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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

Intact theory of mind in TBI with behavioural disturbance.

Behavioural disturbance following TBI is common. Theory of mind(ToM) deficits have been noted in autism where difficulties with social interaction and communication are evident. It was hypothesised that TBI patients with behavioural disturbance would show deficits on ToM tasks independent of executive function. Twenty TBI patients with behavioural disturbance and 20 TBI patients without were assessed on verbal (stories) and non-verbal (cartoons) ToM tasks,standard psychometry, and measures of executive function.TBI patients were unimpaired on the ToM tasks. Both groups were unimpaired on standard tests of executive function (verbal fluency and trail making test) but were impaired on the Behavioural Assessment of Dysexecutive Syndrome (BADS). Groups did not differ significantly on these tests. It is concluded that ToM ability does not predict behavioural disturbance and may be independent of executive functioning.

Analysis of Variance↗

The role of 'shared representations' in social perception and empathy: an fMRI study.

Evidence suggests that we use the same mechanisms for both producing and perceiving actions. Such 'shared representations' may also underlie social perception and empathy. However, this idea raises some important and as yet unresolved questions: (i) how do we distinguish other-orientated empathic responses from a self-orientated reactions such as personal distress and (ii) what are the neural substrates underpinning these processes? We employed event-related functional magnetic resonance imaging (fMRI) to explore whether 'shared representations' were recruited to decode dynamic social stimuli in 12 healthy volunteers. We used an adapted version of the Profile of Non-Verbal Sensitivity (Rosenthal, H., Hall, J.A., DiMatteo, M.R., Rogers, P.L., Archer, D., (1979). Sensitivity to nonverbal communication: the PONS test. The Johns Hopkins University Press, Baltimore) which taps social perception using brief silent video clips. Participants chose one of two words that best described the state conveyed by the actor, or in the control condition using the same clips, the word describing which parts of the body were visible (non-social labelling). Off-line self-report measures of empathy and personal distress engendered by thoughts about others, were also given along with an experimentally-derived index of the degree of self-other overlap during social perception. Brain activation specific to the main experimental condition was found in the inferior frontal gyrus (BA44) and premotor areas (BA6) consistent with the use of 'shared representations'. Somatosensory areas such as the insula and supramarginal gyrus (BA40) were also activated suggesting that participants constructed a qualitative representation of the target state. Activity in the rostral anterior cingulate was associated with self-reports of personal distress and increased blood flow to the anterior cingulate (BA24) and inferior parietal cortex (BA40) was related to self-other overlap.

Adult↗

A critical period for the impact of amygdala damage on the emotional enhancement of memory?

The amygdala is crucial in modulating enhanced memory for emotionally arousing material. The authors provide evidence that unilateral lesions of the human amygdala arising early in development, but not in adulthood, are associated with a loss of the expected superior retrieval of emotionally arousing over neutral material. This adds to evidence for an early critical period in the development of amygdala function.

Adult↗

Antipsychotic depot medication and attitudes of community psychiatric nurses.

Utilization of long-acting antipsychotic injections (depots) shows wide regional variation. In many countries, community psychiatric nurses (CPNs) administer depots but their concerns and attitudes regarding these drugs are seldom considered. We aimed to investigate attitudes and knowledge towards depots in a cross-sectional survey of CPNs in London, and compare them with those of psychiatrists obtained in a previous study. Three subscales of a depot attitude/knowledge questionnaire were used with additional items which referred to aspects of the CPN role. Participants were 70 CPNs who attended an academic meeting. Most CPNs reported that they were involved in treatment decisions (78%) although some CPNs seldom asked their patients about side effects (19%) and felt that they did not have sufficient time for consultations (23%) or training (23%). Several CPNs believed that depots are old fashioned (34%) and stigmatizing (44%). Compared to psychiatrists, CPNs believed more that depots compromised patient autonomy (28%, P = 0.003) and were coercive (42%, P < 0.001). Familiarity with depots and their knowledge of side effects were positively associated with favourable attitudes. CPNs have several strongly endorsed attitudes towards depot medication. Interprofessional group differences also exist which may undermine the treatment process. Training/refresher courses about depots should highlight systematic treatment decision-making and side effect monitoring which, in turn, may improve professionals' attitudes, knowledge and clinical monitoring of depots.

Antipsychotic Agents↗

Differential effects of lesions of the amygdala and prefrontal cortex on recognizing facial expressions of complex emotions.

Humans can detect facial expressions of both simple, basic emotions and expressions reflecting more complex states of mind. The latter includes emotional expressions that regulate social interactions ("social expressions" such as looking hostile or friendly) and expressions that reflect the inner thought state of others ("cognitive expressions" such as looking pensive). To explore the neural substrate of this skill, we examined performance on a test of detection of such complex expressions in patients with lesions of the temporal lobe (n = 54) or frontal lobe (n = 31). Of the temporal group, 18 had unilateral focal lesions of the amygdala and of the frontal group, 14 patients had unilateral lesions of the ventromedial prefrontal cortex-two regions held to be pivotal in mediating social cognitive skills. Damage to either the left or right amygdala was associated with impairment in the recognition of both social and cognitive expressions, despite an intact ability to extract information relating to invariant physical attributes. Lesions to all of the right prefrontal cortex-not just the ventromedial portions-led to a specific deficit in recognizing complex social expressions with a negative valence. The deficit in the group with right prefrontal cortical damage may contribute to the disturbances in social behavior associated with such lesions. The results also suggest that the amygdala has a role in processing a wide range of emotional expressions.

Amygdala↗

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↗

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↗

Measuring empathy: reliability and validity of the Empathy Quotient.

BACKGROUND: Empathy plays a key role in social understanding, but its empirical measurement has proved difficult. The Empathy Quotient (EQ) is a self-report scale designed to do just that. This series of four studies examined the reliability and validity of the EQ and determined its factor structure. METHOD: In Study 1, 53 people completed the EQ, Social Desirability Scale (SDS) and a non-verbal mental state inference test, the Eyes Task. In Study 2, a principal components analysis (PCA) was conducted on data from 110 healthy individuals and 62 people reporting depersonalisation (DPD). Approximately 1 year later, Study 3, involved the re-administration of the EQ (n = 24) along with the Interpersonal Reactivity Index (IRI; n = 28). In the last study, the EQ scores of those with DPD, a condition that includes a subjective lack of empathy, were examined in depth. RESULTS: An association was found between the Eyes task and EQ, and only three EQ items correlated with the SDS. PCA revealed three factors: (1) 'cognitive empathy'; (2) 'emotional reactivity', and (3) 'social skills'. Test-retest reliability was good and moderate associations were found between the EQ and IRI subscales, suggesting concurrent validity. People with DPD did not show a global empathy deficit, but reported less social competence. CONCLUSIONS: The EQ is a valid, reliable scale and the different subscales may have clinical applications.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