Biomedical subjects

Anthony S David

Publications and source records attributed to Anthony S David.

At least 55 records · Page 3Linked to original sources

PubMed2004

Prognostic indicators for early discontinuation of risperidone long-acting injection.

Although efficacy trials have been conducted on risperidone long-acting injection (RLAI), its most appropriate utilization in clinical practice remains unclear. This 6-month, follow-up study investigated prognostic indicators for early discontinuation of RLAI. Consecutive sampling was conducted for adult patients with a psychotic disorder commenced on RLAI, whose injection was dispensed by one of three South London psychiatric hospital pharmacies. Prescription data were collected prospectively and clinical data retrospectively. Eightly-one out of 88 (92.0%) eligible patients were included, of whom 29 (35.8%) had treatment refractoriness and 30 (37.0%) discontinued within 6 months. Patients with a preceding oral antipsychotic were more likely to discontinue RLAI than those with a preceding depot; treatment refractoriness weakly confounded this relationship [summary adjusted odds ratio (OR) 2.68, 95% confidence interval (CI) 0.95-7.53, P=0.061]. After adjusting for preceding antipsychotic type, patients with treatment refractoriness were no more likely to discontinue than those without (summary adjusted OR 1.55, 95% CI 0.59-4.11, P=0.376). Sociodemographic factors and other clinical factors were non-predictive of discontinuation. For this first wave of patients commenced on RLAI, many had treatment refractoriness. RLAI discontinuation is high early on but subsequently tapers off. Preceding antipsychotic type (depot versus oral) is a stronger prognostic indicator than treatment refractoriness for RLAI discontinuation.

Administration, Oral↗

PubMed2004

Dysregulation of arousal and amygdala-prefrontal systems in paranoid schizophrenia.

OBJECTIVE: The authors investigated impaired differentiation of limbic-prefrontal systems by autonomic arousal in schizophrenia. It was predicted that paranoid patients would be distinguished by a disjunction of hyperarousal but reduced amygdala and medial prefrontal activity relative to both healthy comparison subjects and patients with nonparanoid schizophrenia. METHOD: Pictures depicting facial expressions of fear were presented to 27 schizophrenia patients (13 paranoid, 14 nonparanoid) and 22 matched healthy comparison subjects in an implicit perception task to evoke limbic activity. Simultaneous functional magnetic resonance imaging and skin conductance arousal recordings were acquired during presentation of faces expressing fear or neutral emotion. Responses to fear stimuli were further examined by contrasting those that were associated with a skin conductance response ("with arousal") and those that were not ("without arousal"). RESULTS: In the comparison subjects, arousal dissociated amygdala/medial prefrontal ("visceral") networks and hippocampus/lateral prefrontal ("context") networks for fear perception. Excessive arousal responses were elicited in the schizophrenia subjects, but there was an associated reduction in amygdala/medial prefrontal activity. This disjunction was pronounced in paranoid patients relative to both healthy subjects and nonparanoid patients. Paranoid patients also showed a relatively greater prefrontal deficit for "without-arousal" responses. CONCLUSIONS: This is the first study to reveal a functional disconnection in autonomic and central systems for processing threat-related signals in patients with paranoid schizophrenia. Paranoid cognition may reflect an internally generated cycle of misattribution regarding incoming fear signals due to a breakdown in the regulation of these systems.

Adult↗

PubMed2003

Gulf war illness--better, worse, or just the same? A cohort study.

