Circadian rhythms in the sleep/wake cycle, along with a range of physiological measures, are severely disrupted in individuals with major depressive disorder (MDD). Moreover, several central circadian genes have been implicated as potential genetic factors underlying the illness through candidate gene studies and some genome wide association studies. However, investigations into the molecular underpinnings of circadian disturbances in the human brain have been quite challenging. In their recent publication, Li and colleagues have used a novel approach to determine the rhythmic (...) patterns of circadian gene expression in several regions of the human brain, and how these patterns are disrupted in MDD. Their findings demonstrate that in healthy subjects, several brain regions outside the suprachiasmatic nucleus (the master clock) exhibit diurnal gene expression patterns that are disrupted in the brains of MDD subjects. These findings will provide the foundation for future studies of gene‐specific drug targets, and biomarkers for the disease. (shrink)

The lifetime prevalence of major depressive disorder in adolescents is reported to be as high as 20%; thus, MDD constitutes a significant social and public health burden. MDD is often associated with nonsuicidal self-injury behavior, but the contributing factors including cognitive function have not been investigated in detail. To this end, the present study evaluated cognitive impairment and psychosocial factors in associated with MDD with NSSI behavior. Eighteen and 21 drug-naïve patients with first-episode MDD with or without NSSI and 24 (...) healthy control subjects were enrolled in the study. The Hamilton Anxiety Scale, Hamilton Depression Scale, Adolescent Self-injury Questionnaire, Beck Scale for Suicide Ideation–Chinese Version, Shame Scale for Middle School Students, Sensation Seeking Scale and Childhood Trauma Questionnaire were used to assess depression-related behaviors, and event-related potentials were recorded as a measure of cognitive function. The latency of the N1, N2, P3a, P3b, and P50 components of ERPs at the Cz electrode point; P50 amplitude and P50 inhibition showed significant differences between the 3 groups. CTQ scores also differed across three groups, and the NSSI– and NSSI+ groups showed significant differences in scores on the Shame Scale for Middle School Students. Thus, cognitive function was impaired in adolescents with MDD with NSSI behavior, which was mainly manifested as memory decline, attention and executive function deficits, and low anti-interference ability. We also found that childhood abuse, lack of social support, and a sense of shame contributed to NSSI behavior. These findings provide insight into the risk factors for MDD with NSSI behavior, which can help mental health workers more effectively diagnose and treat these patients. (shrink)

Research on the neurobiology and psychosocial features of Major Depressive Disorder has the ability to extend our understanding of affiliative behavior. In depression, decreased hedonic capacity and hypoactivity in dopaminergic and prefrontal circuitries may decrease the ability to experience affiliative relationships as rewarding. We suggest that neurobiological research on depression can provide a test case for theoretical models of affiliation.

Research on electroencephalogram (EEG) characteristics associated with major depressive disorder (MDD) has accumulated diverse neurophysiologic findings related to the content, topography, neurochemistry, and functions of EEG oscillations. Significant progress has been made since the first landmark EEG study on affective disorders by Davidson 35 years ago. A systematic account of these data is important and necessary for building a consistent neuropsychophysiologic model of MDD and other affective disorders. Given the extensive data on frequency-dependent functional significance of EEG oscillations, a frequency (...) domain approach may reveal the types of brain functions involved and disturbed in MDD. In this review, we systematize and integrate diverse and often unconnected observations on the content, topography, neurochemistry, and functions of EEG oscillations involved in MDD within the general concept of an EEG oscillatory pattern. (shrink)

Major depression is a prevalent mental disorder that leads to persistent negative mood and tremendous suffering in affected individuals. However, the biological realization of this disorder and associated symptom clusters remain poorly understood. Recently, phenomenological accounts of major depressive disorder and contributions to the emerging predictive processing account have provided valuable insights into the phenomenological and neuro-functional components that lead to manifestations of major depressive episodes. The purpose of this paper is to weave together these different strands of research (...) to develop a predictive processing account of major depressive disorder. In doing so, I will relate personal-level descriptions of associated phenomenal experiences to a sub-personal-level predictive processing account of the functional realization of major depression. I will argue that pervasive symptoms of the disorder, which include a diminished sense of agency, fatigue, social withdrawal, and rumination, are integrated by existential feelings of loss and impossibility. These phenomenal experiences, I will argue, are associated with dysfunctional processes of prediction error minimization, which are characterized by an overall decrease of the causal contributions of active inference and by distorted precision estimates. The emerging account promises to contribute to a better understanding of the complex processes that give rise to depressive experiences. (shrink)

