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Biomedical subjects

D G Owens

Publications and source records attributed to D G Owens.

At least 19 recordsLinked to original sources

Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia.

BACKGROUND: Structural magnetic resonance imaging (MRI) of the brain in patients with schizophrenia has consistently demonstrated several abnormalities. These are thought to be neurodevelopmental in origin, as they have also been described in first episode cases, although there may be a progressive component. It is not known at which point in development these abnormalities are evident, nor to what extent they are genetically or environmentally mediated. METHODS: One hundred forty-seven high-risk subjects (with at least two affected first or second degree relatives), 34 patients in their first episode, and 36 healthy control subjects received an MRI scan covering the whole brain. After inhomogeneity correction, regions of interest were traced by three group-blind raters with good inter-rater reliability. Regional brain volumes were related to measures of genetic liability to schizophrenia and to psychotic symptoms elicited at structured psychiatric interviews. RESULTS: High-risk subjects had statistically significantly reduced mean volumes of the left and right amygdalo-hippocampus and thalamus, as compared to healthy control subjects. They also had bilaterally larger amygdalo-hippocampi and bilaterally smaller lenticular nuclei than the schizophrenics. High-risk subjects with symptoms had smaller brains than those without. The volumes of the prefrontal lobes and the thalamus were the only consistent associates of genetic liability. CONCLUSIONS: Subjects at high risk of developing schizophrenia have abnormalities of brain structure similar to but not identical to those found in schizophrenia. Our results suggest that some structural abnormalities are genetic trait or vulnerability markers, others are environmentally mediated, and that the development of symptoms is associated with a third overlapping group of structural changes. Particular risk factors for schizophrenia may interact at discrete time points of neurodevelopment with different effects on specific brain regions and may represent relatively distinct disease processes.

Amygdala↗

Diagnostic stability in subjects with multiple admissions for psychotic illness.

BACKGROUND: Although studies investigating changes in diagnosis between psychotic episodes have differed in design, some consistent findings have emerged. This study seeks to clarify and extend these findings by describing and comparing clinical and operationally defined diagnostic stability in a group of subjects with multiple episodes of functional psychotic illness. METHODS: The OPCRIT programme was applied to case notes of 204 subjects with multiple admissions for psychotic illness. Clinical and operationally defined diagnoses were compared and the spread and stability of diagnoses determined. RESULTS: An increase in the frequency of diagnosis of schizophrenia from initial to subsequent episodes was demonstrated. High levels of stability were found for schizophrenia (58 to 98%), moderate levels for affective disorders (24 to 83%), low levels for other non-organic psychotic conditions (27 to 54%) and atypical psychosis (27 to 53%), and very low levels for schizoaffective disorder (5 to 39%) and other conditions (0 to 4%). CONCLUSIONS: The stability levels for schizophrenia and affective disorders are adequate, but the low levels for a range of other psychotic conditions raise questions regarding their predictive validity.

Adult↗

A factor model of the functional psychoses and the relationship of factors to clinical variables and brain morphology.

BACKGROUND: Despite more than 100 years of study, there remains no definitive diagnostic validation of the functional psychoses. Factor analysis suggests the presence of three or more psychopathological syndromes in functional psychoses as a whole. The relationship between these factors and cerebral anatomy has been investigated in schizophrenia only. This study aimed to address the relationship of symptom factors to clinically important variables and cerebral anatomy in a sample of psychotic patients with a spread of diagnoses. METHODS: In a sample of patients with functional psychoses, symptom data was obtained on four consecutive admissions using the OPCRIT symptom checklist. OPCRIT data was used to generate operational diagnoses in accordance with pre-set criteria and a principle components analysis was performed on symptom data. Factor loadings were compared between each admission to examine factor stability over time. Factor scores at first admission were also correlated with clinical variables obtained from patients' case notes. From the sample of 204 patients, 64 subjects were recruited and underwent an MRI scan of the brain. Regional anatomical volumes were compared with diagnosis and factor loadings at first admission. RESULTS: A principal components analysis gave a four-factor solution of 'manic', 'depressive', 'disorganization' and 'reality distortion' factors at each admission. Factors showed a high degree of stability over the four admissions studied. The factors were significantly associated with several clinical variables. Three of the four factors were associated with a specific pattern of cerebral anatomy. CONCLUSIONS: This study suggests that factors may correspond to relatively specific disease processes underlying functional psychotic illness. We propose that the use of symptom factors may facilitate the investigation of the underlying mechanisms of psychotic illness.

