Highlights
IN THIS ISSUE
- CRAIG MORGAN
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- Published online by Cambridge University Press:
- 19 July 2006, pp. 1051-1052
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This issue contains two reviews on cognitive reserve and decline, and five further papers examine various aspects of cognition and psychiatric disorder. Three papers focus on aspects of depression, and three individual papers examine a variety of topics.
Review Article
Cognitive reserve in neuropsychiatry
- J. H. BARNETT, C. H. SALMOND, P. B. JONES, B. J. SAHAKIAN
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- 06 April 2006, pp. 1053-1064
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Background. The idea that superior cognitive function acts as a protective factor against dementia and the consequences of head injury is well established. Here we suggest the hypothesis that cognitive reserve is also important in neuropsychiatric disorders including schizophrenia, bipolar disorder and depression.
Method. We review the history of passive and active models of reserve, and apply the concept to neuropsychiatric disorders. Schizophrenia is used as an exemplar because the effects of premorbid IQ and cognitive function in this disorder have been extensively studied.
Results. Cognitive reserve may impact on neuropsychiatric disorders in three ways: by affecting the risk for developing the disorder, in the expression of symptoms within disorders, and in patients' functional outcome. Cognitive failure below a certain threshold may alone, or in combination with common psychiatric symptoms, produce neuropsychiatric syndromes.
Conclusions. Consideration of cognitive reserve may considerably improve our understanding of individual differences in the causes and consequences of neuropsychiatric disorders. For these reasons, the concept of cognitive reserve should be incorporated in future studies of neuropsychiatric disorder. It may be possible to enhance cognitive reserve through pharmacological or non-pharmacological means, such as education, neurocognitive activation or other treatment programmes.
Brain reserve and cognitive decline: a non-parametric systematic review
- MICHAEL J. VALENZUELA, PERMINDER SACHDEV
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- 02 May 2006, pp. 1065-1073
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Background. A previous companion paper to this report (Valenzuela & Sachdev, Psychological Medicine 2006, 36, 441–454) suggests a link between behavioural brain reserve and incident dementia; however, the issues of covariate control and ascertainment bias were not directly addressed. Our aim was to quantitatively review an independent set of longitudinal studies of cognitive change in order to clarify these factors.
Method. Cohort studies of the effects of education, occupation, and mental activities on cognitive decline were of interest. Abstracts were identified in MEDLINE (1966–September 2004), CURRENT CONTENTS (to September 2004), PsychINFO (1984–September 2004), Cochrane Library Databases and reference lists from relevant articles. Eighteen studies met inclusion criteria. Key information was extracted by both reviewers onto a standard template with a high level of agreement. Cognitive decline studies were integrated using a non-parametric method after converting outcome data onto a common effect size metric.
Results. Higher behavioural brain reserve was related to decreased longitudinal cognitive decline after control for covariates in source studies (ϕ=1·70, p<0·001). This effect was robust to correction for both multiple predictors and multiple outcome measures and was the result of integrating data derived from more than 47000 individuals.
Conclusions. This study affirms that the link between behavioural brain reserve and incident dementia is most likely due to fundamentally different cognitive trajectories rather than confound factors.
Original Article
Theory of Mind (ToM) and counterfactuality deficits in schizophrenia: misperception or misinterpretation?
- DAVID I. LEITMAN, RACHEL ZIWICH, ROEY PASTERNAK, DANIEL C. JAVITT
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- 15 May 2006, pp. 1075-1083
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Background. Theory of Mind (ToM) refers to the ability to infer another person's mental state based upon interactional information. ToM deficits have been suggested to underlie crucial aspects of social interaction failure in disorders such as autism and schizophrenia, although the development of paradigms for demonstrating such deficits remains an ongoing area of research. Recent studies have explored the use of sarcasm perception, in which subjects must infer an individual's sincerity or lack thereof, as a ‘real-life’ index of ToM ability, and as an index of functioning of specific right hemispheric structures. Sarcastic detection ability has not previously been studied in schizophrenia, although patients have been shown to have deficits in ability to decode emotional information from speech (‘affective prosody’).
