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Biomedical subjects

A Kinsella

Publications and source records attributed to A Kinsella.

At least 19 recordsLinked to original sources
PubMed2006

A prospective evaluation of adherence to medication in first episode schizophrenia.

The aim of this study was to identify the features of first episode schizophrenia that predict adherence antipsychotic medication at six-month follow-up. We used validated instruments to assess clinical and socio-demographic variables in all patients with first episode schizophrenia from a defined geographical area admitted to a Dublin psychiatric hospital over a four-year period (N=100). At six-month follow-up (N=60) we assessed adherence to medication using the Compliance Interview. One third of patients with schizophrenia were non-adherent with medication within six months of their first episode of illness. High levels of positive symptoms at baseline, lack of insight at baseline, alcohol misuse at baseline and previous drug misuse predict non-adherence. These results indicate that an identifiable subgroup of patients with first episode schizophrenia is at high risk of early non-adherence to medication. While high positive symptom scores pre-date and predict non-adherence in most patients, reduced insight is the best predictor of non-adherence in patients who do not misuse alcohol or other drugs.

Adult↗
PubMed2005

Early insight predicts depression and attempted suicide after 4 years in first-episode schizophrenia and schizophreniform disorder.

OBJECTIVE: To map the development of insight in the 4 years after presentation with first-episode schizophrenia and schizophreniform disorder and to determine the effects of evolving insight on depression and the likelihood of attempted suicide. METHOD: We assessed 101 individuals at presentation, 6 months and 4 years. We measured insight, including recognition of mental illness, recognition of need for treatment and ability to relabel psychotic symptoms. We measured depression and recorded all suicide attempts. RESULTS: Insight improved with time. Recognition of mental illness at 6 months predicted depression and attempted suicide at 4 years. CONCLUSION: Six months after presentation, the greater the acknowledgement by people that they had a mental illness, the more depressed they were at 4 years and the greater the likelihood that they would attempt suicide by 4 years. This may have implications for disclosure of diagnosis.

Adult↗
PubMed2004

Clinical predictors of admission status in first episode schizophrenia.

Having a diagnosis of schizophrenia is a risk factor for involuntary admission to psychiatric inpatient care, but we have a limited understanding of why some patients and not others require involuntary admission. We aimed to identify the predictors of involuntary admission in first episode schizophrenia. We used validated instruments to assess clinical and socio-demographic variables in all patients (n = 78) with first episode schizophrenia from a defined geographical area admitted to a Dublin psychiatric hospital over a 4-year period. Involuntary patients (n = 17) could not be distinguished from voluntary patients (n = 61) on the basis of age, gender, living status, marital status, drug abuse or duration of untreated psychosis. Neither positive nor negative symptoms were useful predictors of admission status. Lack of insight was a strong predictor of involuntary status.

Adult↗
PubMed2003

Prospective evaluation of neurological soft signs in first-episode schizophrenia in relation to psychopathology: state versus trait phenomena.

BACKGROUND: Although patients with schizophrenia have increased rates of neurological soft signs, few studies have examined prospectively their trait or state characteristics in relation to psychopathology. METHOD: In a prospective study of 97 patients with first-episode schizophrenia (DSM-IV criteria) we assessed neurological soft signs and psychopathology at presentation and at 6 month follow-up for 73 cases. To establish whether soft signs were associated with variations in clinical state, neurological soft signs were measured using two validated examinations (Neurological Evaluation Scale and Condensed Neurological Examination); psychopathology was assessed using the Positive and Negative Syndrome Scale. RESULTS: There was significant improvement in overall neurological function, primarily in motor-related and cortical signs, which were associated with improvement in psychopathology. Conversely, 'harder' signs were unrelated to improvement in psychopathology. CONCLUSIONS: Neurological soft signs in schizophrenia are heterogenous. Motor and cortical signs evidence state-like characteristics and vary with clinical course, while 'harder' signs evidence more static, trait-like characteristics in accordance with a neurodevelopmental basis.

Adult↗
PubMed2003

Topographical Assessment of Ethological and Dopamine Receptor Agonist-Induced Behavioral Phenotype in Mutants with Congenic DARPP-32 'Knockout'.

Congenic (10 backcrosses into C57BL/6J) mutants with targeted gene deletion of DARPP-32, a neuronal phosphoprotein regarded as an essential mediator of the biological effects of dopamine (DA), were assessed phenotypically using an ethologically based approach that resolves all topographies of behavior in the mouse repertoire. Over initial exploration, female, but not male, DARPP-32 mutants evidenced increased locomotion and decreased grooming, while a decrease in rearing seated was evident in mutants of both genders; continuing assessment over several hours did not reveal additional phenotypic effects. Following challenge with the nonselective DA receptor agonist apomorphine, low doses were associated with reduced levels of sniffing, grooming, total rearing, and rearing seated in DARPP-32 mutants relative to wildtypes; this would suggest some role for DARPP-32 in mediating the biological effects of presynaptic D(2)-like autoreceptor or inhibitory postsynaptic D(2)-like receptor activation. Following challenge with higher doses, while stereotyped sniffing and locomotion with chewing was largely unaltered, the additional murine response of Straub tail was essentially abolished in DARPP-32 mutants, indicating some specific involvement of DARPP-32 in mediating this topography of behavior; additionally, there were overall reductions in levels of sniffing, total rearing, rearing seated, and grooming in DARPP-32 mutants that were unrelated to the dose of apomorphine administered, indicating broader topographical effects following the stress of the injection procedure relative to more naturalistic conditions. The developmental absence of DARPP-32 following targeted gene deletion appears to be associated with compensatory processes that maintain certain topographies of spontaneous and agonist-induced DAergic function, while other topographies remain impaired.