Activities of Daily Living↗

Correlations between clinical and historical variables, and cerebral structural variables in people with mild intellectual disability and schizophrenia.

The increased prevalence of schizophrenia in the population with mildly intellectual disability (ID) remains unexplained. The present study explores several possibilities by examining historical/clinical findings in relation to structural neuroimaging findings in three groups: (1) comorbid mild ID and schizophrenia; (2) schizophrenia alone; and (3) mild ID alone. Information about clinical and historical variables was obtained from 101 subjects (39 with comorbidity, 34 with schizophrenia and 28 with mild ID), out of whom 68 (23, 25 and 20, respectively) had had a cerebral magnetic resonance imaging (MRI) scan. Although a number of significant correlations exist between clinical variables and structural MRI abnormalities in all three groups, no clearly predictive inter- or between-group differences emerged. More striking was the finding that showed small amygdalo-hippocampal size to be associated with a history of central nervous system injury, especially meningitis. These findings provide support for the view that cognitive impairment and comorbid psychosis can result from a common cause, such as meningitis or obstetric complications, possibly interacting with other factors, such as family history.

Adolescent↗

Edinburgh high risk study--findings after four years: demographic, attainment and psychopathological issues.

This study reports findings of the Edinburgh High Risk Study four years after it began. This study is designed to explore the pathogenesis of schizophrenia by examining a large sample of young adults aged 16-25 years who are at enhanced risk of developing schizophrenia by having two close relatives with the disorder, and comparing them with matched controls. This paper presents comparisons of the high risk subjects, well controls and subjects with first-episode schizophrenia in terms of demographic, childhood, psychopathological, educational and employment, forensic and social work variables. High risk subjects have more psychological difficulties, poorer educational and employment attainment, and more social work contact than controls. The enhanced social work involvement related to the presence of a schizophrenic parent (especially a mother) but the other difficulties could not be attributed to that situation. Neurotic, partially held psychotic and fully held psychotic symptoms all occurred in both subjects and controls, but all were significantly more common in high risk subjects. Clinical schizophrenia has so far developed in 10 high risk subjects and in no controls. Possible confounding effects of drug or alcohol misuse were considered but were found unlikely to be important.

Adolescent↗

Neuroanatomy of comorbid schizophrenia and learning disability: a controlled study.

BACKGROUND: Reasons for the higher frequency of schizophrenia in learning-disabled populations are uncertain. We investigated the neuroanatomical basis for this phenomenon by structural magnetic resonance imaging (MRI) in patients with learning disability and schizophrenia, learning-disabled patients, and patients with schizophrenia. METHODS: Age-matched and sex-matched patients with learning disability (20 cases), schizophrenia (25), and both disorders (23) underwent MRI scans of the brain. Whole brain areas and specific regions of interest were examined. 29 normal controls were also scanned. FINDINGS: The scans of the group with both disorders were closely similar to those of the schizophrenic group, in terms of both general structures and the structure of the amygdala-hippocampus. However, the amygdala-hippocampus was significantly smaller on both sides than that of normal controls (left 4.1 vs 4.5 cm3, p=0.011; right 4.2 vs 4.99 cm3, p<0.0001). The brains of learning-disabled patients were generally smaller than those of the other three groups, but the amygdalohippocampal complexes were larger. INTERPRETATION: In terms of brain structure, patients with comorbid learning disability and schizophrenia resemble patients with schizophrenia and not those with learning disability. We suggest that the higher frequency of schizophrenia in learning-disabled patients is due to a greater tendency of schizophrenic patients to develop cognitive deficits, and that within the learning-disabled population there may be individuals whose deficits result from undiagnosed schizophrenia.

