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Biomedical subjects

A S David

Publications and source records attributed to A S David.

At least 19 recordsLinked to original sources
PubMed2004

The impact of early and late damage to the human amygdala on 'theory of mind' reasoning.

There is a burgeoning interest in the neural basis of the ability to attribute mental states to others; a capacity referred to as 'theory of mind' (ToM). We examined the effects of lesions of the amygdala which arise at different stages of development on this key aspect of social cognition. Tests of ToM, executive and general neuropsychological function were given to subjects with lesions of the amygdala arising congenitally or in early childhood ('early damage', n = 15), subjects who acquired damage to the amygdala in adulthood ('late damage' n = 11) and matched clinical (n = 14) and healthy comparison groups (n = 38). Subjects with early damage to the amygdala, particularly if the lesion was associated with childhood onset of seizures, were impaired relative to all other groups on more advanced tests of ToM reasoning, such as detecting tactless or ironic comments or interpreting non-literal utterances. These deficits held for subjects with either left or right early amygdala damage and encompassed the understanding of both the beliefs and emotional states of others. In contrast, subjects who acquired damage to the amygdala in adulthood (usually as part of an anterior temporal lobectomy) were not impaired in ToM reasoning relative to both clinical and healthy controls, supporting the position that the amygdala is not part of the neural circuitry mediating the 'on-line' performance of ToM reasoning. In line with theories which claim that ToM is an independent faculty of cognition, we found that the pattern of results held after co-varying for measures of executive function, memory and general intellectual functioning. We discuss the results in the light of recent theories which link early developmental insults to the amygdala with the ToM impairments which are thought to be a core neurocognitive deficit found in disorders such as autism. We conclude that the amygdala may play an important role in the neural systems supporting the normal development of ToM reasoning.

Adult↗
PubMed2004

The epidemiology of depersonalisation and derealisation. A systematic review.

BACKGROUND: Symptoms of depersonalisation (DP) and derealisation (DR) are increasingly recognised in both clinical and non-clinical settings, but their importance and underlying pathophysiology is only now being addressed. METHODS: This paper is a systematic review of the current state of knowledge about the prevalence of depersonalisation and derealisation using computerised databases and citation searches. All potential studies were examined and numerical data included. Three categories of study are reviewed: questionnaire and interview surveys of selected student and non-clinical samples; population-based community surveys using standardised diagnostic interviews; and clinical surveys of depersonalisation/derealisation symptoms occurring within inpatients with psychiatric disorders. In addition, we present newly analysed data of the prevalence of depersonalisation/derealisation from five large population-based studies. RESULTS: Epidemiological surveys demonstrate that transient symptoms of depersonalisation/derealisation in the general population are common, with a lifetime prevalence rate of between 26 and 74% and between 31 and 66% at the time of a traumatic event. Community surveys employing standardised diagnostic interviews reveal rates of between 1.2 and 1.7 % for one month prevalence in a UK sample and a 2.4% current prevalence rate in a Canadian sample. Current prevalence rates in samples of consecutive inpatient admissions are reported between 1 and 16%, although screening measures employed may have resulted in these being an underestimate. Prevalence rates in clinical samples of specific psychiatric disorders vary between 30% of war veterans with PTSD and 60% of those with unipolar depression. There is a high prevalence within panic disorder with rates varying from 7.8 to 82.6%. DISCUSSION: DP and DR symptoms are common in normal and psychiatric populations, but prevalence estimates are hampered by inconsistent definitions and the use of variable time-frames. Population-based surveys using diagnostic interviews yield prevalence rates of clinically significant DP/DR in the region of 1-2%. Surveys of clinical populations in which common screening and assessment instruments were used also yield consistently high prevalence rates. The use of reliable diagnostic assessments and rating scales is needed. The relationship between DP/DR and certain other psychiatric disorders (e. g. panic) suggests possible common pathophysiological or aetiological factors.

Adult↗
PubMed2004

Emotional memory and perception in temporal lobectomy patients with amygdala damage.

