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)

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)

Individuals with major depressive disorder (MDD) often ruminate about past experiences, especially those with negative content. These repetitive thoughts may interfere with cognitive processes related to attention and conflict monitoring. However, the temporal nature of these processes as reflected in event-related potentials (ERPs) has not been well-described. We examined behavioral and ERP indices of conflict monitoring during a modified flanker task and the allocation of attention during an attentional blink (AB) task in 33 individuals with MDD and (...) 36 healthy controls, and whether their behavioral performance and ERPs varied with level of rumination. N2 amplitude elicited by the flanker task was significantly reduced in participants with MDD compared to healthy controls. Level of self-reported rumination was also correlated with N2 amplitude. In contrast, P3 amplitude during the AB task was not significantly different between groups, nor was it correlated with rumination. No significant differences were found in behavioral task performance measures between groups or by rumination levels. These findings suggest that rumination in MDD is associated with select deficits in cognitive control, particularly related to conflict monitoring. (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)

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 (...) class='Hi'>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)

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)

Substantial research indicates that individuals with Major Depressive Disorder (MDD) remember more negative information compared to neutral and positive information. This phenomenon is commonly attributed to attentional biases toward negative over neutral and positive information. A recent attentional resources model suggests that in MDD, negative cues not only capture attention, but also lead to deeper processing of subsequent information, irrespective of its content. This study aimed to replicate findings supporting this attentional resources model and go beyond it (...) by investigating the effect of negative cues on encoding and retrieval processes. Forty-one participants with MDD and no comorbid diagnoses, and 42 healthy-controls completed the emotional recall task with negative or positive videos presented during encoding and retrieval stages of a neutral word-list memory test. During encoding, only the MDD group exhibited a difference between negative and positive videos, such that for negative videos memory recall was improved and for positive words it was reduced. Emotional videos had no effect when presented during retrieval. These results suggest that in MDD, encountering emotional cues not only biases retrieval processes toward recalling more negative content, but rather fundamentally alters the depth of information processing, while not leading to a broad-spectrum recruitment of cognitive resources. (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)

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)

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)

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)

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)

Heterogeneity within MDD has hampered identification of biological markers (e.g., intermediate phenotypes, IPs) that might increase risk for the disorder or reflect closer links to the genes underlying the disease process. The newer characterizations of dimensions of MDD within Research Domain Criteria (RDoC) domains may align well with the goal of defining IPs. We compare a sample of 25 individuals with MDD compared to 29 age and education matched controls in multimodal assessment. The multimodal RDoC assessment included the primary (...) IP biomarker, positron emission tomography (PET) with a selective radiotracer for 5-HT1A ([11C]WAY-100635), as well as event-related functional MRI with a Go/No-go task targeting the Cognitive Control network, neuropsychological assessment of affective perception, negative memory bias and Cognitive Control domains. There was also an exploratory genetic analysis with the serotonin transporter (5-HTTLPR) and monamine oxidase A (MAO-A) genes. In regression analyses, lower 5-HT1A binding potential (BP) in the MDD group was related to diminished engagement of the Cognitive Control network, slowed resolution of interfering cognitive stimuli, one element of Cognitive Control. In contrast, higher/normative levels of 5-HT1A BP in MDD (only) was related to a substantial memory bias toward negative information, but intact resolution of interfering cognitive stimuli and greater engagement of Cognitive Control circuitry. The serotonin transporter risk allele was associated with lower 1a BP and the corresponding imaging and cognitive IPs in MDD. Lowered 5HT 1a BP was present in half of the MDD group relative to the control group. Lowered 5HT 1a BP may represent a subtype including decreased engagement of Cognitive Control network and impaired resolution of interfering cognitive stimuli. Future investigations might link lowered 1a BP to neurobiological pathways and markers, as well as probing subtype-specific treatment targets. (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)

