Temporal Directionality Between Symptoms During Treatment of Depressed Inpatients: A Dynamic Time Warp Network Analysis.

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.

Continuous theta burst stimulation for bipolar depression: A multicenter, double-blind randomized controlled study exploring treatment efficacy and predictive potential of kynurenine metabolites.

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.

Motor learning and performance in schizophrenia and aging: two different patterns of decline.

Psychomotor slowing has consistently been observed in schizophrenia, however research on motor learning in schizophrenia is limited. Additionally, motor learning in schizophrenia has never been compared with the waning of motor learning abilities in the elderly. Therefore, in an extensive study, 30 individuals with schizophrenia, 30 healthy age-matched controls and 30 elderly participants were compared on sensorimotor learning tasks including sequence learning and adaptation (both explicit and implicit), as well as tracking and aiming. This paper presents new findings on an explicit motor sequence learning task, an explicit verbal learning task and a simple aiming task and summarizes all previously published findings of this large investigation. Individuals with schizophrenia and elderly had slower Movement Time (MT)s compared with controls in all tasks, however both groups improved over time. Elderly participants learned slower on tracking and explicit sequence learning while individuals with schizophrenia adapted slower and to a lesser extent to movement perturbations in adaptation tasks and performed less well on cognitive tests including the verbal learning task. Results suggest that motor slowing is present in schizophrenia and the elderly, however both groups show significant but different motor skill learning. Cognitive deficits seem to interfere with motor learning and performance in schizophrenia while task complexity and decreased movement precision interferes with motor learning in the elderly, reflecting different underlying patterns of decline in these conditions. In addition, evidence for motor slowing together with impaired implicit adaptation supports the influence of cerebellum and the cerebello-thalamo-cortical-cerebellar (CTCC) circuits in schizophrenia, important for further understanding the pathophysiology of the disorder.

Long-acting second-generation injectable antipsychotics for the maintenance treatment of bipolar disorder: a narrative review.

INTRODUCTION: Non-adherence to medication significantly affects bipolar disorder outcomes. Long-Acting Injectable antipsychotics show promise by ensuring adherence and averting relapses. AREAS COVERED: This narrative review sought to evaluate the efficacy of second-generation injectable antipsychotics in bipolar disorder through searches in Embase, MEDLINE, and PsycInfo for randomized controlled trials and mirror-image studies.Risperidone and aripiprazole Long-Acting Injectables demonstrated effectiveness in preventing mood recurrences compared to placebos in adults with bipolar disorder. They showed superiority in preventing mania/hypomania relapses over placebos but did not appear to significantly outperform active oral controls. Notably, active controls seem to be more effective in preventing depression relapses than Long-Acting Injectables. Mirror-Image studies point toward the reduction of hospitalization rates following LAI initiation. EXPERT OPINION: The available evidence points thus toward the efficacy of LAIs, especially in managing manic episodes and reducing hospitalizations, The current evidence does not however immediately support prioritizing LAIs over oral medications in bipolar disorder treatment. More high-quality studies, especially comparing LAIs directly with active controls, are crucial to gain a comprehensive understanding of their efficacy. These findings highlight the need for further research to guide clinicians in optimizing treatment strategies for bipolar disorder.

The effect of the cultural formulation interview on therapeutic working alliance: a study protocol.

Background: The Cultural Formulation Interview (CFI) is designed to improve understanding of patients' mental health care needs. The lack of empirical evidence on the impact and effectiveness of CFI use in clarifying people's perspectives, experiences, context, and identity, and in preventing cultural misunderstandings between migrant patients and clinicians, inspired this study. The objective is to examine the effect of the CFI on the strength of therapeutic working alliances, and the potential mediating or moderating role of perceived empathy. Materials and methods: A multicenter randomized controlled trial will be conducted, involving migrant patients, their confidants, and clinicians. The CFI will be administered in the intervention group, but not in the control group. Validated questionnaires will be used to assess therapeutic working alliances and perceived empathy. T-tests and linear regression analyses will be conducted to investigate between-group differences and possible mediating or moderating effects. Results: This study will indicate whether or not the CFI strengthens the therapeutic working alliance between patients and clinicians, as moderated and/or mediated by perceived empathy. Discussion: Research on the effect and impact of using the CFI in mental health care for migrant patients is important to clarify whether its use strengthens the therapeutic working alliance with clinicians. This can lead to a reduction in cultural misunderstandings and improve mental health care for migrant patients. The results may also be important for the implementation of the CFI as a standard of care. Ethics and dissemination: This research protocol was tailored to the needs of patients in collaboration with experts by experience. It was approved by the Ethical Review Board of the Tilburg Law School and registered in the Clinical Trials Register under number NCT05788315. Positive results may stimulate further implementation of the CFI in clinical practice, and contribute to improving the impact of the CFI on the therapeutic working alliances.