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did (...) not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression. (shrink)

The use of placebo as a control condition in clinical trials of major depressive disorder and anxiety disorders continues to be an area of ethical concern. Typically, opponents of placebo controls argue that they violate the beneficent-based, “best proven diagnostic and therapeutic method” that the original Helsinki Declaration of 1964 famously asserted participants are owed. A more consequentialist, oppositional argument is that participants receiving placebo might suffer enormously by being deprived of their usual medication(s). Nevertheless, recent findings of potential for (...) suicidality in young people treated with antidepressants, along with meta-analyses suggesting that antidepressants add no significant clinical benefit over placebos, warrant a re-evaluation of the arguments against placebo. Furthermore, the nature of placebo treatment in short-term clinical trials is often not well understood, and lack of understanding can foster opposition to it. This paper will show how scientific justifications for placebo use are morally relevant. The fundamental ethical importance of placebo controls is discussed in relation to several aspects of clinical trials, including detection of adverse events, accurate assessment of clinical benefit, advancing understanding of the heterogeneity of depression and anxiety disorders and respecting informed consent requirements. Prohibiting the use of placebo controls is morally concerning in that such prohibitions allow for the possibility of serious adverse public health consequences. Moral worries that research participants receiving placebo are being unduly jeopardised will be shown to be exaggerated, especially in relation to the net benefits for end-users to be gained from the quality of data resulting from using placebo controls. (shrink)

Ongoing electroencephalography signals are recorded as a mixture of stimulus-elicited EEG, spontaneous EEG and noises, which poses a huge challenge to current data analyzing techniques, especially when different groups of participants are expected to have common or highly correlated brain activities and some individual dynamics. In this study, we proposed a data-driven shared and unshared feature extraction framework based on nonnegative and coupled tensor factorization, which aims to conduct group-level analysis for the EEG signals from major depression disorder patients (...) and healthy controls when freely listening to music. Constrained tensor factorization not only preserves the multilinear structure of the data, but also considers the common and individual components between the data. The proposed framework, combined with music information retrieval, correlation analysis, and hierarchical clustering, facilitated the simultaneous extraction of shared and unshared spatio-temporal-spectral feature patterns between/in MDD and HC groups. Finally, we obtained two shared feature patterns between MDD and HC groups, and obtained totally three individual feature patterns from HC and MDD groups. The results showed that the MDD and HC groups triggered similar brain dynamics when listening to music, but at the same time, MDD patients also brought some changes in brain oscillatory network characteristics along with music perception. These changes may provide some basis for the clinical diagnosis and the treatment of MDD patients. (shrink)

Background: The vascular depression hypothesis emphasizes the significance of vascular lesions in late-life depression. At present, no meta-analytic model has investigated whether a difference in hyperintensity burden compared to controls between late-life and late-onset depression is evident. By including a substantial number of studies, focusing on a meaningful outcome measure, and considering several moderating and control variables, the present meta-analysis investigates the severity of hyperintensity burden in major depressive disorder (MDD) and bipolar disorder (BD). A major focus (...) of the present meta-analysis refers to the role of age at illness onset. It is analyzed whether late-onset rather than late-life depression characterizes vascular depression. Method: In total, 68 studies were included in the meta-analysis and a multilevel random effects model was calculated using Hedges’ g as the effect size measure. Results: The severity of hyperintensity burden was significantly greater in the patient group compared to the control group. This effect was evident regarding the whole patient group (g = 0.229) as well as both depression subgroups, with a significantly greater effect in BD (g = 0.374) compared to MDD (g = 0.189). Hyperintensity burden was more pronounced in late-onset depression than in early-onset depression or late-life depression. A considerable heterogeneity between the included studies was observed, which is reflected by the large variability in effects sizes. Conclusion: In conclusion, the present meta-analysis underscores the association of hyperintensities with MDD and BD. Especially late-onset depression is associated with an increased hyperintensity burden, which is in line with the vascular depression hypothesis. The results suggest that it might be more feasible to confine the concept of vascular depression specifically to late-onset depression as opposed to late-life depression. Further research is needed to understand the causal mechanisms that might underlie the relation between hyperintensity burden and depression. (shrink)

After the publication of third edition of the Diagnostic and Statistical Manual of Mental Disorders in 1980, psychiatry no longer characterized psychological problems as 'reactions,' which seemed to assume unproven psychoanalytically derived explanations, and referred to them instead as 'disorders,' which, it was thought, could be identified phenomenologically and without theoretical 'presuppositions.' Since then, psychiatrists have typically made diagnoses without reflecting on the fact that any categorization, including psychiatric diagnosis, exists within a framework of beliefs and practices and will, therefore, (...) have implications and consequences. The fact of making a diagnosis, the act of doing so... (shrink)