OBJECTIVES: Firstly, to describe changes in the health of Gulf war veterans studied in a previous occupational cohort study and to compare outcome with comparable non-deployed military personnel. Secondly, to determine whether differences in prevalence between Gulf veterans and controls at follow up can be explained by greater persistence or greater incidence of disorders. DESIGN: Occupational cohort study in the form of a postal survey. PARTICIPANTS: Military personnel who served in the 1991 Persian Gulf war; personnel who served on peacekeeping duties to Bosnia; military personnel who were deployed elsewhere ("Era" controls). All participants had responded to a previous survey. SETTING: United Kingdom. MAIN OUTCOME MEASURES: Self reported fatigue measured on the Chalder fatigue scale; psychological distress measured on the general health questionnaire, physical functioning and health perception on the SF-36; and a count of physical symptoms. RESULTS: Gulf war veterans experienced a modest reduction in prevalence of fatigue (48.8% at stage 1, 43.4% at stage 2) and psychological distress (40.0% stage 1, 37.1% stage 2) but a slight worsening of physical functioning on the SF-36 (90.3 stage 1, 88.7 stage 2). Compared with the other cohorts Gulf veterans continued to experience poorer health on all outcomes, although physical functioning also declined in Bosnia veterans. Era controls showed both lower incidence of fatigue than Gulf veterans, and both comparison groups showed less persistence of fatigue compared with Gulf veterans. CONCLUSIONS: Gulf war veterans remain a group with many symptoms of ill health. The excess of illness at follow up is explained by both higher incidence and greater persistence of symptoms.

Age Factors↗

PubMed2003

Regionally localized thinning of the cerebral cortex in schizophrenia.

BACKGROUND: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps. METHODS: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon. RESULTS: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels. CONCLUSIONS: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure.

Adult↗

PubMed2003

Ketamine and fMRI BOLD signal: distinguishing between effects mediated by change in blood flow versus change in cognitive state.

No human fMRI studies have examined ketamine effects on the BOLD signal change associated with cognitive task performance. We wished to distinguish between effects on 1) cerebral blood flow, with resultant change in BOLD signal; and 2) cognition and neural mechanisms underlying BOLD signal change associated with task performance. Eight right-handed men (mean age 28.75 years) received ketamine or saline i.v. in a randomized, double-blind manner (bolus 0.23 mg/kg; 0.5 mg/kg over 45 min to a maximum 1 hr). Subjects viewed 10 alternating 30-sec blocks of faces with neutral expressions and a fixation cross and discriminated gender of faces. Gradient echo echoplanar images were acquired on a GE Signa 1.5 T Neurovascular system. One hundred T2-weighted images depicting BOLD contrast were acquired over 5 min (for each task) at each of 14 near-axial noncontiguous 7-mm thick planes. Ketamine significantly increased dissociative phenomena and negative symptoms, but did not affect performance of the gender discrimination task. Significant BOLD signal change was demonstrated predominantly in occipitotemporal cortex with both ketamine and placebo. Only two clusters in middle occipital gyrus (BA 18) and precentral gyrus (BA 4) showed significantly decreased BOLD signal change during ketamine compared to placebo. BOLD signal change was not significantly greater in any region during ketamine. Our findings demonstrate subtle rather than major differences between the effects of ketamine and placebo upon the BOLD signal change during perception of face-non face contrast. We suggest that they represent task-dependent effects of the drug/placebo, rather than task-independent effects of the drug per se, and indicate that the effects of ketamine on cerebral blood flow are predominantly focal and task-dependent, rather than global and task-independent.

Adult↗

PubMed2003

Perception of emotions from faces and voices following unilateral brain damage.

The importance of the right hemisphere in emotion perception in general has been well documented but its precise role is disputed. We compared the performance of 30 right hemisphere damaged (RHD) patients, 30 left hemisphere damaged (LHD) patients, and 50 healthy controls on both facial and vocal affect perception tasks of specific emotions. Brain damaged subjects had a single episode cerebrovascular accident localised to one hemisphere. The results showed that right hemisphere patients were markedly impaired relative to left hemisphere and healthy controls on test performance: labelling and recognition of facial expressions and recognition of emotions conveyed by prosody. This pertained at the level of individual basic emotions, positive versus negative, and emotional expressions in general. The impairment remained highly significant despite covarying for the group's poorer accuracy on a neutral facial perception test and identification of neutral vocal expressions. The LHD group were only impaired relative to controls on facial emotion tasks when their performance was summed over all the emotion categories and before age and other cognitive factors were taken into account. However, on the prosody test the LHD patients showed significant impairment, performing mid-way between the right hemisphere patients and healthy comparison group. Recognition of positive emotional expressions was better than negative in all subjects, and was not relatively poorer in the LHD patients. Recognition of individual emotions in one modality correlated weakly with recognition in another, in all three groups. These data confirm the primacy of the right hemisphere in processing all emotional expressions across modalities--both positive and negative--but suggest that left hemisphere emotion processing is modality specific. It is possible that the left hemisphere has a particular role in the perception of emotion conveyed through meaningful speech.

