Comparison of Emotion Regulation between Patients with Schizophrenia and major Depression across Levels of Dissociative Experiences

The role of distinct limbic areas in emotion regulation has been largely inferred from neuroimaging studies. Recently, the opportunity for intracranial recordings from limbic areas has arisen in patients undergoing deep brain stimulation (DBS) for neuropsychiatric disorders including major depressive disorder (MDD) and obsessive compulsive disorder (OCD). Here we test the hypothesis that distinct temporal patterns of local field potential (LFP) activity in the human limbic system reflect disease state and symptom severity in MDD and OCD patients. To this end, we recorded LFPs via implanted DBS electrodes from the bed nucleus of stria terminalis (BNST area) in 12 patients (5 OCD, 7 MDD) and from the subgenual cingulate cortex in 7 MDD patients (CG25 area). We found a distinct pattern of oscillatory activity with significantly higher α-power in MDD compared with OCD in the BNST area (broad α-band 8-14 Hz; P<0.01) and a similar level of α-activity in the CG25 area as in the BNST area in MDD patients. The mean α-power correlated with severity of depressive symptoms as assessed by the Beck depression inventory in MDD (n=14, r=0.55, P=0.042) but not with severity of obsessive compulsive symptoms in OCD. Here we show larger α-band activity in MDD patients compared with OCD recorded from intracranial DBS targets. Our results suggest that α-activity in the limbic system may be a signature of symptom severity in MDD and may serve as a potential state biomarker for closed loop DBS in MDD.

Major depressive disorder (MDD) and bipolar disorder (BD) are difficult to distinguish clinically during the depressed or remitted states. Both mood disorders are characterized by emotion regulation disturbances; however, little is known about emotion regulation differences between MDD and BD. Better insight into these differences would be helpful for differentiation based on disorder-specific underlying pathophysiological mechanisms. Previous studies comparing these disorders often allowed medication use, limiting generalizability and validity. Moreover, patients with MDD and BD were mostly compared during the depressed, but not the remitted, state, while state might potentially modulate differences between MDD and BD. To investigate positive and negative emotion regulation in medication-free patients with MDD and BD in 2 mood states: depressed or remitted. A cross-sectional study conducted from May 2009 to August 2013 comparing behavioral and functional magnetic resonance imaging emotion regulation data of 42 patients with MDD, 35 with BD, and 36 healthy control (HC) participants free of psychotropic medication recruited from several psychiatric institutions across the Netherlands. A voluntary emotion regulation functional magnetic resonance imaging task using positive and negative pictures. Behavioral and functional magnetic resonance imaging blood oxygen level-dependent responses during emotion regulation. In the remitted state, only patients with BD showed impaired emotion regulation (t = 3.39; P < .001; Cohen d = 0.70), irrespective of emotion type and associated with increased dorsolateral prefrontal cortex activity compared with those with MDD and healthy control participants (P = .008). In the depressed state, patients with MDD and BD differed with regard to happy vs sad emotion regulation (t = 4.19; P < .001; Cohen d = 1.66) associated with differences in rostral anterior cingulate activity (P < .001). Patients with MDD regulated sad and happy emotions poorly compared with those with BD and healthy control participants, while they demonstrated no rostral anterior cingulate difference between happy and sad emotion regulation. In contrast, patients with BD performed worse than those with MDD on sad emotion regulation but normal on happy emotion regulation, and they demonstrated significantly less rostral anterior cingulate activity while regulating happy compared with sad emotions. Medication-free patients with MDD vs BD appear to differ in brain activations during emotion regulation, both while depressed and in remission. These different neuropathophysiological mechanisms between MDD and BD may be useful for further development of additional diagnostic tools.

