The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial.

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits.

Genetic co-morbidity between neuroticism, anxiety/depression and somatic distress in a population sample of adolescent and young adult twins.

BACKGROUND: Genetic studies in adults indicate that genes influencing the personality trait of neuroticism account for substantial genetic variance in anxiety and depression and in somatic health. Here, we examine for the first time the factors underlying the relationship between neuroticism and anxiety/depressive and somatic symptoms during adolescence. METHOD: The Somatic and Psychological Health Report (SPHERE) assessed symptoms of anxiety/depression (PSYCH-14) and somatic distress (SOMA-10) in 2459 adolescent and young adult twins [1168 complete pairs (35.4% monozygotic, 53% female)] aged 12-25 years (mean=15.5 ± 2.9). Differences between boys and girls across adolescence were explored for neuroticism, SPHERE-34, and the subscales PSYCH-14 and SOMA-10. Trivariate analyses partitioned sources of covariance in neuroticism, PSYCH-14 and SOMA-10. RESULTS: Girls scored higher than boys on both neuroticism and SPHERE, with SPHERE scores for girls increasing slightly over time, whereas scores for boys decreased or were unchanged. Neuroticism and SPHERE scores were strongly influenced by genetic factors [heritability (h(2)) = 40-52%]. A common genetic source influenced neuroticism, PSYCH-14 and SOMA-10 (impacting PSYCH-14 more than SOMA-10). A further genetic source, independent of neuroticism, accounted for covariation specific to PSYCH-14 and SOMA-10. Environmental influences were largely specific to each measure. CONCLUSIONS: In adolescence, genetic risk factors indexed by neuroticism contribute substantially to anxiety/depression and, to a lesser extent, perceived somatic health. Additional genetic covariation between anxiety/depressive and somatic symptoms, independent of neuroticism, had greatest influence on somatic distress, where it was equal in influence to the factor shared with neuroticism.

Development of a simple screening tool for common mental disorders in general practice.

OBJECTIVE: To develop and validate a self-report screening tool for common mental disorders. DESIGN AND SETTING: Sequential development and validation studies in three cohorts of patients in general practice and one cohort of patients in a specialist psychiatry clinic. PARTICIPANTS: 1585 patients in general practice examined cross-sectionally and longitudinally; 46515 patients attending 386 general practitioners nationwide; 364 patients participating in a longitudinal study of psychiatric disorders in general practice; and 522 patients attending a specialist psychiatry clinic. MAIN OUTCOME MEASURES: Performance of the 12 items from the 34-item SPHERE questionnaire against DSM-III-R and DSM-IV diagnoses of psychiatric disorder, self-reported Brief Disability Questionnaire findings, GPs' ratings of patients' needs for psychological care and degree of risk resulting from mental disorder, and patients' and GPs' reports of reasons for presentation. RESULTS: Six somatic and six psychological questions identify two levels (and three types) of mental disorder: patients reporting both characteristic psychological and somatic symptoms (Level 1, Type 1), and patients reporting either psychological symptoms (Level 2, Type 2) or somatic symptoms (Level 2, Type 3). This classification system predicts disability ratings (Level 1, 8.2 "days out of role in the last month" and Level 2, 4.1 and 5.4 "days out of role in the last month" for Types 2 and 3, respectively), rates of lifetime psychiatric diagnoses (Level 1, 63% and Level 2, 59% and 48%, respectively), both patients' and GPs' report of reasons for presentation, and doctors' ratings of risk as a result of mental disorder. There are important and differing sociodemographic correlates for the three types of mental disorders. CONCLUSION: A classification system based on the 12 items from the 34-item SPHERE questionnaire can be used to identify common mental disorders. This system has acceptable validity and reliability, and is suited specifically for general practice settings.

Unmet need for recognition of common mental disorders in Australian general practice.

