PubMed Health⌕ Search

Biomedical subjects

Peter B Jones

Publications and source records attributed to Peter B Jones.

At least 19 recordsLinked to original sources

Forty-year psychiatric outcomes following assessment for internalizing disorder in adolescence.

OBJECTIVE: The aim of this study was to define the long-term psychiatric outcomes of adolescent internalizing disorder in the general population, using data collected over 40 years from a national birth cohort. METHOD: A total of 3,279 members of the Medical Research Council National Survey of Health and Development (the 1946 British birth cohort) underwent assessments of psychiatric symptoms, primarily anxiety and depression, at ages 13 and 15. Adolescents who had internalizing disorder at both ages 13 and 15 and those who had internalizing disorder at one of the two ages were compared with mentally healthy adolescents on various psychiatric outcomes in adulthood (ages 26-53), including the prevalence of mental disorders, self-reported trouble with "nerves," suicidal ideation, and treatment for psychiatric disorders. RESULTS: About 70% of adolescents who had internalizing disorder at both ages 13 and 15 had mental disorder at age 36, 43, or 53, compared with about 25% of the mentally healthy adolescents. They were also more likely than healthy adolescents to have self-reported "nervous trouble" and to have been treated for psychiatric disorder during adulthood. None of these effects was apparent among subjects who had internalizing disorder at only one of the two adolescent assessments. CONCLUSIONS: The long-term psychiatric outcome for adolescents with persistent or recurrent internalizing disorder was poor, whereas the outcome for those who had a single episode was better than expected. The association between adolescent internalizing disorder and poor psychiatric outcomes in adulthood may be mediated by persistence or severity of symptoms in adolescence.

Adolescent↗

Gender-specific effects of the catechol-O-methyltransferase Val108/158Met polymorphism on cognitive function in children.

OBJECTIVE: The study aimed to determine the cognitive effect of the Val108/158Met polymorphism in the catechol-O-methyltransferase (COMT) gene in children before and during puberty. This polymorphism affects cognitive function in healthy adults and may contribute to risk for schizophrenia. METHOD: COMT genotype was determined for 8,707 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), a geographically defined general population cohort of children born between April 1, 1991, and Dec. 31, 1992, in the southwest of England. Fourteen measures of cognitive function--including working memory, verbal and motor inhibition, attentional control, and IQ--were assessed at ages 8 and 10 years. Any pubertal development at age 9 years was reported by parents. Effects of COMT genotype on cognition and interactions with gender and puberty were assessed using general linear models. RESULTS: In boys, genotype significantly affected executive function and explained up to 10 points normal variation in verbal IQ. The effects on IQ were significantly greater in pubertal than in prepubertal boys. In girls, there were no significant effects of genotype on cognition. CONCLUSIONS: This common polymorphism may be one of the genes of small effect that contribute to normal variation in IQ. The gender-specific nature of the effect and its possible interaction with puberty may be relevant to both normal cognitive and brain development and to abnormal development in disorders such as schizophrenia.

Adolescent↗

Fronto-cerebellar systems are associated with infant motor and adult executive functions in healthy adults but not in schizophrenia.

Delineating longitudinal relationships between early developmental markers, adult cognitive function, and adult brain structure could clarify the pathogenesis of neurodevelopmental disorders such as schizophrenia. We aimed to identify brain structural correlates of infant motor development (IMD) and adult executive function in nonpsychotic adults and to test for abnormal associations between these measures in people with schizophrenia. Representative samples of nonpsychotic adults (n = 93) and people with schizophrenia (n = 49) were drawn from the Northern Finland 1966 general population birth cohort. IMD was prospectively assessed at age 1 year; executive function testing and MRI were completed at age 33-35 years. We found that earlier motor development in infancy was correlated with superior executive function in nonpsychotic subjects. Earlier motor development was also normally associated with increased gray matter density in adult premotor cortex, striatum, and cerebellum and increased white matter density in frontal and parietal lobes. Adult executive function was normally associated with increased gray matter density in a fronto-cerebellar system that partially overlapped, but was not identical to, the gray matter regions normally associated with IMD. People with schizophrenia had relatively delayed IMD and impaired adult executive function in adulthood. Furthermore, they demonstrated no normative associations between fronto-cerebellar structure, IMD, or executive function. We conclude that frontal cortico-cerebellar systems correlated with adult executive function are anatomically related to systems associated with normal infant motor development. Disruption of this anatomical system may underlie both the early developmental and adult cognitive abnormalities in schizophrenia.