Adult↗

PubMed2003

Quantitative magnetic resonance imaging of the amygdala in temporal lobe epilepsy-clinico-pathological correlations (a pilot study).

PURPOSE: We carried out a pilot study of quantitative volumetric MRI of the amygdala in patients undergoing surgery for intractable temporal lobe epilepsy. We wished to explore whether amygdala volume correlated with pre-operative clinical variables and post-operative outcome. METHODS: Ten patients had detailed volumetric measurements of their amygdala and hippocampus according to operationalised anatomical criteria from an optimised MRI imaging sequence. A ratio of volumes from the unoperated to operated side was calculated. Surgical specimens were examined histologically for astrocytosis. RESULTS: The volumes of the amygdala and hippocampus on the operated side were significantly smaller than on the unoperated side. More severe astrocytosis appeared to go along with smaller volume ratios but the relationship was not significant. There were few significant correlations between volumes measures and clinical or outcome variables. CONCLUSION: Reductions in amygdala volume in the to-be-operated temporal lobe in patients with medically intractable epilepsy can be reliably detected using volumetric MRI. Accurate amygdala volume measures do not appear to exert a significant effect on clinical presentation and outcome in the presence of hippocampal volumes reductions, but may be useful in confirming bilateral pathology. Larger studies examining clinico-pathological correlations are recommended.

Amygdala↗

PubMed2003

The perception of emotional chimeric faces in patients with depression, mania and unilateral brain damage.

BACKGROUND: Judgements made on chimeric faces elicit reliably a perceptual bias to the left hemispace, presumed to be due to right hemisphere dominance for emotional processes. Major depressive illness has been shown to attenuate this bias. The aim of this work was to examine lateral perceptual bias in bipolar I and II patients in a hypomanic state and unipolar depressed patients and those with unilateral hemisphere damage following stroke. METHOD: Sixty patients with DSM-IV affective disorder (30 bipolar I or II, currently hypomanic, 30 unipolar depressives), 30 right brain-damaged patients, 30 left brain-damaged patients and 30 healthy controls were given the Happy-Sad Chimeric Faces Test. RESULTS: Right hemisphere damaged and unipolar depressed patients both showed a significantly reduced left hemispatial bias (LHB) compared to controls, bipolars and left brain-damaged patients. No significant difference in mean LHB between controls and both hypomanics and left brain-damaged patients was found. There was no significant association between LHB and clinical variables. CONCLUSIONS: The results suggest a physiological distinction between bipolar and unipolar depression. The significantly diminished left hemifacial bias in depressed patients suggests right hemisphere dysfunction.

Aged↗

PubMed2003

Chronic depersonalization following illicit drug use: a controlled analysis of 40 cases.

AIMS: To examine demographic and clinical features of a group of patients reporting chronic depersonalization (DP) following illicit drug use, and to assess whether depersonalization arising in these circumstances constitutes a distinct clinical syndrome. DESIGN: Case-control comparison using self-reports, standardized questionnaires and clinical assessments in a specialized clinic. SETTING: A tertiary referral depersonalization clinic and research unit affiliated to a psychiatric hospital and research centre. PARTICIPANTS: A total of 164 individuals with chronic DP symptoms who had been in contact with the clinic. Forty of these individuals related the onset of symptoms to an episode of illicit drug use. MEASUREMENTS: A wide range of demographic and clinical variables measured using questionnaires and standardized rating scales. FINDINGS: The drug-induced DP group were significantly younger and had a preponderance of males compared to the non-drug group. Certain clinical and phenomenological differences were found between these groups, but in general the groups are strikingly similar. This is reinforced by the fact that when the drug-induced group was compared with an age and sex-matched subset of the non-drug group, differences between groups largely disappeared. CONCLUSIONS: Drug-induced DP does not appear to represent a distinct clinical syndrome. The neurocognitive mechanisms of the genesis and maintenance of DP are likely to be similar across clinical groups, regardless of precipitants.

