Atypical mood stabilizers : a 'typical' role for atypical antipsychotics

Objective: To assess the potential role of atypical antipsychotics as mood stabilizers.

Method: A MedLine, PsychLIT, PubMed, and EMBASE literature search of papers published up to December 2004 was conducted using the names of atypical antipsychotics and a number of key terms relevant to bipolar disorder. Additional articles were retrieved by scrutinizing the bibliographies of review papers and literature known to the authors. Data pertinent to the objective was reviewed according to the various phases of bipolar disorder.

Results: The data is most substantive for the use of atypical antipsychotics in mania, to the extent that an argument for a class effect of significant efficacy can be made. This does not extend to bipolar depression, however, good data is now emerging for some agents and will need to be considered for each individual agent as it accumulates. As regards mixed states and rapid cycling the evidence is thus far sparse and too few maintenance studies have been conducted to make any firm assertions. However, with respect to long-term therapy the atypical antipsychotics do have clinically significant side-effects of which clinicians need to be aware.

Conclusion: Based on the evidence thus far it is perhaps premature to describe the atypical antipsychotics as mood stabilizers. Individual agents may eventually be able to claim this label, however, much further research is needed especially with respect to maintenance and relapse prevention.

Atypical antipsychotics for bipolar disorder : overblown or blown over?

Objective：Developments in the pharmacological treatment of bipolar disorder are of much interest, as the chronicity and disability of the disorder become better understood, and as treatment goals have shifted to emphasise early control of illness course and maintenance of euthymia in addition to acute episodic remission. Atypical antipsychotics have emerged as treatment options, and this paper aims to review the evidence for their role in bipolar disorder.

Methods：A MEDLINE search was conducted for publications up till October 2006.

Results：The search yielded a number of randomised, controlled clinical trials of various atypical antipsychotics as monotherapy or adjunctive therapy in bipolar disorder. The majority of such trials have investigated their efficacy in acute mania, with fewer studies devoted to acute bipolar depression or maintenance treatment. There are no specific trials on mixed states, which have mainly been studied together with bipolar mania. The most robust evidence supports a class effect of atypical agents in the treatment of mania.

Conclusions：There are placebo-controlled trials that support the efficacy of olanzapine and quetiapine in bipolar depression, and of olanzapine and aripiprazole as maintenance treatment. There is strong support for the role of atypical antipsychotics in bipolar disorder management despite a relatively narrow literature base, chiefly for the treatment of mania. However, these findings need to be replicated, and further investigation is warranted to clarify their spectrum of efficacy in bipolar disorder.

Identification and genetic determination of an early life risk disposition for depressive disorder : atypical stress-related behaviour in early childhood

Progress in psychiatric genetics has been slow despite evidence of high heritability for most mental disorders. We argue that greater use of early detectable intermediate traits (endophenotypes) with the highest likely aetiological significance to depression, rather than complex clinical phenotypes, would be advantageous. Longitudinal data from the Western Australian Pregnancy Cohort (Raine) Study were used to identify an early life behavioural endophenotype for atypical hypothalamic-pituitaryadrenocortical function in adolescence, a neurobiological indicator of anxiety and depression. A set of descriptors representing rigid and reactive behaviour at age 1 year discriminated those in the top 20% of the free salivary cortisol exposure at age 17 years. Genetic association analysis revealed a male-sensitive effect to variation in three specific single nucleotide polymorphisms within selected genes underpinning the overall stress response. Furthermore, support for a polygenic effect on stress-related behaviour in childhood is presented.

Alternative TEL-JAK2 fusions associated with T-cell acute lymphoblastic leukemia and atypical chronic myelogenous leukemia dissected in zebrafish

Background Chromosomal translocations resulting in alternative fusions of the human TEL (ETV6) and JAK2 genes have been observed in cases of acute lymphoblastic leukemia and chronic myelogenous leukemia, but a full understanding of their role in disease etiology has remained elusive. In this study potential differences between these alternative TEL-JAK2 fusions, including their lineage specificity, were investigated.

Design and Methods TEL-JAK2 fusion types derived from both T-cell acute lymphoblastic leukemia and atypical chronic myelogenous leukemia were generated using the corresponding zebrafish tel and jak2a genes and placed under the control of either the white blood cell-specific spi1 promoter or the ubiquitously-expressed cytomegalovirus promoter. These constructs were injected into zebrafish embryos and their effects on hematopoiesis examined using a range of molecular approaches. In addition, the functional properties of the alternative fusions were investigated in vitro.

Results Injection of the T-cell acute lymphoblastic leukemia-derived tel-jak2a significantly perturbed lymphopoiesis with a lesser effect on myelopoiesis in zebrafish embryos. In contrast, injection of the atypical chronic myelogenous leukemia-derived tel-jak2a resulted in significant perturbation of the myeloid compartment. These phenotypes were observed regardless of whether expressed in a white blood cell-specific or ubiquitous manner, with no overt cellular proliferation outside of the hematopoietic cells. Functional studies revealed subtle differences between the alternative forms, with the acute lymphoblastic leukemia variant showing higher activity, but reduced downstream signal transducer and activator of transcription activation and decreased sensitivity to JAK2 inhibition. JAK2 activity was required to mediate the effects of both variants on zebrafish hematopoiesis.

Conclusions This study indicates that the molecular structure of alternative TEL-JAK2 fusions likely contributes to the etiology of disease. The data further suggest that this class of oncogene exerts its effects in a cell lineage-specific manner, which may be due to differences in downstream signaling.

Atypical antipsychotic agents; peas in a pod or chalk and cheese?

With escalating health expenditure and a shrinking purse, there is increased focus on the cost efficacy of still patented versus generic medications in general, and for atypical antipsychotics in particular. In a recent BMC Medicine article, Godman and colleagues presented data indicating poor uptake of the off patent atypical antipsychotic risperidone, arguing for authorities to mandate its greater use. This is under the assumption of clinical equivalence of atypical antipsychotics. This commentary argues that there are clinically meaningful differences between atypical antipsychotics and important inter-individual heterogeneity in clinical response and tolerability. Access to a broad range of atypical antipsychotics enables clinicians to tailor care, taking consideration of differential efficacy and adverse effects profile in order to meet the needs of individual patients with improved real world effectiveness of treatment. Restriction of agent choice risks detracting from optimal clinical care, with possible poorer outcomes and greater costs of care. A balance between encouraging use of cheapest in class agent and allowing access to various atypical agents for tailored care is likely to produce optimal health outcomes.Please see related article: http://www.biomedcentral.com/1741-7015/12/98.

Typical and atypical haemolytic uraemic syndrome: A brief case comparison report for nurses

Background: Haemolytic uraemic syndrome (HUS) is one of the main causes of acute kidney injury in children. It is a multifaceted disease, characterised by microangiopathic haemolytic anaemia and thrombocytopaenia. It can often affect multiple organ systems, including the central nervous and renal systems.

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.

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.

Shiga Toxigenic and Atypical Enteropathogenic Escherichia coli in the Feces and Carcasses of Slaughtered Pigs

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