Serotonin transporter polymorphisms: no association with response to antipsychotic treatment, but associations with the schizoparanoid and residual subtypes of schizophrenia.
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The human serotonin transporter gene (5-HTT) demonstrates two polymorphisms with possible functional impact: a 44-bp insertion/deletion polymorphism of the promoter region and a 17-bp variable number of tandem repeat polymorphism (VNTR) in intron 2 (STin2). Such genetic polymorphisms in the serotoninergic system may increase the susceptibility to schizophrenia or may serve as predictors of therapeutic response. We therefore analyzed these polymorphisms as susceptibility factors for schizophrenia by comparison of 684 schizophrenic inpatients with 587 healthy controls. We furthermore compared the therapeutic outcome of schizophrenic patients differentiated by the 5-HTT genotypes. Schizo-affective patients were more frequently homozygous for the 44-bp insertion allele (Odds ratio, OR: 1.6, 95% confidence interval, CI: 1.1--2.3, P < 0.03) than were all other schizophrenic patients and controls. The 17-bp VNTR alleles found were: STin2.7, 9, 10, and 12. Sequence analysis revealed seven different sequence motifs with an invariable arrangement. Patients with schizo-paranoid schizophrenia were more frequently homozygous for the STin2.12 allele than were controls (OR: 1.4, CI: 1.1--1.8, P < 0.007) and all other schizophrenic patients (OR: 1.6, CI: 1.2--2.3). The STin2.9 allele represented a risk factor for the residual subtype of schizophrenia (OR: 6.4, CI: 2.5--16.2, P < 0.001). On the basis of global clinical impressions, as well as measurements with the positive and negative syndrome scale we found no association of the polymorphisms with therapeutic response. In conclusion, the 44-bp polymorphism may be associated with the schizo-affective and the 17-bp VNTR with the residual and schizo-paranoid subtype of schizophrenia, findings which require further biochemical and epidemiological confirmation. (+info)
Reversal of diminished inhibitory sensory gating in cocaine addicts by a nicotinic cholinergic mechanism.
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Cocaine addiction, as with other stimulant abuse, produces psychotic symptoms. Although often moderate to mild in severity, these symptoms are, nevertheless, associated with poorer over-all outcome. Recent studies suggest diminished nicotinic cholinergic neurotransmission as a mechanism of a physiological deficit found in schizophrenia, failure of auditory sensory inhibition. Diminished inhibitory sensory gating also occurs in cocaine addicts, probably because of their increased catecholaminergic neurotransmission, which blocks the inhibition. In the present study, 11 cocaine addicts in the first week of detoxification were recorded electrophysiologically, after which the effects of 6 mg of nicotine gum, were assessed in a double-blind placebo-controlled crossover design. The test was repeated 10 days later. Treatment with nicotine, but not placebo, briefly reversed the inhibitory abnormality on both test days. Although nicotine itself may not be a desirable therapeutic agent, because desensitization of nicotinic receptors limits the time course of its effect, the study identifies a previously unexploited therapeutic target for new drug development for the neuropsychiatric sequelae of cocaine addiction. (+info)
Psychosocial characteristics and needs of mothers with psychotic disorders.
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BACKGROUND: It is not known whether mothers with psychotic disorders are clinically and socially distinct from women with psychoses who have not had children. AIMS: To determine the proportion of mothers in an epidemiologically representative population of women with psychotic disorders, to examine the factors associated with having children, and to examine the factors associated with having children 'looked after' by social services. METHOD: Descriptive analysis and two case-control studies. RESULTS: Sixty-three per cent of women with psychotic disorders were mothers. There were no clinical differences between women with or without children, but mothers were more likely to be older and live in unsupported accommodation. Having had a 'looked after' child was associated with Mental Health Act detention, younger age, a forensic history and being Black African. CONCLUSION: Many women with psychoses are mothers. Mothers with psychoses are as disabled and have as many needs as women with psychoses without children. (+info)
Aggressive incidents in first-episode psychosis.
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BACKGROUND: Recent research has reported increased risk of aggressive incidents by individuals with psychotic illness. AIMS: To examine acts of aggression in first-episode psychosis. METHOD: Subjects with a first-episode psychosis were ascertained from a defined catchment area (Nottingham, UK) and reassessed at 3 years (n=166) using clinical interview, informants, health care and forensic records. RESULTS: Of the subjects, 9.6% demonstrated at least one act of serious aggression (defined as weapon use, sexual assault or victim injury) during at least one psychotic episode and 23.5% demonstrated lesser acts of aggression (defined as all other acts of aggression). For all aggressive subjects (33.1%), unemployment (OR=3.6, 95% C11.6-8.0), comorbid substance misuse (OR=3.1, C1 1.1-8.8) and symptoms of overactivity at service contact (OR=6.9,C1 2.7-17.8) had independent effects on risk of aggression. CONCLUSIONS: We confirmed some previously reported demographic and clinical associations with aggression in first-episode psychosis but no relationship with specific psychotic symptoms or diagnostic groups was observed. (+info)
Factors that influence the cost of caring for patients with severe psychotic illness: report from the UK 700 trial.