OBJECTIVE: To determine the rate and predictors of unmet need for recognition of common mental disorders in Australian general practice. DESIGN AND SETTING: Cross-sectional national audit of general practices throughout Australia in 1998-1999. PARTICIPANTS: 46 515 ambulatory care patients attending 386 GPs. SCREENING TOOLS: Prevalence of common mental disorders--12 items from the 34-item SPHERE self-report questionnaire and associated classification system; prevalence of recognition of mental disorders by GPs--GPs reporting whether patients had depression, anxiety, mixed depression/anxiety, somatoform, or other psychological disorder; predictors of unmet need for recognition of mental disorders--self-report questions about demography for patients and GPs, and about practice organisation for GPs. MAIN OUTCOME MEASURES: Reported recognition of psychological disorders by GPs; actual prevalence of disorders; and patient, GP and practice characteristics predicting the failure to recognise disorders. RESULTS: GPs did not recognise mental disorder in 56% (11922/21210) of patients. These comprised 46% (5134/11060) of patients in the higher level of mental disorders, and (in the second level of disorders) 58% (2906/5036) of patients with predominantly psychological symptoms, and 76% (3882/5114) of those with predominantly somatic symptoms. Patients more likely to have their need for psychological assessment met had the following characteristics: middle-aged (odds ratio [OR], 1.76; 95% CI, 1.59-1.96), female (OR, 1.19; 95% CI, 1.12-1.27), Australian-born (OR, 1.16; 95% CI, 1.08-1.24), unemployed (OR, 1.75; 95% CI, 1.64-1.89), single (OR, 1.52; 95% CI, 1.41-1.61), presenting with mainly psychological symptoms (OR, 3.54; 95% CI, 3.28-3.81), and presenting for psychological reasons (OR, 4.20; 95% CI, 3.02-5.82). Characteristics of doctors associated with meeting patients' need for assessment were being aged over 35 years (OR, 1.51; 95% CI, 1.09-2.08), having an interest in mental health (OR, 1.27; 95% CI, 1.15-1.41), having had previous mental health training (OR, 1.29; 95% CI, 1.15-1.45), being in part-time practice (OR, 1.23; 95% CI, 1.09-1.39), seeing fewer than 100 patients per week (OR, 1.29; 95% CI, 1.13-1.47), working in practices with fewer than 2000 patients (OR, 1.28; 95% CI, 1.13-1.45) and working in regional centres (OR, 1.16; 95% CI, 1.05-1.28). CONCLUSION: Unmet need for recognition of common mental disorders remains high. Predictors of unmet need include a somatic symptom profile and practitioner and organisational characteristics which impede the provision of high quality mental health services.

Treatment of common mental disorders in Australian general practice.

OBJECTIVE: To determine the rates and predictors of treatments for patients with common mental disorders in Australian general practice. DESIGN AND SETTING: Cross-sectional national audit of general practices throughout Australia in 1998-1999. PARTICIPANTS: 46 515 ambulatory care patients attending 386 GPs. SCREENING TOOLS: Prevalence of common mental disorders--12 items from the 34-item SPHERE self-report questionnaire and associated classification system; pharmacological and non-pharmacological treatment provided, as reported by the GPs--questions relating to treatments provided; predictors of treatments--self-report questions about demography for patients and GPs, and about practice organisation for GPs. MAIN OUTCOME MEASURES: GPs' reported provision of pharmacological and nonpharmacological treatments; and patient, GP and practice characteristics predicting treatment provision. RESULTS: There were complete data on treatment for 39 983 patients. 27% (10752) of all patients received some form of intervention; 21% (8304) received non-pharmacological and 12% (4765) received pharmacological treatments. Non-pharmacological treatments were mostly non-specific counselling and support (83%; 6892/8304). Among the 10303 patients with the most severe level of psychological disorders, only 50% (5152) received any intervention (38% [3872] received non-pharmacological and 27% [2766] pharmacological treatments). Evidence-based treatments were provided to only 12% (4961) of all patients (and only 27% [2802] of the 10303 with the most severe disorders). Although the newer antidepressant agents were commonly prescribed, older medications (mainly tricyclic antidepressants) were prescribed to older (OR, 1.29; 95% CI, 1.07-1.56), less educated (OR, 1.41; 95% CI, 1.12-1.79) and female (OR, 1.44; 95% CI, 1.23-1.70) patients. Among the 8304 patients receiving non-pharmacological treatments, specific (evidence-based) treatments were provided to only 17% (1412); these patients were typically middle-aged (OR, 2.94; 95% CI, 2.32-3.73) and the providing GPs were typically not in full-time practice (OR, 3.34; 95% CI, 2.56-4.17). CONCLUSION: Practitioners largely provide non-specific, non-pharmacological interventions for patients with common mental disorders. Even among those with the most severe disorders, only a minority receive pharmacological or specific evidence-based non-pharmacological treatments.