Adolescent↗

Correlates of insight and insight change in schizophrenia.

Various theories have been proposed to account for poor insight in schizophrenia. This study examined the relationships between insight, mood, schizophrenic symptoms and cognitive functioning. The relationship between longitudinal changes in insight and changes in symptoms and mood was also investigated. One-hundred patients with DSM-III-R schizophrenia, recently recovered from a relapse of their illness, were rated on the Insight and Treatment Attitudes Questionnaire (ITAQ), the Positive and Negative Syndrome Scale (PANSS), the Montgomery Asberg Depression Rating Scale (MADRS), the Rivermead Behavioural Memory Test and tests of current and premorbid IQ. A random sample of 53 were then given an educational package (video and booklets) designed to improve their insight. Follow-up ratings on the ITAQ, PANSS and MADRS were subsequently obtained. At baseline, better insight was significantly correlated with lower mood and fewer positive symptoms. It was not related to cognitive functioning. Improvement in insight at follow up was related to worsening of mood, but not to change in positive symptoms. The results are consistent with the concept that poor insight, at least in part, results from the psychotic disease process itself. In addition, they suggest that poor insight may protect against depression in the early stages of recovery from schizophrenia.

Adolescent↗

Magnetic resonance imaging of brain in people at high risk of developing schizophrenia.

BACKGROUND: Schizophrenia is a multifactorial disorder that is associated with disturbed cerebral development. Structural brain-imaging studies have consistently shown that the volumes of some parts of the brain, particularly the mesial temporal lobes, are smaller in patients with schizophrenia than in healthy people. Whether these abnormalities of brain structure predate the onset of symptoms is not known. METHODS: 100 people at high risk of developing schizophrenia (two or more first-degree or second-degree relatives affected), 20 patients in their first episode of schizophrenia, and 30 healthy controls underwent magnetic resonance imaging of the brain. The volumes of regions of interest were measured by standard techniques. FINDINGS: Mean whole-brain volume was 1356 cm3 (SD 178) in the first-episode group, 1347 cm3 (122) in the high-risk group, and 1334 cm3 (149) in the controls (p=0.8). The mean volume of the left amygdala-hippocampal complex (AHC) was lower in the first-episode group (4.3 cm3 [0.6]) than in the high-risk group (4.6 cm3 [0.6]), and in turn than in the controls (4.8 cm3 [0.7]); these differences were significant (p<0.05) both for absolute volumes and values adjusted for brain volume and other confounders. The right AHC showed a similar pattern (absolute volumes 4.5 cm3 [0.7], 4.8 cm3 [0.6], 4.9 cm3 [0.9], respectively). Both thalamic nuclei were significantly smaller in the high-risk group than in the control group. INTERPRETATION: People at high risk of developing schizophrenia for genetic reasons have several structural brain abnormalities that are similar to those in patients with the disorder. If at-risk individuals with particularly small AHC or thalami are most likely to develop schizophrenia, this feature might assist in early detection and treatment.

Adolescent↗

Life events in suicide and undetermined death in south-east Scotland: a case-control study using the method of psychological autopsy.

BACKGROUND: Adverse life events have been associated with increased risk of suicide. Mental disorders are also major risk factors for suicide. Matching cases and controls for mental disorder is thus appropriate in studies of suicide. This procedure was used to study the degree to which excess adversity was more common in cases who committed suicide as opposed to living controls matched for mental disorder. METHODS: The study formed part of a retrospective case-control comparison of cases of suicide/undetermined death with living controls using psychological autopsy in south-east Scotland. Cases and controls were matched for age, sex and mental disorder. Informants were those closest to cases and controls. Cases and controls were assessed for life events using the Interview for Life Events. The subjects were 45 cases of suicide/undetermined death and 40 living controls. RESULTS: Cases and controls did not differ significantly in severity of mental disorder. Adverse interpersonal events within the family (P = 0.01) with an odds ratio (OR) of 9.0 (95% CI, 1.3-399) and adverse physical health-related events (OR 5.0, 95% CI 1.1-47, P = 0.04) were significantly more common in cases than controls. CONCLUSIONS: Cases had significantly more adverse life events than controls overall. The categories accounting for these differences were interpersonal family adversity and physical ill-health. There were no significant differences in either the number or severity of ongoing difficulties between cases and controls. Recent adverse life events contribute to the increased risk of suicide even when age, sex and mental disorder are controlled for. Future research should examine interactions between social support and acute and chronic adversity.

