Association analysis of monoamine genes with measures of depression and anxiety in a selected community sample of siblings.

Evidence indicates the genetic susceptibility to depression and anxiety is both overlapping and dimensional. In the current study, a quantitative phenotype had been created from several depression and anxiety-related measures in order to index this common genetic susceptibility (G). This has been studied in 119 sibships comprising 312 individuals, selected for extreme scores on G, from a community-based sample of 34,371 individuals. In a pathway based candidate gene study, we examined five microsatellite markers located within or nearby to five serotonin system genes (5HT2C, 5HT1D, 5HT1B, TPH1, and MAOB). Statistical analysis, carried out using QTDT, gave a significant association with a microsatellite downstream of TPH1. Further analysis included a life-events composite as a co-variable, this lead to a stronger association of TPH1. To our knowledge, this is the first study to report an association of the 3' end of TPH1 with continuous measures of depression and anxiety.

Life events and depression in a community sample of siblings.

BACKGROUND: The overall aim of the GENESiS project is to identify quantitative trait loci (QTLs) for anxiety/depression, and to examine the interaction between these loci and psychosocial adversity. Here we present life-events data with the aim of clarifying: (i) the aetiology of life events as inferred from sibling correlations; (ii) the relationship between life events and measures of anxiety and depression, as well as neuroticism; and (iii) the interaction between life events and neuroticism on anxiety/depression indices. METHODS: We assessed the occurrence of one network and three personal life-event categories and multiple indices of anxiety/depression including General Health Questionnaire, Anhedonic Depression, Anxious Arousal and Neuroticism in a large community-based sample of2150 sib pairs, 410 trios and 81 quads. Liability threshold models and raw ordinal maximum likelihood were used to estimate within-individual and between-sibling correlations of life events. The relationship between life events and indices of emotional states and personality were assessed by multiple linear regression and canonical correlations. RESULTS: Life events showed sibling correlations of 0-37 for network events and between 0-10 and 0.19 for personal events. Adverse life events were related to anxiety and depression and, to a less extent, neuroticism. Trait-vulnerability (as indexed by co-sib's neuroticism, anxiety and depression) accounted for 11% and life events for 3% of the variance in emotional states. There were no interaction effects. CONCLUSIONS: Life events show moderate familiality and are significantly related to symptoms of anxiety and depression in the community. Appropriate modelling of life events in linkage and association analyses should help to identify QTLs for depression and anxiety.

Phonological awareness of syllables, rhymes, and phonemes in deaf children.

Phonological awareness is important for reading development in hearing children, in whom it develops at the three consecutive levels of the syllable, rhyme, and phoneme. Deaf children typically have literacy difficulties, and previous research has been equivocal about whether deaf children can develop phonological awareness. Three experiments are presented that investigate the phonological skills of deaf children (mean age 11 years) at the three linguistic levels of syllable, rhyme, and phoneme. The first experiment showed that deaf children's syllable awareness can be equivalent to that of chronological age-matched hearing controls. In the second experiment, deaf children's ability to make rhyme judgements was above chance, but poorer than that of younger reading-matched hearing controls. The third experiment showed that deaf children could phonologically recode nonsense words at a level above chance, suggesting that they could draw on phonemic skills in certain conditions. We conclude that deaf children can develop phonological awareness, but that their phonological skills lag those of hearing children and may develop in different ways. Differences between our tasks and those used in other studies are discussed.

GENESiS: creating a composite index of the vulnerability to anxiety and depression in a community-based sample of siblings.

There is considerable evidence for a unitary and dimensional view of the genetic vulnerability to symptoms of anxiety and depression. The GENESiS (Genetic Environmental-Nature of Emotional States in Siblings) Study aims to use a multivariate approach to detect genetic loci that contribute to individual differences in this vulnerability dimension. The study used the UK General Practice Research Framework to generate a community-based sample of siblings. Questionnaire measures of anxiety/depression included the short form of the neuroticism scale from the revised Eysenck Personality Questionnaire (EPQ-N), the General Health Questionnaire (GHQ-12), and the anxious arousal and high positive affect subscales from the Mood and Anxiety Symptoms Questionnaire (MASQ-AA and MASQ-HPA). Genetic model-fitting of 2658 unselected sibships provided evidence for a single common genetic (familial) factor that accounted for a substantial proportion of the genetic variances and covariances of these four measures. Using the parameter estimates of this model, we constructed a composite index of this common genetic factor. This index, which has a sib correlation of 0.22, will be used as a quantitative phenotype in the molecular genetic phase of GENESiS.

A novel method of guideline development for the diagnosis and management of mild to moderate hypertension.

