Anti-manic effect of deep brain stimulation of the ventral tegmental area in an animal model of mania induced by methamphetamine.

BACKGROUND: Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD. AIM: The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m-amph). METHODS: Wistar rats were given 14 days of m-amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low-frequency stimulation (LFS) or continuous high-frequency stimulation (HFS). Immediately after DBS, manic-like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open-field tests and fast-scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry. RESULTS: M-amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M-amph increased DA reuptake time post-sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc. CONCLUSION: These results demonstrate that both VTA LFS and HFS DBS exert anti-manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti-manic effects.

Association between electroconvulsive therapy and time to readmission after a manic episode.

OBJECTIVE: The majority of patients hospitalized for treatment of a manic episode are readmitted within 2 years despite maintenance treatment. Electroconvulsive therapy (ECT) has been associated with lower rehospitalization rates in some psychiatric conditions, but its association with readmission after a manic episode has not been investigated. Therefore, the aim of this study was to determine whether the time to readmission in patients with mania treated with ECT was longer than in patients not treated with ECT and whether there were subgroups of patients that benefited more. METHODS: This was a nationwide register-based, observational study. All patients diagnosed with bipolar disorder, manic episode, admitted to any hospital in Sweden between 2012 and 2021 were included. Patients contributed data to the study for every admission. All admissions were followed up until psychiatric readmission, death, or the end of the study (December 31, 2021). Association between ECT and time to readmission was analyzed. A paired samples model was performed for 377 patients with at least two admissions for mania, treated with ECT at one admission and without ECT at the other admission. Times to readmission were analyzed. RESULTS: A total of 12,337 admissions were included; mean (SD) age 47.7 (17.2), 5443 (44.1%) men. Readmission rate within 1 year was 54.6%. ECT was administered in 902 (7.3%) admissions. Within 30 days after admission, 182 out of 894 (20.4%) patients treated with ECT versus 2105 out of 11,305 (18.6%) patients treated without ECT were readmitted. There was no association between ECT and time to readmission (aHR 1.00, 95% CI 0.86-1.16, p = 0.992) in the model with all admissions. The paired samples model included 754 admissions (377 patients), mean (SD) age during admission without ECT was 45.6 (16.5), and with ECT 46.6 (16.4), 147 (39.0%) were men. In that model, readmission rate within 30 days for treatment with ECT was 19.0%, and for treatments without ECT, 24.1% (aHR 0.75, 95% CI 0.55-1.02, p = 0.067). CONCLUSION: Readmission rates after inpatient treatment of mania were high. ECT was not significantly associated with longer time to readmission, but there was a trend toward a protective effect of ECT when admissions with and without ECT were compared within the same patients.

Blue-blocking glasses as additive treatment for mania: Effects on actigraphy-derived sleep parameters.

Improvement of sleep is a central treatment goal for patients in a manic state. Blue-blocking (BB) glasses as adjunctive treatment hasten overall recovery from mania. This method is an evolvement from dark therapy and builds on the discovery of the blue-light-sensitive retinal ganglion cell that signals daytime to the brain. We report effects of adjunctive BB glasses on actigraphy-derived sleep parameters for manic inpatients as compared to placebo. Hospitalized patients with bipolar disorder in a manic state aged 18-70 years were recruited from five clinics in Norway from February 2012 to February 2015. The participants were randomly allocated to wearing BB glasses or placebo (clear glasses) as an adjunctive treatment from 18:00 to 08:00 hours for seven consecutive nights. Sleep and wake were monitored by actigraphy. From 32 eligible patients, 10 patients in each group qualified for the group analyses. The BB group's mean sleep efficiency was significantly higher at night 5 as compared to the placebo group (92.6% vs. 83.1%, p = .027). The 95% confidence interval (CI) was 89.4%-95.8% in the BB group and 75.9%-90.3% in the placebo group. There were fewer nights of interrupted sleep in the BB group: 29.6% versus 43.8% in the placebo group. The BB group received less-intensive sleep-promoting pharmacological treatment and showed significantly higher sleep efficiency and more consolidated sleep as compared to the placebo group. Our findings suggest sleep-promoting effects through deactivating mechanisms. Adjunctive BB glasses seem to be useful for improving sleep for manic patients in the hospital setting.

Predictive factors and treatment of postpartum mania: a representative case.