Adult↗

Suicide and undetermined death in south east Scotland. A case-control study using the psychological autopsy method.

BACKGROUND: Mental disorders are major risk factors for suicide. Not all those who suffer from mental disorders kill themselves. Additional information is required to differentiate higher and lesser risk patients. METHODS: Retrospective case-control comparison was made of cases of suicide/undetermined death with living controls using psychological autopsy in South East Scotland. Cases and controls were matched for age, sex and mental disorder. Informants were those closest to cases and controls. The subjects were 45 cases of suicide/undetermined death and 40 living controls. RESULTS: Cases and controls did not differ significantly in severity of mental disorder. The main factors independently associated with undetermined death or suicide were: a history of deliberate self-harm (adjusted OR 4 1); physical ill health (adjusted OR 7.8); and engagement by mental health services (adjusted OR 0.01). Other antecedents associated with increased risk (criminal record, police involvement, financial problems and failure to vote) and those associated with decreased risk (contact with a doctor and in-patient care) did not exert effects after controlling for confounding. CONCLUSIONS: Controls were receiving more care of whatever kind. Treatment of mental disorder comorbid with physical illness and a history of deliberate self-harm may be especially important. Factors that separate those with mental disorder at high risk from those at lesser risk relate to care levels provided, which may be a function of engagement by and with health services. The role of mental health professionals is beneficial in suicide prevention. The focusing of that role towards engaging alienated or 'difficult' patients should be addressed.

Adult↗

Does a four-week delay in the introduction of medication alter the course of functional psychosis?

This study is an analysis of findings of a follow-up study of 105 patients with functional psychotic illness who had participated in a random and blind 4-week trial of pimozide, lithium, both and placebo. The intention was to examine the question of whether a 4-week delay in initiating antipsychotic treatment has a detrimental effect 2.5 years later. Detailed follow-up measures included need for care over the 2.5 years, treatments required, occupational decline, police contact, substance misuse, psychopathology and cognitive function. There was no evidence at all that those initially randomized to placebo had a poorer outcome in terms of any of these variables. It is concluded that a 4-week delay in initiating active treatment in patients with functional psychosis has no long-term adverse effects.

Adolescent↗

Theory of mind and psychoses.

BACKGROUND: A cardinal feature of schizophrenia is the sufferer's difficulty in interacting appropriately within the social milieu. This deficit has recently been associated with the concept of theory of mind, more commonly constructed as a working model to understand behavioural patterns in autistic children. In this paper the complex relationships between theory of mind, IQ and psychoses are addressed. METHODS: Five experimental groups were used; non-psychiatric controls, affective disorder, schizophrenia with normal pre-morbid IQ, schizophrenia with pre-morbid IQ in the mildly learning disabled range, and mild learning disability with no history of psychiatric illness. All subjects were given a first order Theory of Mind Task and if successful, a second order Theory of Mind Task was then administered. All subjects were rated using the Positive and Negative Symptom Scale (PANSS). RESULTS: Subjects with schizophrenia and subjects with mild learning disability show impaired ability on a second order theory of mind task. However, when patients who are unable to answer reality questions are removed from the analysis specific impairment of theory of mind is only seen in subjects with schizophrenia. Furthermore, this impairment is relatively specific to particular psychopathological clusters in subjects with schizophrenia. Even though the same clusters of psychopathology are also seen in patients with affective disorder, their presence is not associated with poor second order theory of mind performance. CONCLUSIONS: Impaired theory of mind on second order tests is specific to schizophrenia when compared to mild learning disability and affective disorder control groups. Subjects with schizophrenia and pre-morbid mild learning disability show greater impairment than subjects with schizophrenia and a pre-morbid IQ within the normal range.