Adolescent↗

PubMed2003

A placebo-controlled, cross-over trial of lamotrigine in depersonalization disorder.

There is evidence to support the view that glutamate hyperactivity might be relevant to the neurobiology of depersonalization. We tested the efficacy of lamotrigine, which reduces glutamate release, as a treatment for patients with depersonalization disorder. A double-blind, placebo-controlled, cross-over design was used to evaluate 12 weeks of treatment of lamotrigine. Subjects comprised nine patients with DSM-IV depersonalization disorder. Changes on the Cambridge Depersonalization Scale and the Present State Examination depersonalization/derealization items were compared across the two cross-over periods. Lamotrigine was not significantly superior to placebo. None of the nine patients was deemed a responder to the lamotrigine arm of the cross-over. Lamotrigine does not seem to be useful as a sole medication in the treatment of depersonalization disorder.

Adult↗

PubMed2003

Depersonalisation disorder: clinical features of 204 cases.

BACKGROUND: Depersonalisation disorder is a poorly understood and underresearched syndrome. AIMS: To carry out a large and comprehensive clinical and psychopathological survey of a series of patients who made contact with a research clinic. METHOD: A total of 204 consecutive eligible referrals were included: 124 had a full psychiatric examination using items of the Present State Examination to define depersonalisation/derealisation and 80 had either a telephone interview (n=22) or filled out a number of self-report questionnaires. Cases assessed were diagnosed according to DSM-IV criteria. RESULTS: The mean age of onset was 22.8 years; early onset was associated with greater severity. There was a slight male preponderance. The disorder tended to be chronic and persistent. Seventy-one per cent met DSM-IV criteria for primary depersonalisation disorder. Depersonalisation symptom scores correlated with both anxiety and depression and a past history of these disorders was commonly reported. 'Dissociative amnesia' was not prominent. CONCLUSIONS: Depersonalisation disorder is a recognisable clinical entity but appears to have significant comorbidity with anxiety and depression. Research into its aetiology and treatment is warranted.

Adolescent↗

PubMed2002

Neural correlates of British sign language comprehension: spatial processing demands of topographic language.

In all signed languages used by deaf people, signs are executed in "sign space" in front of the body. Some signed sentences use this space to map detailed "real-world" spatial relationships directly. Such sentences can be considered to exploit sign space "topographically." Using functional magnetic resonance imaging, we explored the extent to which increasing the topographic processing demands of signed sentences was reflected in the differential recruitment of brain regions in deaf and hearing native signers of the British Sign Language. When BSL signers performed a sentence anomaly judgement task, the occipito-temporal junction was activated bilaterally to a greater extent for topographic than nontopographic processing. The differential role of movement in the processing of the two sentence types may account for this finding. In addition, enhanced activation was observed in the left inferior and superior parietal lobules during processing of topographic BSL sentences. We argue that the left parietal lobe is specifically involved in processing the precise configuration and location of hands in space to represent objects, agents, and actions. Importantly, no differences in these regions were observed when hearing people heard and saw English translations of these sentences. Despite the high degree of similarity in the neural systems underlying signed and spoken languages, exploring the linguistic features which are unique to each of these broadens our understanding of the systems involved in language comprehension.

Adolescent↗

PubMed2002

The mental health of UK Gulf war veterans: phase 2 of a two phase cohort study.