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 Depressive Disorder (MDD) is a serious condition with a large disease burden. It is often claimed that MDD is a “brain disease.” What would it mean for MDD to be a brain disease? I argue that the best interpretation of this claim is as offering a substantive empirical hypothesis about the causes of the syndrome of depression. This syndrome-causal conception of disease, combined with the idea that MDD is a disease of the brain, commits the brain (...) disease conception of MDD to the claim that brain dysfunction causes the symptoms of MDD. I argue that this consequence of the brain disease conception of MDD is false. It incorrectly rules out genuine instances of content-sensitive causation between adverse conditions in the world and the characteristic symptoms of MDD. Empirical evidence shows that the major causes of depression are genuinely psychological causes of the symptoms of MDD. This rules out, in many cases, the “brute” causation required by the brain disease conception. The existence of cases of MDD with non-brute causes supports the reinstatement of the old nosological distinction between endogenous and exogenous depression. (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)

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)

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)

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)

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)

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)

In this paper, I examine recent phenomenological research on both depressive and manic episodes, with the intention of showing how phenomenologically oriented studies can help us overcome the apparently paradoxical nature of mixed states. First, I argue that some of the symptoms included in the diagnostic criteria for depressive and manic episodes in the DSM-5 are not actually essential features of these episodes. Second, I reconsider the category of major depressive disorder (MDD) from the perspective (...) of phenomenological psychopathology, arguing that severe depressive episodes should not be characterized by any particular moods (such as sadness, hopelessness, or guilt), and should instead be characterized by a diminished capacity for finding ourselves situated in and attuned to the world at all. In other words, the affective dimension of depression should be characterized as a change in the way we have moods, not as a change from one kind of mood to another. Third, I turn to mania, arguing that manic episodes, taken as the opposite of depressive episodes, should be characterized not by any particular moods (such as euphoria, grandiosity, or even irritability), but should instead be characterized by an enhanced or heightened capacity for finding ourselves situated in and attuned to the world. In other words, the affective dimension of mania, like the affective dimension of depression, should be understood as a change in the way we have moods, not as a change from one kind of mood to another. Fourth, I return to the phenomenon of mixed states and argue that the affective dimension of depression and mania, when conceived along the phenomenological lines I set forth in the previous sections, dissolves the paradox of mixed states by showing that the essential characteristics of depression and mania cannot and do not coincide. Many cases of mixed states are diagnosed because moods that we take to be essential features of either depression or mania arise within the context of what is considered to be the opposite kind of episode (e.g. dysphoria, typically associated with depression, often arises in what is otherwise considered a manic state). However, if we conceive of the affective dimension of depression as a decrease in the degree to which one is situated in and attune to the world through moods, and the affective dimension of mania as an increase in the degree to which one is situated in and attuned to the world through moods, then the particular mood one finds oneself in is simply irrelevant to the diagnosis of either depression or mania. As a result, the manifestation of any particular moods in what otherwise seems to be a pure manic or depressive episode does not constitute a mixed state. (shrink)

Time is an essential feature in bipolar disorder (BP). Manic and depressed BP patients perceive the speed of time as either too fast or too slow. The present article combines theoretical and empirical approaches to integrate phenomenological, psychological, and neuroscientific accounts of abnormal time perception in BP. Phenomenology distinguishes between perception of inner time, ie, self-time, and outer time, ie, world-time, that desynchronize or dissociate from each other in BP: inner time speed is abnormally slow (as in depression) or (...) fast (as in mania) and, by taking on the role as default-mode function, impacts and modulates the perception of outer time speed in an opposite way, ie, as too fast in depression and too slow in mania. Complementing, psychological investigation show opposite results in time perception, ie, time estimation and reproduction, in manic and depressed BP. Neuronally, time speed can be indexed by neuronal variability, ie, SD. Our own empirical data show opposite changes in manic and depressed BP (and major depressive disorder [MDD]) with abnormal SD balance, ie, SD ratio, between somatomotor and sensory networks that can be associated with inner and outer time. Taken together, our combined theoretical-empirical approach demonstrates that desynchronization or dissociation between inner and outer time in BP can be traced to opposite neuronal variability patterns in somatomotor and sensory networks. This opens the door for individualized therapeutic “normalization” of neuronal variability pattern in somatomotor and sensory networks by stimulation with TMS and/or tDCS. (shrink)

