the SESS. They were re-interviewed on two further occasions during the follow-up period, and the VDQ was also re-administered at the time of first follow-up. Onset of clinical depression during the follow-up was assessed by interview at each contact. RESULTS: Comparison of VDQ and SESS interview classification of participants' vulnerability at first contact indicated that the questionnaire had good sensitivity and specificity. Test-retest scores for the VDQ indicated satisfactory levels of reliability. VDQ scores also predicted onset of clinical depression in the follow-up period. CONCLUSIONS: Results suggest that the VDQ is an economical and effective means of screening large populations for the purposes of risk assessment, to aid future research into clinical depression and to facilitate the implementation of intervention strategies.

D-amphetamine and antipsychotic drug effects on latent inhibition in mice lacking dopamine D2 receptors.

Drugs that induce psychosis, such as D-amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd2-/-), we first investigated whether D2 is required for AMP disruption of latent inhibition (LI). LI is a process of learning to ignore irrelevant stimuli. Disruption of LI by AMP models impaired attention and abnormal salience allocation consequent to dysregulated dopamine relevant to schizophrenia. AMP disruption of LI was seen in both wild-type (WT) and Drd2-/-. This was in contrast to AMP-induced locomotor hyperactivity, which was reduced in Drd2-/-. AMP disruption of LI was attenuated in mice lacking dopamine receptor D1 (Drd1-/-), suggesting that D1 may play a role in AMP disruption of LI. Further supporting this possibility, we found that D1 antagonist SKF83566 attenuated AMP disruption of LI in WT. Remarkably, both haloperidol and clozapine attenuated AMP disruption of LI in Drd2-/-. This demonstrates that antipsychotic drugs can attenuate AMP disruption of learning to ignore irrelevant stimuli in the absence of D2 receptors. Data suggest that D2 is not essential either for AMP to disrupt or for antipsychotic drugs to reverse AMP disruption of learning to ignore irrelevant stimuli and further that D1 merits investigation in the mediation of AMP disruption of these processes.

Measuring memory impairment in community-based patients with schizophrenia. Case-control study.

BACKGROUND: The majority of memory impairment studies in schizophrenia are cohort studies using laboratory-based tests, which make it difficult to estimate the true extent and relevance of memory impairment in patients with schizophrenia in the community. AIMS: To examine the extent of memory impairment in community-based patients with schizophrenia using a clinically relevant test. METHOD: All patients with schizophrenia (n=190) in one catchment area were identified, of whom 133 were potentially eligible for the study; 73 patients volunteered to take part. They were assessed using the Rivermead Behavioural Memory Test (RBMT), the National Adult Reading Test, the Positive and Negative Syndrome Scale, the Health of the Nation Outcome Scales and the Scales and the Office for National Statistics Classification of Occupation. Their performance on the memory test was compared with that of matched controls (n=71). RESULTS: Patients as a group performed significantly worse (P<0.001) than controls on the RBMT. Using the RBMT normative scores, 81% of patients were found to have impaired memory compared with 28% of controls. CONCLUSIONS: Using a clinically relevant test, the majority of community-based patients with schizophrenia may have memory impairment.

Single mothers, poverty and depression.

The present study set out to examine the relationship between marital status, poverty and depression in a sample of inner-city women. Single and married mothers were followed up over a 2-year period during which time rates of psychosocial risk factors, onset of depression and experience of chronic episodes were measured. Risk of onset was double among single mothers. Single mothers were twice as likely as their married counterparts to be in financial hardship, despite being twice as likely to be in full-time employment. Both of these factors were independently associated with onset in single mothers. The link between them and onset was via their association with humiliating or entrapping severe life events. Single parents were at a much raised risk of experiencing these events. Onset was also more likely to follow such an event when women had poor self-esteem and lack of support, both of which were more common among single mothers. These risk factors were more frequently found among those in financial hardship. Financial hardship was also related to risk of having a chronic episode (lasting at least a year), of which single parents were also at greater risk. The majority of chronic episodes among single mothers had their origins in prior marital difficulties or widowhood and rates of chronicity reduced with length of time spent in single parenthood. Results are discussed in terms of an aetiological model of onset in which financial hardship probably influences outcome at a wide variety of points.