BACKGROUND: The human amygdala is implicated in the formation of emotional memories and the perception of emotional stimuli--particularly fear--across various modalities. OBJECTIVES: To discern the extent to which these functions are related. METHODS: 28 patients who had anterior temporal lobectomy (13 left and 15 right) for intractable epilepsy were recruited. Structural magnetic resonance imaging showed that three of them had atrophy of their remaining amygdala. All participants were given tests of affect perception from facial and vocal expressions and of emotional memory, using a standard narrative test and a novel test of word recognition. The results were standardised against matched healthy controls. RESULTS: Performance on all emotion tasks in patients with unilateral lobectomy ranged from unimpaired to moderately impaired. Perception of emotions in faces and voices was (with exceptions) significantly positively correlated, indicating multimodal emotional processing. However, there was no correlation between the subjects' performance on tests of emotional memory and perception. Several subjects showed strong emotional memory enhancement but poor fear perception. Patients with bilateral amygdala damage had greater impairment, particularly on the narrative test of emotional memory, one showing superior fear recognition but absent memory enhancement. CONCLUSIONS: Bilateral amygdala damage is particularly disruptive of emotional memory processes in comparison with unilateral temporal lobectomy. On a cognitive level, the pattern of results implies that perception of emotional expressions and emotional memory are supported by separate processing systems or streams.

Adult↗
PubMed2004

Schizophrenia-like psychosis arising de novo following a temporal lobectomy: timing and risk factors.

OBJECTIVES: To clarify risk factors for the development of schizophrenia-like psychotic disorders following temporal lobectomy, and to explore the possibility that the early postoperative period is a time of high risk for the onset of such chronic psychotic disorders. METHODS: Patients who developed schizophrenia-like psychosis were identified from a series of 320 patients who had a temporal lobectomy for medically intractable epilepsy. The relationship of their disorders to both the operation and subsequent seizure activity was examined. Using a retrospective case-control design, risk factors for the development of schizophrenia-like psychosis were established. RESULTS: Eleven patients who developed schizophrenia-like psychosis postoperatively were identified and compared with 33 control subjects who remained free of psychosis postoperatively. The onset of de novo psychotic symptoms was typically in the first year following the operation. No clear relationship between postoperative seizure activity and fluctuations in psychotic symptoms emerged. Compared with the controls, patients who become psychotic had more preoperative bilateral electroencephalogram (EEG) abnormalities, pathologies other than mesial temporal sclerosis in the excised lobe and a smaller amygdala on the unoperated side. CONCLUSIONS: Temporal lobectomy for medically intractable epilepsy may precipitate a schizophrenia-like psychosis. Patients with bilateral functional and structural abnormalities, particularly of the amygdala, may be at particular risk for the development of such psychoses.

Adolescent↗
PubMed2003

Evidence for heterogeneous forms of the snake venom metalloproteinase jararhagin: a factor contributing to snake venom variability.

The reprolysin subfamily of metalloproteinases includes snake venom metalloproteinases (SVMP) and mammalian disintegrin/metalloproteinase. These proteins are synthesized as zymogens and undergo proteolytic processing resulting in a variety of multifunctional proteins. Jararhagin is a P-III SVMP isolated from the venom of Bothrops jararaca. In crude venom, two forms of jararhagin are typically found, full-length jararhagin and jararhagin-C, a proteolytically processed form of jararhagin that is composed of the disintegrin-like and cysteine-rich domains of jararhagin. To better understand the structural and mechanistic bases for these forms of jararhagin in the venom of B. jararaca and the source of venom complexity in general, we have examined the jararhagin forms isolated from venom and the autolysis of isolated jararhagin under the conditions of varying pH, calcium ion concentration, and reducing agents. From our results, jararhagin isolated from venom appears as two forms: a predominant form that is stable to in vitro autolysis and a minor form that is susceptible to autolysis under a variety of conditions including alkaline pH, low calcium ion concentrations, or reducing agent. The autolysis site for production of jararhagin-C from isolated jararhagin was different from that observed for jararhagin-C as isolated from crude venom. Taken together, these data lead us to the conclusion that during the biosynthesis of jararhagin in the venom gland at least three forms are present: one form which is rapidly processed to give rise to jararhagin-C, one form which is resistant to processing in the venom and autolysis in vitro, and one minor form which is susceptible to autolysis under conditions that promote destabilization of its structure. The presence of these different forms of jararhagin contributes to greater structural and functional complexity of the venom and may be a common feature among all snake venoms. The biological and biochemical features in the venom gland responsible for these jararhagin isoforms are currently under investigation.

Amino Acid Sequence↗
PubMed2003

Depersonalisation disorder: a cognitive-behavioural conceptualisation.