Cramer et al. persuasively conceptualize major depressive disorder (MDD) and generalized anxiety disorder (GAD) as network disorders, rejecting latent variable accounts. But how does their radical picture generalize across the suite of mental and personality disorders? Addictions are Axis I disorders that may be better characterized by latent variables. Their comorbidity relationships could be captured by inserting them as nodes in a super-network of Axis I conditions.

Current theories suggest that the brain is the sole source of mental illness. However, affective disorders, and major depressive disorder (MDD) in particular, may be better conceptualized as brain-body disorders that involve peripheral systems as well. This perspective emphasizes the embodied, multifaceted physiology of well-being, and suggests that afferent signals from the body may contribute to cognitive and emotional states. In this review, we focus on evidence from preclinical and clinical studies suggesting that afferent thermosensory signals contribute (...) to well-being and depression. Although thermoregulatory systems have traditionally been conceptualized as serving primarily homeostatic functions, increasing evidence suggests neural pathways responsible for regulating body temperature may be linked more closely with emotional states than previously recognized, an affective warmth hypothesis. Human studies indicate that increasing physical warmth activates brain circuits associated with cognitive and affective functions, promotes interpersonal warmth and prosocial behavior, and has antidepressant effects. Consistent with these effects, preclinical studies in rodents demonstrate that physical warmth activates brain serotonergic neurons implicated in antidepressant-like effects. Together, these studies suggest that (1) thermosensory pathways interact with brain systems that control affective function, (2) these pathways are dysregulated in affective disorders, and (3) activating warm thermosensory pathways promotes a sense of well-being and has therapeutic potential in the treatment of affective disorders. (shrink)

In light of the recent calls for integrating phenomenology and psychiatry, I will address the problem of heterogeneity in major depressive disorder (MDD) using the phenomenological account of depression put forth by Fernandez (Fernandez, 2014). I will first go over the distinction between two of the major specifiers of major depressive disorder, namely melancholic and atypical depression. Then, I review the account of depression developed by Fernandez, which considers some of the people diagnosed (...) with MDD to have an erosion of the capacity for the category of moods as opposed to a particular kind of mood. I will apply this conception to the diagnostic and statistical manual criteria for melancholic and atypical depression, and consider how reactive and unreactive depressed moods can be clarified using this conception. I argue that we can help our understanding of MDD by viewing melancholic depression as primarily characterized by structural erosion of the person’s situatedness (observed as a lack of mood reactivity) and atypical depression as a state in which the capacity for moods in general has not been eroded (hence, the retention of mood reactivity), with the psychopathology rooted only in the content of experience (the moods themselves). I discuss how this conception related to other phenomenological accounts of depression and why it can be useful in making sense of some clinical observations between the two specifiers, namely the differences in illness severity and symptoms of depersonalization and derealization, before concluding the work by considering its relationship with the operationalized approach of the DSM. (shrink)

ABSTRACTHedonic deficits are linked to protracted dysphoric affect in depression, a disorder characterised by emotion context insensitivity. Recent findings from daily life studies contradict the ECI view. This study longitudinally investigated DA across laboratory and daily life contexts and the conditions associated with discrepancies in DA reactivity. Thirty-three healthy controls and 41 adults with major depressive disorder provided responses to neutral and positive films viewed in the laboratory and daily events recorded over the course of three (...) days using ecological momentary assessment methodology. The current study reports on participants’ appraisals of films and events and their subsequent DA, both rated individually after each task and daily event. Despite large group similarities in appraisals of the positive film and life events, MDDs appraised the neutral film and neutral life events as less important and less pleasant (film: d =... (shrink)

