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Background: While theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing treatment parameters is crucial in the pursuit of rapid symptom relief. Moreover, aligning with personalized treatment strategies and increased interest in immunopsychiatry, biomarker-based stratification of patients most likely to benefit from TBS might improve remission rates. We investigated treatment effectiveness of continuous TBS (cTBS) compared to sham in BD-D, and assessed the capacity of plasma kynurenine pathway metabolites to predict treatment outcome., Methods: Thirty-seven patients with BD-D underwent accelerated active or sham cTBS treatment in a multicenter, double-blind, randomized controlled trial. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before treatment (T0), 3-4 days posttreatment (T1) and 10-11 days posttreatment (T2). Plasma tryptophan, kynurenine, kynurenic acid and quinolinic acid concentrations were quantified with ELISA. Linear mixed models were used for statistical analyses., Results: Although the total sample showed depressive symptom improvement, active cTBS did not demonstrate greater symptom alleviation compared to sham. However, higher baseline quinolinic acid significantly predicted symptom improvement in the active treatment group, not in sham-stimulated patients., Limitations: The modest sample size limited the power to detect significant differences with regard to treatment effect. Also, the follow-up period was 10-11 days, whereas similar studies usually follow up for at least one month., Conclusion: More research is required to optimize cTBS for BD-D and explore the involvement of quinolinic acid in treatment outcome., Competing Interests: Declaration of competing interest MM, VC: received research funding from Johnson & Johnson Belgium, Lundbeck Belgium, Boehringer Ingelheim Belgium and Takeda Pharmaceuticals Japan for research unrelated to the current project. The authors state that the content of this manuscript was not influenced by any of these agencies. AD, KH, DZ, CBa, GDF, CBe, SDW, BS: Declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Depression is generally perceived from the perspective of the common-cause disease model. However, the network perspective assumes mutual influence of individual symptoms and stresses the importance of investigating symptom dynamics. Gaining a better understanding of symptom dynamics within individuals might contribute to more effective treatments., Methods: Current exploratory longitudinal research studied the associations and directionality between 43 symptoms from the generic questionnaire Symptom Questionnaire-48 (SQ-48) using dynamic time warp (DTW) analyses, in which trajectories with similar time-dependent patterns can be identified. Data from individuals were analysed first, yielding distance matrices for all symptom trajectories, after which the data were aggregated., Results: The 148 included patients were all admitted for the treatment of their clinical depression. Undirected DTW analyses of three patients with longer time series but otherwise randomly chosen showed large variability among individuals. Group-level undirected DTW analyses showed numerous significant edges between symptoms, largely clustering symptoms according to the eight pre-existing subscales of the SQ-48. Group-level directed DTW analyses showed five symptoms with significant outstrength: 'hopeless', 'restless', 'down/depressed', 'feeling tense' and 'no enjoyment', meaning that change in these key symptoms preceded change in other symptoms., Limitations: The 43 included symptoms of the SQ-48 primarily focus on internalizing problems in severely depressed inpatients, potentially limiting generalizability., Conclusions: DTW networks provided us with five key symptoms based on the dynamics of symptom scores. Future studies could explore whether process-based therapy targeted at symptoms with high outstrength might result in more effectivity as part of personalized treatment., (© 2024 The Author(s). Clinical Psychology & Psychotherapy published by John Wiley & Sons Ltd.)

Background: Psychiatry may currently hold unprecedented knowledge in the diagnosis and treatment of psychiatric conditions. Yet, there is a widely held belief that this knowledge is not adequately integrated, nor does it fully account for the complexity of the phenomena under study., Objective: To assess the effectiveness of a system-oriented and network-focused approach in capturing and integrating the complexity of psychiatric disorders. Next, to explore the epistemological implications of such an approach., Method: Narrative literature review., Results: Psychiatric research is still too often characterized by reductionism, linear-causal pathogenesis, and traditional nosology. There appears to be a need for a different metatheoretical model in psychiatry., Conclusion: The development from General System Theory to complex dynamic systems thinking and network theory holds significant epistemological implications for the future of the field, how we conduct science, and the way we frame and structure our care systems.