Adult↗

Incidence of schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP Study.

BACKGROUND: The incidence of schizophrenia in the African-Caribbean population in England is reported to be raised. We sought to clarify whether (a) the rates of other psychotic disorders are increased, (b) whether psychosis is increased in other ethnic minority groups, and (c) whether particular age or gender groups are especially at risk. METHOD: We identified all people (n=568) aged 16-64 years presenting to secondary services with their first psychotic symptoms in three well-defined English areas (over a 2-year period in Southeast London and Nottingham and a 9-month period in Bristol). Standardized incidence rates and incidence rate ratios (IRR) for all major psychosis syndromes for all main ethnic groups were calculated. RESULTS: We found remarkably high IRRs for both schizophrenia and manic psychosis in both African-Caribbeans (schizophrenia 9.1, manic psychosis 8.0) and Black Africans (schizophrenia 5.8, manic psychosis 6.2) in men and women. IRRs in other ethnic minority groups were modestly increased as were rates for depressive psychosis and other psychoses in all minority groups. These raised rates were evident in all age groups in our study. CONCLUSIONS: Ethnic minority groups are at increased risk for all psychotic illnesses but African-Caribbeans and Black Africans appear to be at especially high risk for both schizophrenia and mania. These findings suggest that (a) either additional risk factors are operating in African-Caribbeans and Black Africans or that these factors are particularly prevalent in these groups, and that (b) such factors increase risk for schizophrenia and mania in these groups.

Adolescent↗

Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia.

There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia. It is less clear if clozapine is more effective than the other second-generation antipsychotic (SGA) drugs. A noncommercially funded, pragmatic, open, multisite, randomized controlled trial was conducted in the United Kingdom National Health Service (NHS). Participants were 136 people aged 18-65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs. Participants were randomly allocated to clozapine or to one of the class of other SGA drugs (risperidone, olanzapine, quetiapine, amisulpride) as selected by the managing clinician. Outcomes were assessed blind to treatment allocation. One-year assessments were carried out in 87% of the sample. The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score (3.63 points; CI: 0.46-7.71; p = .08) but did show an advantage in Positive and Negative Syndrome Scale (PANSS) total score that was statistically significant (-4.93 points; CI: -8.82 to -1.05; p = .013) during follow-up. Clozapine showed a trend toward having fewer total extrapyramidal side effects. At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs. In conclusion, in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs, there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year.

Adolescent↗

Gray matter abnormalities associated with duration of untreated psychosis.

PURPOSE: A long duration of untreated psychosis (DUP) is associated with relatively poor clinical and social outcomes. In order to identify whether an anatomically mediated mechanism may give rise to poorer outcomes, it is important to identify whether a long DUP is associated with greater brain structural abnormalities. METHOD: 81 patients with first-episode psychosis (schizophrenia, affective, and other psychoses) were scanned using high resolution Magnetic Resonance Imaging. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with mental health services. High-resolution MRI images and voxel-based methods of image analysis were used to investigate brain structure in these patients. RESULTS: Longer DUP was associated with gray matter reductions in left middle and inferior temporal, left occipital and left fusiform cortices, and with gray matter excess of the left basal ganglia. All findings remained significant when co-varying for exposure to antipsychotic treatment. CONCLUSIONS: Temporal gray matter reductions are more marked in patients with a long DUP. This could reflect a progressive pathological process that is active prior to treatment. Alternatively, these abnormalities could be associated with a more insidious onset of illness and a later presentation to services.

Adolescent↗

Antipsychotic type and correlates of antipsychotic treatment discontinuation in the outpatient treatment of schizophrenia.