Psychedelic-assisted Psychotherapy combines the use of psychedelic compounds, such as psilocybin, with psychotherapy. PAP has shown some promise as a novel treatment for Major Depressive Disorder, and empirical research suggests that its efficacy turns on the altered states induced by psychedelic compounds. In this paper we draw on the literature of phenomenology to explain the therapeutic potential of psychedelic experiences. Svenaeus characterises mental illness as a form of suffering that entails three distinct but related experiences of alienation or “unhomelike being-in-the-world”: (...) illness suffering, which relates to embodiment; existential suffering, which relates to self-narratives, and political suffering, which relates to social relationships. Ratcliffe further characterises the experience of MDD in phenomenological terms as a loss of pre-intentional possibility that manifests as excessive noematic feeling in the experience of embodiment, restrictive narratives in the construction of self, and disconnectedness in experience of the social world. We contend that PAP ameliorates the suffering associated with MDD by inducing and consolidating a state of broadened pre-intentional possibility—one that entails sudden, profound and enduring changes in embodiment, self-narratives, and social experience. We argue further that this phenomenological account is consistent with a bio-psycho-social model of mental health and illness, and we frame it as an argument supporting the plausibility of recent claims about treatment success. This helps to justify ongoing future empirical research in this setting. (shrink)

Based on previous studies implicating increased functional connectivity within the self-referential brain network in major depressive disorder (MDD), and considering the functional roles of three distinct modules of such brain net (responsible for three-dimensional components of Selfhood) together with the documented abnormalities of self-related processing in MDD, we tested the hypothesis that patients with depression would exhibit increased connectivity within each module of the self-referential brain network and that the strength of these connections would correlate positively with depression (...) severity. Applying the electroencephalogram (EEG) operational synchrony analysis to extract three modules of the self-referential brain network in 12 medication-free depressive outpatients and 10 control subjects we have found an increase in the strength of EEG synchrony within all three modules in depressive patients (though non-significant for the right module). Furthermore, multiple regression analysis that used 3 factors (values of synchrony strength for all three modules) as input indicated that combined increase in the strength of synchrony in all three modules was positively associated with severity of depression. Taken together the findings of this study suggest that depression is primarily associated with hypersynchrony in all three modules of the brain self-referential network (the anterior module been responsible for “witnessing observation and first–person perspective”, the left posterior module been responsible for “reflective agency and narration” and the right posterior module been responsible for “bodily representational-emotional agency”), thus contributing to excessive self-focus, rumination, and body tension. (shrink)

Anxious major depressive disorder is a common subtype of major depressive disorder; however, its unique neural mechanism is not well-understood currently. Using multimodal MRI data, this study examined common and specific alterations of amygdala subregions between patients with and without anxiety. No alterations were observed in the gray matter volume or intra-region functional integration in either patient group. Compared with the controls, both patient groups showed decreased functional connectivity between the left superficial amygdala and the left putamen, and between the (...) right superficial amygdala and the bilateral anterior cingulate cortex and medial orbitofrontal cortex, while only patients with anxiety exhibited decreased activity in the bilateral laterobasal and superficial amygdala. Moreover, the decreased activity correlated negatively with the Hamilton depression scale scores in the patients with anxiety. These findings provided insights into the pathophysiologic processes of anxious major depressive disorder and may help to develop new and effective treatment programs. (shrink)

We examined amygdala subregion volumes in patients with a first episode of major depression and in healthy subjects. Covariate-adjusted linear regression was performed to compare the MD and healthy groups, and adjustments for age, gender, and total estimated intracranial volume showed no differences in amygdala subregion volumes between the healthy and MD groups. Within the MD group, we examined the association between amygdala subregion volume and the 17-item Hamilton Rating Scale for Depression score and the HAMD subscale score, (...) and found no association in the left amygdala. In the right amygdala, however, there was an inverse linear association between the HAMD total and the HAMD core and lateral nucleus and anterior-amygdaloid-regions. Furthermore, an inverse linear association was seen between the HAMD psychic and the lateral nucleus, anterior-amygdaloid-regions, transition, and whole amygdala. The findings of this study suggest that the severity of MD and some symptoms of MD are associated with right amygdala volume. There have been few reports on the relationship between MD and amygdala subregional volume, and further research is needed to accumulate more data for further validation. (shrink)