Comorbidity of common mental disorders and alcohol or other substance misuse in Australian general practice.

OBJECTIVE: To determine in patients attending general practice 1) the extent of comorbidity of mental disorders and alcohol or other substance misuse, and consequent disability; and 2) GPs' diagnosis and management of patients with comorbidity. DESIGN AND SETTING: Cross-sectional national audit of general practices throughout Australia in 1998-1999. PARTICIPANTS: 46 515 ambulatory care patients attending 386 GPs. SCREENING TOOLS: Prevalence of common mental disorders--12 items from the 34-item SPHERE self-report questionnaire and associated classification system; prevalence of alcohol or other substance misuse--two self-report screening questions, defining "probable" misuse (a positive response to both questions) and "possible" misuse (a positive response to one of the questions); disability--four items from the Brief Disability Questionnaire, and self-reported "days out of role" and "days in bed" in the past month; and rates of psychological diagnosis, treatment and referral by GPs, and GPs' rating of patients' psychological risk. MAIN OUTCOME MEASURES: Comorbidity of mental disorders and alcohol or other substance misuse; disability; and correlation with GPs' diagnosis and management. RESULTS: The screening questions revealed possible alcohol or other substance misuse in 11% of patients (5171/46515), and probable misuse in an additional 8% of patients (3593/46515). Comorbidity of mental disorders and substance misuse occurred in 12% (5672/46515) of patients. Patients with comorbidity (compared with those with alcohol or other substance misuse alone) were: more disabled--mean "days out of role in the last month", 8.4 (95% CI, 7.7-9.1) v 3.6 (95% CI, 2.9-4.3); at greater psychological risk (as rated by GPs)--22% v 7%, respectively; more frequently given psychological diagnoses by GPs--51% v 21%; more frequently treated for a psychological condition by GPs--47% v 17%; and more frequently referred to mental health specialists by GPs--9% v 2%. CONCLUSION: Comorbidity of mental disorders and alcohol or other substance misuse is common in patients attending general practice, and results in considerable disability. Such patients receive inadequate attention (diagnosis and management) from GPs. GPs identifying one of these two types of behaviour disorder in a patient should ascertain whether the other type is also present.

Variability and predictors of mental disorder rates and medical practitioner responses across Australian general practices.

OBJECTIVE: To determine the variation in prevalence of common mental disorders and general practitioner (GP) responses across Australian general practices, and to identify practice characteristics that predict these rates. DESIGN: Cross-sectional national audit of general practices throughout Australia in 1998-1999. PARTICIPANTS: 46515 ambulatory care patients attending 386 GPs. MAIN OUTCOME MEASURES: Practice-based prevalence of mental disorders (based on patient-reported symptoms) and GP-reported rates of psychological diagnoses and treatment (median and range, excluding the upper and lower 10% of practices); practice characteristics (patient, doctor and organisational) that predict prevalences and rates, determined by multiple regression analysis. RESULTS: Even after omitting the upper and lower 10% of practices, there were large variations between practices in prevalence of common mental disorders (range, 39% to 59% of patients; median, 48%), and substance misuse (range, 3%-13%; median, 7%). There were also large variations between practices in rates at which GPs made psychological diagnoses in each practice (range, 12%-51%; median, 27%), judged patients to be at risk to self or others (range, 6%-54%; median, 23%), provided psychological treatments (range, 8%-41%; median, 22%) and referred patients to specialist services (range, 1%-10%; median, 4%). Practice-based rates of disorders and GP responses were predicted not only by sociodemographic characteristics of patients in each practice (eg, mean age or proportion of unemployed people), but also by doctor characteristics (eg, age and sex) and practice organisation characteristics (eg, urban versus regional or rural location). CONCLUSION: We identified patient, GP and practice characteristics that predict rates of mental disorder and treatments provided. These could be used to guide mental health service reform in general practice and assist with targeting relevant education and practice support programs.

Effects of mental health training and clinical audit on general practitioners' management of common mental disorders.