Analysis of Variance↗
PubMed2002

Phenotypic resolution of spontaneous and D1-like agonist-induced orofacial movement topographies in congenic dopamine D1A receptor 'knockout' mice.

A novel system was used to assess the role of D(1)-like dopamine receptors in distinct topographies of orofacial movements in mice with congenic D(1A) receptor knockout. Under spontaneous conditions, vertical jaw movements in wild-types declined with time at a rate that was reduced in D(1A) mutants, while horizontal jaw movements emerged progressively in wild-types but not in D(1A) mutants; tongue protrusions were absent in D(1A) mutants, while incisor chattering was initially reduced in D(1A) mutants but rose subsequently to reach the level of wild-types. D(1A) receptors exert a topographically specific role in regulating individual spontaneous orofacial movements, and these involve interactions with psychomotor processes which 'sculpt' behavioural change over time. The anomalous D(1)-like agonist SK&F 83959, which fails to stimulate, and indeed inhibits the stimulation of adenylyl cyclase induced by dopamine, readily stimulated vertical jaw movements, tongue protrusions and incisor chattering, and these response topographies were absent in D(1A) mutants. These results suggest that D(1A) receptors may exert some form of permissive role over orofacial topographies initiated via a novel, putative D(1)-like site not linked to adenylyl cyclase, or that some D(1A) receptors might be coupled to a transduction system other than adenylyl cyclase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2002

Essential fatty acids given from conception prevent topographies of motor deficit in a transgenic model of Huntington's disease.

Transgenic R6/1 mice incorporate a human genomic fragment containing promoter elements exon 1 and a portion of intron 2 of the Huntingtin gene responsible for Huntington's disease. They develop late-onset neurological deficits in a manner similar to the motor abnormalities of the disorder. As essential fatty acids are phospholipid components of cell membranes which may influence cell death and movement disorder phenotype, R6/1 and normal mice were randomised to receive a mixture of essential fatty acids or placebo on alternate days throughout life. Over mid-adulthood, topographical assessment of behaviour revealed R6/1 transgenics to evidence progressive shortening of stride length, with progressive reductions in locomotion, elements of rearing, sniffing, sifting and chewing, and an increase in grooming. These deficits were either not evident or materially diminished in R6/1 transgenics receiving essential fatty acids. R6/1 transgenics also showed reductions in body weight and in brain dopamine D(1)-like and D(2)-like quantitative receptor autoradiography which were unaltered by essential fatty acids.These findings indicate that early and sustained treatment with essential fatty acids are able to protect against motor deficits in R6/1 transgenic mice expressing exon 1 and a portion of intron 2 of the Huntingtin gene, and suggest that essential fatty acids may have therapeutic potential in Huntington's disease.

Aging↗
PubMed2001

Relationship of the factor structure of psychopathology in schizophrenia to the timing of initial intervention with antipsychotics.

Timing of intervention with antipsychotic medication may influence long-term outcome in schizophrenia in a manner that is poorly understood. This study evaluated psychopathology, its factor structure, and cognitive dysfunction in older patients with chronic schizophrenia in relation to the intervals from onset of psychosis to initiation of treatment with antipsychotics, and from initiation of antipsychotic treatment to current assessments. The subjects were 129 patients with schizophrenia, many of whom became ill in the preneuroleptic era. Their current psychopathology was assessed using the Positive and Negative Syndrome Scale, and its factor structure examined using principal component analysis. Current general and executive cognitive function was evaluated using the Mini-Mental State Examination and the Executive Interview, respectively. Using multiple regression modelling, increasing duration of initially unmedicated psychosis, but not the much longer duration of subsequently treated illness, was the primary predictor of psychomotor poverty (negative symptoms) but not of reality distortion or disorganisation over the three domains of psychopathology resolved; duration of initially unmedicated psychosis marginally predicted the severity of general, but not of executive, cognitive dysfunction. Delayed intervention with antipsychotics appears associated with poorer long-term course in terms of increased severity of psychopathology in the psychomotor poverty domain.

Aged↗
PubMed2001

Topographical assessment and pharmacological characterization of orofacial movements in mice: dopamine D(1)-like vs. D(2)-like receptor regulation.

