A meta-analysis of emotional reactivity in major depressive disorder

Three alternative views regarding how Major Depressive Disorder (MDD) alters emotional reactivity have been featured in the literature: positive attenuation (reduced positive reactivity), negative potentiation (increased negative reactivity), and emotion context insensitivity (ECI; reduced positive and negative reactivity). Although empirical studies have accumulated on emotional reactivity in MDD, this report is to our knowledge the first systematic quantitative review of this topic area. In omnibus analyses of 19 laboratory studies comparing the emotional reactivity of healthy individuals to that of individuals with MDD, MDD was characterized by reduced emotional reactivity to both positively and negatively valenced stimuli, with the reduction larger for positive stimuli (d=-.53) than for negative stimuli (d=-.25). Results were similar when 3 major emotion response systems (self-reported experience, expressive behavior, and peripheral physiology) were analyzed individually. The ECI view of emotional reactivity in MDD is well supported by laboratory data. Implications for the understanding of emotions in MDD are discussed.     

Respiratory sinus arrhythmia reactivity predicts emotion regulation and depressive symptoms in at-risk and control children

We examined respiratory sinus arrhythmia (RSA), emotion regulation (ER), and prospective depressive symptoms in children at risk for depression and controls. Of the 65 children (35 boys; 5–13 years) in the sample, 39 had a parent with childhood-onset mood disorder and 26 had a parent with no history of major psychiatric disorder. RSA during pre- and post-film baselines and RSA reactivity to sad film clip were measured. Later, children's ER responses (focusing on sad/distressing affect) were assessed using a parent-reported questionnaire, and depressive symptoms were measured via clinical ratings. Results indicated that, compared to the initial baseline, a greater decrease in RSA (i.e., more vagal withdrawal) in response to the sad film clip predicted more adaptive ER responses and lower levels of clinician-rated depressive symptoms. However, tests for ER as a mediator of the association between RSA reactivity and depressive symptoms were precluded because maladaptive, but not adaptive, ER was associated with depressive symptoms. Overall, results suggest that cardiac vagal withdrawal (a greater decrease in RSA) in response to an emotional stimulus reflects more adaptive parasympathetic activity, which could facilitate children's ability to effectively manage their sadness and distress and predict lower risk of depressive symptoms over time.     

Increased neural sensitivity to self‐relevant stimuli in major depressive disorder

The current research examined how individuals with depression process emotional, self‐relevant stimuli. Across two studies, individuals with depression and healthy controls read stimuli that varied in self‐relevance while EEG data were recorded. We examined the late positive potential (LPP), an ERP component that captures the dynamic allocation of attention to motivationally salient stimuli. In Study 1, participants read single words in a passive‐viewing task. Participants viewed negative, positive, or neutral words that were either normative or self‐generated. Exploratory analyses indicated that participants with depression exhibited affective modulation of the LPP for self‐generated stimuli only (both positive and negative) and not for normative stimuli; healthy controls exhibited similar affective modulation of the LPP for both self‐relevant and normative stimuli. In Study 2, using a separate sample and a different task, stimuli were provided within the context of sentence stems referring to the self or other people. Participants with depression were more likely to endorse negative self‐referent sentences and reject positive ones compared to healthy controls. Depressed participants also exhibited an increased LPP to negative stimuli compared to positive or neutral stimuli. Together, these two studies suggest that depression is characterized by relatively increased sensitivity to affective self‐relevant stimuli, perhaps in the context of a broader reduction in emotional reactivity to stimuli that are not self‐relevant. Thus, depression may be characterized by a more nuanced pattern based on the degree of stimulus self‐relevance than either a global decrease or increase in reactivity to affective stimuli.     

Autobiographical memories in major depressive disorder

The objective of this research was to study the relation between the processing and recall of information in major depressive disorder. An autobiographical memory task was applied to 42 subjects with a diagnosis of major depressive disorder, 28 subjects with a diagnosis of panic disorder and 51 subjects without any psychological disorder. We used clinical scales for the evaluation of depression and anxiety. The results of the three groups, and both assessment periods of depressed subjects, were compared. The results indicate the existence, in severely depressed subjects, of a bias in processing and recalling negative information. We associate this situation to the existence of negative contents in self-schemas and processing and recall of information consistent with these schema contents. Based on the obtained results, we consider that the onset and maintenance of depression is more related to the information encoding and recall processes, controlled by the self's negative schemas, than with negative thoughts.     

RSA fluctuation in major depressive disorder

Cardiac vagal control, as measured by indices of respiratory sinus arrhythmia (RSA), has been investigated as a marker of impaired self-regulation in mental disorders, including depression. Past work in depressed samples has focused on deficits in resting RSA levels, with mixed results. This study tested the hypothesis that depression involves abnormal RSA fluctuation. RSA was measured in depressed and healthy control participants during rest and during two reactivity tasks, each followed by a recovery period. Relative to controls, depressed persons exhibited lower resting RSA levels as well as less RSA fluctuation, primarily evidenced by a lack of task-related vagal suppression. Group differences in RSA fluctuation were not accounted for by differences in physical health or respiration, whereas group differences in resting RSA level did not survive covariate analyses. Depression may involve multiple deficits in cardiac vagal control.     

