Pharmacotherapy of bipolar disorder: the role of atypical antipsychotics and experimental strategies.

Bipolar disorder, despite being a common and debilitating illness, has remarkably few pharmacological therapeutic options, the majority of which, with the exception of lithium, have been borrowed from other medical indications. Furthermore the quantity and quality of controlled clinical data are considerably smaller than in conditions of comparable severity and frequency. Not surprisingly, the clinical outcome of bipolar disorder is frequently suboptimal. Fortunately there are a growing number of novel therapeutic options for its treatment such as atypical antipsychotics, calcium channel blockers and omega-3 fatty acids. This paper summarizes some of the data regarding these "experimental" therapeutic options, focusing principally on atypical antipsychotics as these are now widely prescribed in the management of bipolar disorder.

Epitope-specific CD4+, but not CD8+, T-cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection

Tuberculosis remains a global health problem, in part due to failure of the currently available vaccine, BCG, to protect adults against pulmonary forms of the disease. We explored the impact of pulmonary delivery of recombinant influenza A viruses (rIAVs) on the induction of Mycobacterium tuberculosis (M. tuberculosis)-specific CD4(+) and CD8(+) T-cell responses and the resultant protection against M. tuberculosis infection in C57BL/6 mice. Intranasal infection with rIAVs expressing a CD4(+) T-cell epitope from the Ag85B protein (PR8.p25) or CD8(+) T-cell epitope from the TB10.4 protein (PR8.TB10.4) generated strong T-cell responses to the M. tuberculosis-specific epitopes in the lung that persisted long after the rIAVs were cleared. Infection with PR8.p25 conferred protection against subsequent M. tuberculosis challenge in the lung, and this was associated with increased levels of poly-functional CD4(+) T cells at the time of challenge. By contrast, infection with PR8.TB10.4 did not induce protection despite the presence of IFN-γ-producing M. tuberculosis-specific CD8(+) T cells in the lung at the time of challenge and during infection. Therefore, the induction of pulmonary M. tuberculosis epitope-specific CD4(+), but not CD8(+) T cells, is essential for protection against acute M. tuberculosis infection in the lung.

Atypical neural activity in males but not females with autism spectrum disorder

The medial prefrontal cortex (mPFC) and the right temporo-parietal junction (rTPj) are highly involved in social understanding, a core area of impairment in autism spectrum disorder (ASD). We used fMRI to investigate sex differences in the neural correlates of social understanding in 27 high-functioning adults with ASD and 23 matched controls. There were no differences in neural activity in the mPFC or rTPj between groups during social processing. Whole brain analysis revealed decreased activity in the posterior superior temporal sulcus in males with ASD compared to control males while processing social information. This pattern was not observed in the female sub-sample. The current study indicates that sex mediates the neurobiology of ASD, particularly with respect to processing social information.

Atypical features and treatment choices in bipolar disorders: a result of the National Bipolar Mania Pathway Survey in China.

In this study, we examined the point prevalence rate of atypical features in bipolar disorder, and estimated the potential impact of these features on treatment practices in China. Using the atypical features criteria of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV), we documented the atypical symptoms in 3 906 consecutive participants with bipolar disorder enrolled at 26 psychiatric services across China. We further assessed the association between atypical features and the treatment approaches, including the prescription of antidepressants. The overall point prevalence rate of atypical features was 9.1% among patients with various bipolar disorder subtypes. When the definition was broadened to include atypical features B, the overall rate increased to 11.8%. Interestingly, among patients with the mixed state and remission subtypes, there was a significant difference in the rates of antidepressant medication usage between patients who met and those who did not meet the criteria for atypical features B. These findings indicate a trend of using antidepressants for these two types of patients with atypical features. Further, for both mixed state and remission patients, treatment approaches were related to atypical features B. Our findings provide evidence to assist clinicians to readily recognize atypical features in bipolar subtypes and can propose treatments based on these diagnoses.

Modelling the maturation of grip selection planning and action representation: insights from typical and atypical motor development

We investigated the purported association between developmental changes in grip selection planning and improvements in an individual’s capacity to represent action at an internal level (i.e., motor imagery). Participants were groups of healthy children aged 6-7 years and 8-12 years respectively, while a group of adolescents (13-17 years) and adults (18-34 years) allowed for consideration of childhood development in the broader context of motor maturation. A group of children aged 8-12 years with probable DCD (pDCD) was included as a reference group for atypical motor development. Participants’ proficiency to generate and/or engage internal action representations was inferred from performance on the hand rotation task, a well-validated measure of motor imagery. A grip selection task designed to elicit the end-state comfort (ESC) effect provided a window into the integrity of grip selection planning. Consistent with earlier accounts, the efficiency of grip selection planning followed a non-linear developmental progression in neurotypical individuals. As expected, analysis confirmed that these developmental improvements were predicted by an increased capacity to generate and/or engage internal action representations. The profile of this association remained stable throughout the (typical) developmental spectrum. These findings are consistent with computational accounts of action planning that argue that internal action representations are associated with the expression and development of grip selection planning across typical development. However, no such association was found for our sample of children with pDCD, suggesting that individuals with atypical motor skill may adopt an alternative, sub-optimal strategy to plan their grip selection compared to their same-age control peers.

Mycobacterium ulcerans treatment - can antibiotic duration be reduced in selected patients?

Mycobacterium ulcerans (M. ulcerans) is a necrotizing skin infection endemic to the Bellarine Peninsula, Australia. Current treatment recommendations include 8 weeks of combination antibiotics, with adjuvant surgery if necessary. However, antibiotic toxicity often results in early treatment cessation and local experience suggests that shorter antibiotic courses may be effective with concurrent surgery. We report the outcomes of patients in the Barwon Health M. ulcerans cohort who received shorter courses of antibiotic therapy than 8 weeks. A retrospective analysis was performed of all M. ulcerans infections treated at Barwon Health from March 1, 1998 to July 31, 2013. Sixty-two patients, with a median age of 65 years, received < 56 days of antibiotics and 51 (82%) of these patients underwent concurrent surgical excision. Most received a two-drug regimen of rifampicin combined with either ciprofloxacin or clarithromycin for a median 29 days (IQR 21–41days). Cessation rates were 55% for adverse events and 36% based on clinician decision. The overall success rate was 95% (98% with concurrent surgery; 82% with antibiotics alone) with a 50% success rate for those who received < 14 days of antibiotics increasing to 94% if they received 14–27 days and 100% for 28–55 days (p<0.01). A 100% success rate was seen for concurrent surgery and 14–27 days of antibiotics versus 67% for concurrent surgery and < 14 days of antibiotics (p = 0.12). No previously identified risk factors for treatment failure with surgery alone were associated with reduced treatment success rates with < 56 days of antibiotics. In selected patients, antibiotic treatment durations for M. ulcerans shorter than the current WHO recommended 8 weeks duration may be associated with successful outcomes.

Treatment and prevention of Mycobacterium ulcerans infection (Buruli ulcer) in Australia: guideline update

• Guidelines reflecting contemporary clinical practice in the management of Buruli ulcer (Mycobacterium ulcerans infection) in Australia were published in 2007.

• Management has continued to evolve, as new evidence has become available from randomised trials, case series and increasing clinical experience with oral antibiotic therapy.

• Therefore, guidelines on the diagnosis, treatment and prevention of Buruli ulcer in Australia have been updated. They include guidance on the new role of antibiotics as first-line therapy; the shortened duration of antibiotic treatment and the use of all-oral antibiotic regimens; the continued importance, timing and role of surgery; the recognition and management of paradoxical reactions during antibiotic treatment; and updates on the prevention of disease.