OBJECTIVES: To examine the prevalence of psychiatric disorders in veterans of the Gulf war with or without unexplained physical disability (a proxy measure of ill health) and in similarly disabled veterans who had not been deployed to the Gulf war (non-Gulf veterans). DESIGN: Two phase cohort study. SETTING: Current and ex-service UK military personnel. PARTICIPANTS: Phase 1 consisted of three randomly selected samples of Gulf veterans, veterans of the 1992-7 Bosnia peacekeeping mission, and UK military personnel not deployed to the Gulf war (Era veterans) who had completed a postal health questionnaire. Phase 2 consisted of randomly selected subsamples from phase 1 of Gulf veterans who reported physical disability (n=111) or who did not report disability (n=98) and of Bosnia (n=54) and Era (n=79) veterans who reported physical disability. MAIN OUTCOME MEASURE: Psychiatric disorders assessed by the schedule for clinical assessment in neuropsychiatry and classified by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. RESULTS: Only 24% (n=27) of the disabled Gulf veterans had a formal psychiatric disorder (depression, anxiety, or alcohol related disorder). The prevalence of psychiatric disorders in non-disabled Gulf veterans was 12%. Disability and psychiatric disorders were weakly associated in the Gulf group when confounding was adjusted for (adjusted odds ratio 2.4, 99% confidence interval 0.8 to 7.2, P=0.04). The prevalence of psychiatric disorders was similar in disabled non-Gulf veterans and disabled Gulf veterans ( 19% v 24%; 1.3, 0.5 to 3.4). All groups had rates for post-traumatic stress disorder of between 1% and 3%. CONCLUSIONS: Most disabled Gulf veterans do not have a formal psychiatric disorder. Post-traumatic stress disorder is not higher in Gulf veterans than in other veterans. Psychiatric disorders do not fully explain self reported ill health in Gulf veterans; alternative explanations for persistent ill health in Gulf veterans are needed.

Cohort Studies↗

PubMed2002

Autonomic response in depersonalization disorder.

BACKGROUND: Emotional-processing inhibition has been suggested as a mechanism underlying some of the clinical features of depersonalization and/or derealization. In this study, we tested the prediction that autonomic response to emotional stimuli would be reduced in patients with depersonalization disorder. METHODS: The skin conductance responses of 15 patients with chronic depersonalization disorder according to DSM-IV, 15 controls, and 11 individuals with anxiety disorders according to DSM-IV, were recorded in response to nonspecific elicitors (an unexpected clap and taking a sigh) and in response to 15 randomized pictures with different emotional valences: 5 unpleasant, 5 pleasant, and 5 neutral. RESULTS: The skin conductance response to unpleasant pictures was significantly reduced in patients with depersonalization disorder (magnitude of 0.017 micro siemens in controls and 0.103 micro siemens in patients with anxiety disorders; P =.01). Also, the latency of response to these stimuli was significantly prolonged in the group with depersonalization disorder (3.01 seconds compared with 2.5 and 2.1 seconds in the control and anxiety groups, respectively; P =.02). In contrast, latency to nonspecific stimuli (clap and sigh) was significantly shorter in the depersonalization and anxiety groups (1.6 seconds) than in controls (2.3 seconds) (P =.03). CONCLUSIONS: In depersonalization disorder, autonomic response to unpleasant stimuli is reduced. The fact that patients with depersonalization disorder respond earlier to a startling noise suggests that they are in a heightened state of alertness and that the reduced response to unpleasant stimuli is caused by a selective inhibitory mechanism on emotional processing.

Adult↗

PubMed2002

Sex differences in functional brain activation during a lexical visual field task.

Functional MRI was used to investigate sex differences in brain activation during a paradigm similar to a lexical-decision task. Six males and 6 females performed two runs of the lexical visual field task (i.e., deciding which visual field a word compared with a pseudoword was presented to). A sex difference was noted behaviorally: The reaction time data showed males had a marginal right visual field advantage and women a left visual field advantage. Imaging results showed that men had a strongly left-lateralized pattern of activation, e.g., inferior frontal and fusiform gyrus, while women showed a more symmetrical pattern in language related areas with greater right-frontal and right-middle-temporal activation. The data show evidence of task-specific sex differences in the cerebral organization of language processing.