Immediately before the release of DSM-5, a group of psychiatric thought leaders published the results of field tests of DSM-5 diagnostic criteria. They characterized the interrater reliability for diagnosing major depressive disorder by two trained mental health practitioners as of “questionable agreement.” These field tests confirmed an open secret among psychiatrists that our current diagnostic criteria for diagnosing major depressive disorder are unreliable and neglect essential experiences of persons in depressive episodes. Alternative diagnostic criteria exist, but psychiatrists rarely encounter them, (...) forestalling the discipline’s epistemological crisis. In Alsadair MacIntyre’s classic essay, such crises occur in science when a person encounters a rival schemata that is incompatible with their current schemata and subsequently constructs a narrative that allows them to reconstruct their own tradition. In search of rival schemata that are in conversation with their own tradition, psychiatric practitioners can utilize alternative diagnostic criteria like the Cultural Formulation Interview, embrace an epistemologically humble psychiatry, and attend to the narrative experience of a person experiencing a depressive episode. (shrink)

Previous studies have provided evidence that automatic emotion regulation, which is primed by control goals, can change emotion trajectory unconsciously. However, the cognitive mechanism and associated changes in depression remain unclear. The current study aimed to examine whether subliminal goal priming could change the emotional response inhibition among patients with major depressive disorder and their healthy controls. A group of patients with depression and a healthy control group were both primed subliminally by playing control goal related or neutral (...) words for 20 ms each; afterward, they judged the gender of happy or angry faces in an emotional Go/No-Go task. A group of depressed patients and a healthy control group both were both primed subliminally with control goal-related words or neutral words, and they judged the gender of happy or angry faces in an emotional Go/No-Go task. Among patients with depression, there were fewer false alarms of the No-Go response to emotional stimulus after priming with control goal rather than neutral words. Meanwhile, patients with MDD in the subliminal regulation goal priming condition reacted faster to happy rather than angry faces; no significant difference was found in the subliminal neutral priming condition. These findings suggest the malleability of inhibitory control in depression using subliminal priming goals. (shrink)

Major depressive disorder (MDD) is a severe mental illness that affects 5 to 20% of the general population. Current antidepressant drugs exerts only a partial clinical efficacy because approximately 30% of depressed patients failed to respond to these drugs and antidepressants produce remission only in 30% of patients. This can be explained by the fact that the complex pathophysiology of depression has not been completely elucidated, and treatments have been mainly developed following the “monoaminergic hypothesis” of depression without (...) considering the key role of other factors involved in the pathogenesis of MDD, such as the role of chronic stress and neuroinflammation. Chronic stress acts as a risk factor for the development of MDD through the impairment of neurotrophins signaling such as brain-derived neurotrophic factor (BDNF) and transforming-growth-factor-β1 (TGF-β1). Stress-induced depressive pathology contributes to altered BDNF level and function in MDD patients and, thereby, an impairment of neuroplasticity at the regional and circuit level. Recent studies demonstrate that aerobic exercise strongly increases BDNF production and it may contribute as a non-pharmacological strategy to improve the treatment of cognitive and affective symptoms in MDD. Here we will provide a general overview on the possible synergism between physical activity and antidepressants in MDD. Physical activity can synergize with antidepressant treatment by rescuing neurotrophin signaling in MDD patients, promoting neuronal health and recovery of function in MDD-related circuits, finally enhancing pharmacotherapeutic response. This synergism might be particularly relevant in elderly patients with late-life depression, a clinical subgroup with an increased risk to develop dementia. (shrink)

Electroencephalography (EEG) is a non-invasive method to identify markers of treatment response in major depressive disorder (MDD). In this review, existing literature was assessed to determine how EEG markers change with different modalities of MDD treatments, and to synthesize the breadth of EEG markers used in conjunction with MDD treatments. PubMed and EMBASE were searched from 2000 to 2021 for studies reporting resting EEG (rEEG) and transcranial magnetic stimulation combined with EEG (TMS-EEG) measures in patients undergoing MDD treatments. The search (...) yielded 966 articles, 204 underwent full-text screening, and 51 studies were included for a narrative synthesis of findings along with confidence in the evidence. In rEEG studies, non-linear quantitative algorithms such as theta cordance and theta current density show higher predictive value than traditional linear metrics. Although less abundant, TMS-EEG measures show promise for predictive markers of brain stimulation treatment response. Future focus on TMS-EEG measures may prove fruitful, given its ability to target cortical regions of interest related to MDD. (shrink)