Reviewing the neurobiology of electroconvulsive therapy on a micro- meso- and macro-level.

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.

An update on pharmacotherapy for recurrent depression in 2022.

INTRODUCTION: Major depressive disorder remains a major challenge due to its biopsychosocial burden with increased morbidity and mortality. Despite successful treatment options for the acute episode, recurrence rates are high, on average four times in a life span. AREAS COVERED: Both pharmacological as non-pharmacological evidence-based therapeutic options to prevent and treat recurrent depression are discussed. EXPERT OPINION: Although some risk factors for recurrence are well known, better evidence is needed. Antidepressant medication should be continued after acute treatment at its full therapeutic dose for longer periods, at least 1 year. There are no clear differences between classes of antidepressant medication when treatment is focused on preventing relapse. Bupropion is the only antidepressant with a proven efficacy to prevent recurrence in seasonal affective disorder. Recent findings conclude maintenance subanesthetic ketamine and esketamine treatment can be effective in sustaining antidepressant effect following remission. Furthermore, the pharmacological approach must be integrated with lifestyle interventions, especially aerobic exercise. Finally, combining pharma- and psychotherapy seems to improve outcome. Network and complexity sciences will help to decrease the high recurrence rates of MDD by developing more integrative and personalized approaches.

Differential effect of panic on the DNA methylation of the glucocorticoid receptor gene exon 1F in chronic subjective tinnitus with distress.

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.

Unlocking asylum seekers' voices: protocol of a mixed-method clinical study on the use of the cultural formulation interview with asylum seekers in Belgium.

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.

Cognitive performance among older adults with psychotic depression compared to non-psychotic depression.

It remains unclear whether psychotic depression (PD) compared to non-psychotic depression (non-PD) among older adults is associated with poorer cognitive performance. For inpatients (60+) with a major depressive episode, cognitive performance in PD and non-PD (categorical) were compared as well as the relationship between symptom severity for depression and psychosis (dimensional) and cognition. Of 90 participants (on average 72.7 years old; range 60-92), 64% were female. The severity of depressive- and psychotic symptoms are both negatively associated with cognitive functioning among older adults with depression. This is of relevance for the treatment of this vulnerable group of patients.

White matter changes following electroconvulsive therapy for depression: a multicenter ComBat harmonization approach.

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.

Cognitive trajectories during and after electroconvulsive therapy in patients with MDE: Taking different perspectives.

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.

Evaluation of a new online cognitive assessment tool in breast cancer survivors with cognitive impairment: a prospective cohort study.

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.

The Role of Kynurenines in Cognitive Dysfunction in Bipolar Disorder.

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.

Impaired Sensorimotor Adaption in Schizophrenia in Comparison to Age-Matched and Elderly Controls.

BACKGROUND: The "cognitive dysmetria hypothesis" of schizophrenia proposes a disrupted communication between the cerebellum and cerebral cortex, resulting in sensorimotor and cognitive symptoms. Sensorimotor adaptation relies strongly on the function of the cerebellum. OBJECTIVES: This study investigated whether sensorimotor adaptation is reduced in schizophrenia compared with age-matched and elderly healthy controls. METHODS: Twenty-nine stably treated patients with schizophrenia, 30 age-matched, and 30 elderly controls were tested in three motor adaptation tasks in which visual movement feedback was unexpectedly altered. In the "rotation adaptation task" the perturbation consisted of a rotation (30° clockwise), in the "gain adaptation task" the extent of the movement feedback was reduced (by a factor of 0.7) and in the "vertical reversal task," up- and downward pen movements were reversed by 180°. RESULTS: Patients with schizophrenia adapted to the perturbations, but their movement times and errors were substantially larger than controls. Unexpectedly, the magnitude of adaptation was significantly smaller in schizophrenia than elderly participants. The impairment already occurred during the first adaptation trials, pointing to a decline in explicit strategy use. Additionally, post-adaptation aftereffects provided strong evidence for impaired implicit adaptation learning. Both negative and positive schizophrenia symptom severities were correlated with indices of the amount of adaptation and its aftereffects. CONCLUSIONS: Both explicit and implicit components of sensorimotor adaptation learning were reduced in patients with schizophrenia, adding to the evidence for a role of the cerebellum in the pathophysiology of schizophrenia. Elderly individuals outperformed schizophrenia patients in the adaptation learning tasks.