Ruminations and their correlates in depressive episodes: Between-group comparison in patients with unipolar or bipolar depression and healthy controls

Reduced fractional anisotropy (FA) associated with Major Depressive Disorder (MDD) overlaps anatomically with effects of childhood maltreatment experiences. The aim of this study was, therefore, to replicate the negative effect of childhood maltreatment on white matter fiber structure and to demonstrate, that alterations in MDD might be partially attributed to the higher occurrence of childhood maltreatment in MDD. Two independent cohorts (total N = 1 256) were investigated in a diffusion tensor imaging study: The Münster Neuroimaging Cohort (MNC, N = 186 MDD, N = 210 healthy controls, HC) as discovery sample and the Marburg-Münster Affective Disorders Cohort Study (MACS, N = 397 MDD, N = 462 HC) as replication sample. The effects of diagnosis (HC vs. MDD) and Childhood Trauma Questionnaire (CTQ) scores on FA were analyzed. A main effect of diagnosis with higher FA in MDD patients compared with HC was found in the MNC (pFWE = 0.021), but not in the MACS (pFWE = 0.52) before correcting for CTQ. A significant negative correlation of FA with CTQ emerged in both cohorts (MNC: pFWE = 0.006, MACS: pFWE = 0.012) in several tracts previously described in the literature. No CTQ × diagnosis interaction could be detected. Any main effect of diagnosis was abolished after correcting for CTQ (MNC: pFWE = 0.562, MACS: pFWE = 0.115). No differences in FA between MDD and HC could be found after correcting for childhood maltreatment, suggesting that previously reported group differences might be attributed partially to higher levels of maltreatment experiences in MDD rather than diagnosis itself. Furthermore, a well-established finding of reduced FA following childhood maltreatment experiences was replicated.

Impact of Social Anxiety Disorder on Employment Among Women Receiving Welfare Benefits

Major Depressive Disorder (MDD) and Borderline Personality Disorder (BPD) are both significant mental health conditions that impact millions of individuals and have deleterious effects. There is a high rate of co-morbidity between these two disorders; in particular individuals with BPD report high levels of MDD symptoms. Identification of shared and specific vulnerabilities, both in terms of trait and emotion regulation variables, is an important step in explaining this overlap and developing interventions that address symptoms common or specific to these disorders. Dimensions of affect (i.e., negative affect, positive affect, affect intensity), avoidant emotion regulation (i.e., experiential avoidance, thought suppression, expressive suppression, nonacceptance), and symptoms of MDD and BPD were assessed in an unselected college sample. Results indicated that negative affect was related to both MDD and BPD symptoms whereas positive affect was only related to MDD symptoms and affect intensity was only related to BPD symptoms. Additionally, avoidant emotion regulation partially mediated the relation between dimensions of affect and symptoms. Implications and future directions are discussed.

Emotional dysregulation is a central topic of interest in many clinical studies. It plays a vital role in making or breaking interpersonal and interpersonal relationships in clinical populations as well as healthy controls. This study seeks to investigate the nature, intensity and extensity patterns of emotional regulation in patients diagnosed as major depression (N: 254) and borderline personality disorder (N: 69). By using a one-shot cross sectional purposive sample survey design, this hospital-based study targeted a random sample of subjects from both gender between 18-30 years. Following clinical interviews and diagnosis as per the chosen inclusion and exclusion criteria, participants were recruited based on ICD-10 criteria and after they secured a minimum cut-off score on McLean’s Screening Instrument for Borderline Personality Disorder and Hamilton Depression Rating Scale. The selected participants were administered Difficulties in Emotion Regulation Scale and Cognitive Emotion Regulation Questionnaire. Results show significantly high scores on emotion regulation in patients with borderline personality disorder than major depressive disorder (p:&lt;0.05). These differences are maintained across all domains except for cognition mediated areas like ‘awareness’, ‘self-blame’, ‘acceptance’, ‘rumination’, and ‘positive refocusing’. Associated variables like genderand marital status appear to influence only some aspects of non-cognitive emotional dysregulation. The findings are discussed along with their implications for therapy in the context of cultural factors unique to Indian settings.

The Critical Relationship Between Anxiety and Depression.