Schuklenk and van de Vathorst's paper is a very welcome addition to the literature on the assisted dying debate and will be of great interest to clinicians working in the field of mental health.1 Many psychiatrists will have had patients who have asked them to allow them to die, to desist in their efforts to prevent their suicide, and one of us has had personal experience, outside of professional life, of being asked to aid in someone's attempt to end their (...) life in the context of an episode of mood disorder. The person with depression asking professionals, friends and family members to aid them in ending their life is a very real phenomenon. In their discussion, Schuklenk and van de Vathorst's paper uses two principles that we endorse and add weight to their argument: namely, the reality of suffering in depression and the parity of mental and physical illness. Indeed, the case Schuklenk and van de Vathorst make is a strong one and our commentary will focus on the premise of the argument around choosing death and some empirical clarification about competence in depression and the nature of treatment-resistant depression (TRD) and its prognosis. The conceptual concern we wish to discuss in relation to assisted dying, endorsed by the state and legislature, is not linked to any moral or religious concern, or even on grounds related to ‘slippery slope’ or ‘abuse’ arguments. Rather the worry is how one could operationalise decisions around assisted dying as based on competence and capacity and view such decisions as rational. I think this concern is not limited to depressive illness, but to all decisions regarding choosing non-existence. Schuklenk and van de Vathorst offer the following useful criteria to regulate assisted suicide:1. (shrink)

Several decades of research converge on the formulation that individuals diagnosed with major depressive disorder exhibit negative biases in their processing of emotional information. It is becoming increasingly clear, however, that traditional between-group comparisons have obscured the substantial heterogeneity of cognitive and affective dysfunction that is associated with depressive symptomatology. In this article, we review the findings of research examining attention to and memory for negative emotional information using a more dimensional perspective on depression. Specifically, we explore studies that (...) assess cognitive biases along a continuum of depressive symptom severity and consider the influence of co-occurring dimensions of functioning, in particular the severity of anxiety symptoms. Finally, we identify critical empirical questions and issues in this growing literature. (shrink)

The neurotransmitters GABA and glutamate have been suggested to play a role in Major Depressive Disorder (MDD) through an imbalance between cortical inhibition and excitation. This effect has been highlighted in higher brain areas, such as the prefrontal cortex, but has also been posited in basic sensory cortices. Based on this, magnetic resonance spectroscopy (MRS) was used to investigate potential changes to GABA+ and glutamate+glutamine (Glx) concentrations within the occipital cortex in MDD patients (n = 25) and healthy controls (n (...) = 25). No difference in occipital GABA+ or Glx concentrations, nor in the GABA+/Glx ratio, was found between groups. An analysis of an extended MDD patient and unmatched control dataset (n = 90) found no correlation between metabolite concentrations and depressive symptoms. These results were integrated with prior studies through metabolite-specific meta-analyses, revealing no difference in occipital GABA and Glx concentrations between patients and controls. An effect of publication year on GABA group differences was found, suggesting that previously reported results may have been artifacts of measurement accuracy. Taken together, our results suggest that, contrary to some prior reports, MRS measurements of occipital GABA and Glx do not differ between MDD patients and controls. (shrink)

Major depressive disorder is a highly prevalent psychiatric disorder, and recurrent depression is associated with severe and chronic impairment. Identifying markers of risk is imperative to i...

We propose the “microbiota‐inflammasome” hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long‐lasting feelings of sadness). We hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro‐inflammatory pathways mediated by the Nod‐like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further compounds gut (...) dysbiosis. In this review we describe MDD/chronic stress‐induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive‐like behavior and gut microbiota composition. The implication is that novel therapeutic strategies could emerge for MDD and co‐morbid conditions. A number of testable predictions surface from this microbiota‐gut‐inflammasome‐brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change. (shrink)

Nowadays, the major depressive disorder is a common disease that negatively affects the life quality of many people around the world. As MDD symptoms are closely related with the changes in food and eating, the relation between patients’ emotional responses and food tastes could be used as criteria for diagnostic. Until now, studies on the emotional response to different food tastes for patients affected by MDD have been poorly described in literature. Therefore, the aim of this study was to evaluate (...) the emotional response of patients suffering from MDD to the imagined different food tastes and to compare the results with a control group. Emotional responses in tested participants were induced by using cards with words of basic food tastes such as “sweet,” “salty,” “bitter,” “sour,” and “neutral.” The assessment of emotional response was performed with FaceReader 6 software. The outcome of this study showed that participants with MDD expressed lower “happy” and “contempt” and higher “surprised” emotions, along with a higher negative valence mean, in comparison with controls for all tested basic tastes of food. When Likert scale was used, significant differences in response were only found for “sour” and “salty” imaginary tastes between healthy group and patients with MDD. The findings of this study provide the additional data on food–associated emotion analysis of MDD patients and could be useful for the further development of the contactless method for early diagnosis of MDD. (shrink)

