Major Depressive Disorder is a major public health problem and has a high rate of treatment resistance. Fear conditioning has been proposed as a potential mechanism sustaining negative affect in mood ...disorders. With the aim of exploring cognitive effects of rapid-acting antidepressant treatments as a potential mechanism of action that can be targeted by neuromodulation, we performed a narrative review of the extant literature on effects of electroconvulsive therapy, ketamine or esketamine, and sleep deprivation on emotional/fear memory retrieval-reconsolidation. We explore interference with reconsolidation as a potential common pathway that explains in part the efficacy of rapid-acting antidepressant treatments with disparate mechanisms of action. We propose the testable hypothesis that fear learning circuits can be specifically targeted by neuromodulation to attempt rapid amelioration of depressive symptoms (especially repetitive negative thinking) while limiting unspecific, untoward cognitive side effects.
•Electroconvulsive therapy, ketamine, and sleep deprivation interfere with reconsolidation of emotional memories after retrieval.•Repetitive negative thinking can be conceptualized as a cycle of emotional memory retrieval-reconsolidation.•Emotional memory reconsolidation can be a direct target of neuromodulation in depression.
As neuroethics continues to grow as an established discipline, it has been charged with not being sufficiently sensitive to the way in which the identification, conceptualization, and management of ...the ethical issues raised by neuroscience and its applications are shaped by local systems of knowledge and structures. Recently there have been calls for explicit recognition of the role played by local cultural contexts and for the development of cross-cultural methodologies that can facilitate meaningful cultural engagement. In this article, we attempt to fill this perceived gap by providing a culturally situated analysis of the practice of electroconvulsive therapy (ECT) in Argentina. ECT was introduced as a psychiatric treatment in Argentina in the 1930s but it is largely underutilized. While the use of ECT remains low in several countries, what makes the Argentinian case interesting is that the executive branch of government has taken a stance regarding both the scientific and moral appropriateness of ECT, recommending its prohibition. Here, we begin with a recent controversy over the use of ECT in Argentina and explain the legal recommendation to ban its application. Next, we offer an overview of some of the salient aspect of the international and local discussions on ECT. We argue that the governmental recommendation to ban the procedure should be rethought. While acknowledging the role that contexts and local conditions play in shaping the identification and assessment of the relevant ethical issues, we caution against using contextual and cultural considerations to avoid a necessary ethical debate on controversial issues.
Repetitive negative thinking (RNT) is a transdiagnostic symptom associated with poor outcomes in major depressive disorder (MDD). MDD is characterized by altered interoception, which has also been ...associated with poor outcomes. The present study investigated whether RNT is directly associated with altered interoceptive processing. Interoceptive awareness toward the heart and stomach was probed on the Visceral Interoceptive Attention (VIA) task with fMRI in MDD individuals who were propensity-matched on the severity of depression and anxiety symptoms and relevant demographics but different in RNT intensity (High RNT H-RNT, n = 48 & Low RNT L-RNT, n = 49), and in matched healthy volunteers (HC, n = 27). Both H-RNT and L-RNT MDD individuals revealed reduced stomach interoceptive processing compared to HC in the left medial frontal region and insular cortex (H-RNT: β = −1.04, L-RNT: β = −0.97), perirhinal cortex (H-RNT: β = −0.99, L-RNT: β = −1.03), and caudate nucleus (H-RNT: β = −1.06, L-RNT: β = −0.89). However, H-RNT was associated with decreased right medial temporal lobe activity including the hippocampus and amygdala during stomach interoceptive trials (β = −0.61) compared to L-RNT. Insular interoceptive processing was similar in H-RNT and L-RNT participants (β = −0.07, p = 0.92). MDD individuals with high RNT exhibited altered gastric interoceptive responses in brain areas that are important for associating the information with specific contexts and emotions. Attenuated interoceptive processing may contribute to RNT generation, non-adaptive information processing, action selection, and thus poor treatment outcome.
Rumination is associated with greater cognitive dysfunction and treatment resistance in major depressive disorder (MDD), but its underlying neural mechanisms are not well understood. Because ...rumination is characterized by difficulty in controlling negative thoughts, the current study investigated whether rumination was associated with aberrant cognitive control in the absence of negative emotional information.