Dysfunction in emotion regulation (ER) and autobiographical memory are components of major depressive disorder (MDD). However, little is known about how they mechanistically interact with mood disturbances in real time. Using machine learning-based neural signatures, we can quantify negative affect (NA), ER, and memory continuously to evaluate how these processes dynamically interact in MDD. Unmedicated individuals with MDD (N = 45) and healthy volunteers (HV; N = 38) completed a negative autobiographical memory functional magnetic resonance imaging task wherein they recalled, distanced from (an ER strategy), and immersed into memories. We used a negative affect signature (PINES) and an emotion regulation signature (ERS) to quantify moment-to-moment NA and ER. We then examined whether memory engagement, indexed by hippocampal activity, predicted subsequent change in PINES and ERS over time. During memory recall and immersion, greater hippocampal activity predicted increased PINES across groups. During distancing, greater hippocampal activity in HVs predicted increased ERS but not PINES. In MDD, greater hippocampal activity predicted increased PINES but not ERS. Findings suggest abnormalities in the real-time relationship between memory, NA, and ER in MDD. During distancing, as predicted, HVs showed an attenuation of the linkage between memory engagement and NA, and they had subsequent increases in ER following memory reactivation. In contrast, MDD was characterized by continued linkage between memory engagement and NA, without subsequent increases in ER. Deficits in engagement of ER and ineffective modulation of NA following negative memory recall may contribute to the mood disturbances in MDD and are potential targets for clinical intervention.

The diagnosis of major depressive disorder consists of the core features of depressed mood and/or the loss of interest or pleasure. Yet, accompanying vegetative symptoms can be polar opposites, including insomnia or hypersomnia, psychomotor agitation or retardation, and increase or decrease in appetite. This variability in symptom presentation suggests that major depressive disorder is not a unitary disorder. From a neurobiological point of view, major depressive disorder symptoms appear likely to be caused by differential and reciprocal disruption of the interconnected networks of awareness, interoception, and reward, all of which have been implicated in emotional regulation. Insight into individual differences in dysfunction among regional “nodes” of these circuits might lead to greater insight regarding more tailored treatment of phenotypic subgroups of depression. The development of the Research Domain Criteria (RDoC) project supported by the National Institute of Mental Health is an example of this conceptual shift away from framing disorders by discrete categories to an understanding of symptom clusters basedonbrain-behavior relationships (https://www. nimh.nih.gov/research-priorities/rdoc/index.shtml). In this issue of the Journal, W. Kyle Simmons, Ph.D., et al. (1) investigate activity in brain regions associated with responsivity to food stimuli in major depressive disorder subjectswith increasedordecreasedappetite.Theauthorsuseda task-based functional MRI (fMRI) measure to compare their major depressive disorder subjects to a control group of nondepressed, healthy individuals (N516 per group). Most participants were women, and all had similar body mass index values. The main measure of brain activity was the bloodoxygen-level-dependent (BOLD) response when participants passively viewed pictures of food compared with nonfood. In the healthy comparison group, an interconnected network of brain areas associated with viewing food included regions within the visual cortex, bilateral insula, medial orbitofrontal and prefrontal cortices, and right amygdala. These regions have been implicated to underlie interoceptive processing (2). Many other studies also show that these regions have altered activity in depressed patients and emotional processing in healthy control subjects (3, 4). In the Simmons et al. study, different patterns of change emerged for major depressive disorder subjects with appetite increases versus decreases. Themajor depressive disorder group with increased appetite had increased BOLD response in brain regions implicated in the reward system (anterior insula, orbitofrontal cortex, ventral striatum, ventral pallidum,andputamen) (5),while the appetitedecrease group generally showed decreased mid-insula BOLD activity compared with the other groups. Simmons et al. suggest that this altered reactivity of the interoceptive system when confronted with food stimuli leads to a disconnect of signaling from the periphery of a need to eat and a typical response to being presented with food (e.g., the depressed subjectwith lowappetitemaynot “feel like”eatingandwillnot choose to eat even though she may have visceral changes that usually cue hunger). The authors also examine brain regional connectivity changes, comparing resting-state fMRI as a functionof participant foodpleasantness scores. Thisprovides more support for differential changes based on appetite condition in themajordepressivedisordergroups, usingmeasures that are not dependent on specificity of neural changes associated with task-based fMRI. They find regional connectivity results with similar relationships to their findings with the task-based BOLD response. The role of brain regions critical in interoceptive processing appears promising to lead to exciting discoveries for some major depressive disorder treatment. A key role for interoception is maintaining homeostasis. Conceptualizing depression as a disruption of maintenance of homeostasis is an important consideration for novel medications or targets for invasive and noninvasive treatments (3, 6–8). Indeed, this approach to depression has been considered in conceptualizing how cognitive-behavioral therapy and related therapies alleviate symptoms (9). The Simmons laboratory focuses on appetite and the insula rather than on the general category of major depressive disorder. In this study, they did not include a group of major depressive disorder individuals who do not show a change in appetite. Therefore, we cannot predict what an anhedonic major depressive disorder group of individuals who do not have appetite problemswould show on either the fMRI tasks or the food preference responses. However, having major depressive disorder appetite changes studied by those interested in homeostasis regulation and obesity may help the field approach these worrisome symptoms of depression from a different vantage point. Coupled with depression research, examining the reciprocal nature of these interconnected Having major depressive disorder appetite changes studied by those interested in homeostasis regulation and obesity may help the field approach these worrisome symptoms of depression from a different vantage point.