Depersonalisation (DP) and derealisation (DR) are subjective experiences of unreality in, respectively, one's sense of self and the outside world. These experiences occur on a continuum from transient episodes that are frequently reported in healthy individuals under certain situational conditions to a chronic psychiatric disorder that causes considerable distress (depersonalisation disorder, DPD). Despite the relatively high rates of reporting these symptoms, little research has been conducted into psychological treatments for this disorder. We suggest that there is compelling evidence to link DPD with the anxiety disorders, particularly panic. This paper proposes that it is the catastrophic appraisal of the normally transient symptoms of DP/DR that results in the development of a chronic disorder. We suggest that if DP/DR symptoms are misinterpreted as indicative of severe mental illness or brain dysfunction, a vicious cycle of increasing anxiety and consequently increased DP/DR symptoms will result. Moreover, cognitive and behavioural responses to symptoms such as specific avoidances, 'safety behaviours' and cognitive biases serve to maintain the disorder by increasing awareness of the symptoms, heightening the perceived threat and preventing disconfirmation of the catastrophic misinterpretations. A coherent model facilitates the development of potentially effective cognitive and behavioural interventions.

Adult↗
PubMed2003

Reality monitoring and visual hallucinations in Parkinson's disease.

Between 8 and 40% of Parkinson disease (PD) patients will have visual hallucinations (VHs) during the course of their illness. Although cognitive impairment has been identified as a risk factor for hallucinations, more specific neuropsychological deficits underlying such phenomena have not been established. Research in psychopathology has converged to suggest that hallucinations are associated with confusion between internal representations of events and real events (i.e. impaired-source monitoring). We evaluated three groups: 17 Parkinson's patients with visual hallucinations, 20 Parkinson's patients without hallucinations and 20 age-matched controls, using tests of visual imagery, visual perception and memory, including tests of source monitoring and recollective experience. The study revealed that Parkinson's patients with hallucinations appear to have intact visual imagery processes and spatial perception. However, there were impairments in object perception and recognition memory, and poor recollection of the encoding episode in comparison to both non-hallucinating Parkinson's patients and healthy controls. Errors were especially likely to occur when encoding and retrieval cues were in different modalities. The findings raise the possibility that visual hallucinations in Parkinson's patients could stem from a combination of faulty perceptual processing of environmental stimuli, and less detailed recollection of experience combined with intact image generation.

Aged↗
PubMed2003

Psychiatrists' attitudes to maintenance medication for patients with schizophrenia.

BACKGROUND: Maintenance antipsychotic medication is the mainstay of relapse prevention in patients with schizophrenia. Long acting depot antipsychotics were developed to promote treatment adherence and yet their utilization is variable, perhaps due to negative attitudes of both patients and psychiatrists. Recently, a shift away from depots has occurred, in favour of the newer atypical oral antipsychotics. METHOD: This study investigated the current attitudes and knowledge concerning depots, with a newly designed questionnaire, in a cross-sectional postal survey of qualified psychiatrists working in south-east England. RESULTS: A substantial minority of psychiatrists believe that depots are old fashioned (40%), stigmatizing (48%) and are associated with more side-effects than typical oral antipsychotics (38%). Many believe that depots are as efficacious as oral medication (91%) but are less acceptable to patients (69%) and relatives (66%). A large majority consider depots enhance patient compliance (81%) and prevent relapse (94%). Psychiatrists would be persuaded to prescribe depots if they were associated with fewer side-effects, in patients where compliance is an issue, and if atypical depot antipsychotics were available, presumably because they would have a lower incidence of side-effects. Additionally, psychiatrists' knowledge about depots was positively associated with attitudes. More favourable patient-centred attitudes were reported by psychiatrists with higher depot use. CONCLUSION: Practising psychiatrists have several strongly endorsed attitudes towards depot medication that are associated with knowledge and prescribing habits. By updating psychiatrists' knowledge about depots, in turn their attitudes may become more positive and prescribing practices may subsequently change.

Adult↗
PubMed2003

Insight: its relationship with cognitive function, brain volume and symptoms in schizophrenia.

BACKGROUND: Lack of insight is frequently observed in schizophrenia. Relationships have been noted between poor insight, clinical symptoms and cognitive impairments but the findings are inconsistent. There have been some recent attempts to relate poor insight to neuro-anatomical measures. METHOD: We assessed insight, positive and negative symptoms of schizophrenia, cognitive performance, and whole brain volumes in a sample of 78 DSM-IV male schizophrenics and 36 normal male comparison subjects matched for age and IQ. Subjects underwent a dual-echo MRI brain scan to establish grey, white and whole brain volumes. RESULTS: Poor Wisconsin Card Sorting Test performance inversely correlated with insight in schizophrenic patients, as did the symptoms alogia, anhedonia, avolition/apathy, affective flattening, inappropriate affect, thought disorder and delusions. The presence of inappropriate affect, delusions and thought disorder, showed the most significant impact on insight levels. There were no significant correlations between whole brain, white and grey matter volume and degree of insight. CONCLUSIONS: The results suggest that poor insight is significantly related to schizophrenic psychopathology, and confirm that there is a relationship between insight and executive performance. Awareness of illness is not related to any global brain measures, suggesting future investigations should pay attention to more specific cortical regions such as the frontal cortex.

