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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.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

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., (Copyright © 2021. Published by Elsevier B.V.)

Background: Electroconvulsive therapy (ECT) is the most effective biological treatment for depression. Aside the well-known therapeutic effect on mood symptoms, it has also a unique positive impact on psychomotor agitation and retardation, which are core symptoms of depression. The neurobiology behind these effects, however, remains unclear. The basal ganglia are proposed to be important regions in the pathogenesis of psychomotor symptoms in depression. Since ECT can trigger neuroplasticity in these subcortical nuclei, we speculate that ECT-induced volumetric changes of the basal ganglia will positively influence psychomotor symptoms., Methods: Psychomotor symptoms were analyzed in 17 patients with severe depression before and after an acute ECT course using a CORE assessment of the retardation, agitation, and non-interaction domains. The volumes of the caudate, putamen, pallidum, and accumbens regions were determined using magnetic resonance imaging one week before and after ECT., Results: Psychomotor functions had improved significantly after ECT and significant volume increases were found for the accumbens region, the putamen, and pallidum. The volume increase of the nucleus accumbens correlated with an improvement of psychomotor retardation, while the volume increase of the pallidum correlated negatively with an improvement of the agitation subscore., Conclusion: Our findings support the notion of an association between the impact of ECT on depression-related psychomotor symptoms and volume increases of the accumbens region and pallidum, pointing to the importance of the basal ganglia in the therapeutic effect of ECT on psychomotor functioning., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Major Depressive Disorder (MDD) covers a wide spectrum of symptoms, including cognitive dysfunction, which can persist during remission. Both inflammatory states and psychosocial stress play a role in MDD pathogenesis., Methods: The effects of inflammatory (i.e., Salmonella typhi vaccine) and psychosocial stressor (i.e., Trier Social Stress Test), as well as their combination were investigated on cognition in women (aged 25-45 years, n = 21) with (partially) remitted MDD and healthy controls (n = 18) in a single-blind placebo-controlled study. In a crossover design, patients received on the first day one of the aforementioned interventions and on the other day a placebo, or vice versa, with a washout period of 7-14 days. Short-term and verbal memory, working memory, attention, verbal fluency, information processing speed, psychomotor function, and measures of attentional bias to emotions were measured. Exploratory analyses were performed to assess the correlation between biomarkers of inflammation and the Hypothalamic-Pituitary-Adrenal axis and cognitive functioning., Results: In patients, inflammatory stress decreased information processing speed and verbal memory, and increased working memory; after psychosocial stress, there was an increase in attention. There was also an increased negative attentional bias in patients after inflammatory stress. Neither stressor had any effect in controls., Limitiations: Limitations are the relatively small sample size and antidepressant use by a part of the participants. The effects of the stressors were also measured a relatively short period after administration., Conculsion: Patients were sensitive to the cognitive effects of inflammation and psychosocial stress on cognition, while controls were not., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The high prevalence of Problem Behaviours (PB) in persons with intellectual disability (ID) and Autism Spectrum Disorder (ASD) has been associated by some researchers to a proportionate frequency of Major Depressive Disorder (MDD), which have a different presentation in persons with ID and ASD than in the general population, mostly as behavioural changes. Nevertheless, evidence on this behavioural equivalency is still scarce. The present study aims at evaluating the rate of MDD in persons with ID and ASD presenting PB. Two groups of persons with mild-to-moderate ID and ASD, with and without PB underwent a complex clinical (Diagnostic Manual - Intellectual Disability) and instrumental (Reiss Screen for Maladaptive Behaviour; Mini Psychiatric Assessment Schedule for Adults with Developmental Disabilities). The prevalence of MDD was found to be significantly higher in the group with PB. The severity of depressive symptoms resulted to have a strong correlation with the scores of instrumental assessment of PB. Our findings support previous literature on a high association between PB and MDD in persons with ID and ASD. The level of the equivalency between specific MDD symptoms and different PB deserves further investigations., (Copyright © 2018. Published by Elsevier B.V.)