Substance Use Disorders as a Critical Element for Decision-Making in Forensic Assertive Community Treatment: A Systematic Review.

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.

Movement, mood and cognition: Preliminary insights into the therapeutic effects of electroconvulsive therapy for depression through a resting-state connectivity analysis.

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for depression but how it achieves its clinical effects remains unclear. METHODS: We set out to study the brain's response to ECT from a large-scale brain-network perspective. Using a voxelwise analysis, we looked at resting-state functional connectivity before and after a course of ECT at the whole-brain and the between- and within-network levels in 17 patients with a depressive episode. Using a group-independent component analysis approach, we focused on four networks known to be affected in depression: the salience network (SN), the default mode network (DMN), the cognitive executive network (CEN), and a subcortical network (SCN). Our clinical measures included mood, cognition, and psychomotor symptoms. RESULTS: We found ECT to have increased the connectivity of the left CEN with the left angular gyrus and left middle frontal gyrus as well as its within-network connectivity. Both the right CEN and the SCN showed increased connectivity with the precuneus and the anterior DMN with the left amygdala. Finally, improvement of psychomotor retardation was positively correlated with an increase of within-posterior DMN connectivity. LIMITATIONS: The limitations of our study include its small sample size and the lack of a control dataset to confirm our findings. CONCLUSION: Our voxelwise data demonstrate that ECT induces a significant increase of connectivity across the whole brain and at the within-network level. Furthermore, we provide the first evidence on the association between an increase of within-posterior DMN connectivity and an improvement of psychomotor retardation, a core symptom of depression.

Inflammatory Markers May Inform the Effects of Electroconvulsive Therapy on Cognition in Patients with Depression.

INTRODUCTION: The neurobiological mechanisms underlying the acute cognitive effects of electroconvulsive therapy (ECT) remain poorly understood. Prior research has shown that proinflammatory cytokines such as IL-6, TNF-α, IL1-ß, and IL-10 may interfere with cognitive functioning. Interestingly, immunomodulation is one of the proposed modes of action of ECT. This study investigates whether changes of peripheral levels of IL-6, TNF-α, IL1-ß, and IL-10 are related to changes in cognitive functioning following ECT. METHODS: In the week before and 1 week after an acute course of ECT, 62 patients suffering from depression underwent a neuropsychological evaluation to assess their processing speed using the Symbol Digit Substitution Test (SDST), verbal episodic memory using the Hopkins Verbal Learning Test-Revised (HVLT-R), and their retrospective autobiographic memory using the Autobiographical Memory Interview (AMI) with the peripheral inflammatory markers being measured at the same 2 time points. RESULTS: Patients improved drastically following ECT, while their main performance on both the HVLT-R and AMI declined and their SDST scores remained stable. The levels of IL-6 and IL1-ß had both decreased, where the decrease in IL-6 was related to the decrease in HVLT-R scores. Higher baseline IL-10 levels were associated with a more limited decrease of the HVLT-R scores. CONCLUSION: Our findings tentatively suggest that the effects of ECT on verbal episodic memory may be related to the treatment's immunomodulatory properties, most notably due to decreased IL-6 levels. Moreover, baseline IL-10 appears to be a potential biomarker to predict the effects of ECT on verbal episodic memory. Whilst compelling, the results of this study should be interpreted with caution as, due to its exploratory nature, no correction for multiple comparisons was made. Further, a replication in larger cohorts is warranted.