OBJECTIVE: To evaluate the effects of a seminar-based training program and clinical practice audit on general practitioners' (GPs') knowledge and management of common mental disorders. DESIGN: Survey of GPs' knowledge before and after training, and clinical practice audit and re-audit after feedback. PARTICIPANTS AND SETTING: GP volunteers from around Australia in 1998-1999: 1008 completed the pre-training test, 190 the post-training test, 386 the first audit (33235 patients), and 157 of these the re-audit (13280 patients), with 57 undertaking both audit and training. INTERVENTIONS: Four-seminar, 12-hour training program focused on improving GPs' capacity to identify and manage patients with depression and anxiety; practice audit with patient- and practice-based feedback on diagnosis and treatment of common mental disorders. MAIN OUTCOME MEASURES: Scores on pre- and post-training knowledge tests; self-rated improvements in confidence in managing patients with mental disorders after training; rates of psychological diagnoses and treatment by GPs on first audit and re-audit. RESULTS: GPs' knowledge of pharmacological treatments and clinical management improved after the training program (P<0.001), and 97% of GPs reported increased confidence in their management skills. GPs who undertook training had higher diagnosis rates for common mental disorders in the first audit than those who did not undertake training (36% versus 29%; P<0.001), and their diagnosis rates increased over time (36% to 39%; P<0.01), while those of GPs who did not undertake training were unchanged. Similarly, GPs who undertook training provided more mental health treatments than those who did not (30% versus 27% in the first audit [P<0.001], and 31% versus 24% at reaudit [P<0.001]). They also place greater emphasis on use of nonpharmacological treatments (24% versus 21% at first audit [P<0.001], and 25% versus 19% at re-audit [P<0.001]). CONCLUSION: Clinical audits may heighten awareness of mental disorders, but, on their own, they do not improve mental health practice. A relatively brief but skills-based training program may contribute to better management of patients with common mental disorders by increasing GPs' confidence and competence.

Screening for prolonged fatigue syndromes: validation of the SOFA scale.

BACKGROUND: The identification of syndromes characterised by persistent and disabling mental and/or physical fatigue is of renewed interest in psychiatric epidemiology. This report details the development of two specific instruments: the SOFA/CFS for identification of patients with chronic fatigue syndrome (CFS) in specialist clinics and the SOFA/GP for identification of prolonged fatigue syndromes (PFS) in community and primary care settings. METHODS: Patients with clinical diagnoses of CFS (n = 770) and consecutive attenders at primary care (n = 1593) completed various self-report questionnaires to assess severity of current fatigue-related symptoms and other common somatic and psychological symptoms. Quality receiver operating characteristic curves were used to derive appropriate cut-off scores for each of the instruments. Comparisons with other self-report measures of anxiety, depression and somatic distress are noted. Various multivariate statistical modelling techniques [latent class analysis (LCA), longitudinal LCA] were utilised to define the key features of PFS and describe its longitudinal characteristics. RESULTS: The SOFA/CFS instrument performs well in specialist samples likely to contain a high proportion of patients with CFS disorders. Cut-off scores of either 1/2 or 2/3 can be used, depending on whether the investigators wish to preferentially emphasise false-negatives or false-positives. Patients from these settings can be thought of as consisting not only of those with a large number of unexplained medical symptoms, but also those with rather specific musculoskeletal and pain syndromes. The SOFA/GP instrument has potential cut-off scores of 1/2 or 2/3, with the latter preferred as it actively excludes all non-PFS cases (sensitivity = 81%, specificity = 100%). Patients with these syndromes in the community represent broader sets of underlying classes, with the emergence of not only musculoskeletal and multisymptomatic disorders, but also persons characterised by significant cognitive subjective impairment. Twelve-month longitudinal analyses of the primary care sample indicated that the underlying class structure was preserved over time. Comparisons with other measures of psychopathology indicated the relative independence of these constructs from conventional notions of anxiety and depression. CONCLUSIONS: The SOFA/GP instrument (which is considerably modified from the SOFA/CFS in terms of anchor points for severity and chronicity) is preferred for screening in primary care and community settings. Patients with PFS and CFS present a range of psychopathology that differs in its underlying structure, cross-sectionally and longitudinally, from coventional notions of anxiety and depression.