Individuals with MDD (n = 176) and healthy control individuals (n = 52) completed the stop signal task with varied stop signal difficulty during functional magnetic resonance imaging. In the task, a longer stop signal asynchrony made stopping difficult (hard stop), whereas a shorter stop signal asynchrony allowed more time for stopping (easy stop).
In participants with MDD, higher rumination intensity was associated with greater neural activity in response to difficult inhibitory control in the frontoparietal regions. Greater activation for difficult inhibitory control associated with rumination was also positively related to state fear. The imaging results provide compelling evidence for the neural basis of inhibitory control difficulties in individuals with MDD with high rumination.
The association between higher rumination intensity and greater neural activity in regions involved in difficult inhibitory control tasks may provide treatment targets for interventions aimed at improving inhibitory control and reducing rumination in this population.
•Childhood adversity moderates association between groups and cortical thickness.•Greater the adversity, the greater the thinning of emotion-related brain regions in BPD.•The aftermath of childhood ...adversity would ultimately increase the risk for BPD.•Trauma-based early intervention/prevention strategies may be considered.
Adverse childhood experiences (ACEs) negatively affect the function and structure of emotion brain circuits, increasing the risk of various psychiatric disorders. It is unclear if ACEs show disorder specificity with respect to their effects on brain structure. We aimed to investigate whether the structural brain effects of ACEs differ between patients with major depression (MDD) and borderline personality disorder (BPD). These disorders share many symptoms but likely have different etiologies. To achieve our goal, we obtained structural 3T-MRI images from 20 healthy controls (HC), 19 MDD patients, and 18 BPD patients, and measured cortical thickness and subcortical gray matter volumes. We utilized the Adverse Childhood Experiences (ACE) questionnaire to quantify self-reported exposure to childhood trauma. Our findings suggest that individuals with MDD exhibit a smaller cortical thickness when compared to those with BPD. However, ACEs showed a significantly affected relationship with cortical thickness in BPD but not in MDD. ACEs were found to be associated with thinning in cortical regions involved in emotional behavior in BPD, whereas HC showed an opposite association. Our results suggest a potential mechanism of ACE effects on psychopathology involving changes in brain structure. These findings highlight the importance of early detection and intervention strategies.
Recent functional imaging studies in schizophrenia consistently report a disruption of brain connectivity. However, most of these studies analyze the brain connectivity during resting state. Since ...psychological stress is a major factor for the emergence of psychotic symptoms, we sought to characterize the brain connectivity reconfiguration induced by stress in schizophrenia. We tested the hypothesis that an alteration of the brain's integration-segregation dynamic could be the result of patients with schizophrenia facing psychological stress. To this end, we studied the modular organization and the reconfiguration of networks induced by a stress paradigm in forty subjects (twenty patients and twenty controls), thus analyzing the dynamics of the brain in terms of integration and segregation processes by using 3T-fMRI. Patients with schizophrenia did not show statistically significant differences during the control task compared with controls, but they showed an abnormal community structure during stress condition and an under-connected reconfiguration network with a reduction of hub nodes, suggesting a deficit of integration dynamic with a greater compromise of the right hemisphere. These results provide evidence that schizophrenia has a normal response to undemanding stimuli but shows a disruption of brain functional connectivity between key regions involved in stress response, potentially leading to altered functional brain dynamics by reducing integration capacity and showing deficits recruiting right hemisphere regions. This could in turn underlie the hyper-sensitivity to stress characteristic of schizophrenia.
•Patients with schizophrenia have a normal brain community structure to undemanding stimuli but show abnormalities during stress•Patients with schizophrenia show a disruption between areas that are key to stress response and a deficit recruiting right hemisphere regions•All findings suggest an alteration of functional brain dynamics by reducing information flow and integration capacity
Repetitive negative thinking (RNT) is a cognitive process focusing on self-relevant and negative experiences, leading to a poor prognosis of major depressive disorder (MDD). We previously identified ...that connectivity between the precuneus/posterior cingulate cortex (PCC) and right temporoparietal junction (rTPJ) was positively correlated with levels of RNT.
In this double-blind, randomized, sham-controlled, proof-of-concept trial, we employed real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) to delineate the neural processes that may be causally linked to RNT and could potentially become treatment targets for MDD.
MDD-affected individuals were assigned to either active (n = 20) or sham feedback group (n = 19). RNT was measured by the Ruminative Response Scale-brooding subscale (RRS-B) before and 1 week after the intervention.