BackgroundCognitive deficits are one of the core features of major depressive disorder that play crucial role in functional recovery. Studies have explored cognitive deficits in MDD, however, given inconsistent results, especially in mild-moderate MDD. Recently, studies have explored music as cognitive ability in various clinical conditions. In MDD, large focus has been on evaluating emotion deficits and just a handful on music cognition. With growing evidence on use of music based intervention to target cognitive deficits, it is (...) imperative to explore nature of music cognitive ability in MDD.AimTo examine musical and neuro-cognitive deficits in patients with mild-moderate MDD.MethodsPatients diagnosed with mild or moderate MDD and matched healthy controls were evaluated on selected tests from NIMHANS Neuropsychological test battery and Montreal battery for evaluation of amusia.ResultsMDD group performed significantly lower than HC on working memory, verbal learning and retention. Three indices were computed for a comprehensive evaluation. Groups did not differ significantly in any of the indices- focused attention, executive function, learning and memory as well as on music cognition. Focused attention and memory index predicted music cognition in HC and the combined group. Attention alone contributed to 62.1% of variance in music cognition. Similarly, music cognition significantly predicted focused attention.ConclusionIndividuals with mild-moderate MDD show significant deficits in working memory, verbal learning and memory, however, not in music cognition. There exists a significant relationship between music cognition and attention, which could be implicated in use of music interventions to ameliorate cognitive deficits. Limitations of study include small sample size and heterogeneity. Future studies on larger cohort examining musical emotion perception and neurocognition is imperative to have deeper understanding of this debilitating condition. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Postmodern Assumptions of Philosophy of PsychiatryThe author reports no conflicts of interest.This paper makes claims for relevance of philosophy to psychopathology, as inspired in part by the work of Karl Jaspers. Yet there is no such thing as philosophy, in a general sense; there are philosophies, or as Jaspers would prefer, there is philosophizing (Ehrlich & George, 1994; Jaspers, 1951). Jaspers' approach to philosophy was akin to Freud's approach (...) to psychology: the goal was to make unconscious assumptions conscious. The unconscious assumption in the present paper is that there is such a thing as philosophy, which could then be useful for psychopathology. In effect, the author is probably meaning academic philosophy, or mainstream thinking in current philosophy of psychiatry. If that is the meaning, then Jaspers' question would be: What are the unconscious underlying assumptions of modern academic philosophy of psychiatry? The author's paper does not ask that question. But if we do, my answer would be that current mainstream philosophy of psychiatry has a basic worldview, another concept very central to Jaspers' thinking (Rindermann, 2021). Its worldview is postmodernist relativism about truth and skepticism about science, especially biology as applied to psychiatry. This unconscious assumption in modern philosophy of psychiatry is a major impediment in any benefits it might provide to psychiatry and psychopathology, as will be explained in the rest of this commentary.The paper refers to major depressive disorder (MDD) without appreciating that the term itself makes assumptions which the paper wishes to argue should be in the province of philosophy to analyze. The term MDD is not the same as depression, although the paper synonymizes the two. This synonym is an unanalyzed assumption, namely, that the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic system validly defines psychopathology. It clearly does not, for reasons that modern philosophy of psychiatry has not accurately analyzed (Ghaemi, 2014).About a decade ago, when DSM-5 was being developed, colleagues in the field of philosophy of psychiatry had worked for decades on psychiatric diagnosis, and there was initial hope that the time had come for an impact (Kendler et al., 2008). The leader of the prior edition of DSM was unhappy [End Page 17] with the fifth revision. A set of essays were published where philosophers and psychiatrists engaged the former DSM leader about psychiatric diagnosis (Frances, 2013). His response, with a somewhat derisive reference to "philosophyland," was eye opening to me. He explicitly stated that DSM revisions were not based on science or facts, but on "pragmatism," on the beliefs of DSM leaders about what was best for the profession or society. In short, it was admitted that DSM was a social construction, just as postmodern thinking had said about psychiatric diagnosis since Foucault. Yet this admission was made unconsciously; DSM leadership does not use that phrase, nor does it understand its conceptual foundations. Surprisingly to me, colleagues in the world of philosophy and psychiatry also failed to make the obvious connection, or if they did, they seemed to have little problem with it (Phillips et al., 2012). Social constructionism was their worldview too.In effect, philosophy of psychiatry had nothing to provide; it did not analyze or critique the philosophical worldview of DSM leadership; it shared that worldview and participated in it (Kendler, 2013).The result, in my view, is that mainstream philosophy of psychiatry has failed in the role which it could have played, the role of making the unconscious postmodern assumptions of psychiatry conscious, and criticizing those assumptions. Instead, it applauded them.My broader critique of mainstream philosophy of psychiatry gets played out in papers such as this one in relation to the DSM term MDD, which should be dropped because it is not a scientifically sound term; it has many conceptual and scientific falsehoods within it, which both a philosophical analysis and a scientific analysis would demonstrate.The term MDD was invented in the DSM-III process in the late 1970s to get votes for passage of that third revision by the American Psychiatric Association in 1980 (Decker, 2013). It literally was a social construction. To the extent that it had any scientific basis, it had its roots in the... (shrink)