Antipsychotic medication maintenance and the factors influencing it were analyzed using data from the SOHO study, a large observational study of the outcomes of antipsychotic treatment for schizophrenia in Europe. A total of 7186 adult patients in the outpatient setting who were initiating or changing their antipsychotic medication and who were prescribed only one antipsychotic after the baseline visit were analyzed. Medication maintenance at 12 months varied with the type of antipsychotic prescribed, being highest with clozapine (79.5%) and olanzapine (77.0%), and lowest with quetiapine (51.4%) and amisulpride (58.2%). Multiple logistic regression analysis demonstrated that the type of antipsychotic prescribed at baseline was the most important predictor of medication maintenance. Alcohol dependency, taking mood stabilizers, compulsory admission or arrest in the previous 6 months, greater clinical severity, and changing antipsychotic medication due to lack of effectiveness at baseline predicted a higher frequency of medication discontinuation in the subsequent 12 months. In contrast, medication maintenance was higher among patients who were treatment naïve at baseline, socially active or who had loss of libido at baseline. The findings from this study should be interpreted conservatively because of its non-randomized observational design.

Adult↗

Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1).

CONTEXT: Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms. OBJECTIVE: To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs. DESIGN: A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis. SETTING: Fourteen community psychiatric services in the English National Health Service. PARTICIPANTS: Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects. INTERVENTIONS: Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist. MAIN OUTCOME MEASURES: Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care. RESULTS: The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar. CONCLUSIONS: In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.

Adolescent↗

Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study.

CONTEXT: Convention suggests uniformity of incidence of schizophrenia and other psychoses; variation would have implications for their causes and biological characteristics. OBJECTIVE: To investigate variability in the incidence of psychotic syndromes in terms of place, ethnicity, age, and sex. DESIGN: Three-center, prospective, comprehensive survey of clinically relevant first-onset psychotic syndromes over a 2-year period (1997-1999). Census data provided the denominator. SETTING: Southeast London, Nottingham, and Bristol, England. PARTICIPANTS: One million six hundred thousand person-years yielded 568 subjects aged 16 to 64 years with clinically relevant psychotic syndromes. MAIN OUTCOME MEASURES: The World Health Organization Psychosis Screen and the Schedules for Clinical Assessment in Neuropsychiatry to classify, blind to ethnicity, all DSM-IV psychotic syndromes and the subclasses of schizophrenia, other nonaffective disorders, affective disorders, and substance-induced psychosis. RESULTS: All syndromes showed a characteristic age distribution. Schizophrenia was significantly more common in men (incidence rate ratio [IRR], 2.3 [95% confidence interval (CI), 1.7-3.1]); affective disorders occurred equally in men and women (IRR, 1.0 [95% CI, 0.7-1.3]). All psychoses were more common in the black and minority ethnic group (crude IRR, 3.6 [95% CI, 3.0-4.2]). Differences in age, sex, and study center accounted for approximately a quarter of this effect (adjusted IRR, 2.9 [95% CI, 2.4-3.5]) in each psychosis outcome. The age-sex standardized incidence rate for all psychoses was higher in Southeast London (IRR, 49.4 [95% CI, 43.6-55.3]) than Nottingham (IRR, 23.9 [95% CI, 20.6-27.2]) or Bristol (IRR, 20.4 [95% CI, 15.1-25.7]). Rates of all outcomes except affective disorders remained significantly higher in Southeast London when the model was expanded to control for ethnicity. CONCLUSIONS: There is significant and independent variation of incidence of schizophrenia and other psychoses in terms of sex, age, ethnicity, and place. This confirms that environmental effects at the individual, and perhaps neighborhood level, may interact together and with genetic factors in the etiology of psychosis.

Adolescent↗

Three decades of antidepressant, anxiolytic and hypnotic use in a national population birth cohort.

BACKGROUND: Psychotropic medication use is common and increasing. Use of such drugs at the individual level over long periods has not been reported. AIMS: To describe antidepressant, anxiolytic and hypnotic drug use, and associations between such medication use and common mental disorder, over a 22-year period. METHOD: Questions about psychotropic medication use and symptoms of common mental disorder were asked of more than 3000 members of the 1946 British birth cohort at multiple time points between ages 31 and 53 years. RESULTS: Prevalence of any antidepressant, anxiolytic or hypnotic use increased significantly from 1977 (30.6 per 1000) to 1999 (59.1 per 1000) as the cohort aged. Less than 30% with mental disorder used antidepressants, anxiolytics or hypnotics. Previous use of antidepressant, anxiolytic or hypnotic was a strong predictor of future use during an episode of mental disorder (odds ratios 3.0-8.4); this association became weaker over time. CONCLUSIONS: Pharmacotherapy is infrequently used by individuals with common mental disorder in Britain; this has not changed in the past three decades.