Adult↗
PubMed2003

The health effects of peace-keeping in the UK Armed Forces: Bosnia 1992-1996. Predictors of psychological symptoms.

BACKGROUND: Peace-keeping duties are associated with unique stresses for military personnel. There have been few reports on the effects of peace-keeping on psychological health. METHOD: We used data from a cross-sectional study originally established to examine health effects of service in the Gulf War, which included a control group who had been deployed in Bosnia (N= 2049). This group was examined to establish which demographic, occupational, and deployment-related risk factors were associated with psychological distress measured on the General Health Questionnaire (GHQ-12) and stress symptoms akin to a post-traumatic stress reactions. RESULTS: The main risk factors for stress symptoms in the Bosnia group were--lower rank, being deployed early in the campaign, having more deployment-related exposures, and serving on staff duties. There was no protective effect of previous deployments to the Falklands or Northern Ireland, and time off following deployment was not protective. For GHQ-12 cases, the main risk factors were: female gender, lower rank, increased deployment-related exposures and serving on staff duties. CONCLUSIONS: This study suggests that stress symptoms and GHQ-12 cases, are strongly predicted both by experiences during deployment and demographic factors.

Adult↗
PubMed2002

The human amygdala: a systematic review and meta-analysis of volumetric magnetic resonance imaging.

The structure and function of the human amygdala is attracting increasing attention in the scientific literature, particularly since the advent of high resolution magnetic resonance imaging (MRI). We carried out a systematic review of the published literature reporting left and right amygdala volumes from MRI in non-clinical subjects. Our aim was to estimate the normal range of the volume of the amygdala and to account for heterogeneity of the measures. The factors we considered included the detail given regarding various subject factors, the plane of scan acquisition, slice thickness and contiguity, magnet strength, positional and volume correction, and the reliability of measurement. Thirty-nine studies with 51 data sets fulfilled selection criteria. The mean+/-95% confidence interval for the left amygdala volume was 1726.7 mm(3)+/-35.1, and right was 1691.7 mm(3)+/-37.2. The left-right difference did not reach statistical significance. The overall range of reported volumes was 1050 mm(3) to 3880 mm(3). The amygdala is significantly larger in men and shows an inverse correlation with age. The main methodological factor found to influence amygdala measurement was anatomical definition. Studies using 'Watson's criteria' (Neurology 42 (1992) 1743) produced significantly larger volumes than the remainder. An index of study quality revealed an inverse relationship with volume-the higher the quality the smaller the volume. This reflected such factors as slice thickness, correction for brain volume, positional correction and number of subjects. We conclude by putting forward a detailed operationalized anatomical delineation of the amygdala, based on Watson's criteria. This work should guide future research in obtaining accurate and reliable amygdala volume measures which in turn will aid comparisons with clinical groups and the specification of structural-functional relationships.

Amygdala↗
PubMed2002

Searching for a Gulf War syndrome using cluster analysis.

BACKGROUND: Gulf veterans report medically unexplained symptoms more frequently than non-Gulf veterans did. We examined whether Gulf and non-Gulf veterans could be distinguished by their patterns of symptom reporting. METHOD: A k-means cluster analysis was applied to 500 randomly sampled veterans from each of three United Kingdom military cohorts of veterans; those deployed to the Gulf conflict between 1990 and 1991; to the Bosnia peacekeeping mission between 1992 and 1997; and military personnel who were in active service but not deployed to the Gulf (Era). Sociodemographic, health variables and scores for ten symptom groups were calculated. RESULTS: The gap statistic indicated the five-group solution as one that provided a particularly informative description of the structure in the data. Cluster 1 consisted of low scores for all symptom groups. Cluster 2 had veterans with highest symptom scores for musculoskeletal symptoms and high scores for psychiatric symptoms. Cluster 3 had high scores for psychiatric symptoms and marginally elevated scores for the remaining nine groups symptom groups. Cluster 4 had elevated scores for musculoskeletal symptoms only and cluster 5 was distinguishable from the other clusters in having high scores in all symptom groups, especially psychiatric and musculoskeletal. CONCLUSION: The findings do not support the existence of a unique syndrome affecting a subgroup of Gulf veterans but emphasize the excess of non-specific self-reported ill health in this group.