Background: Electroconvulsive therapy (ECT) remains the one of the most effective of biological antidepressant interventions. However, the exact neurobiological mechanisms underlying the efficacy of ECT remain unclear. A gap in the literature is the lack of multimodal research that attempts to integrate findings at different biological levels of analysis METHODS: We searched the PubMed database for relevant studies. We review biological studies of ECT in depression on a micro- (molecular), meso- (structural) and macro- (network) level., Results: ECT impacts both peripheral and central inflammatory processes, triggers neuroplastic mechanisms and modulates large scale neural network connectivity., Conclusions: Integrating this vast body of existing evidence, we are tempted to speculate that ECT may have neuroplastic effects resulting in the modulation of connectivity between and among specific large-scale networks that are altered in depression. These effects could be mediated by the immunomodulatory properties of the treatment. A better understanding of the complex interactions between the micro-, meso- and macro- level might further specify the mechanisms of action of ECT., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Tinnitus can be regarded as a chronic stressor, leading to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. There is important comorbidity with anxiety, particularly panic, potentially associated with differences in HPA axis functioning and methylation patterns of HPA axis-related genes. This study examines DNA methylation of the glucocorticoid receptor gene ( NR3C1 ) exon 1F in adults with chronic subjective tinnitus and the possible differential effect of panic., Methods: In a well characterized tinnitus sample ( n  = 22, half of which had co-occurring panic attacks), and unaffected controls ( n  = 31) methylation patterns of the CpG sites were determined using pyrosequencing and compared between groups through linear mixed models. Gene expression was determined using quantitative PCR on mRNA., Results: Comparing the combined tinnitus groups to the control group, no DNA methylation differences were observed; however, the tinnitus group with panic attacks showed consistently higher mean methylation values across all CpGs compared to the tinnitus-only and the control group ( P  = 0.03 following Tukey correction), which became even more pronounced when accounting for childhood trauma ( P  = 0.012). Moreover, a significant positive correlation was found between methylation of the CpG7 site and the Beck Anxiety Inventory total score ( P  = 0.001) in the total population. NR3C1 -1F expression was not significantly different between the three groups., Conclusion: Panic is associated with higher DNA methylation of the NR3C1 exon 1F in adults with chronic subjective tinnitus, consistent with the reduced negative glucocorticoid feedback and HPA axis hyperfunction observed in individuals with panic disorder., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Despite a high prevalence of mental disorders among asylum seekers, many barriers to mental healthcare exist. Cultural and contextual factors strongly influence the experience and expression of psychological distress, putting asylum seekers at greater risk of misdiagnosis and inappropriate treatment. The Cultural Formulation Interview (CFI) is a useful tool to map out cultural and contextual factors of mental disorders; however, to the best of our knowledge, it has not yet been investigated in asylum seekers specifically. The primary aim of this study is to evaluate the value of the CFI in the psychiatric assessment of asylum seekers. Second, we will describe the themes relevant to psychiatric distress in asylum seekers that are identified by the CFI. In addition, asylum seekers' experience of the CFI will be evaluated., Methods and Analysis: This cross-sectional, mixed-method clinical study aims to recruit a group of 60-80 asylum seekers (age 15-29) with mental health symptoms. Data will be collected using structured (MINI, PCL-5, HDRS-17, WHOQoL-BREF & BSI) and semi-structured (CFI & CFI-debriefing) questionnaires to assess cultural background, contextual factors, and illness severity. Multidisciplinary case discussions will be held after the completion of interviews, following a methodological stepped approach. Combining qualitative and quantitative research techniques, this study aims to generate reliable knowledge on working with the CFI in asylum seekers. Based on the findings, recommendations for clinicians will be developed., Discussion: This study addresses the knowledge gap on using the CFI in asylum seekers. Compared to prior studies, it will provide new insights into the use of the CFI in the specific context of working with asylum seekers., Ethics and Dissemination: Prior research on the CFI in asylum seekers is limited, partly because of their high vulnerability and low access to care. The study protocol has been tailored in close collaboration with several stakeholders and validated after piloting. Ethical approval has already been obtained. Together with the stakeholders, the results will be translated into guidelines and training materials. Recommendations to policymakers will also be provided., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Claus, Schouler-Ocak, Braakman, Sabbe, Van Beuren and van den Ameele.)

Background: As the guidelines and evidence for the use of electroconvulsive therapy (ECT) in patients with a recent or past history of stroke are unclear, ECT tends to be avoided in this population., Aim: To give a systematic review the literature on the risk and incidence of cerebrovascular accidents after ECT in these patients., Method: A systematic literature search was performed according to the PRISMA guidelines in PubMed and in the Cochrane Library. Publications in which ECT was applied in patients with a history of stroke were included by using specific MeSH terms., Results: The following 19 articles met the criteria for review: 1 wide-scale prospective study, 1 small-scale prospective study with a control group, 3 small-scale retrospective studies, and 14 case reports. In the vast longitudinal Danish study, ECT was not associated with an elevated risk of recurrent stroke. Similarly, none of the other studies found the risk to be raised., Conclusion: Despite the limited number of prospective studies and the methodological discrepancies in the reports, ECT does not seem to be associated with an elevated risk of recurrent stroke. This review supports the safe use of ECT in patients with a recent or past history of stroke, if prior neurologic and cardiovascular assessments are being performed, as well as monitoring during the treatment.