Adult↗

The acceptability of routine inquiry about domestic violence towards women: a survey in three healthcare settings.

BACKGROUND: Domestic violence is frequently only disclosed when healthcare staff directly inquire. Healthcare staff worry that inquiry may offend. AIM: To identify the characteristics of women who find inquiry about domestic violence by healthcare staff unacceptable. DESIGN OF STUDY: Anonymous interview based cross-sectional study. SETTING: Three general practice surgeries, one antenatal clinic and one emergency department in Cambridge, England, with a total of 2306 women attending for health care. METHOD: Cross-sectional survey. RESULTS: In total 1452 completed questionnaires were returned; response rate 63%. One hundred and twenty-two women (8.4%) indicated that they found inquiry by healthcare staff unacceptable. Women at the emergency department and GP surgeries were more likely to find inquiry unacceptable (odds ratio [OR] = 3.3, 95% confidence interval [CI] = 1.1 to 9.9) and (OR = 3.9, 95% CI = 1.3 to 11.5) respectively, than in the antenatal clinic. Women at the antenatal clinic reported lower rates of abuse within 1 year than at the emergency department or antenatal clinic. Abuse within 1 year was strongly associated with finding inquiry unacceptable (OR = 4.5, 95% CI = 1.8 to 11.4), but not lifetime abuse (OR = 0.9, 95% CI = 0.5 to 1.9). CONCLUSIONS: Inquiry about domestic violence by healthcare staff is acceptable to most women. Acceptability is highest in women who have not been abused in the last year and who are attending the antenatal clinic. Women who attend the antenatal clinic have lower rates of abuse within 1 year.

Adolescent↗

The structural brain correlates of neurological soft signs in healthy individuals.

It has yet to be established whether neurological soft signs (NSS), which include poor motor coordination, sensory perceptual difficulties and difficulties in sequencing of complex motor tasks, result from specific or diffuse brain structural abnormalities. Studying the neuroanatomical basis of NSS in healthy individuals may help to identify which brain areas are specifically associated with these signs, while excluding the potential confounding effects of psychiatric and neurological disorders. We investigated the relationship between brain structure and NSS in 43 healthy individuals, using the Neurological Evaluation Scale for neurological assessment, and high resolution MRI and voxel-based methods of image analysis to investigate brain structure. Higher rates of NSS were associated with a reduction of inferior frontal gyrus, middle and superior temporal gyrus, and anterior cingulate gyrus. It is of note that in a previous study of patients with psychosis we found that an excess of NSS was associated with a reduction of similar cortical areas. Therefore, we suggest that these cortical brain structural changes represent a common neuroanatomical substrate of NSS, across healthy individuals and patients with psychosis.

Adolescent↗

Predictors of schizophrenia--a review.

Schizophrenia is an aetiologically heterogeneous syndrome that usually becomes overtly manifest in adolescence and early adulthood, but in many cases subtle impairments in neurointegrative function are present from birth; hence it is considered to be a disorder with a neurodevelopmental component. The strongest risk factor that has been identified is familial risk with genetic loading. Other risk factors include pregnancy and delivery complications, infections during pregnancy, disturbances of early neuromotor and cognitive development and heavy cannabis use in adolescence. Unfortunately, to date it has not been possible to utilize the predictors of the disorder that have been identified in primary preventative interventions in a general population. However, some authors have claimed that in future it might be possible to reduce the risk for developing schizophrenia through general health policy. In clinical settings, it is helpful to map out possible early risk factors, at least familial risk for psychosis, especially in child, adolescent and young adult mental patients. Furthermore, in the future we may have predictive models combining data from genetic factors for schizophrenia, antenatal risk factors, childhood and adolescent development and clinical symptomatology, as well as brain structural and functional abnormalities.

Adolescent↗

Expressed emotion: relevance to rehospitalization in schizophrenia over 7 years.