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BACKGROUND: Many factors influence the type and quantity of services received by patients and, thus, the total cost of care. Knowledge of these factors can aid budgetary and service-planning decisions. AIMS: To investigate factors that influence the cost of caring for patients with severe psychotic illness. METHOD: Univariate and multivariate analyses were used to examine associations between baseline characteristics and subsequent 2-year total direct costs in 667 patients from the UK 700 case management trial. RESULTS: Significantly more money was spent on younger patients, those with longer duration of illness, those who had spent less time living independently and those who had spent longer in hospital for psychiatric reasons. CONCLUSIONS: Total costs of caring for patients with severe psychotic illness appear to be influenced to a large extent by age, duration of illness and past levels of dependence on statutory services. The strength of these relationships is greater than the impact of illness severity. (+info)
Acute psychosis after CPAP treatment in a schizophrenic patient with sleep apnoea-hypopnoea syndrome.
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A 52-yr-old man with a residual phase of schizophrenia developed sleep apnoea-hypopnoea syndrome (SAHS). After five days of continuous positive airway pressure (CPAP) treatment, the patient developed an aggressive mood with incoherence, prominent hallucinations and agitation, and attempted to hit his relatives. He was finally admitted to the hospital with an acute psychotic episode. Withdrawal of CPAP, and neuroleptic treatment controlled the episode, and clinical symptoms of SAHS reappeared 10 days later. Schizophrenia associated to sleep apnoea-hypopnoea syndrome has rarely been reported, but, to the authors' knowledge, the induction of a psychotic episode by continuous positive airway pressure treatment in a patient with sleep apnoea-hypopnoea syndrome and coexisting schizophrenia has never been previously reported. (+info)
A review of MRI findings in schizophrenia.
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After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin, E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described 'dementia praecox' and the 'schizophrenias', were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82-120) was the first to investigate the neuropathology of schizophrenia, though he went on to study more tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137-147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the neuropathology of schizophrenia is largely due to advances in in vivo MRI techniques. These advances have now led to the identification of a number of brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier post-mortem findings, and most are small and subtle, rather than large, thus necessitating more advanced and accurate measurement tools. These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly, there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi-92% of studies reviewed, basal ganglia-68% of studies reviewed, corpus callosum-63% of studies reviewed, and thalamus-42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed). The timing of such abnormalities has not yet been determined, although many are evident when a patient first becomes symptomatic. There is, however, also evidence that a subset of brain abnormalities may change over the course of the illness. The most parsimonious explanation is that some brain abnormalities are neurodevelopmental in origin but unfold later in development, thus setting the stage for the development of the symptoms of schizophrenia. Or there may be additional factors, such as stress or neurotoxicity, that occur during adolescence or early adulthood and are necessary for the development of schizophrenia, and may be associated with neurodegenerative changes. Importantly, as several different brain regions are involved in the neuropathology of schizophrenia, new models need to be developed and tested that explain neural circuitry abnormalities effecting brain regions not necessarily structurally proximal to each other but nonetheless functionally interrelated. (ABSTRACT TRUNCATED) (+info)
UCSD Performance-Based Skills Assessment: development of a new measure of everyday functioning for severely mentally ill adults.
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Instruments to assess everyday functioning have utilized self-report, proxy report, clinician ratings, or direct observation of performance. Each of these methods has strengths and weaknesses. In this article we argue for the inclusion of performance-based measures of functional capacity in studies of severely mentally ill persons and describe a new measure, the UCSD Performance-Based Skills Assessment (UPSA). We administered the UPSA to 50 middle-aged and older outpatients with schizophrenia or schizoaffective disorder, and 20 normal comparison subjects. Participants' performance in five domains of functioning (Household Chores; Communication; Finance; Transportation; and Planning Recreational Activities) was assessed in standardized role-play situations. Administration of the UPSA required an average of 30 minutes to complete. Interrater reliability of ratings was excellent. Patients' performance was significantly more impaired than that of normal subjects. Among patients, the UPSA performance correlated significantly with severity of negative symptoms and of cognitive impairment but not with that of positive or depressive symptoms. The UPSA scores correlated highly with those on another performance-based measure. We believe that UPSA would be useful for assessing everyday functioning in severely mentally ill adults. (+info)