Are antidepressants all the same? Surveying the opinions of Australian psychiatrists.

OBJECTIVE: Controlled trials do not suggest differences in efficacy between antidepressant compounds. Psychiatrists, however, frequently express the view that real differences do exist and are relevant to clinical practice. Since multiple comparative trials are not feasible, an alternative method for expanding the evidence base is to survey regularly the opinions of practising psychiatrists. METHOD: Two surveys of psychiatrists' opinions were conducted. Participants in the first survey were drawn from contact with 'SPHERE: A National Depression Project', while those in the second survey responded to a brief questionnaire distributed with Australasian Psychiatry. RESULTS: Reported volumes of scripts written, ratings of efficacy and tolerability, and preferences in specific clinical situations indicate that clinical psychiatrists now strongly prefer the newer antidepressant agents. They rate serotonin and noradrenalin re-uptake inhibitors (SNRIs) and selective serotonin re-uptake inhibitors (SSRIs) highest for antidepressant efficacy, serotonin receptor subtype 2 (5HT2) antagonists and some SSRIs highest for anti-anxiety efficacy, and some SSRIs and reversible inhibitors of monoamine oxidase inhibitor-A (RIMAs) lowest for side-effect burden. Further, SSRIs were their first preferences for most clinical situations. Serotonin and noradrenalin re-uptake inhibitors were the preferred choice for treatment-resistant depression and patients who had failed to respond to one SSRI. Serotonin receptor subtype 2 antagonists were the second choice to SSRIs for mixed anxiety and depression, and major depression with sleep disturbance. Reversible inhibitors of monoamine oxidase inhibitor-A were the second choice to SSRIs for adolescents with major depression, patients aged over 65 years, patients with serious medical illnesses and patients with chronic fatigue. Tricyclic antidepressants (TCAs) were the preferred choice for patients with chronic pain, and second choice to SSRIs for patients with major depression with panic disorder, postnatal disorders and patients with psychotic depression. CONCLUSION: Psychiatrists believe that important differences do exist between available antidepressant compounds. Such opinions are divergent from limited controlled data but may be influenced by a wide range of factors other than direct clinical experience. The role of such surveys in ongoing evaluation of clinical practice is emphasised.

Enhancing the evidence base for clinical psychiatry: are practice surveys a useful tool?

Clinical practice guidelines for psychiatry are now being developed, but important deficits in the evidence base are apparent. For many of the new treatments, clinical decisions can be idiosyncratic or based on limited knowledge. There is a need not only to perform properly constructed trials, but also to make immediate use of less rigorous forms of evidence, such as clinical practice surveys. An example is a recent survey of psychiatrists' use of antidepressant drugs. Such surveys are now part of a wider movement towards a more coordinated system of practice-based outcome assessment.

Diabetes-induced alterations in the properties of muscarinic cholinergic receptors in rat vas deferens.

Muscarinic cholinergic receptors were identified and characterized by radioligand receptor binding assay using [3H]quinuclidinyl benzilate (QNB) in rat vas deferens membrane particulates of three experimental groups: 1) 8-week diabetic, 2) 8-week diabetic insulin-treated and 3) age-matched control. Diabetes was induced by the intravenous injection of 65 mg./kg. streptozotocin (STZ). The density of muscarinic receptors (Bmax values), as determined by saturation experiments with [3H]QNB, was demonstrated to be higher in the vas deferens of diabetic rats than in the vas deferens of control and diabetic insulin-treated rats. The equilibrium dissociation constants (KD values), however, were similar in all three groups. Muscarinic cholinergic antagonists competed with [3H]QNB binding sites in the vas deferens membrane particulates with the following rank order of Ki values: atropine < methoctramine < or = 4-DAMP < AF-DX 116 < HHSiD < pirenzepine = pfHHSiD. The pharmacological profile of muscarinic receptors was similar in all three groups. Additional pharmacological studies showed a similar rank order of Ki values for vas deferens, bladder dome and heart, but this rank order was significantly different in cerebral cortex and prostate. This is consistent with the predominance of the M2 muscarinic cholinergic receptor subtype in the rat vas deferens. It is concluded that STZ-induced diabetes causes an upregulation of muscarinic cholinergic receptor density in the rat vas deferens that can be prevented by the administration of insulin.