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Background: Approximately 1 in every 50 to 100 people is affected with bipolar disorder (BD), making this disease a major economic burden. The introduction of induced pluripotent stem cell methodology enabled better modeling of this disorder., Methods: Having previously studied the phenotype of dentate gyrus granule neurons, we turned our attention to studying the phenotype of CA3 hippocampal pyramidal neurons of 6 patients with BD compared with 4 control individuals. We used patch clamp and quantitative polymerase chain reaction to measure electrophysiological features and RNA expression by specific channel genes., Results: We found that BD CA3 neurons were hyperexcitable only when they were derived from patients who responded to lithium; they featured sustained activity with large current injections and a large, fast after-hyperpolarization, similar to what we previously reported in dentate gyrus neurons. The higher amplitudes and faster kinetics of fast potassium currents correlated with this hyperexcitability. Further supporting the involvement of potassium currents, we observed an overexpression of KCNC1 and KCNC2 in hippocampal neurons derived from lithium responders. Applying specific potassium channel blockers diminished the hyperexcitability. Long-term lithium treatment decreased the hyperexcitability observed in the CA3 neurons derived from lithium responders while increasing sodium currents and reducing fast potassium currents. When differentiating this cohort into spinal motor neurons, we did not observe any changes in the excitability of BD motor neurons compared with control motor neurons., Conclusions: The hyperexcitability of BD neurons is neuronal type specific with the involvement of altered potassium currents that allow for a sustained, continued firing activity., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: We recently reported a hyperexcitability phenotype displayed in dentate gyrus granule neurons derived from patients with bipolar disorder (BD) as well as a hyperexcitability that appeared only in CA3 pyramidal hippocampal neurons that were derived from patients with BD who responded to lithium treatment (lithium responders) and not in CA3 pyramidal hippocampal neurons that were derived from patients with BD who did not respond to lithium (nonresponders)., Methods: Here we used our measurements of currents in neurons derived from 4 control subjects, 3 patients with BD who were lithium responders, and 3 patients with BD who were nonresponders. We changed the conductances of simulated dentate gyrus and CA3 hippocampal neurons according to our measurements to derive a numerical simulation for BD neurons., Results: The computationally simulated BD dentate gyrus neurons had a hyperexcitability phenotype similar to the experimental results. Only the simulated BD CA3 neurons derived from lithium responder patients were hyperexcitable. Interestingly, our computational model captured a physiological instability intrinsic to hippocampal neurons that were derived from nonresponder patients that we also observed when re-examining our experimental results. This instability was caused by a drastic reduction in the sodium current, accompanied by an increase in the amplitude of several potassium currents. These baseline alterations caused nonresponder BD hippocampal neurons to drastically shift their excitability with small changes to their sodium currents, alternating between hyperexcitable and hypoexcitable states., Conclusions: Our computational model of BD hippocampal neurons that was based on our measurements reproduced the experimental phenotypes of hyperexcitability and physiological instability. We hypothesize that the physiological instability phenotype strongly contributes to affective lability in patients with BD., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

It has been reported that, at any time, over half of the people with bipolar disorder are receiving no active treatment. Despite the availability of effective medications and psychotherapies, research concludes that the care of bipolar disorder in everyday practice is often deficient. Evidence base reports the effectiveness of psychosocial interventions using many of the same ideas as the recovery approach; both attempt to place clients at the heart of service delivery. This paper reports on the development and implementation of three pilot group programmes for service users with bipolar disorder, in a community clinical setting in South East England. The group programme design and development was based upon the evidence-based psychosocial interventions advocated in national clinical guidelines and research literature. The programme incorporated the key effective psychosocial interventions and self-management mechanisms within its 12 sessions spanning over 3 months, followed by three booster sessions in 6 months' time. Twenty-three service users have to date completed the programme. Participant feedback will be discussed and reported to inform further development and research implications of such innovative evidence-based interventions for service users with bipolar disorder., (© 2011 Blackwell Publishing.)

A 36-year-old woman developed mania in association with bupropion treatment. The literature regarding the etiological relationship of bupropion to secondary mania is reviewed.

Two manic-depressive patients are described who presented with acute renal failure and concurrent lithium toxicity. In both cases the etiology of the renal failure was not a direct result of the use of lithium. Controversy concerning the nephrotoxicity of lithium is discussed, and recommendations for the evaluation of renal failure during lithium therapy are provided.