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Background: Structured care pathways (SCPs) consist of treatment algorithms that patients advance through with the goal of achieving remission or response. These SCPs facilitate the application of current evidence and adequate treatment, which potentially benefit patients with mood disorders. The aim of this systematic review was to provide an updated synthesis of SCPs for the treatment of depressive disorders and bipolar disorder (BD)., Method: PubMed, PsycINFO, and Embase were searched through June 2022 for peer-reviewed studies examining outcomes of SCPs. Eligibility criteria included being published in a peer-reviewed journal in the English language, reporting of intervention used in the SCP, and having quantitative outcomes. Studies Cochrane risk of bias tool was used to assess quality of RCTs., Results: Thirty-six studies including 15,032 patients were identified for qualitative synthesis. Six studies included patients with BD. The studies were highly heterogeneous in design, outcome measures, and algorithms. More than half of the studies reported superiority of SCPs over treatment as usual, suggesting that the standardized structure and consistent monitoring inherent in SCPs may be contributing to their effectiveness. We also found accumulating evidence supporting feasibility of SCPs in different settings, although dropout rates were generally higher in SCPs. The studies included were limited to being published in peer-reviewed journals in English language. The heterogeneity of studies did not allow quantitative evaluation., Conclusions: The findings of our study suggest that SCPs are equally or more effective than treatment as usual in depression and BD. Further studies are required to ascertain their effectiveness, particularly for BD, and to identify factors that influence their feasibility and success., (© 2023. The Author(s).)

Neuroimaging findings in people at either genetic risk or at clinical high-risk for psychosis (CHR-P) or bipolar disorder (CHR-B) remain unclear. A meta-analytic review of whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies in individuals with genetic risk or CHR-P or CHR-B and controls identified 94 datasets (N = 7942). Notwithstanding no significant findings were observed following adjustment for multiple comparisons, several findings were noted at a more liberal threshold. Subjects at genetic risk for schizophrenia or bipolar disorder or at CHR-P exhibited lower gray matter (GM) volumes in the gyrus rectus (Hedges' g = -0.19). Genetic risk for psychosis was associated with GM reductions in the right cerebellum and left amygdala. CHR-P was associated with decreased GM volumes in the frontal superior gyrus and hypoactivation in the right precuneus, the superior frontal gyrus and the right inferior frontal gyrus. Genetic and CHR-P were associated with small structural and functional alterations involving regions implicated in psychosis. Further neuroimaging studies in individuals with genetic or CHR-B are warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Repetitive transcranial magnetic stimulation (rTMS) is commonly used in unipolar depression; yet, its evidence in bipolar disorder (BD) is limited. We sought to review the evidence on the use of rTMS across the different stages of BD., Methods: MEDLINE database was systematically searched using the PubMed interface following the PRISMA guidelines. Inclusion criteria were as follows: (i) randomized clinical trials (RCTs), open-label studies, and case series; (ii) specific evaluation of the treatment outcomes using psychometric scales; (iii) clinical studies in adults; and (iv) articles in the English language. The systematic review has been registered on PROSPERO (CRD42020192788)., Results: Thirty-one papers were included in the review. Most studies included participants diagnosed with a bipolar depressive episode (N = 24), have yielded mixed findings, and have yet to reach a consensus on the most effective rTMS protocol. Few studies examined the effect of rTMS during manic (N = 5) or mixed episode (N = 1), or as maintenance treatment (N = 1). The limited data thus far suggest rTMS to be relatively safe and well tolerated. Small sample sizes, heterogeneity among study designs, patients and control groups recruited, rTMS parameters, and outcome measures are among the most significant limitations to these studies., Conclusion: The current data regarding the application of rTMS in BD patients remain limited. More adequately powered sham-controlled studies are required to verify its efficacy. Large-scale clinical trials are needed to also determine whether its effects extend to manic and mixed episodes, as well as its role in mood stabilization and amelioration of suicidal behavior., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Long-term clinical monitoring in bipolar disorder (BD) is an important therapeutic tool. The availability of smartphones and wearables has sparked the development of automated applications to remotely monitor patients. This systematic review focus on the current state of electronic (e-) monitoring for episode prediction in BD., Methods: We systematically reviewed the literature