Disturbances in emotion regulation have been identified as a core feature of patients with a borderline personality disorder (BPD). Findings of studies using experimental measures of emotion processing are mixed, which may be partially explained by the heterogeneity of the BPD population. To address this issue, we investigated differences in experimental measures of emotional action tendencies (approach-avoidance behaviour) and attentional bias to emotional stimuli in BPD subtypes. Data of the Approach-Avoidance Task (AAT) and the Emotional Stroop Task (EST) were collected in 140 BPD patients, previously clustered into four BPD subtypes based on temperament dimensions. We investigated (1) the relationship between temperament dimensions and the performance on the AAT and EST and (2) compared performance on these tasks in previous defined BPD subtypes. The results of the present study demonstrated a positive relationship between effortful control (EC) and AAT effect-scores. A higher level of EC was positively associated with a general emotional action tendency towards faces with directed gaze, even when controlling for gender, age and BPD severity. Preliminary results on the comparison of the BPD subtypes demonstrated no significant differences in AAT and EST performance. These findings emphasize the relevance of EC in emotional action tendencies in BPD patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Cytokine level alterations suggest a role for the immune system in the pathophysiology of bipolar disorder (BD). Pharmacotherapy is an important confounding factor in clinical research on cytokine levels. In this systematic review we collate the evidence on blood cytokine levels in medication-free BD and the effects of single mood-stabilizing drugs on these levels., Methods: A systematic review was conducted according to the PRISMA statement. We searched the Pubmed and Embase databases for clinical studies reporting either on cytokine levels in medication-free BD or on the effects of single mood-stabilizing drugs on cytokine levels in BD., Results: Of the 564 articles screened, 17 were included. Fourteen articles report on medication-free patients with BD and indicate state-related cytokine alterations. Six articles discuss the effect of lithium. Whereas no data on short-term effects of lithium were found, ≥2 months lithium use in euthymic populations is associated with normal cytokine levels. Two studies report no effect of valproate and no studies were found on carbamazepine, lamotrigine or antipsychotics., Limitations: The available studies are characterized by a broad methodological heterogeneity and limited replication between studies., Conclusions: This systematic review suggests the presence of state-related cytokine level alterations in medication-free BD with most evidence pointing to a proinflammatory cytokine response in mania. Euthymia and long-term lithium use are associated with normal cytokine levels. To improve our understanding of the impact of mood-stabilizing drugs on cytokine levels, longitudinal studies with medication-free baseline, randomized controlled single-drug treatment protocols and close mood state monitoring are needed., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Schizophrenia is characterized by social deficits. Correctly monitoring own and others' performance is crucial for efficient social behavior. Deficits in monitoring own performance as reflected in reduced error-related negativity (rERN) amplitudes, have been demonstrated repeatedly in schizophrenia. A similar ERP component (observed ERN; oERN) is elicited when observing others' mistakes. However, possible deficits in monitoring others' performance have never been investigated in schizophrenia. The current ERP-study compared a group of schizophrenia patients (N=22) and healthy controls (N=21) while performing a Simon task and the social Simon task, enabling the investigation of own (rERN) and others' (oERN) performance monitoring. Patients showed slower reaction times, but comparable accuracy and compatibility effects in both tasks. As expected, patients' rERN amplitudes were reduced. Importantly however, oERN amplitudes were comparable between both groups. While monitoring own performance is compromised in schizophrenia, monitoring others' performance seems intact. This divergence between internal and external performance monitoring in patients is in line with studies showing normal neurophysiological responses to negative feedback. The presently found dissociation may improve our understanding of cognitive and neural mechanisms underlying monitoring of own and others' performance and may stimulate treatment development aimed at learning from external rather than internal error information in schizophrenia., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Although psychomotor retardation (PR) and cognitive disfunctioning are essential symptoms of elderly depressed patients, the differential effect of treatment with an SSRI in the elderly on these symptoms has hardly got any attention in studies with objective experimental measures. Since effects appear relatively slower in elderly, this study evaluates the effect on cognitive and psychomotor functioning as compared to mood, on four points during a twelve week follow up of monotreatment with escitalopram., Method: 28 non-demented elderly unipolar depressive patients on 5-20mg escitalopram were compared to 20 matched healthy elderly. All participants underwent a test battery containing clinical depression measures, cognitive measures of processing speed, executive function and memory, clinical ratings of PR, and objective computerized fine motor skill-tests at the start and after 2, 6 and 12 weeks. Statistical analysis consisted of a General Linear Model (GLM) repeated measures multivariate analysis of variance of completers to compare the psychomotor and cognitive outcomes of the two groups., Results: Although, apart from the significant mood effect, no interaction effects were found for the psychomotor and cognitive tasks, the means in general show a trend of differential effects in cognitive and psychomotor functions, with smaller effects and delayed timeframes and with presence of subgroups compared to mood effects., Limitation: Longer follow up studies are necessary to evaluate differential long term effects., Conclusion: In elderly, moderate effects of SSRI treatment on mood precede slow or limited effects on cognition and psychomotor retardation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: An important gender difference has been reported regarding suicidal behavior with an overrepresentation of females in nonfatal suicidal behavior and a preponderance of males in completed suicide, also known as the 'gender paradox of suicidal behavior'. The concept of a 'suicidal process' classifies suicidal behavior chronologically; this process starts with suicidal ideation and then implies a progression of suicidality ranging from suicidal ideation over plans to suicide attempts and finally fatal suicide., Aims/methods: The current paper aims to deepen the knowledge on the gender paradox by collecting and discussing the recent literature on this topic: the most relevant, impacting gender-related factors will be discussed within the suicidal process concept., Results: Several factors had a gender-dependent impact on suicidal behavior: psychosocial life stressors such as stressful life events but also sociodemographical or socio-economical factors, and sexual abuse. The gender differences in psychiatric (co)morbidity and in response to or attitude towards antidepressant treatment also appear to have an impact. Furthermore, not only suicide methods but also the gender-dependent variation in reporting suicide has an influence. Finally, the gender differences in help seeking behavior as well as region-dependent cultural beliefs and societal attitudes are discussed., Conclusions: Especially life-events seem to exert an important influence at the beginning of a suicidal process, whereas the other factors occur at a further stage in the process, however without a fixed chronology. Also, the duration of the suicidal process is much shorter in male than in females. Finally, some implications with regard to clinical practice and suicide prevention are suggested., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Although recent studies focusing on major depressive disorder (MDD) suggest altered social decision-making, studies using the Ultimatum Game (UG) in patients with severe, clinical MDD do not exist. Moreover, all aforementioned studies so far focused on responder behavior and thus fairness considerations; to this date, no one investigated social interactive behavior which involves proposer behavior possibly requiring second-order mentalizing as well., Methods: Thirty-nine MDD patients and 22 healthy controls played a modified UG, both in the roles of responder and proposer against the same partner., Results: MDD patients accepted both fair and unfair offers as many times as the healthy controls in their role as responder. Importantly, however, in the role of proposer MDD patients offered significantly more than the control group did., Limitations: Most patients were treated with psychotropic medication., Conclusions: Responder behavior demonstrates that MDD patients are capable of making social decisions on fairness considerations in the same way as healthy controls do. The observed proposer behavior, however, could indicate that MDD patients are more focused on avoiding rejection. These findings provide unique evidence that social decision-making--as studied in a realistic context--is disturbed in MDD., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Most research points to cognitive slowing in chronic fatigue syndrome (CFS), although there have been negative reports. The present study is one of few that examines fine motor processing and the inhibition of automatic responses in a well-characterised CFS population. A total of 35 female CFS patients without current major depression and 25 female controls performed two computerised figure-copying tasks. The cognitive and fine motor processing of visual-spatial information was measured by recording reaction time (RT) and movement time (MT), respectively. The inhibition of automatic responses was assessed by introducing 'conflicting patterns' (i.e., patterns that were difficult to draw from the preferred left to right). A multivariate general linear model was adopted for the statistical analysis of the movement recordings. As a result, CFS was significantly associated with longer RT and MT in the pooled and in the task-specific analyses. However, there was no interaction between disease status and conflicting character of the patterns. In conclusion, these performance data on the figure-copying tasks provide confirmatory evidence for psychomotor slowing in CFS, but not for a disturbed inhibition of automatic responses. Computerised figure-copying tasks may be promising tools for use in neurobiological research and clinical trials in CFS., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