Method. Twenty-two schizophrenia patients and 17 control subjects were tested on their ability to detect sarcasm from spoken speech as well as measures of affective prosody and basic pitch perception.
Results. Despite normal overall intelligence, patients performed substantially worse than controls in ability to detect sarcasm (d=2·2), showing both decreased sensitivity (A′) in detection of sincerity versus sarcasm and an increased bias (B″) toward sincerity. Correlations across groups revealed significant relationships between impairments in sarcasm recognition, affective prosody and basic pitch perception.
Conclusions. These findings demonstrate substantial deficits in ability to infer an internal subjective state based upon vocal modulation among subjects with schizophrenia. Deficits were related to, but were significantly more severe than, more general forms of prosodic and sensorial misperception, and are consistent with both right hemispheric and ‘bottom-up’ theories of the disorder.
Dissociable mechanisms for memory impairment in bipolar disorder and schizophrenia
- DAVID C. GLAHN, JENNIFER BARRETT, CARRIE E. BEARDEN, JIM MINTZ, MICHAEL F. GREEN, E. SERAP MONKUL, PABLO NAJT, JAIR C. SOARES, DAWN I. VELLIGAN
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- 31 May 2006, pp. 1085-1095
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Background. Although memory deficits are consistently reported in schizophrenia and bipolar disorder, the mechanisms underlying these impairments are poorly understood. Clarifying the nature and degree of overlap in memory deficits between the two illnesses could help to distinguish brain systems disrupted in these illnesses, and indicate cognitive remediation strategies to improve patient outcomes.
Method. We examined performance on a non-verbal memory task in clinically stable out-patients with bipolar disorder (n=40), schizophrenia (n=40), and healthy comparison subjects (n=40). This task includes conditions in which distinct mnemonic strategies – namely, using context to organize familiar stimuli or using holistic representation of novel stimuli – facilitate performance.
Result. When compared to a reference condition, bipolar patients had deficits consistent with organizational dysfunction and poor detection of novel information. Although patients with schizophrenia performed worse than the other groups, they were only differentially impaired when organizational demands were significant. Task performance was not correlated with severity of clinical symptomatology.
Conclusions. This pattern of distinct memory impairments implies disturbances in partially overlapping neural systems in bipolar disorder and schizophrenia. Evidence of impairment in detection of novel stimuli that is unique to bipolar disorder suggests that, while the absolute level of cognitive dysfunction is less severe in bipolar disorder as compared to schizophrenia, subtle disruptions in memory are present. These findings can be used to plan targeted cognitive remediation programs by helping patients to capitalize on intact functions and to learn new strategies that they do not employ without training.
Abnormal function of the brain system supporting motivated attention in medicated patients with schizophrenia: an fMRI study
- PETER F. LIDDLE, KRISTIN R. LAURENS, KENT A. KIEHL, ELTON T. C. NGAN
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- 02 May 2006, pp. 1097-1108
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Background. Patients with schizophrenia have an impaired ability to generate activity that is appropriate to current circumstances and goals.
Method. We report a study using functional magnetic resonance imaging (fMRI) to examine cerebral activity during a three-tone auditory oddball target detection task in a sample of 28 patients with schizophrenia and 28 healthy controls.
Results. The patients exhibited significantly less activation in response to target stimuli relative to baseline in an extensive set of sites in association neocortex, paralimbic cortex, limbic structures and subcortical nuclei, yet demonstrated a normal level of activation in the sensorimotor cortex. Comparison of activity elicited by rare target stimuli with that elicited by equally rare novel stimuli makes it possible to distinguish cerebral activity associated with attention to behaviourally salient stimuli from activity associated with attending to other attention-capturing stimuli. This comparison revealed that the patients with schizophrenia also exhibited a deficit in activation of basal forebrain areas that mediate motivation during the processing of behaviourally salient stimuli, including the amygdala, ventral striatum, orbital frontal cortex and rostral anterior cingulate cortex.
Conclusion. Patients with schizophrenia have a deficit in function of the brain system concerned with mediating motivation, in addition to a more general deficit in the cerebral response to attention-captivating stimuli.