ECT is proposed to exert a therapeutic effect on WM microstructure, but the limited power of previous studies made it difficult to highlight consistent patterns of change in diffusion metrics. We initiated a multicenter analysis and sought to address whether changes in WM microstructure occur following ECT. Diffusion tensor imaging (DTI) data (n = 58) from 4 different sites were harmonized before pooling them by using ComBat, a batch-effect correction tool that removes inter-site technical variability, preserves inter-site biological variability, and maximizes statistical power. Downstream statistical analyses aimed to quantify changes in Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (AD), by employing whole-brain, tract-based spatial statistics (TBSS). ECT increased FA in the right splenium of the corpus callosum and the left cortico-spinal tract. AD in the left superior longitudinal fasciculus and the right inferior fronto-occipital fasciculus was raised. Increases in MD and RD could be observed in overlapping white matter structures of both hemispheres. At baseline, responders showed significantly smaller FA values in the left forceps major and smaller AD values in the right uncinate fasciculus compared with non-responders. By harmonizing multicenter data, we demonstrate that ECT modulates altered WM microstructure in important brain circuits that are implicated in the pathophysiology of depression. Furthermore, responders appear to present a more decreased WM integrity at baseline which could point toward a specific subtype of patients, characterized by a more altered neuroplasticity, who are especially sensitive to the potent neuroplastic effects of ECT., (© 2022. The Author(s).)

Cognitive function during an ECT care pathway is mainly investigated at the group level by analyzing mean cognitive test scores over time. However, there are important inter-individual differences, with some patients experiencing residual invalidating cognitive deficits. This study provides a nuanced examination of cognitive functioning during and after ECT by combining three approaches for data analysis. A cognitive test battery was assessed in seventy-three ECT-treated patients with a Major Depressive Episode (MDE) at up to five time points (baseline, immediately prior to the third session and 1 week, 3 months and 6 months after completion of the index course). Group-level changes in cognitive function were investigated using linear mixed models and individual-level changes were examined using Reliable Change Indices (RCI). The presence of patient subgroups with similar cognitive trajectories was explored using Latent Class Growth Analysis (LCGA). At the group level, there was a temporary deterioration in processing speed, verbal memory and retrograde amnesia during and after index course of ECT. Individual-level analyses revealed considerable variability in cognitive effects of ECT. Three patient classes with a similar cognitive trajectory could be identified, all with a rather parallel courses over time, thus mainly differing in terms of pre-ECT cognitive functioning., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway metabolites are key inflammatory mediators, studies investigating the association between KYN metabolism and cognition in BD are scarce. We aimed to explore the relationship between KYN metabolism and cognitive functioning across different mood states in BD., Methods: Sixty-seven patients with BD (35 depressed and 32 [hypo] manic) and 29 healthy controls were included. Cognitive functioning was assessed at 3 time intervals (baseline, 4, and 8 months) assessing processing speed, sustained attention, verbal memory, working memory, and response inhibition. Plasma samples for quantification of 3-hydroxykynurenine, quinolinic acid, and kynurenic acid (KYNA) were concurrently provided. Linear mixed models were used for statistical analysis., Results: The manic group showed deficits in all assessed cognitive domains with the exception of verbal memory at all test moments. The bipolar depression group showed deficits in the processing speed at all test moments. Throughout the whole follow-up period, KYNA was significantly lower in both patient groups than in controls. Only in the bipolar depression group, low KYNA was associated with worse global cognitive functioning (B = 0.114, p = 0.02) and slower processing speed in particular (B = 0.139, p = 0.03)., Conclusion: Only in the bipolar depression group, lower KYNA was associated with worse cognitive functioning. Future large-scale longitudinal studies are warranted to confirm the role of KYN metabolites in cognitive impairment in patients with BD and the possible therapeutic implications of this relationship., (© 2021 S. Karger AG, Basel.)