In schizophrenia, psychomotor slowing and stereotypy are poorly delineated from cognitive deficits like diminished processing speed. Inpatients' performance outcomes on a line-copying task, a task assessing stereotypy and a processing-speed task are compared. Results suggested that psychomotor slowing and stereotypy are related and may represent a catatonic symptom cluster.

Background: Psychomotor disturbances have been described repeatedly over many centuries. More recently, Sobin and Sackeim [Sobin, C., Sackeim, H.A., 1997. Psychomotor symptoms of depression. Am. J. Psychiatry. 154, 4-17.] discussed the relevance of psychomotor symptoms in depression in an extensive review. Since their report, new pathophysiological, diagnostic and therapeutic findings have been published. In the current review of the recent literature, we aim to argue the importance of psychomotor symptoms in depression and propose directions for future research., Method: A review of all the relevant reports on this topic, published between 1996 and 2006, was conducted., Results: Several assessment methods demonstrate the diagnostic and pathophysiological significance of psychomotor symptoms. Antidepressants show differential effects on psychomotor performance and findings concerning the symptoms' predictive capacity for clinical response are contradictory. Numerous imaging studies as well as studies on the neurotransmitter systems and the HPA-axis contribute to the elucidation of the neurobiological processes underlying impaired psychomotor functioning in depression., Conclusions: Psychomotor disturbances are of great diagnostic significance for the depressive subtype of melancholia. To enhance the conceptualisation of the construct 'psychomotor' a standardised battery for their assessment is recommended. As to the symptoms' predictive therapeutic power, to date research into functional outcome and studies applying objective experimental assessment methods are lacking. Moreover, the reported pathophysiological importance of dopamine for 'retarded depression' still warrants translation to the daily practice.