Adult↗

'Pfropfschizophrenie' revisited. Schizophrenia in people with mild learning disability.

BACKGROUND: It is reported that people with mild learning disability have a higher point prevalence of schizophrenia than the normal population, the reasons for which are unclear. METHOD: Thirty-nine subjects with mild learning disability and schizophrenia, 34 control subjects with schizophrenia and 28 control subjects with mild learning disability were seen. Interviews with relatives and carers were also conducted. Assessments were made of clinical variables, psychopathology, neurological 'soft' signs, IQ, memory and family history. Blood was taken for karyotypic analysis from comorbid subjects. RESULTS: The comorbid group had more negative symptoms, episodic memory deficits, soft neurological signs, epilepsy and receive more community supports than control subjects with schizophrenia. Comorbid subjects had a tendency to belong to multiply affected families and show high rates of chromosomal variants on routine karyotypic testing. CONCLUSIONS: Future work on the generality of schizophrenia should include people with premorbid learning disability, as a discrete subtype from whom valuable genetic aetiological clues may be obtained.

Adult↗

A study of enhanced management in patients with treatment-resistant schizophrenia.

The clinical efficacy of two intensive treatment packages (one including the new antipsychotic risperidone and the other not doing so) was compared with that of standard management in 43 patients with long-standing treatment-resistant schizophrenia. Significant differences between the groups in terms of total positive or total negative symptoms were not demonstrated, but the pattern of change between the treatment groups differed, so that benefit in positive symptomatology was seen in both intensive treatment groups and in negative symptomatology in the intensive treatment/risperidone group and the standard group. Changes in general psychopathology were most marked in the risperidone group and were compatible with a relatively non-sedative profile. Using the Disability Assessment Schedule, substantial significant advantages for the intensive treatment groups were found.

Adult↗

The use of videotaped assessment in relation to a study of enhanced management in treatment-resistant schizophrenia.

Videotaped assessments of standardized interviews were used to ensure blindness in relation to a clinical trial of multifaceted programmes of management in patients with treatment-resistant schizophrenia. The technique, although laborious, was feasible in all patients studied and offered advantages in relation not only to blindness but also to assessing the nature of psychopathological changes in patients with schizophrenic deficit syndrome of severe degree. The method is likely to be useful in further studies assessing the possible advantages of newer antipsychotic drugs.

Adult↗

Ethical aspects of research on brain morphology in psychiatric patients.

Morphometric and functional brain research is now an integral part of the most concentrated effort in a century to understand some of the most distressing illnesses to which man can fall victim. It will undoubtedly expand. The only ones with anything to fear from this work are those who, for ideological reasons, cannot accept its basic premises. The ethical issues it raises are not in general insurmountable, though the questions posed by the concept of informed consent remain.

Attitude to Health↗

The nature of 'transient' and 'partial' psychoses: findings from the Northwick Park 'Functional' Psychosis Study.

Three hundred and twenty-six consecutively admitted patients with definite or possible functional psychotic illnesses to which no diagnostic classification had been applied were followed up after 2.5 years. In 86 cases symptomatology had been inadequate for the patients to enter the functional psychosis study, and in 75 cases this was because the symptoms were partial or transient. These patients were compared at follow-up with those who fulfilled operational criteria for schizophrenic, affective or schizoaffective psychoses. Differences between the 'partial' cases and those fulfilling specific diagnostic criteria were few, but the transient cases fared significantly better. Although the transient illnesses were recurrent, at follow-up at 2.5 years they appeared to have a good outcome in terms of social variables and symptomatology.

Affective Disorders, Psychotic↗