ABSTRACTBackground and Objectives: Major depression disorder (MDD) and social anxiety disorder (SAD) are characterized by the use of perseverative cognition (PC) as a dysfunctional coping strategy. We sought to investigate the dysfunctional physiological and psychological consequences of PC and how the valence of social interactions moderates such consequences in these psychopathological conditions.Design/Methods: The study combined 24-hour heart rate variability (HRV) and ecological momentary assessments in 48 individuals with MDD, SAD, and sex-matched controls.Results: In all participants, PC was associated with mood worsening and reduced ability of the parasympathetic nervous system, mainly the vagus, to inhibit sympathetic arousal (i.e., reduced HRV). Individuals with SAD had the highest frequency of daily PC, while those with MDD reported that PC interfered more with their ongoing activities. In SAD, daily PC was associated with significantly lower HRV after negative social interactions. Individuals with MDD reported higher levels of sadness during PC irrespective of the valence of the preceding social interaction but higher levels of anxiety and efforts to inhibit PC following positive interactions.Conclusions: Results highlight the need to account for important moderators like the valence of social interaction when looking at the physiological consequences of maladaptive emotion regulation strategies.

Understanding Emotion Regulation in Borderline Personality Disorder: Contributions of Neuroimaging

Impairments in affect regulation as well as cognitive reactivity have been considered to play important roles in the development, maintenance, and recurrence of major depressive disorder (MDD). However, there is a lack of studies investigating, (a) whether certain difficulties in emotion regulation are specific for MDD, (b) whether certain meta-mood beliefs are associated with an increased risk for MDD, and (c) whether reduced abilities to engage in mood-incongruent information processing and to disengage from negative information are associated with depression vulnerability, and whether those specific mood regulation processes underlie the mechanism of cognitive reactivity. Therefore, Study 1 of this dissertation compared patients with MDD with a clinical and a healthy control group regarding a comprehensive set of central and clinically relevant emotion regulation difficulties. Study 2 investigated two specific kinds of meta-mood beliefs [i.e., generalized negative mood regulation (NMR) expectancies and a generalized motive to avoid emotional experience (EA)] in formerly-depressed and never-depressed subjects. Finally, Study 3 tested whether two specific mood regulation processes (i.e., mood-incongruent information processing and disengagement from negative information) differentially appear in vulnerable and non-vulnerable individuals, and whether they can account for differences in cognitive reactivity. Patients with MDD reported greater emotion regulation difficulties than healthy controls and did not differ from the clinical control group regarding difficulties with the experience and differentiation of emotions, however, patients with MDD reported greater difficulties than clinical controls regarding the attenuation and modulation of emotions (Study 1). As expected, vulnerable individuals reported lower NMR expectancies and stronger EA as compared to non-vulnerable individuals, and NMR expectancies were furthermore found to be inversely associated with EA (Study 2). In the second but not in the first phase of an autobiographical memory task, vulnerable subjects retrieved fewer mood-incongruent (positively toned) emotion words than non-vulnerable subjects (Study 3). Furthermore, vulnerable subjects with a high cognitive reactivity retrieved more negatively toned emotion words. For non-vulnerable subjects a different pattern occurred: Subjects with a high cognitive reactivity retrieved less positively toned emotion words. The findings of the three studies suggest that emotion regulation difficulties constitute transdiagnostic phenomena, and that MDD may be characterized by particularly broad and pronounced deficits in this domain. The results also suggest that maladaptive meta-mood beliefs are associated with depression vulnerability and that individuals with low confidence in their negative mood regulation abilities are concurrently characterized by a stronger avoidance of emotional experience. Furthermore, the results suggest that a reduced ability of mood-incongruent information processing is associated with depression vulnerability, and that two different memory processes of mood regulation may account for cognitive reactivity in individuals who are at high versus low risk for depression. The cross-sectional designs and the use of self-report measures as well as the relatively small sample sizes in two of the studies limit the interpretation of the obtained results. Notwithstanding, the findings of these three studies call for an implementation of specific elements that foster adaptive affect regulation (e.g., computer-assisted training of cognitive processes) into existing treatment packages for MDD.