on e-monitoring for episode prediction in adult BD patients. The systematic review was done according to the guidelines for reporting of systematic reviews and meta-analyses (PRISMA) and was registered in PROSPERO on April 29, 2020 (CRD42020155795). We conducted a search of Web of Science, MEDLINE, EMBASE, and PsycINFO (all 2000-2020) databases. We identified and extracted data from 17 published reports on 15 relevant studies., Results: Studies were heterogeneous and most had substantial methodological and technical limitations. Models varied widely in their performance. Published metrics were too heterogeneous to lend themselves to a meta-analysis. Four studies reported sensitivity (range: 0.21 - 0.95); and two reported specificity for prediction of mood episodes (range: 0.36 - 0.99). Two studies reported accuracy (range: 0.64 - 0.88) and four reported area under the curve (AUC; range: 0.52-0.95). Overall, models were better in predicting manic or hypomanic episodes, but their performance depended on feature type., Limitations: Our conclusions are tempered by the lack of appropriate information impeding our ability to synthesize the available evidence., Conclusions: Given the clinical variability in BD, predicting mood episodes remains a challenging task. Emerging e-monitoring technology for episode prediction in BD requires more development before it can be adopted clinically., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD) but may be associated with adverse cognitive effects. Magnetic seizure therapy (MST) is a promising alternative convulsive treatment with a safer cognitive profile. Although there is emerging evidence for the efficacy of MST for TRD as an acute treatment, there are no published studies of continuation MST for the prevention of relapse., Methods: Patients with TRD with a DSM-IV diagnosis of major depressive disorder or bipolar disorder who met response criteria after acute MST were offered continuation MST in a prospective, open-label trial between February 2012 and June 2019. They received 12 continuation MST sessions with decreasing frequency over the course of 6 months, with additional booster sessions if their depression symptoms started to worsen. The primary outcome was relapse of depression or psychiatric hospitalization. Secondary outcomes included relapse of suicidal ideation and neurocognitive outcomes., Results: Thirty participants completing at least one assessment during continuation MST were included in the analysis; 10 (33.3%) relapsed, with no significant differences in survival distributions between unipolar and bipolar groups (χ 2  = 0.3, P  = .58). Mean (SD) survival time was 18.6 (1.6) weeks. All 17 participants who achieved resolution of baseline suicidality after acute MST remained free of suicidality during the continuation phase. Except for improvement in verbal fluency, neurocognitive test scores did not change during continuation MST., Conclusions: During 6 months of continuation MST, two-thirds of participants sustained improvements in depressive symptoms without any adverse cognitive effects. Future studies of continuation MST are warranted, particularly in comparison to ECT., Trial Registration: ClinicalTrials.gov identifier: NCT01596608., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression., Methods: Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests., Results: Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory., Limitations: The open-label study design and modest sample size did not allow for comparisons between stimulation parameters., Conclusion: In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy., Clinical Trial Registration: NCT01596608; clinicaltrials.gov, Competing Interests: D. Blumberger reports grants from Magventure during the conduct of the study; other funding from Brainsway; and grants from the National Institute of Mental Health, the Canadian Institutes of Health Research, Brain Canada and the Patient Centred Outcomes Research Institute, outside the submitted work. S. McClintock reports grants from the National Institutes of Health and personal fees from Pearson Assessment during the conduct of the study. D. Voineskos reports grants from the Ontario Mental Health Foundation and the Innovation Fund of the Alternate Funding Plan for the Academic Health Sciences Centres of Ontario, outside the submitted work. J. Downar reports personal fees from Restorative Brain Clinics, TMS Neuro Health and Neurostim TMS Clinics, outside the submitted work. B. Mulsant reports grants from Brain Canada, the Canadian Institutes of Health Research, the Centre for Addiction and Mental Health Foundation, the Patient-Centred Outcomes Research Institute and the United States National Institutes of Health; and non-financial support from Eli Lilly, Pfizer, Capital Solutions Design LLC, HAPPYneuron and General Electric, outside the submitted work. P. Fitzgerald is supported by a National Health and Medical Research Council Practitioner Fellowship (1078567) and has received equipment for research from MagVenture A/S, Medtronic Ltd, Neuronetics and Brainsway Ltd. and funding for research from Neuronetics; he is on scientific advisory boards for Bionomics Ltd and LivaNova and is a founder of TMS Clinics Australia. No other competing interests were declared., (© 2020 Joule Inc. or its licensors)