Researchers have been interested in what retrieval process is responsible for overgeneral autobiographical memories (OGM) in depression. Previous cross-sectional studies demonstrated that, for negatively valenced cues, directly retrieved OGM, rather than generatively retrieved OGM, are associated with depression. However, longitudinal evidence of this relationship is still lacking and needs to be tested. We conducted a re-analysis of the online computerised memory specificity training (c-MeST) data to examine whether directly retrieved OGM for negative cues prospectively predicts high levels of (...) depression 1 month later. Participants who met the criteria of current major depressive disorders (N = 116; n = 58 in the c-MeST group and n = 58 in the control group) recalled autobiographical memories for positive and negative cues and judged each retrieval process (i.e. direct or generative). The results supported our prediction, and directly retrieved OGM for negative cues predicted high levels of depressive symptoms 1 month later even after controlling for the group effect, baseline depressive symptoms, executive functioning and rumination. Exploratory analysis showed that direct retrieval of specific memories prospectively predicted low levels of depression. These results support the theory that elevated accessibility of negatively valenced general memory representations is a vulnerability factor for depressive symptoms. (shrink)

BackgroundRecurrent Major Depressive Disorder is one of the most disabling mental disorders in modern society. Prior research has shown that self-compassion protects against ruminative tendencies, a key feature of recurrent MDD. In addition, self-compassion has been found to be positively related to higher psychophysiological flexibility in young, healthy adults. To our knowledge, there is a lack of studies on how self-compassion relates to vmHRV in patients with recurrent MDD. The aim of the current study was to investigate whether higher self-compassion (...) would associate with lower ruminative tendencies and higher vmHRV in a sample of adults with recurrent MDD.MethodsWe included a sample of 63 patients between 20 and 71 years old with a history of three or more depressive episodes. They filled out the Self-Compassion Scale, Beck Depression Inventory, and Rumination Rating Scale. ECG was acquired while resting and the square root of the mean squared differences of successive RR interval values was calculated as measure of vmHRV.ResultsAs hypothesized, self-compassion was associated with lower ruminative tendencies. However, self-compassion was not associated with level of vmHRV. Several confounding variables were controlled for in the statistical analyses, and higher age predicted lower vmHRV across all statistical analyses.ConclusionThe results confirmed our hypothesis that higher self-compassion would be associated with lower ruminative tendencies in recurrent MDD. Contrary to our expectation, we did not find that the tendency to be more self-compassionate was associated with higher vmHRV. As such, higher self-compassion seems to relate with a lower tendency to ruminate about past mistakes and events but does not seem to relate to a flexible autonomic stress response. Other potential explanatory factors for lower vmHRV in recurrent MDD is suggested as focus for exploration in future studies. (shrink)

Background: Frailty is a common syndrome among older adults and patients with several comorbidities. Grip strength is a representative parameter of frailty because it is a valid indicator of current and long-term physical conditions in the general population and patients with severe mental illnesses. Physical and cognitive capacities of people with SMIs are usually impaired; however, their relationship with frailty or social functioning have not been studied to date. The current study aimed to determine if GS is a valid predictor (...) of changes in cognitive performance and social functioning in patients with type-2 diabetes mellitus and SMIs. Methods: Assessments of social functioning, cognitive performance, and GS were conducted in 30 outpatients with type 2 diabetes mellitus, 35 with major depressive disorder, 42 with bipolar disorder, 30 with schizophrenia, and 28 healthy controls, twice during 1-year, follow-up period. Descriptive analyses were conducted using a one-way analysis of variance for continuous variables and the chi-squared test for categorical variables. Differences between groups for the motor, cognitive, and social variables at T1 and T2 were assessed using a one-way analysis of covariance, with sex and age as co-variates. To test the predictive capacity of GS at baseline to explain the variance in cognitive performance and social functioning at T2, a linear regression analysis was performed. Results: Predictive relationships were found among GS when implicated with clinical, cognitive, and social variables. These relationships explained changes in cognitive performance after one year of follow-up; the variability percentage was 67.7%, in patients with type-2 diabetes mellitus and 89.1% in patients with schizophrenia. Baseline GS along with other variables, also predicted changes in social functioning in major depressive disorder, bipolar disorder, and schizophrenia, with variability percentages of 67.3, 36, and 59%, respectively. Conclusion: GS combined with other variables significantly predicted changes in cognitive performance and social functioning in people with SMIs or type-2 diabetes mellitus. Interventions aimed to improve the overall physical conditions of patients who have poor GS could be a therapeutic option that confers positive effects on cognitive performance and social functioning. (shrink)