Postpartum mania and psychosis puts both the person giving birth and their child at significant risk, so predicting its onset and determining effective treatment is crucial. Here, a representative case is presented of a patient started on an antidepressant during her pregnancy who suffered a postpartum manic episode with psychosis. The case describes many of the risk factors and treatment issues faced by clinicians when caring for patients with these symptoms in the postpartum period. Subsequent discussion provides guidance for clinicians to help predict postpartum mania and reviews factors that may increase the risk of its onset. The evidence for psychiatric treatment is also reviewed to both prevent and treat postpartum mania and psychosis.

Electroconvulsive Therapy in Mania: A Review of 80 Years of Clinical Experience.

Resistance to pharmacological agents is commonly encountered in the treatment of acute episodes of mania. In contemporary practice guidelines, electroconvulsive therapy (ECT), once a widely used standalone intervention for mania, is no longer considered a first-line treatment. Stigma, logistics, and ethical factors constrain ECT administration in this condition and lead to its underutilization. However, the past three decades have produced promising research regarding the use of ECT in mania. Randomized controlled trials, albeit in limited numbers, the adoption of ultrabrief ECT, examination of the safety and efficacy of combining ECT with pharmacological agents, including lithium, and use of ECT as a maintenance strategy have enhanced our understanding of how and when to utilize this intervention in mania. In this comprehensive review, the authors summarize the evidence regarding the efficacy and safety of ECT in mania, including related syndromes, such as delirious mania and mixed affective states. The impact of technical parameters, particularly the choice of treatment frequency, electrode placements, and pulse width, are discussed in the light of recent evidence.

Treatment of Electroconvulsive Therapy-Emergent Hypomania and Mania: A Systematic Review of the Literature.

Objective: Electroconvulsive therapy (ECT)-emergent hypomania/mania is a clinically significant problem that has lacked evidence-based guidelines for effective management. The aim of this systematic literature review is to compile the current published literature on treating ECT-emergent hypomania/mania to help guide treatment course in patients with unipolar and bipolar depression.Data Sources: MEDLINE/PubMed was searched for studies published from 1980 through August 2020 that evaluated the treatment of ECT-emergent hypomania/mania. Search terms included Boolean combinations of the following: mania, hypomania, ECT, ECT induced mania, and ECT induced hypomania.Study Selection: There were 1,662 articles reviewed, and all published studies detailing the treatment of ECT-emergent hypomania/mania written in English that met inclusion criteria were included. Due to the limited number of articles, there were no restrictions.Data Extraction: Two reviewers extracted relevant articles and assessed each study based on inclusion criteria.Results: The literature review identified 12 articles that described the treatment course of ECT-emergent hypomania/mania in 17 patients. There were 9 patients who had no known history of manic or hypomanic episodes and were diagnosed with unipolar depression and 8 patients diagnosed with bipolar disorder. There were 4 primary treatment courses identified: continuing ECT alone, continuing ECT in conjunction with lithium, discontinuing ECT with no medication treatment, or discontinuing ECT and starting a medication.Conclusions: The available data are insufficient to support definitive conclusions; however, potential treatment guidelines are suggested within the review to providers based on the limited data available.

Mapping mania symptoms based on focal brain damage.

BACKGROUNDAlthough mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets.METHODSLesion locations associated with mania were identified using a systematic literature search (n = 41) and mapped onto a common brain atlas. The network of brain regions functionally connected to each lesion location was computed using normative human connectome data (resting-state functional MRI, n = 1000) and contrasted with those obtained from lesion locations not associated with mania (n = 79). Reproducibility was assessed using independent cohorts of mania lesions derived from clinical chart review (n = 15) and of control lesions (n = 490). Results were compared with brain stimulation sites previously reported to induce or relieve mania symptoms.RESULTSLesion locations associated with mania were heterogeneous and no single brain region was lesioned in all, or even most, cases. However, these lesion locations showed a unique pattern of functional connectivity to the right orbitofrontal cortex, right inferior temporal gyrus, and right frontal pole. This connectivity profile was reproducible across independent lesion cohorts and aligned with the effects of therapeutic brain stimulation on mania symptoms.CONCLUSIONBrain lesions associated with mania are characterized by a specific pattern of brain connectivity that lends insight into localization of mania symptoms and potential therapeutic targets.FUNDINGFundação para a Ciência e Tecnologia (FCT), Harvard Medical School DuPont-Warren Fellowship, Portuguese national funds from FCT and Fundo Europeu de Desenvolvimento Regional, Child Neurology Foundation Shields Research, Sidney R. Baer, Jr. Foundation, Nancy Lurie Marks Foundation, Mather's Foundation, and the NIH.