Reasoning under uncertainty: heuristic judgments in patients with persecutory delusions or depression
- RHIANNON CORCORAN, SINEAD CUMMINS, GEORGINA ROWSE, ROSIE MOORE, NIGEL BLACKWOOD, ROBERT HOWARD, PETER KINDERMAN, RICHARD P. BENTALL
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- 31 May 2006, pp. 1109-1118
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Objective. The substantial literature examining social reasoning in people with delusions has, to date, neglected the commonest form of decision making in daily life. We address this imbalance by reporting here the findings of the first study to explore heuristic reasoning in people with persecutory delusions.
Method. People with active or remitted paranoid delusions, depressed and healthy adults performed two novel heuristic reasoning tasks that varied in emotional valence.
Results. The findings indicated that people with persecutory delusions displayed biases during heuristic reasoning that were most obvious when reasoning about threatening and positive material. Clear similarities existed between the currently paranoid group and the depressed group in terms of their reasoning about the likelihood of events happening to them, with both groups tending to believe that pleasant things would not happen to them. However, only the currently paranoid group showed an increased tendency to view other people as threatening.
Conclusion. This study has initiated the exploration of heuristic reasoning in paranoia and depression. The findings have therapeutic utility and future work could focus on the differentiation of paranoia and depression at a cognitive level.
Cognitive function in unaffected twins discordant for affective disorder
- MAJ VINBERG CHRISTENSEN, KIRSTEN OHM KYVIK, LARS VEDEL KESSING
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- 31 May 2006, pp. 1119-1129
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Background. Patients may present with cognitive impairment in the euthymic phase of affective disorder, but it is unclear whether the impairment is prevalent before onset of the illness. The aim of the present study was to examine the hypothesis that genetic liability to affective disorder is associated with cognitive impairment.
Method. In a cross-sectional high-risk case–control study, healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. Cognitive performance of 203 High-Risk and Low-Risk twins was compared.
Results. Healthy twins discordant for unipolar disorder showed lower performance on almost all measures of cognitive function: selective and sustained attention, executive function, language processing and working and declarative memory, and also after adjustment for demographic variables, subclinical symptoms and minor psychopathology. Healthy twins discordant for bipolar disorder showed lower performance on tests measuring episodic and working memory, also after adjustment for the above-mentioned covariables. The discrete cognitive impairment found seemed to be related to genetic liability, as the MZ High-Risk twins showed significant impairment on selective and sustained attention, executive function, language processing and working and declarative memory, whereas the DZ High-Risk twins presented with significantly lower scores only on language processing and episodic memory.
Conclusions. The hypothesis that discrete cognitive impairment is present before the onset of the affective disorder and is genetically transmitted was supported. Thus, cognitive function may be a candidate endophenotype for affective disorders.
Assessing personality traits associated with depression: the utility of a tiered model
- GORDON PARKER, VIJAYA MANICAVASAGAR, JO CRAWFORD, LUCY TULLY, GEMMA GLADSTONE
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- 02 May 2006, pp. 1131-1139
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Background. We sought to develop a refined measure of eight personality traits or constructs observed in those who develop depression. We report the psychometric properties of the derived Temperament and Personality (T&P) questionnaire, as well as a pilot study examining its capacity to differentiate over-represented personality traits in those with depression.
Method. The factor structure of the T&P measure was examined in a general practice sample of 529 subjects. We imposed a range of factorial solutions to determine how higher-order molar constructs arborized to eight lower-order constructs. Scale scores generated at each derived tier were contrasted for 52 out-patients with major depression and control subjects from the general practice sample to pursue over-represented personality constructs, and to clarify if an optimal number of constructs could be identified.
Results. In the factor analysis, some 90% of the items loaded on their a priori construct. The questionnaire showed high internal consistency, test–retest reliability and minimal sensitivity to mood state effects. Analyses rejected the hypothesis that risk to depression might be generally affected by individuals merely scoring high on all ‘normal’ personality styles, whether higher-order or lower-order traits.