Adult↗

PubMed2002

Early psychological adjustment in breast cancer patients: a prospective study.

OBJECTIVE: A significant proportion of breast cancer patients experiences psychiatric morbidity in the first year after a breast cancer diagnosis and/or beginning of treatment. This study attempted to identify and understand the risk factors for developing such problems. METHODS: A consecutive series of 87 patients, aged 40-75 years, was assessed prior to diagnosis of breast cancer and followed-up approximately 8 weeks after beginning of cancer treatment and again 9 months after first follow-up. Assessments included measures of psychiatric morbidity using the General Health Questionnaire (GHQ-12), coping style using the Mental Adjustment to Cancer (MAC) Scale, symptom attribution, beliefs about breast cancer, social support, socio-demographic and clinical variables. RESULTS: A total of 85.1% of patients completed both follow-ups. Pre-diagnostically, 32.2% of breast cancer patients scored as a GHQ-12 'case.' GHQ scores fell significantly between pre-diagnostic and both post-diagnostic assessments, especially in women who had thought they had cancer. Predictors of psychological morbidity at first follow-up included pre-diagnostic GHQ-12 score, lack of social support and feelings of 'personal responsibility/avoidance.' GHQ-12 'caseness' at second follow-up was predicted by lack of social support alone. CONCLUSIONS: Overall, psychiatric morbidity is higher prior to, than following, a definitive diagnosis of breast cancer. Early reactions of this kind are predictive of post-treatment adjustment. However, only the presence of social support in this study seems to be associated with successful adjustment in the first year following a breast cancer diagnosis. Women at increased risk of psychological morbidity after a breast cancer diagnosis may be thus identifiable and targeted therapeutically.

Adaptation, Psychological↗

PubMed2002

The neural correlates of intentional and incidental self processing.

The neuroscientific study of the 'Self' is just beginning to emerge. We used functional Magnetic Resonance Imaging (fMRI) to investigate cerebral activation while subjects processed words describing personality traits and physical features, in two experiments with contrasting designs: incidental and intentional. In the first experiment (intentional self processing), subjects were presented with personality trait adjectives and made judgements as to their self descriptiveness (versus non self descriptiveness). In the second experiment (incidental self processing), subjects categorised words according to whether they described physical versus psychological attributes, while unaware that the words had been arranged in blocks according to self descriptiveness. The subjects had previously rated all words for self descriptiveness 6 weeks prior to the scanning session. A reaction time advantage was present in both experiments for self descriptive trait words, suggesting a facilitation effect. Common areas of activation for the two experiments included the left superior parietal lobe, with adjacent regions of the lateral prefrontal cortex also active in both experiments. Differential signal changes were present in the left precuneus for the intentional and the right middle temporal gyrus for the incidental experiment. The results suggest that self processing involves distinct processes and can occur on more than one cognitive level with corresponding functional neuroanatomic correlates in areas previously implicated in the awareness of one's own state.

Adult↗

PubMed2002

Speechreading circuits in people born deaf.

In hearing people, silent speechreading generates bilateral activation in superior temporal regions specialised for the perception of auditory speech [Science 276 (1997) 593; Neuroreport 11 (2000) 1729; Proceedings of the Royal Society London B 268 (2001) 451]. In the present study, FMRI data were collected from deaf and hearing volunteers while they speechread numbers and during a control task in which they counted nonsense mouth movements (gurns). Brain activation for silent speechreading in oral deaf participants was found primarily in posterior cingulate cortex and hippocampal/lingual gyri. In contrast to the pattern observed in the hearing group, deaf participants showed no speechreading-specific activation in left lateral temporal regions. These data suggest that acoustic experience shapes the functional circuits for analysing speech. We speculate on the functional role, the posterior cingulate gyrus may play in speechreading by profoundly congenitally deaf people.

Acoustics↗