A novel procedure for the assessment of orofacial movement topographies in mice was used to study, for the first time, the individual and interactive involvement of dopamine D(1)-like vs. D(2)-like receptors in their regulation. The dopamine D(1)-like receptor agonists A 68930 ([1R,3S]-1-aminomethyl-5,6-dihydroxy-3-phenyl-isochroman) and SK&F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine) each induced vertical jaw movements with tongue protrusions and incisor chattering. The dopamine D(1)-like receptor antagonists SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and BW 737C ([S]-6-chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) antagonised these responses, while the dopamine D(2)-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide) attenuated those to SK&F 83959 and released horizontal jaw movements. These findings suggest some role for a dopamine D(1)-like receptor that is coupled to a transduction system other than/additional to adenylyl cyclase, and for dopamine D(1)-like:D(2)-like receptor interactions, in the regulation of individual orofacial movement topographies in the mouse. This methodology will allow the use of knockout mice to clarify the roles of individual dopamine receptor subtypes in their regulation.

Animals↗
PubMed2001

Vulnerability to involuntary movements over a lifetime trajectory of schizophrenia approaches 100%, in association with executive (frontal) dysfunction.

This study assessed the prevalence of involuntary movements among older inpatients with severe schizophrenia, many of whom had experienced a lifetime of illness and its treatment, and examined their neuropsychological correlates. The subjects of this study were 128 inpatients with a DSM-IV diagnosis of schizophrenia. They were assessed using the Abnormal Involuntary Movement Scale, the Mini-Mental State Examination for general cognitive impairment and the Executive Interview for executive dyscontrol; additionally, their medical records were reviewed in detail for treatment histories. Prevalence of involuntary movements was examined and their clinical correlates determined in relation to topography of movement disorder using logistic regression. In schizophrenia, prevalence of involuntary movements was: age <65years, 63%; 65-75years, 80%; >75years, 93%. The primary correlate both of overall and of orofacial movements was poor executive function, whereas the primary correlate of limb-trunkal movements was poor general cognitive function. On approaching the limits of human longevity following a lifetime trajectory of illness and its treatment, essentially 'all' patients with schizophrenia appear inherently vulnerable to the emergence of involuntary movements in topographically specific association with cognitive deficits.

Adult↗
PubMed2001

Number of older siblings of individuals diagnosed with schizophrenia.

One of the most consistent epidemiological findings in schizophrenia research is the small excess of late winter/early spring births. There is also evidence that schizophrenia is associated with urban birth and with later birth order. One interpretation of these three findings is that respiratory viral infections brought into the household by children in crowded areas could disrupt foetal brain development and predispose to schizophrenia in later life. To further explore this hypothesis, case register data were used to assess if schizophrenics with a greater number of older siblings are more likely to be born in urban areas and during late winter/early spring months. Data from the Dublin and Three County Case Register were compiled relating to 2969 patients with schizophrenia and 5904 patients with neurosis. We used logistic regression analysis to determine if the number of older siblings differentiated schizophrenia from neurosis after controlling for the effects of gender, urban/rural birth, season of birth and sibship size, and to examine whether any interactions existed. The number of older siblings did not predict a diagnosis of schizophrenia over neurosis. There was no interaction between number of older siblings and urban birth, between number of older siblings and spring birth, or between number of older siblings, season of birth and urban birth. These data do not support the hypothesis that schizophrenia, by comparison with neurosis, is associated with an increased number of older siblings or that there is an interaction between number of older siblings, urban birth or season of birth.

Birth Order↗
PubMed2001

Comparative, topographically-based evaluation of behavioural phenotype and specification of D(1)-like:D(2) interactions in a line of incipient congenic mice with D(2) dopamine receptor 'knockout'.

Phenotypes were assessed topographically in mice lacking functional D(2) dopamine receptors ['knockouts'], using an ethologically based approach to assess all behaviours in the natural repertoire. D(2)-null mice evidenced an ethogram characterised initially by modest reductions in locomotion and shifts in rearing topographies. Subsequently, topographies of behaviour habituated similarly for wildtypes and 'knockouts'. Following challenge with the D(2)-like agonist RU 24213, both inhibition of rearing at a lower dose and induction of stereotyped sniffing and ponderous locomotion at higher doses were essentially absent in D(2)-null mice. Following challenge with the D(1)-like agonist A 68930, vacuous chewing was released in D(2)-null mice. This topographical approach to phenotypic characterisation implicates: (i) the D(2) receptor in these D(2)-like agonist effects and in oppositional D(1)-like: D(2)-like interactions; and (ii) the operation of material compensatory processes consequent to the developmental absence of D(2) receptors which are able to maintain ethological function under tonic, 'naturalistic' conditions but not under 'phasic' challenge.

Animals↗
PubMed2001

Telehealth interventions for PPS.

The ongoing challenge for nurses using home telehealth in PPS will be defining and routinely redefining what works to help patients better manage themselves and their treatment and care routines. This process requires careful thought and customization of telehealth routines and interventions. In PPS there is clearly a demand that nurses document that patients have followed needed care directives to reach successful outcomes, whether or not they have followed a conventional telehealth path to get there.

Home Care Services↗