Objective: The aim of the study was to identify clinical variables associated with changes in specific domains of self-reported depression during treatment by antidepressant and/or repetitive Transcranial Magnetic Stimulation in patients with Major Depressive Disorder.Methods: Data from a trial involving 170 patients with MDD receiving either venlafaxine, rTMS or both were re-analyzed. Depressive symptoms were assessed each week during the 2 to 6 weeks of treatment with the 13-item Beck Depression Inventory. Associations between depression changes on BDI13 (...) domains, treatment arm, time, and clinical variables were tested in a mixed linear model.Results: A significant decrease of self-reported depressive symptoms was observed over time. The main characteristics associated with persistent higher depressive symptomatology on Negative Self-Reference domain of the BDI13 were personality disorders, a past history of suicide attempt, age under 65 years old, and female sex.Conclusions: Early cognitive intervention targeting specifically negative self-referencing process could be considered during pharmacological or rTMS treatment for patients with personality disorders and past history of suicide attempt. (shrink)

Several functional magnetic resonance imaging studies have demonstrated abnormalities in static intra- and interhemispheric functional connectivity among diverse brain regions in patients with major depressive disorder. However, the dynamic changes in intra- and interhemispheric functional connectivity patterns in patients with MDD remain unclear. Fifty-eight first-episode, drug-naive patients with MDD and 48 age-, sex-, and education level-matched healthy controls underwent resting-state fMRI. Whole-brain functional connectivity, analyzed using the functional connectivity density approach, was decomposed into ipsilateral and contralateral functional connectivity. We computed (...) the intra- and interhemispheric dynamic FCD using a sliding window analysis to capture the dynamic patterns of functional connectivity. The temporal variability in functional connectivity was quantified as the variance of the dFCD over time. In addition, intra- and interhemispheric static FCD patterns were calculated. Associations between the dFCD variance and sFCD in abnormal brain regions and the severity of depressive symptoms were analyzed. Compared to HCs, patients with MDD showed lower interhemispheric dFCD variability in the inferior/middle frontal gyrus and decreased sFCD in the medial prefrontal cortex/anterior cingulate cortex and posterior cingulate cortex/precuneus in both intra- and interhemispheric comparisons. No significant correlations were found between any abnormal dFCD variance or sFCD at the intra- and interhemispheric levels and the severity of depressive symptoms. Our results suggest intra- and interhemispheric functional connectivity alterations in the dorsolateral prefrontal cortex and default mode network regions involved in cognition, execution and emotion. Furthermore, our study emphasizes the essential role of altered interhemispheric communication dynamics in the DLPFC in patients with MDD. These findings contribute to our understanding of the pathophysiology of MDD. (shrink)

The neuromodulatory effects of brain stimulation therapies notably involving repetitive transcranial magnetic stimulation on nocturnal sleep, which is critically disturbed in major depression and other neuropsychiatric disorders, remain largely undetermined. We have previously reported in major depression patients that prefrontal rTMS sessions enhanced their slow wave activity power, but not their sigma power which is related to sleep spindle activity, for electrodes located nearby the stimulation site. In the present study, we focused on measuring the spindle density to (...) investigate cumulative effects of prefrontal rTMS sessions on the sleep spindle activity. Fourteen male inpatients diagnosed with medication-resistant unipolar or bipolar depression were recruited and subjected to 10 daily rTMS sessions targeting the left dorsolateral prefrontal cortex. All-night polysomnography data was acquired at four time points: Adaptation, Baseline, Post-1, and Post-2. Clinical and cognitive evaluations were longitudinally performed at Baseline, Post-1, and Post-2 time points to explore associations with the spindle density changes. The PSG data from 12 of 14 patients was analyzed to identify sleep spindles across the sleep stages II–IV at four electrode sites: F3, F4, P3, and P4. Statistical analysis by two-way ANOVA revealed that spindle density at F3 increased at Post-1 but decreased at Post-2 time points. Moreover, the local and transient increase of spindle density at F3 was associated with the previously reported SWA power increase at F3, possibly reflecting a shared mechanism of thalamocortical synchronization locally enhanced by diurnal prefrontal rTMS sessions. Clinical and cognitive correlations were not observed in this dataset. These findings suggest that diurnal rTMS sessions transiently modulate nocturnal sleep spindle activity at the stimulation site, although clinical and cognitive effects of the local changes warrant further investigation. (shrink)