Conclusions. Findings suggest that, while identified constructs linked well with the widely accepted theoretical model of personality (the Five Factor Model) at one tier, such a fixed model may be too inflexible. We therefore detail potential advantages to using a multi-tiered model of personality traits in application studies.
A controlled longitudinal 5-year follow-up study of children at high and low risk for panic disorder and major depression
- JOSEPH BIEDERMAN, CARTER PETTY, DINA R. HIRSHFELD-BECKER, AUDE HENIN, STEPHEN V. FARAONE, DANIELLE DANG, ALEKSANDRA JAKUBOWSKI, JERROLD F. ROSENBAUM
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- 15 May 2006, pp. 1141-1152
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Background. To evaluate the longitudinal course of psychiatric disorders in children of parents with panic disorder (PD) and major depression (MD) as they transition through the period of risk from childhood into adolescence.
Method. Over a 5-year follow-up, we compared psychiatric disorders in four groups of children: (1) offspring of parents with PD plus MD (n=136); (2) offspring of parents with PD without MD (n=27); (3) offspring of parents with MD but without PD (n=53); and (4) offspring of non-PD non-MD parents (n=103).
Results. Parental PD was significantly associated with increased risk for anxiety disorders, irrespective of parental MD. Parental MD was associated with increased risk for MD, disruptive behavior disorders, and deficits in psychosocial functioning, irrespective of parental PD.
Conclusions. These longitudinal findings confirm and extend previous cross-sectional results documenting significant associations between PD and MD in parents and patterns of psychopathology and dysfunction in their offspring.
The temporal relationship of the onsets of alcohol dependence and major depression: using a genetically informative study design
- PO-HSIU KUO, CHARLES O. GARDNER, KENNETH S. KENDLER, CAROL A. PRESCOTT
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- 31 May 2006, pp. 1153-1162
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Background. Although alcohol dependence (AD) and major depression (MD) are highly co-morbid, their causal relationship is unclear. In this longitudinal study, we used a genetically informative population-based twin sample to examine the age-at-onset distributions and the temporal relationship of AD and MD.
Method. Our sample included 7477 twins, whose diagnoses of AD and MD and age-at-onset information were obtained from structured interviews. Individual-level survival analyses were conducted based on 2603 monozygotic (MZ) twins, and co-twin diagnosis was included in models as an index of familiar liability to AD and MD.
Results. The age-at-onset distributions of AD and MD differed substantially. Most onsets of AD were in young adulthood, whereas MD had a flatter distribution across age. Most subjects, especially women, had an onset of MD preceding AD. Prior MD significantly affected risk for developing AD, and this risk decreased over time. By contrast, preceding AD had negligible effects on the risk for future MD. Familial risk was transmitted within disorders but there was little evidence of additional familial liability shared across disorders.
Conclusions. Risk for developing AD was substantially increased by a prior episode of MD. The association was only partially accounted for by familial factors, providing support for a direct causal effect such as self-medication. The etiologic path from AD to MD was insignificant.
The influence of emotions on inhibitory functioning in borderline personality disorder
- GREGOR DOMES, BRITTA WINTER, KNUT SCHNELL, KNUT VOHS, KRISTINA FAST, SABINE C. HERPERTZ
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- 15 May 2006, pp. 1163-1172
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Background. Borderline personality disorder (BPD) is characterized by an emotionally unstable and impulsive cognitive and behavioral style. Inhibitory dysfunction has been hypothesized as playing a crucial role in BPD psychopathology. This study aimed to systematically investigate differential inhibitory functions in patients with BPD as compared to healthy controls, and to investigate their expected impairment in the context of aversive emotions by comparing performances in neuropsychological tasks that present both neutral and emotional material.
Method. Unmedicated female patients with BPD (n=28) were compared with age-matched healthy female controls (n=30) in the following tasks: the emotional Stroop test (inhibition of interference), directed forgetting (intentional, resource-dependent inhibition), and an emotional variant of the negative priming task (automatic, resource-independent inhibition).