The search for biological targets in psychiatric disorders is essential to better understand illness mechanisms and also to monitor and predict response to currently available therapeutic interventions. To this end, the combination of transcranial magnetic stimulation with electroencephalography (TMS-EEG) has emerged as a powerful clinical research tool. TMS-EEG allows cortical properties, such as excitability, inhibition, oscillatory activity, and connectivity, to be directly probed within a specific region of the cortex. This review will summarize the state of the current literature on TMS-EEG and its potential to uncover biological targets in psychiatric illnesses, with a focus on major depressive disorder, bipolar disorder, and schizophrenia. Collectively, the reviewed studies suggest that alterations in gamma-aminobutyric acid-mediated inhibition and gamma oscillations in the dorsolateral prefrontal cortex and neighboring frontal regions are potential shared biomarkers in psychiatry, highlighting the potential of TMS-EEG to help identify translational biomarkers., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

Bipolar depression (BD) is a highly prevalent condition with limited therapeutic options. Deep (H1-coil) transcranial magnetic stimulation (dTMS) is a novel TMS modality with established efficacy for unipolar depression. We conducted a randomized sham-controlled trial to evaluate the efficacy and safety of dTMS in treatment-resistant BD patients. Patients received 20 sessions of active or sham dTMS over the left dorsolateral prefrontal cortex (H1-coil, 55 18 Hz 2 s 120% MT trains). The primary outcome was changes in the 17-item Hamilton Depression Rating Scale (HDRS-17) from baseline to endpoint (week 4). Secondary outcomes were changes from baseline to the end of the follow-up phase (week 8), and response and remission rates. Safety was assessed using a dTMS adverse effects questionnaire and the Young Mania Rating Scale to assess treatment-emergent mania switch (TEMS). Out of 50 patients, 43 finished the trial. There were 2 and 5 dropouts in the sham and active groups, respectively. Active dTMS was superior to sham at end point (difference favoring dTMS=4.88; 95% CI 0.43 to 9.32, p=0.03) but not at follow-up. There was also a trend for greater response rates in the active (48%) vs sham (24%) groups (OR=2.92; 95% CI=0.87 to 9.78, p=0.08). Remission rates were not statistically different. No TEMS episodes were observed. Deep TMS is a potentially effective and well-tolerated add-on therapy in resistant bipolar depressed patients receiving adequate pharmacotherapy.

Background/objective: To explore the therapeutic benefit of sequential bilateral repetitive transcranial magnetic stimulation (rTMS) in the treatment of bipolar depression., Method: A 2 arm randomized controlled parallel design trial comparing the use of active sequential bilateral rTMS to a sham form of stimulation in 49 patients with bipolar disorder and treatment resistant depression., Results: There was no significant difference in mean reduction in depression rating scale scores or response rates between active and sham stimulation., Limitations: The study was of limited sample size and the use of bilateral rTMS limited generalizability to other forms of rTMS., Conclusions: This study provides no support to the use of active sequential bilateral rTMS in the treatment of the depressive phase of bipolar affective disorder. Although this result is not definitive, we suggest that future research may be better focused on trials evaluating the use of unilateral types of rTMS., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Magnetic seizure therapy (MST) is a novel brain stimulation modality used to treat refractory depression through the induction of seizures. It is currently being investigated as a potential alternative treatment to electroconvulsive therapy. To our knowledge, there have not been any previous reports of MST-induced mania., Objective: We aim to describe 2 cases of patients with a major depressive episode who developed acute symptoms of mania during a course of MST., Methods: The current report describes 2 cases of mania that occurred in the context of an ongoing open-label study of MST in treatment-resistant depression. The MST was administered 2 or 3 times per week and applied directly over the left and right dorsolateral prefrontal cortex. Treatment is administered until patients achieve remission or a maximum of 24 treatments. A MagVenture Twin coil and MST stimulator were used for treatment. The center of each coil was placed over F3 and F4 according to the 10-20 electroencephalography system., Results: Patient 1 had developed manic symptoms precipitously after the sixth MST treatment, and patient 2 developed manic symptoms after the 23rd MST treatment. In both patients, the MST treatment course was stopped. Their manic symptoms resolved rapidly with pharmacotherapy after cessation of MST treatments., Conclusions: As with electroconvulsive therapy, switches to mania or hypomania should be considered as potential adverse effects of MST.