Expressed emotion (EE) is an established factor in short-term relapse in schizophrenia. However, data on its long-term predictive ability are scarce. We extended our short-term investigation over 7 years' followup. The study population consisted of 108 patients, 93 with schizophrenia and 15 with schizoaffective disorder. EE of the key relatives was rated with the Five Minute Speech Sample (FMSS). Patient households were categorized by EE and its two components: criticism (CR) and emotional overinvolvement (EOI). High CR was associated with earlier first and second readmissions (Breslow p = 0.002 and 0.04, respectively). High CR was associated with a higher rate of readmissions (p = 0.01) and a longer hospital stay (p = 0.02) compared with low CR. Both compliance with pharmacotherapy and the interaction of high-CR x poor compliance were additional contributors to time to first readmission. This study is the first to demonstrate the prolonged predictive validity of EE. Our results support the value of CR as a prognostic indicator of the course of schizophrenia. The FMSS appears to have predictive power in respect to psychiatric hospitalization. Therapies aimed at lowering high EE seem warranted as a long-term preventive approach.

Adult↗

Cannabis use and outcome of recent onset psychosis.

PURPOSE: To test the hypothesis that recent onset psychotic patients who use cannabis will have psychotic symptoms that are more severe and more persistent than those who do not use cannabis. SUBJECTS AND METHODS: We carried out a 4-year follow-up study of a cohort of 119 patients with recent onset of psychosis. The patients were divided into four groups according to duration of cannabis use, taking index admission and follow-up as reference points. RESULTS: Those subjects who persisted in the use of cannabis had more positive (but not negative) symptoms and a more continuous illness at follow-up. LIMITATIONS: The main limitations of the study were: the relatively small sample size, and that the excess of male subjects and the presence of cannabis induced psychosis could have a confusing impact on the interpretation of the results. CONCLUSION: It is possible that psychotic patients who use cannabis are at a greater risk of a more continuous illness with more positive symptoms than those who do not.

Adult↗

Visuospatial learning and executive function are independently impaired in first-episode psychosis.

BACKGROUND: Demonstrating specific cognitive impairments in psychotic disorders is difficult. However, specific deficits in memory and executive functions have often been claimed. The Cambridge Neuropsychological Test Automated Battery (CANTAB) tasks of IDED attention-shifting (an executive task) and visuospatial paired associates learning (PAL, a memory task) require intact frontal and temporo-hippocampal functioning, respectively; both have been suggested as markers of disease progress in psychosis. METHOD: Seventy-one subjects with a first-episode psychosis or at-risk mental state were assessed on these two tasks during referral to a specialist service, the Cambridge-based CAMEO early intervention team. RESULTS: Performance on the two tasks was dissociated. Poor performance on the PAL test was associated with increased symptom levels and poorer global function, while failure on the IDED executive test was not found to have significant clinical associations. Duration of illness was not associated with performance on either task. CONCLUSIONS: Visuospatial PAL failure may be a marker of clinical severity at the onset of psychosis while IDED performance may reflect a more stable, trait-like impairment. Dissociated performance on the executive and associative learning tasks may reflect independent, neurally dissociated impairments that do not arise in a fixed order. This may explain some of the heterogeneity of cognitive function seen in early psychosis.

Adult↗

Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study.

Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (AESOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.

Adolescent↗

The subjective and cognitive effects of acute phenylalanine and tyrosine depletion in patients recovered from depression.

Although there is evidence for the involvement of dopamine (DA) in unipolar depression, no published study has yet used the technique of acute phenylalanine and tyrosine depletion (APTD), a dietary intervention that selectively lowers DA synthesis, in order to investigate the role of DA in mood disturbance. Tyrosine and phenylalanine depleted and placebo amino acid drinks were administered to 20 patients recovered from depression in a double-blind, placebo-controlled, crossover design. Measures included subjective effects, Hamilton Depression Rating Scale scores, and a comprehensive battery of well-validated computerized cognitive tests. APTD induced a substantial reduction in the ratio of plasma tyrosine and phenylalanine to large neutral amino acids. However, relapse of depressive symptoms was not seen. Although performance on most cognitive tests was unaffected, there was a selective effect on decision-making, with APTD causing participants to bet significantly less. In conclusion, These results suggest a specific role for the involvement of DA in reward/punishment processing in humans. While APTD did not induce relapse in any participant, it did cause patients recovered from depression to show lowered sensitivity to reward in a gambling game. It is hypothesized that tests involving reward/punishment processing are preferentially affected by DA depletion, and that a more complete account of depression is likely to result from considering the roles played by serotonin, noradrenaline, and DA in mediating the various cognitive and clinical symptoms, including anhedonia.

Adult↗