BACKGROUND: There are large numbers of clinical guidelines available covering many clinical areas. However, the variable quality of their content has meant that doctors may have been offered advice that has been poorly researched or is of a conflicting nature. It has been shown that local involvement in guideline development increases the likelihood of their use. AIM: To develop a guideline to be used by general practitioners in six practices in Birmingham from existing evidence-based guidelines. METHOD: Recommendations from the four most cited international hypertension guidelines, and the more recently published New Zealand guidelines, were divided into subject areas and tabulated to facilitate direct comparison. Where there was complete or majority (> or = 3/5) agreement, the recommendation was taken as acceptable for inclusion in the new guideline. Where there was disagreement (< or = 2/5), recommendations were based on the best available evidence following a further MEDLINE literature search and critical appraisal of the relevant literature. Each recommendation was accompanied by a grade of evidence (A-D), as defined by the Canadian Hypertension Society, and an 'action required' statement of either 'must', 'should', or 'could', based on the Eli-Lilly National Clinical Audit Centre Hypertension Audit criteria. The recommendations were summarized into a guideline algorithm and a supporting document. The final format of both parts of the guideline was decided after consultation with the practice teams. The practices individually decided on methods of data collection. RESULTS: The guideline was presented as a double-sided, A4 laminated sheet and an A4 bound supporting document containing a synthesis of the original guidelines in tabular form, a table of the resulting recommendations, and appendices of current literature reviews on areas of disagreement. The content of the final Birmingham Clinical Effectiveness Group (BCEG) guideline differed minimally from any of the original guidelines. CONCLUSION: The main strength of this method of guideline development may lie, not in the actual content of the resulting guideline, but in the strength of ownership felt by the BCEG and the practices following its development. While the full process is unlikely to be possible for general practitioners working outside an academic environment, the techniques used could provide a framework for practitioners to adapt national and international guidelines for use at a local level.

Patient characteristics and expectancy measures as factors that influence the expectancy-improvement relationship.

A recent study found factored measures of patient's expectancies for therapeutic gain significantly correlated with 1 of 15 objective measures of treatment outcome for the hospitalized patients. A subsequent study of the same relationship that used unfactored expectancy measured with a diagnostically homogenous sample of patients found the patients' expectancies significantly correlated with 10 of the same 15 measures of improvement. This study reexamined the initial expectancy-improvement data using unfactored measures of expectancy. The overall results showed that characteristics of samples of Ss and the adequacy of expectancy measures both significantly influence the results of tests of the expectancy-improvement relationship.

IQ deficit in schizophrenia: a test of competing theories.

This study tested competing interpretations of IQ deficit in schizophrenic patients. One interpretation (concomitancy hypothesis) holds that IQ loss is a product of schizophrenic symptoms and is remedied as the symptoms remit. The second (prodromal hypothesis) holds that IQ deficit preceeds and facilitates the development of schizophrenic disorder and is not remedied with symptom remission. The IQs of schizophrenic patients were obtained before and three times after hospital treatment. All mean IQs fell within average limits and did not increase significantly after treatment although test-retest correlations suggested slight disruption of IQ in the morbid state. Remitting cases did not differ significantly from nonremitting cases. Paradoxically, chronic patients earned slightly higher IQs than acute patients. The findings are interpreted as providing some support for both interpretations of schizophrenic IQ deficit. It is concluded that the specific IQ tests used and the nature of the patient samples tested will have a significant bearing on which hypothesis is supported in individual studies of schizophrenic IQ deficit.

Therapists prophesy.

Therapists' expectancies for therapeutic gain in patients reputedly are linked to the actual outcome of treatment for their patients. Theoretical papers have suggested that therapists' expectancies may cause or facilitate patient therapeutic response to treatment. Unfortunately, empirical data related to these notions are greatly lacking. The present study tested the relationship between therapist expectancy and treatment outcome for hospitalized schizophrenic patients. It also tested two opposing hypotheses re the nature of the link between therapist expectancy and outcome (causative vs. predictive). Multiple regression analyses revealed that therapists' expectancies are multi-dimensional, formed partly on the basis of therapists' knowledge of psychopathology in general and partly on their perception of their patients' pretreatment adjustment. The analyses also revealed that therapists' expectancies were associated significantly with treatment outcome; the data supported a predictive, not causative, interpretation of the nature of therapists' expectancies.

Patients' expectancies and hospital outcome.

Although it is widely held that patients' expectancies for therapeutic gain are related causally to treatment outcome, a recent review of expectancy research found scant evidence for the hypothesized expectancy-outcome relationship. Supportive findings were reported only in studies with serious methodological weaknesses. This study tested the relationship between the prognostic expectancies of hospitalized schizophrenic patients and several objective measures of hospital outcome. It also tested the hypothesis that expectancies may bear primarily a predictive, not causal, relationship to outcome. Multiple regression analyses found patients' expectancies to be correlated significantly with 8 of 15 measures of posthospital adjustment and with 14 of 15 measures of prehospital adjustment. The findings supported the expectancy-outcome relationship and also were consistent with a predictive interpretation of patients' expectancies.

Affection for patients as a factor in therapists' outcome judgements.

This study was concerned with psychotherapists' evaluations of the outcome of therapy. Staff and resident psychiatrists employed in 23-item questionnaire to rate the seccess of psychotherapy with 85 of their inpatients. These were patients for whom psychotherapy constituted a significant part of the treatment that they received in the hospital. The therapists' responses to the questionnaire items were intercorrelated. The results indicated that a major aspect of a psychotherapist's judgment of the success of treatment-as these judgments usually are employed in current psychotherapy research-is the therapist's affective reaction to the patient, Better-liked patients were viewed as having improved more. However, when the therapists' responses were subjected to factor analysis, independent Improvement and Affection factors emerged. It is suggested that when therapists' ratings of success are used in psychotherapy research they should be treated or refined statistically to minimize potential confounding with their affection for patients.