Differing levels of occipital lobe asymmetry and enlarged lateral ventricles have been reported within patients with bipolar disorder (BD) compared with healthy controls, suggesting different rates of occipital bending (OB). This may exert pressure on subcortical structures, such as the hippocampus, reduced among psychiatric patients. We investigated OB prevalence in 35 patients with BD and 36 healthy controls, and ventricular and occipital volumes. Prevalence was four times higher among BD patients (12/35 [34.3%]) than in control subjects (3/36 [8.3%]), as well as larger lateral ventricular volumes (LVVs). Furthermore, we found OB to relate to left-to-right ventricular and occipital lobe volume (OLV) ratios. Those with OB also had reduced left-to-right hippocampal volume ratios. The results suggest that OB is more common among BD patients than healthy subjects, and prevalent in both BD Type I and Type II patients. We posit that anomalies in neural pruning or ventricular enlargement may precipitate OB, consequently resulting in one occipital lobe twisting around the other. Although the clinical implications of these results are unclear, the study suggests that asymmetrical ventricular volume matched with a pattern of oppositely asymmetrical occipital volume is related to OB and may be a marker of psychiatric illness., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Neuroanatomic evidence suggests that patients with bipolar disorder (BD) have impaired cortical inhibition (CI). However, there is little in vivo neurophysiological evidence supporting the occurrence of such impairments in this disorder. Using 3 transcranial magnetic stimulation paradigms, known as short-interval CI (SICI), cortical silent period (SP), and interhemispheric inhibition (IHI), the authors measured inhibition in the motor cortex., Method: Fifteen patients with BD and 15 healthy subjects were enrolled. Short-interval CI involves stimulating with a subthreshold pulse a few milliseconds before a suprathreshold pulse, thereby inhibiting the size of the motor-evoked potential (MEP) produced by the suprathreshold pulse. In the SP paradigm, inhibition is reflected by the SP duration (ie, the duration of electromyographic activity cessation following a transcranial magnetic stimulation-induced MEP). Interhemispheric inhibition involves a subthreshold conditioning stimulus applied to the right motor cortex several milliseconds before a suprathreshold test stimulus is applied to the left motor cortex which inhibits the size of the MEP produced by the test stimulus by 50% to 75%., Results: Patients with BD demonstrated deficits in all 3 paradigms: SICI (F1,28 = 5.55, P = 0.03; Cohen d = 0.86), SP (F1,28 = 5.24, P = 0.03; Cohen d = 0.84), and IHI (F1,28 = 3.41, P = 0.02; Cohen d = 0.77) compared with healthy volunteers with a large effect size., Conclusions: Our study supports the hypothesis that CI is decreased in BD. Further understanding of the neurophysiology of such deficiencies may help to elucidate future treatment options.