Background: Electroconvulsive therapy is one of the most effective treatments for major depressive disorder. Recently, there has been increasing attention to evaluate the effect of ECT on resting-state functional magnetic resonance imaging. This study aims to compare rs-fMRI of depressive disorder patients with healthy participants, investigate whether pre-ECT dynamic functional network connectivity network estimated from patients rs-fMRI is associated with an eventual ECT outcome, and explore the effect of ECT on brain network states.Method: Resting-state functional magnetic resonance imaging data were (...) collected from 119 patients with depression or depressive disorder, and 61 healthy participants, with an age mean of 52.25 years old. The pre-ECT and post-ECT Hamilton Depression Rating Scale were 25.59 ± 6.14 and 11.48 ± 9.07, respectively. Twenty-four independent components from default mode and cognitive control network were extracted, using group-independent component analysis from pre-ECT and post-ECT rs-fMRI. Then, the sliding window approach was used to estimate the pre-and post-ECT dFNC of each subject. Next, k-means clustering was separately applied to pre-ECT dFNC and post-ECT dFNC to assess three distinct states from each participant. We calculated the amount of time each subject spends in each state, which is called “occupancy rate” or OCR. Next, we compared OCR values between HC and DEP participants. We also calculated the partial correlation between pre-ECT OCRs and HDRS change while controlling for age, gender, and site. Finally, we evaluated the effectiveness of ECT by comparing pre- and post-ECT OCR of DEP and HC participants.Results: The main findings include depressive disorder patients had significantly lower OCR values than the HC group in state 2, where connectivity between cognitive control network and default mode network was relatively higher than other states, Pre-ECT OCR of state, with more negative connectivity between CCN and DMN components, is linked with the HDRS changes. This means that those DEP patients who spent less time in this state showed more HDRS change, and The post-ECT OCR analysis suggested that ECT increased the amount of time DEP patients spent in state 2.Conclusion: Our finding suggests that dynamic functional network connectivity features, estimated from CCN and DMN, show promise as a predictive biomarker of the ECT outcome of DEP patients. Also, this study identifies a possible underlying mechanism associated with the ECT effect on DEP patients. (shrink)

While previous research has suggested that adults with a history of childhood sexual abuse may be more prone to produce false memories, little is known about the consequences of childhood neglect on basic memory processes. For this reason, the authors investigated how a group of women with a history of childhood emotional neglect and diagnosed with recurrent Major Depressive Disorder performed on the Deese–Roediger–McDermott paradigm in comparison to control groups. The results indicated that women with MDD and CEN were actually (...) less prone to produce false memories relative to both women with MDD but no CEN and healthy women without MDD and any form of childhood maltreatment. These findings were explained in terms of the inability to extract/retrieve gist memories that support false recognition of critical lures, an explanation that seems to fit well with emerging MRI findings linking childhood neglect to reduced volume of brain regions associated to memory function. (shrink)

ObjectiveThis study aims to investigate the effectiveness of mindfulness-based cognitive therapy combined with medication therapy in preventing the recurrence of major depressive disorder in convalescent patients.MethodsA total of 130 patients with convalescent MDD were enrolled in this prospective study. Sixty-five patients were assigned to the experimental group and received medication therapy combined with MBCT, and 65 patients were assigned to the control group and treated with medication alone. The recurrence rate and related hormonal changes were compared between the two groups.ResultsAfter (...) 1 year of MBCT intervention, eight patients experienced recurrence in the experimental group, a recurrence rate of 12.31%, and 19 patients experienced recurrence in the control group, a recurrence rate of 29.23%. The Hamilton Depression Rating Scale and the World Health Organization Quality of Life Scale scores in both the experimental and the control groups were significantly improved after treatment. The difference in the HAM-D scores before and after treatment in the experimental group was 16.74 ± 4.54; this was significantly higher than that of the control group. The WHOQOL-BREF scores in the experimental group were significantly improved compared with those of the control group. The differences in the levels of corticotrophin-releasing hormone, adrenocorticotropic hormone, and cortisol before and after treatment in the experimental group and the control group were statistically significant. The difference in CRH before and after treatment in the experimental group was 16.8 ± 7.2, which was higher than that of the control group. The intervention with MBCT had a significant impact on the recurrence of MDD [β = 1.206, P = 0.039, 95% CI = 0.0790–1.229]. The difference in the HAM-D scores also had a significant impact on the recurrence of MDD.ConclusionCompared with medication therapy alone, the use of MBCT combined with medication therapy can effectively prevent the recurrence of MDD in convalescent patients. (shrink)