Bosnia and Herzegovina↗
PubMed2002

Cognitive functioning and disturbances of mood in UK veterans of the Persian Gulf War: a comparative study.

BACKGROUND: Complaints of poor memory and concentration are common in veterans of the 1991 Persian Gulf War as are other symptoms. Despite a large research effort, such symptoms remain largely unexplained. METHOD: A comprehensive battery of neuropsychological tests and rating scales was administered to 341 UK servicemen who were returnees from the Gulf War and peace keeping duties in Bosnia, plus non-deployed military controls. All were drawn from a large randomized survey. Most were selected on the basis of impaired physical functioning defined operationally. RESULTS: Group comparisons revealed an association between physical functioning and symptoms of depression, post-traumatic stress reactions, increased anger and subjective cognitive failures. Poorer performance on some general cognitive measures, sequencing and attention was also seen in association with being 'ill' but virtually all differences disappeared after adjusting for depressed mood or multiple comparisons. Deployment was also associated with symptoms of post-traumatic stress and subjective cognitive failures, independently of health status, as well as minor general cognitive and constructional impairment. The latter remained significantly poorer in the Gulf group even after adjusting for depressed mood. CONCLUSIONS: Disturbances of mood are more prominent than quantifiable cognitive deficits in Gulf War veterans and probably lead to subjective underestimation of ability. Task performance deficits can themselves be explained by depressed mood although the direction of causality cannot be inferred confidently. Reduced constructional ability cannot be explained in this way and could be an effect of Gulf-specific exposures.

Adult↗
PubMed2002

Separating depersonalisation and derealisation: the relevance of the "lesion method".

OBJECTIVES: Depersonalisation (DP) and derealisation (DR) are often met with in patients with a wide range of localisable neurological conditions. This suggests that the "lesion method" might be a valid approach to study the neurobiology of DP/DR. However, the fact that anxiety can trigger DP/DR makes it difficult to establish whether the presence of DP/DR in neurological patients is mainly determined by coexisting anxiety or by lesion location. To overcome this difficulty, we suggest the study of neurological phenomena, which although not considered as DP/DR, bear enough phenomenological resemblance with them as to warrant their use as models. METHODS: One patient with "visual hypoemotionality" and another with "hemiasomatognosia" are described in detail together with a selective literature review. RESULTS: Complaints of patients with visual hypoemotionality are indistinguishable from those of patients with "visual derealisation". There is also a phenomenological overlap between "asomatognosia" and the symptom of "body alienation", which is a central feature of depersonalisation. CONCLUSIONS: Phenomenological similarities between visual hypoemotionality and DR suggest that a disruption of the process by means of which perception becomes emotionally coloured may be an underlying mechanism in both conditions. Likewise, phenomenological overlaps with asomatognosia suggest that DP might result from parietal mechanisms disrupting the experience of body ownership and agency. These findings give validity to the notion that DP and DR may have distinct neurobiological mechanisms.

Adult↗
PubMed2001

Depersonalization disorder: thinking without feeling.

Patients with depersonalization disorder (DP) experience a detachment from their own senses and surrounding events, as if they were outside observers. A particularly common symptom is emotional detachment from the surroundings. Using functional magnetic resonance imaging (fMRI), we compared neural responses to emotionally salient stimuli in DP patients, and in psychiatric and healthy control subjects. Six patients with DP, 10 with obsessive-compulsive disorder (OCD), and six volunteers were scanned whilst viewing standardized pictures of aversive and neutral scenes, matched for visual complexity. Pictures were then rated for emotional content. Both control groups rated aversive pictures as much more emotive, and demonstrated in response to these scenes significantly greater activation in regions important for disgust perception, the insula and occipito-temporal cortex, than DP patients (covarying for age, years of education and total extent of brain activation). In DP patients, aversive scenes activated the right ventral prefrontal cortex. The insula was activated only by neutral scenes in this group. Our findings indicate that a core phenomenon of depersonalization--absent subjective experience of emotion--is associated with reduced neural responses in emotion-sensitive regions, and increased responses in regions associated with emotion regulation.

Adult↗