Objectives.Preclinical studies suggest that cortical alterations within the prefrontal cortex (PFC) are critical to the pathophysiology of alcohol dependence. Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows direct assessment of cortical excitability and inhibition within the PFC of human subjects. We report the first application of TMS-EEG to measure these indices within the PFC of alcohol-dependent (ALD) patients post-detoxification.Methods.Cortical inhibition was assessed in 12 ALD patients and 14 healthy controls through single and paired-pulse TMS paradigms. Long-interval cortical inhibition indexed cortical inhibition in the PFC. In the motor cortex (MC), short- interval intracortical inhibition and cortical silent period determined inhibition, while intracortical facilitation measured facilitation, resting and active motor threshold indexed cortical excitability.Results.ALD patients demonstrated altered cortical inhibition across the bilateral frontal cortices relative to controls. There was evidence of altered cortical excitability in ALD patients; however, no significant differences in MC inhibition.Conclusions.Our study provides first direct evidence of reduced cortical inhibition in the PFC of ALD patients post-detoxification. Altered cortical excitability in the MC may reflect hyper-excitability within the cortex associated with chronic alcohol consumption. These findings provide initial neurophysiological evidence of disrupted cortical excitability within the PFC of ALD patients. [ABSTRACT FROM AUTHOR]

Abstract: Magnetic seizure therapy (MST) has shown efficacy in adult patients with treatment-resistant depression with limited impairment in memory. To date, the use of MST in adolescent depression has not been reported. Here we describe the first successful use of MST in the treatment of an adolescent patient with refractory bipolar depression. This patient received MST in an ongoing open-label study for treatment-resistant major depression. Treatments employed a twin-coil MST apparatus, with the center of each coil placed over the frontal cortex (ie, each coil centered over F3 and F4). MST was applied at 100 Hz and 100% machine output at progressively increasing train durations. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale and cognitive function was assessed with a comprehensive neuropsychological battery. This adolescent patient achieved full remission of clinical symptoms after an acute course of 18 MST treatments and had no apparent cognitive decline, other than some autobiographical memory impairment that may or may not be related to the MST treatment. This case report suggests that MST may be a safe and well tolerated intervention for adolescents with treatment-resistant bipolar depression. Pilot studies to further evaluate the effectiveness and safety of MST in adolescents warrant consideration. [ABSTRACT FROM AUTHOR]

Several lines of evidence suggest that deficits in γ-aminobutyric acid (GABA) inhibitory neurotransmission are implicated in the pathophysiology of schizophrenia, bipolar disorder, major depressive disorder and obsessive-compulsive disorder. Cortical inhibition refers to a neurophysiological process, whereby GABA inhibitory interneurons selectively attenuate pyramidal neurons. Transcranial magnetic stimulation (TMS) represents a noninvasive technique to measure cortical inhibition, excitability and plasticity in the cortex. These measures were traditionally specific to the motor cortex, which is an important limitation when nonmotor neurophysiological processes are of primary interest. Recently, TMS has been combined with electro encephalography (EEG) to derive such measurements directly from the cortex. This review focuses on neurophysiological studies related to inhibitory and excitatory TMS paradigms, linking dysfunctional GABAergic neurotransmission to disease states. We review evidence that suggests cortical inhibition deficits among psychiatric populations and demonstrate how each disorder has a specific neurophysiological response to treatment. We conclude by discussing the future directions of TMS combined with EEG, demonstrating the potential to identify biological markers of neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Previous studies have shown that patients with schizophrenia and bipolar disorder have deficits in cortical inhibition. Through the combination of interleaved transcranial magnetic stimulation and electroencephalography, we have recently reported on methods in which cortical inhibition can be measured from the dorsolateral prefrontal cortex, a cortical region that is more closely associated with the pathophysiology of schizophrenia. Furthermore, it is possible to index cortical inhibition of specific oscillatory frequencies including the gamma band (30–50 Hz) whose modulation has been related to higher order cortical processing. In this study, we show that patients with schizophrenia have significant deficits of cortical inhibition of gamma oscillations in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder, while no deficits are demonstrated in the motor cortex. These results suggest that the lack of inhibition of gamma oscillations in the dorsolateral prefrontal cortex may represent an important frontal neurophysiological deficit, which may be responsible for the spectrum of deficits commonly found in schizophrenia. [ABSTRACT FROM PUBLISHER]