Results. In comparison with the controls, the BPD patients showed reduced inhibition of negative material in the directed forgetting task and in the negative priming task. No effect was found in the emotional Stroop test. Significant correlations with current affect as well as trait anxiety and anger (but not impulsiveness) were found in the BPD group specifically for negative stimuli, while no such correlations were found in the control group. In addition to inhibitory deficiencies, BPD patients had difficulties remembering positive words in the directed forgetting task.
Conclusions. Our data suggest that individuals with BPD have difficulties in actively suppressing irrelevant information when it is of an aversive nature. Inhibitory dysfunction appears to be closely related to state and trait variables of unstable affect, but not to self-reported impulsiveness.
Behavioural and neuropsychological correlates of frontal lobe features in dementia
- SEBASTIAAN ENGELBORGHS, KAREN MAERTENS, PETER MARIËN, ELLEN VLOEBERGHS, NORE SOMERS, GUY NAGELS, PETER P. DE DEYN
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- 15 May 2006, pp. 1173-1182
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Background. In order to characterize frontal lobe features and their behavioural and cognitive correlates across diagnostic categories, we performed a cross-sectional analysis of behavioural and neuropsychological data from a large, prospective Belgian study on behavioural and psychological signs and symptoms of dementia (BPSD).
Method. Patients with probable Alzheimer's disease (AD) (n=170), frontotemporal dementia (FTD) (n=28), mixed dementia (MXD) (n=29) and dementia with Lewy bodies (DLB) (n=21) were included and underwent neuropsychological and behavioural assessment by means of a battery of tests and scales. Frontal lobe symptoms were quantified by means of the Middelheim Frontality Score (MFS).
Results. In AD (and to a lesser extent in MXD), MFS total scores were negatively correlated with scores on MMSE (Spearman: r=−0·36, p<0·001) and a Verbal Fluency Task (r=−0·38, p<0·001) and were associated with increased severity and frequency of psychosis (r=0·24, p<0·01), activity disturbances (r=0·44, p<0·001) and aggressiveness (r=0·43, p<0·001). In DLB, MFS total scores were negatively correlated with MMSE scores (r=−0·50, p=0·020). No associations were found in FTD patients.
Conclusions. A cross-sectional analysis of frontal lobe features, behavioural characteristics and neuropsychological data demonstrated that, in AD (and to a lesser extent in MXD) patients, frontal lobe symptoms were associated with more pronounced cognitive deficits (of frontal origin), with increased severity and frequency of agitated and aggressive behaviour, and with increased severity of psychosis and depressive symptoms. Given the small sample sizes of the DLB and FTD patient groups, negative findings in these patient groups should be interpreted cautiously.
Pre-morbid IQ and response to routine outcome assessment
- MIKE SLADE, MORVEN LEESE, MATT GILLARD, ELIZABETH KUIPERS, GRAHAM THORNICROFT
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- 17 May 2006, pp. 1183-1191
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Background. Routine use of standardized outcome measures within adult mental health services is compulsory in many countries, but not common in clinical practice. As well as political and professional factors, one reason may be that there is little empirical evidence of benefit for patients. It is therefore important to identify predictors of response. Pre-morbid intellectual functioning has predicted response to other interventions. This paper tests the hypothesis that pre-morbid IQ impacts on the effectiveness of routine assessment and feedback of outcome measures.
Method. The Feedback of Outcomes to Users and Staff (FOCUS) single-blind randomized controlled trial (RCT) investigated routine completion and feedback of outcome measures for 160 (101 intervention, 59 control) adult mental health service patients in Croydon, South London (International Standard RCT Number 16971059).
Results. Patients in the top quarter (pre-morbid IQ>110) differentially improved in patient-rated unmet need (adjusted difference 3·4, 95% CI 0·8 to 5·9, p=0·012) and in the top half (pre-morbid IQ>99) in quality of life (adjusted difference −0·6, 95% CI −1·1 to −0·1, p=0·02). The top quarter result remained when controlling for the influence of baseline (p=0·004) and baseline plus follow-up variables (p=0·047).
Conclusions. Feedback of routine outcome measures may improve outcome for patients with higher pre-morbid IQ. There is a need to understand more how routine outcome information is used by staff and patients to inform care. If the goal of routine use of outcome measures is to benefit patients directly, then targeted policies are required.