Individuals in the active but not in the sham group showed a significant reduction in the RRS-B; however, a greater reduction in the PCC-rTPJ connectivity was unrelated to a greater reduction in the RRS-B. Exploratory analyses revealed that a greater reduction in the retrosplenial cortex (RSC)-rTPJ connectivity yielded a more pronounced reduction in the RRS-B in the active but not in the sham group.
RtfMRI-nf was effective in reducing RNT. Considering the underlying mechanism of rtfMIR-nf, the RSC and rTPJ could be part of a network (i.e., default mode network) that might collectively affect the intensity of RNT. Understanding the relationship between the functional organization of targeted neural changes and clinical metrics, such as RNT, has the potential to guide the development of mechanism-based treatment of MDD.
The objective of the present study was to assess sleep-wake differences of autonomic activity in patients with mild cognitive impairment (MCI) compared to control subjects. As a post-hoc objective, ...we sought to evaluate the mediating effect of melatonin on this association.
A total of 22 MCI patients (13 under melatonin treatment) and 12 control subjects were included in this study. Sleep-wake periods were identified by actigraphy and 24hr-heart rate variability measures were obtained to study sleep-wake autonomic activity.
MCI patients did not show any significant differences in sleep-wake autonomic activity when compared to control subjects. Post-hoc analyses revealed that MCI patients not taking melatonin displayed lower parasympathetic sleep-wake amplitude than controls not taking melatonin (RMSSD -7 ± 1 vs 4 ± 4, p = 0.004). In addition, we observed that melatonin treatment was associated with greater parasympathetic activity during sleep (VLF 15.5 ± 0.1 vs 15.1 ± 0.1, p = 0.010) and in sleep-wake differences in MCI patients (VLF 0.5 ± 0.1 vs 0.2 ± 0.0, p = 0.004).
These preliminary findings hint at a possible sleep-related parasympathetic vulnerability in patients at prodromal stages of dementia as well as a potential protective effect of exogenous melatonin in this population.
Abstract The Alzheimer's Disease Neuroimaging Initiative (ADNI), launched in 2004, has worked to accelerate drug development by validating imaging and blood/cerebrospinal fluid biomarkers for ...Alzheimer's disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public-private partnership, the initiative has set a new standard for data sharing without embargo and for the use of biomarkers in dementia research. The ADNI effort in North America is not the only such effort in the world. The Alzheimer's Association recognized these global efforts and formed Worldwide ADNI (WW-ADNI). By creating a platform for international collaboration and cooperation, WW-ADNI's goals are to harmonize projects and results across geographical regions and to facilitate data management and availability to investigators around the world. WW-ADNI projects include those based in North America, Europe, Japan, Australia, Korea, and Argentina.
•Patients with major depression or borderline personality disorder display similar peripheral autonomic stress response.•Central processing abnormalities are different in major depression and ...borderline personality disorders.•The present findings might help discern diverse pathophysiological mechanisms in two syndromes with a significant clinical overlap.
Major depressive disorder (MDD) and borderline personality disorder (BPD) are highly prevalent and often comorbid psychiatric conditions, with abnormal processing of negative affect resulting from psychological stress. Characteristics of central processing of autonomic response to stress in each disorder are not clearly settled.
We obtained whole brain 3T fMRI with concurrent skin conductance, respiration rate, and heart rate variability measures in a cohort of MDD (N=19), BPD (N=19) patients, and healthy (N=20) individuals. Experiments were conducted in resting conditions, during a control mental arithmetic task, during highly stressful mental arithmetic, and in the period immediately following psychological stress.
Widespread activation of central autonomic network (CAN) structures was observed during stress compared to a control task in the group of healthy participants, whereas CAN activation during stress was less intense in both BPD and MDD. Both patient groups displayed increased sympathetic and decreased parasympathetic activation compared to healthy subjects, as previously reported. The relationship between peripheral sympathetic or parasympathetic activity and simultaneous regional brain BOLD activity was similar in BPD patients and healthy subjects, and markedly different from that seen in MDD patients.
The sample size, the fact it belonged to a single study site, and low grade affective symptomatology in both patient groups limit the generalizability of the present findings.
The diverging neurobiological signature in the homeostatic response to stress in MDD and BPD possibly represents a heuristically valuable candidate biomarker to help discern MDD and BPD patients.
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