This chapter relates the problem of demarcating the pathological from the non-pathological in psychiatry to the general problem of defining ‘disease’ in the philosophy of medicine. Section 2 revisits three prominent debates in medical nosology: naturalism versus normativism, the three dimensions of illness, sickness, and disease, and the demarcation problem. Sections 3–5 reformulate the demarcation problem in terms of semantic vagueness. ‘Disease’ exhibits vagueness of degree by drawing no sharp line in a continuum and is combinatorially vague because there are (...) several criteria for the term’s use that might fall apart. Combinatorial vagueness explains why the other two debates appear hopeless: Should we construe ‘disease’ in a naturalistic or in a normative way? Neither answer is satisfactory. How should we balance the three dimensions of pathology? We do not have to, because illness, sickness and disease (narrowly conceived) are non-competing criteria for the application of the cluster term ‘disease’. (shrink)

ABSTRACTRumination and worry are two perseverative, negatively valenced thought processes that characterise depressive and anxiety disorders. Despite significant research interest, little is known about the everyday precipitants and consequences of rumination and worry. Using an experience sampling methodology, we examined and compared rumination and worry with respect to their relations to daily events and affective experience. Participants diagnosed with Major Depressive Disorder, Generalized Anxiety Disorder, co-occurring MDD–GAD, or no diagnosis carried an electronic device for one (...) week and reported on rumination, worry, significant events, positive affect, and negative affect. Across the clinical groups, occurrences of everyday events predicted subsequent increases in rumination, but not worry. Further, higher momentary levels of rumination, but not worry, predicted subsequent decreases in PA and increases in NA. Thus, in these clinical groups, rumination was more susceptible to... (shrink)

Deep Brain Stimulation is an invasive device-based neuromodulation technique that allows the therapeutic direct stimulation of subcortical and deep cortical structures following the surgical placement of stimulating electrodes. DBS is approved by the U.S. Federal Drug Administration for the treatment of movement disorders and obsessive-compulsive disorder, while new indications, including Major Depressive Disorder, are in experimental development. We report the case of a patient with MDD who received DBS to the ventral internal capsule and ventral striatum (...) bilaterally and presented with 2 weeks of voltage-dependent Tourette-like symptoms including brief transient episodes of abrupt-onset and progressively louder coprolalia and stuttered speech; tic-like motor behavior in his right arm and leg; rushes of anxiety, angry prosody, angry affect; and moderate amnesia without confusion. We describe the results of the inpatient neuropsychiatric workup leading to the diagnosis of iatrogenic voltage-dependent activation of cortico-subcortical circuits and discuss insights into the pathophysiology of Tourette as well as safety considerations raised by the case. (shrink)