Stage managing bipolar disorder.

OBJECTIVES: Clinical staging is widespread in medicine - it informs prognosis, clinical course, and treatment, and assists individualized care. Staging places an individual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at-risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end-stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and individualized intervention approaches. METHODS: We provide a narrative review of the relevant information. RESULTS: In bipolar disorder, the validity of staging is informed by a range of findings that accompany illness progression, including neuroimaging data suggesting incremental volume loss, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Staging informs the adoption of a number of approaches, including the active promotion of both indicated prevention for at-risk individuals and early intervention strategies for newly diagnosed individuals, and the tailored implementation of treatments according to the stage of illness. CONCLUSIONS: The nature of bipolar disorder implies the presence of an active process of neuroprogression that is considered to be at least partly mediated by inflammation, oxidative stress, apoptosis, and changes in neurogenesis. It further supports the concept of neuroprotection, in that a diversity of agents have putative effects against these molecular targets. Clinically, staging suggests that the at-risk state or first episode is a period that requires particularly active and broad-based treatment, consistent with the hope that the temporal trajectory of the illness can be altered. Prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity. Staging highlights the need for interventions at a service delivery level and implementing treatments at the earliest stage of illness possible

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Brain activation during processing of genuine facial emotion in depression: Preliminary findings

Objective The current study aimed to examine the neural correlates of processing genuine compared with posed emotional expressions, in depressed and healthy subjects using a novel functional magnetic resonance imaging (fMRI) paradigm Method During fMRI scanning, sixteen depressed patients and ten healthy controls performed an Emotion Categorisation Task, whereby participants were asked to distinguish between genuine and non-genuine (posed or neutral) facial displays of happiness and sadness. Results Compared to controls, the depressed group showed greater activation whilst processing genuine versus posed facial displays of sadness, in the left medial orbitofrontal cortex, caudate and putamen. The depressed group also showed greater activation whilst processing genuine facial displays of sadness relative to neutral displays, in the bilateral medial frontal/orbitofrontal cortex, left dorsolateral prefrontal cortex, right dorsal anterior cingulate, bilateral posterior cingulate, right superior parietal lobe, left lingual gyrus and cuneus. No differences were found between the two groups for happy facial displays. Limitations Relatively small sample sizes and due to the exploratory nature of the study, no correction was made for multiple comparisons. Conclusion The findings of this exploratory study suggest that depressed individuals may show a different pattern of brain activation in response to genuine versus posed facial displays of sadness, compared to healthy individuals. This may have important implications for future studies that wish to examine the neural correlates of facial emotion processing in depression

Cognitive effects of adjunctive N-acetyl cysteine in psychosis

BACKGROUND: Cognitive deficits are predictors of functional outcome in patients with psychosis. While conventional antipsychotics are relatively effective on positive symptoms, their impact on negative and cognitive symptoms is limited. Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis. N-acetylcysteine (NAC), a glutathione precursor with glutamatergic properties, has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder, respectively. However, there are few evidence-based approaches for managing cognitive impairment in psychosis. The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder. METHOD: A sample of 58 participants were randomized in a double fashion to receive 2 g/day of NAC (n = 27) or placebo (n = 31) for 24 weeks. Attention, working memory and executive function domains were assessed. Differences between cognitive performance at baseline and end point were examined using Wilcoxon\u27s test. The Mann-Whitney test was used to examine the differences between the NAC and placebo groups at the end point. RESULTS: Participants treated with NAC had significantly higher working memory performance at week 24 compared with placebo (U = 98.5, p = 0.027). CONCLUSIONS: NAC may have an impact on cognitive performance in psychosis, as a significant improvement in working memory was observed in the NAC-treated group compared with placebo; however, these preliminary data require replication. Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis

Does the "Silver bullet" lose its shine over the time? Assessment of loss of lithium response in a preliminary sample of bipolar disorder outpatients

Background: Though often perceived as a "silver bullet" treatment for bipolar disorder (BD), lithium has seldom reported to lose its efficacy over the time. Objective: The aim of the present study was to assess cases of refractoriness toward restarted lithium in BD patients who failed to preserve maintenance. Method: Treatment trajectories associated with re-instituted lithium following loss of achieved lithium-based maintenance in BD were retrospectively reviewed for 37 BD-I patients (median age 52 years; F: M=17: 20 or 46% of the total) over an 8.1-month period on average. Results: In our sample only 4 cases (roughly 11% of the total, of whom F: M=2: 2) developed refractoriness towards lithium after its discontinuation. Thirty-three controls (F: M=15: 18) maintained lithium response at the time of re-institution. No statistically significant difference between cases and controls was observed with respect to a number of demographic and clinical features but for time spent before first trial ever with lithium in life (8.5 vs. 3 years; U=24.5, Z=-2.048, p=.041) and length of lithium discontinuation until new therapeutic attempt (5.5 vs. 2 years; U=8, Z=-2.927, p=.003) between cases vs. controls respectively. Tapering off of lithium was significantly faster among cases vs. controls (1 vs. 7 days; U=22, Z=-2.187), though both subgroups had worrisome high rates of poor adherence overall. Conclusion: Although intrinsic limitations of the present preliminary assessment hamper the validity and generalizability of overall results, stating the clinical relevance of the topic further prospective research is warranted. The eventual occurrence of lithium refractoriness may indeed be associated with peculiar course trajectories and therapeutic outcomes ultimately urging the prescribing clinicians to put efforts in preserving maintenance of BD in the absence of any conclusive research insight on the matter. © Fornaro et al

Clinical practice recommendations for bipolar disorder

Objective:  To provide clinically relevant evidence-based recommendations for the management of bipolar disorder in adults that are informative, easy to assimilate and facilitate clinical decision-making.Method:  A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. These preliminary recommendations underwent extensive consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives.Results:  The clinical practice recommendations for bipolar disorder (bipolar CPR) summarise evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative.Conclusion:  These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of bipolar disorder. Further, the novel style and practical approach should promote their uptake and implementation