Introduction: Currently cancer-related cognitive impairment (CRCI) is mainly assessed by means of questionnaires, which is very laborious for the patients and the supervising physician. We evaluated a new online cognitive assessment tool, the MyCognition Quotient (MyCQ, Cambridge) in breast cancer survivors with CRCI, and compared the results with a psychometric test measuring cognitive complaints, depression, and anxiety., Materials and Methods: In this prospective study, 46 adult patients between 18 and 70 years old with a diagnosis of BC were studied, all complaining of disturbing cognitive impairment. They participated in a physical cognitive rehabilitation program. The patients had an online cognitive assessment (MyCQ Med by MyCognition) every 4 weeks on their home computer. In addition patients were assessed in the outpatient clinic by the principal investigator at baseline, after 3 and 6 months using the following validated neuro-psychological surveys: the Hospital Anxiety and Depression Scale (HADS), Beck Cognitive Insight Scale (BCIS), and Cognitive Failure Questionnaire (CFQ). MyCQ scores were correlated with the results of these surveys., Results: Only weak correlations could be found between overall MyCQ or the MyCQ subtests with the psychometric tests (between - 0.43 and 0.458) at baseline and when combining data at time point 0, 3, and 6 months. Linear mixed models showed there was a significant association between Latency Choice Reaction Time and CFQ (continuous; p = 0.026). An AUC of 0.640 and a cut-off of 481.5 ms in Latency Choice Reaction Time were found to distinguish patients with CFQ below 44 to patients with CFQ above 44 (sensitivity 0.63 and specificity 0.73). In Latency Coding an AUC of 0.788 and a cut-off of 1316 ms were found to distinguish non-depressive patients from patients likely to present with depressive symptoms (sensitivity 0.75 and specificity 0.76)., Conclusion: MyCQ cannot replace the various psychometric tests. However, abnormal Latency in cognitive tests, Choice Reaction Time and Coding, seems promising to be used as a screening tool to detect specific aspects of abnormal cognitive functioning in patients with cognitive complaints and depressive symptoms., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background  Despite high prevalence of psychopathology, the use of mental health services by asylum seekers seems low. Barriers to care may play an important role in this. Aim  To explore the barriers in mental health care for adult and adolescent asylum seekers and their care providers in high-income countries. Method  A narrative literature review, based on a systematic evaluation of the current scientific literature. Results  In a narrative synthesis of the results, we identified the following six categories of barriers: lack of knowledge of the healthcare system, language barriers, discrepant beliefs and expectations of mental healthcare, lack of trust towards authority, and structural difficulties. Conclusion  Six thematic barriers were retained. Different interventions are possible to address these barriers. Further research into needs and interventions is recommended, with specific attention to the Belgian and Dutch context.

Introduction: The prevalence of substance use disorders in forensic populations is high. They are an important factor linked to negative outcomes in mentally ill offenders and are detrimental to forensic or non-forensic outcome measures. In contrast, substance use disorders are often underdiagnosed and undertreated, especially in forensic settings. Forensic Assertive Community Treatment is a forensic adaptation of regular assertive community treatment, combined with essential elements of forensic rehabilitation theories. Little is known however on the effectivity of forensic assertive community treatment when it comes to substance use disorders or what their exact role is on the outcome measures. In this paper, we explore how SUD is treated in Forensic assertive community treatment and how it relates to the forensic and non-forensic outcome measures. Methods: We performed a systematic review (PRISMA) of forensic Assertive community treatment teams that followed the main evidence-based principles of regular assertive community treatment and added basic elements of forensic rehabilitation. We analyzed articles the Psychinfo and Medline databases dating from 2005 to 2020. Fifteen studies fit the search criteria and were included in the analysis. The Quality of the studies was assessed using the Newcastle-Ottawa scale. Results: SUD was highly prevalent in all studies. Patients entered FACT through two pathways, either from a care continuum or directly from prison. The severity of SUD at intake emerges as a critical element when deciding which pathway to choose, as a high severity-score at the start of FACT follow-up was linked to recidivism. While differing in method all studies offered integrated SUD treatment. These included evidence-based techniques like CBT, therapeutic communities, and Substance Abuse Management Module. Though results on SUD outcomes were mixed 4 studies mentioned abstinence in 50-75%. The severity of SUD tended to increase initially and to stabilize afterwards. Conclusion: Severity of SUD at intake emerges as a decisive element in decision-making on entering FACT teams directly from prison or through a care-continuum. The ways to provide SUD treatment varied and outcomes for SUD were mixed. SUD was found to be detrimental to forensic and non-forensic outcome measures, such as recidivism or hospitalizations during FACT treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Marquant, Van Nuffel, Sabbe and Goethals.)