Corticotropin-releasing factor-binding protein (CRF-BP) regulates the availability of free CRF and is a functional candidate gene for affective disorders. Previous research showed an association between polymorphisms in the CRF-BP gene and recurrent major depression (MDD) in a Swedish sample. The purpose of the current study was to re-evaluate the previous findings in an extended Swedish sample and in an independent Belgian sample of patients with recurrent MDD and in control samples. In total, 317 patients and 696 control individuals were included. Five single nucleotide polymorphisms (SNPs) and a deletion polymorphism in the CRF-BP gene were genotyped and the haplotype block structure of the gene was assessed. In the extended Swedish population, there was a trend towards an association between two SNPs and MDD. The subsequent gender analysis showed significant associations of three SNPs (CRF-BPs2 T; CRF-BPs11 T and CRF-BPs12 C) and haplotype G_T_C_T_C with MDD in Swedish males. However, these findings did not withstand correction for multiple testing and there were no significant SNP or haplotype associations in the Belgian MDD sample. In conclusion, this study does not provide confirmatory evidence for a role of the CRF-BP gene in the vulnerability for MDD in general. The association between genetic CRF-BP variants and MDD may be sexually dimorphic, but this issue requires further investigation in a larger sample.

Humans need to monitor their actions continuously to detect errors as fast as possible and to adjust their performance to prevent future errors. This process of action monitoring can be investigated by measuring the error-related negativity (ERN), an ERP component elicited immediately after an error. In the current study, we investigated action monitoring after administration of the classic antipsychotic haloperidol (2.5 mg), the atypical antipsychotic olanzapine (10 mg), and the antidepressant paroxetine (20 mg), a selective serotonin reuptake inhibitor. Healthy volunteers (N = 14) were administered the three compounds and placebo in a randomized, double-blind, single-dose, four-way cross-over design. All participants performed a speeded two-choice reaction task, while event-related potentials and behavioral measurements were obtained. Both haloperidol and olanzapine significantly reduced ERN amplitudes. After paroxetine, the ERN was not different from placebo. N2 congruency effects were not affected by treatment condition. Only olanzapine demonstrated behavioral effects, namely a slowing of responses, an increase in error rates, and the absence of performance adjustments. The attenuated ERNs after the dopamine antagonist haloperidol are in line with the presumed role of dopamine in action monitoring. Haloperidol is thought to block dopaminergic signaling, thus reducing ERN amplitudes. On the other hand, the effects of olanzapine are mainly caused by its sedative side effects, leading to a decline in motivation and appraisal of errors. Finally, the absence of any effects after paroxetine suggests that serotonin transmission does not play a direct role in regulating mechanisms related to action monitoring.

Background: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a prominent neurobiological finding during a major depressive episode, reflecting a state dependent factor. An issue under investigation is whether the dysfunction of the HPA axis has also a role to play as a state-independent or trait factor for major depressive disorder (MDD). In relation to this, it is important to examine HPA axis function in patients who are clinically remitted from depression., Methods: Twenty-three remitted outpatients with recurrent MDD and 23 age- and gender-matched control individuals without a history of MDD participated in the sensitive combined dexamethasone/corticotropin-releasing factor (DEX/CRF) test., Results: Free salivary cortisol responses were not significantly different between the two groups, although three patients (13%) displayed extremely elevated cortisol responses after CRF., Limitations: Limited sample size. All but one patient were under treatment with an antidepressant., Conclusions: This study shows no evidence for a disturbed DEX/CRF test as a state-independent factor in recurrent MDD on a group level. However, MDD is a complex and heterogenic disorder. Probably, there is a subgroup of patients who show a disturbed DEX/CRF test due to an inherited and/or acquired predisposition or as a biological scar after previous depressive episodes.

Background: Depressed individuals display a deficit in effectively solving social problem situations (e.g., []). Recent research suggests that rumination may interfere with such effective problem-solving (e.g., []). However, little is known, as yet, about the mechanisms that are underlying this relation between rumination and poor problem-solving. The present study investigated the role of reduced specificity of autobiographical memories as a mediator of this relationship., Methods: 24 depressed patients (15 women) completed the Autobiographical Memory Test (AMT), the Means-Ends Problem-Solving Task (MEPS), the Ruminative Response Scale (RRS) and the Rumination on Sadness Scale (RSS)., Results: Consistent with previous studies, rumination, ineffective problem-solving and reduced memory specificity were significantly associated. Regression analyses further extended these findings by showing that reduced memory specificity mediated the association between rumination and problem-solving effectiveness., Limitations: The correlational nature of this study limits to some extent the conclusions that can be drawn on the directionality of the observed relationships., Conclusions: Results offer support for the idea that lack of autobiographical memory specificity mediates the known relationship between rumination and poor problem-solving.

The oral administration of a single dose of levodopa (L-dopa) in 10 healthy human male subjects induced cognitive, not motor, changes during figure-copying tasks that were unrelated to the neuroendocrine and behavioural effects of levodopa. Results point to a decrease in alertness induced by levodopa.