Convenient synthesis of alternatively bridged tryptophan ketopiperazines and their activities against trypanosomatid parasites

This work was supported through funding from the EPSRC (grant number EP/J500549/1) and the University of St Andrews School of Chemistry.There is an urgent need for the development of new treatments against trypanosomatid parasites; the causative agents of some of the most debilitating diseases in the developing world. This work targets an interesting 6-5-6-6 fused carboline scaffold, accessing a range of substituted derivatives through stereospecific intramolecular Pictet-Spengler condensation. Modification of the cyclisation conditions allowed retention of the carbamate protecting group and gave insight into the reaction mechanism. Compounds' bioactivities were measured against T. brucei, T. cruzi, L. major and HeLa cells. We have identified promising pan-trypanocidal lead compounds based on the core scaffold, and highlight key SAR trends which will be useful for the future development of these compounds as potent trypanocidal agents.PostprintPeer reviewe

Improving access for rural Australians to treatment for anxiety and depression : the University of Melbourne Depression and Anxiety Research and Treatment Group–Bendigo Health Care Group initiative

Rural Australians have limited access to care for mental health problems. We describe a collaboration between the University of Melbourne Departments of Psychology and Psychiatry and a rural Area Mental Health Service to provide a specialist anxiety and depression treatment service in rural Victoria. The clinical service and the education and training approach are described

The development of a clinic for the management of depression and anxiety: the Depression and Anxiety Research and Treatment (DART) Clinical Program

Many community-based surveys have established the high prevalence of mood and anxiety disorders. The 12-month prevalence of anxiety and mood disorders in Australia recently documented in the National Mental Health and Wellbeing Survey is 9.7% and 5.8% respectively. These disorders have been shown to be chronic and disabling. There has been recent interest in the development of the World Health Organization Global Burden of Disease study which reported that the 'burden of psychiatric conditions has been heavily underestimated'. In developed nations as reported in 1996, mental disorders contributed 17% of the total burden of disease, with affective disorders accounting for 7.7% and anxiety disorders 2.3% to this figure. The high level of psychiatric comorbidity in patients with mood and anxiety disorders has also been well documented. The National Mental Health Policy developed in 1992 focussed the delivery of mental health services on a group of patients with 'serious mental illness'. In adult psychiatry, this group of patients was most commonly defined as patients with schizophrenia or bipolar affective disorder. The trend towards treating the severely mentally ill addressed the concerns of the government and the community to better manage this very disadvantaged group of patients with mental illness. However, this strategy has been at the expense of providing treatment to other groups of patients with mental illness who have also been shown to be disabled and are now disadvantaged by the current mental health system. For example, in Victoria, this led to a change in public mental health service delivery with patients with anxiety or depressive disorders rarely included in the caseload of a community mental health clinic. The Depression and Anxiety Research and Treatment (DART) Program, was developed by a group of senior academic clinicians concerned about the lack of treatment available for patients with mood and anxiety disorders. This paper will outline the development of the DART clinical program, which provided assessment and treatment of patients with depression and anxiety

A comparison of the Composite International Diagnostic Interview (CIDI-Auto) with clinical assessment in diagnosing mood and anxiety disorders

Objective: Increasingly, epidemiological studies are employing computerized and highly standardized interviews, such as the Composite International Diagnostic Interview (CIDI-Auto), to assess the prevalence of psychiatric illness. Recent studies conducted in specialist units have reported poor agreement between experienced clinicians' and CIDI-Auto diagnoses. In this study we investigated the concordance rate between clinicians and the CIDI-Auto for the diagnosis of six anxiety disorders and two mood disorders, whereby the CIDI-Auto was treated as the 'gold standard'. Method: Subjects were 262 patients who were assessed by a clinical psychologist or psychiatrist and completed the CIDI-Auto at a tertiary referral unit for anxiety and mood disorders. Agreement between the clinicians' diagnoses and the diagnoses generated by the CIDI-Auto according to both DSM-IV and ICD-10 codes, were examined by kappa statistics. Sensitivity and specificity values were also calculated. Results: Agreement between clinicians and the CIDI-Auto (DSM-IV) ranged from poor for social phobia and posttraumatic stress disorder (&#0954; < 0.30) to moderate for obsessive-compulsive disorder (OCD; &#0954; = 0.52). Agreement between clinicians and the CIDI-Auto (ICD-10) ranged from poor for major depressive episode (&#0954; = 0.25) to moderate for OCD (&#0954; = 0.57). With the CIDI diagnosis treated as the gold standard, clinicians' diagnoses showed low sensitivity (&#0954; < 0.70) for all the disorders except for OCD (for ICD-10), but high specificity (&#0954; > 0.70) for all the disorders. Conclusion: Poor agreements between experienced clinicians and the CIDI-Auto were reported for anxiety and mood disorders in the current study. A major implication is that if diagnosis alone directed treatment, then patients could receive different treatments, depending on whether the computer, or a clinician, made the diagnosis