There is extensive evidence implicating dysfunctions in stress responses and adaptation to stress in the pathophysiological mechanism of major depressive disorder (MDD) in humans. Endogenous opioid neurotransmission activating mu-opioid receptors is involved in stress and emotion regulatory processes and has been further implicated in MDD. To examine the involvement of mu-opioid neurotransmission in the regulation of affective states in volunteers with MDD and its relationship with clinical response to antidepressant treatment. Measures of mu-opioid receptor availability in vivo (binding potential [BP]) were obtained with positron emission tomography and the mu-opioid receptor selective radiotracer carbon 11-labeled carfentanil during a neutral state. Changes in BP during a sustained sadness challenge were obtained by comparing it with the neutral state, reflecting changes in endogenous opioid neurotransmission during the experience of that emotion. Clinics and neuroimaging facilities at a university medical center. Fourteen healthy female volunteers and 14 individually matched patient volunteers diagnosed with MDD were recruited via advertisement and through outpatient clinics. Sustained neutral and sadness states, randomized and counterbalanced in order, elicited by the cued recall of an autobiographical event associated with that emotion. Following imaging procedures, patients underwent a 10-week course of treatment with 20 to 40 mg of fluoxetine hydrochloride. Changes in mu-opioid receptor BP during neutral and sustained sadness states, negative and positive affect ratings, plasma cortisol and corticotropin levels, and clinical response to antidepressant administration. The sustained sadness condition was associated with a statistically significant decrease in mu-opioid receptor BP in the left inferior temporal cortex of patients with MDD and correlated with negative affect ratings experienced during the condition. Conversely, a significant increase in mu-opioid receptor BP was observed in healthy control subjects in the rostral region of the anterior cingulate. In this region, a significant decrease in mu-opioid receptor BP during sadness was observed in patients with MDD who did not respond to antidepressant treatment. Comparisons between patients with MDD and controls showed significantly lower neutral-state mu-opioid receptor BP in patients with MDD in the posterior thalamus, correlating with corticotropin and cortisol plasma levels. Larger reductions in mu-opioid system BP during sadness were obtained in patients with MDD in the anterior insular cortex, anterior and posterior thalamus, ventral basal ganglia, amygdala, and periamygdalar cortex. The same challenge elicited larger increases in the BP measure in the control group in the anterior cingulate, ventral basal ganglia, hypothalamus, amygdala, and periamygdalar cortex. The results demonstrate differences between women with MDD and control women in mu-opioid receptor availability during a neutral state, as well as opposite responses of this neurotransmitter system during the experimental induction of a sustained sadness state. These data demonstrate that endogenous opioid neurotransmission on mu-opioid receptors, a system implicated in stress responses and emotional regulation, is altered in patients diagnosed with MDD.

Diurnal variation of heart rate variability as a physiological index of mood and emotion regulation processes in Major Depression and Borderline Personality Disorder