Automaticity in anxiety disorders and major depressive disorder

In this paper we examine the nature of automatic cognitive processing in anxiety disorders and Major Depressive Disorder (MDD). Rather than viewing automaticity as a unitary construct, we follow a social cognition perspective (Bargh, 1994) that argues for four theoretically independent features of automaticity: unconscious (processing of emotional stimuli occurs outside awareness), efficient (processing emotional meaning uses minimal attentional resources), unintentional (no goal is needed to engage in processing emotional meaning), and uncontrollable (limited ability to avoid, alter or terminate processing emotional stimuli). Our review of the literature suggests that most anxiety disorders are characterized by uncontrollable, and likely also unconscious and unintentional, biased processing of threat-relevant information. In contrast, MDD is most clearly typified by uncontrollable, but not unconscious or unintentional, processing of negative information. For the anxiety disorders and for MDD, there is no sufficient evidence to draw firm conclusions about efficiency of processing, though early indications are that neither anxiety disorders nor MDD are characterized by this feature. Clinical and theoretical implications of these findings are discussed and directions for future research are offered. In particular, it is clear that paradigms that more directly delineate the different features of automaticity are required to gain a more comprehensive and systematic understanding of the importance of automatic processing in emotion dysregulation.     

Neural mechanisms of cognitive reappraisal in remitted major depressive disorder

Background

Down-regulation of negative emotions by cognitive strategies relies on prefrontal cortical modulation of limbic brain regions, and impaired frontolimbic functioning during cognitive reappraisal has been observed in affective disorders. However, no study to date has examined cognitive reappraisal in unmedicated euthymic individuals with a history of major depressive disorder relative to symptom-matched controls. Given that a history of depression is a critical risk factor for future depressive episodes, investigating the neural mechanisms of emotion regulation in remitted major depressive disorder (rMDD) may yield novel insights into depression risk.

Method

We assessed 37 individuals (18 rMDD, 19 controls) with functional magnetic resonance imaging (fMRI) during a task requiring cognitive reappraisal of sad images.

Results

Both groups demonstrated decreased self-reported negative affect after cognitive reappraisal and no group differences in the effects of cognitive reappraisal on mood were evident. Functional MRI results indicated greater paracingulate gyrus (rostral anterior cingulate cortex, Brodmann area 32) activation and decreased right midfrontal gyrus (Brodmann area 6) activation during the reappraisal of sad images.

Limitations

Trial-by-trial ratings of pre-regulation affect were not collected, limiting the interpretation of post-regulation negative affect scores.

Conclusions

Results suggest that activation of rostral anterior cingulate cortex, a region linked to the prediction of antidepressant treatment response, and of the right midfrontal gyrus, a region involved in cognitive control in the context of cognitive reappraisal, may represent endophenotypic markers of future depression risk. Future prospective studies will be needed to validate the predictive utility of these neural markers.     

Major depressive disorder in adolescents: family psychiatric history predicts severe behavioral disinhibition

BACKGROUND: Major Depressive Disorder (MDD) becomes increasingly prevalent during adolescence and is associated with substantial psychiatric comorbidity and psychosocial impairment. The marked behavioral heterogeneity evident among adolescents with MDD suggests the possibility of distinct subtypes. This study was designed to determine whether family psychiatric histories differ between groups of MDD adolescents defined by the presence or absence of severe behavioral disinhibition. METHODS: Adolescents with MDD (n = 71) completed the Buss-Durkee Hostility Inventory--Adapted, Adolescent Aggressive Incidents Interview (AAII), Measure of Aggression, Violence, and Rage in Children, Diagnostic Interview Schedule for Children, Suicidal Ideation Questionnaire-JR., Suicidal Behavior Inventory, and Reynolds Adolescent Depression Scale. Parents completed the Family Informant Schedule and Criteria, Children's Affective Liability Scale, AAII, and a partial DISC. Behavioral disinhibition (BD) measures were used to assign adolescents to MDD+BD (n = 41) and MDD-BD (n = 30) groups. RESULTS: The MDD+BD group had a higher prevalence of drug use disorders in biological fathers than the MDD-BD group. The MDD+BD group also had higher proportions of paternal second degree relatives with alcohol use disorders, drug use disorders, and psychiatric hospitalizations, and a higher proportion of maternal second degree relatives with antisocial personality disorder. LIMITATIONS: Limitations include reliance on single informants for family psychiatric histories and the failure to distinguish between child- and adolescent-onset depression. CONCLUSIONS: Family psychiatric histories differentiated MDD adolescents grouped by the presence or absence of behavioral disinhibition, suggesting possible etiologic mechanisms. Further research on subtypes or comorbid presentations may assist in the development of targeted treatment strategies.     

Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder

Dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis is believed to play a role in the pathophysiology of depression. To investigate mechanisms that may underlie this effect, we examined several indices of HPA axis function – specifically, diurnal cortisol slope, cortisol awakening response, and suppression of cortisol release following dexamethasone administration – in 26 pre-menopausal depressed women and 23 never depressed women who were matched for age and body mass index. Salivary cortisol samples were collected at waking, 30 min after waking, and at bedtime over three consecutive days. On the third day, immediately after the bedtime sample, participants ingested a 0.5 mg dexamethasone tablet; they then collected cortisol samples at waking and 30 min after waking the following morning. As predicted, depressed women exhibited flatter diurnal cortisol rhythms and more impaired suppression of cortisol following dexamethasone administration than non-depressed women over the three sampling days. In addition, flatter diurnal cortisol slopes were associated with reduced cortisol response to dexamethasone treatment, both for all women and for depressed women when considered separately. Finally, greater self-reported depression severity was associated with flatter diurnal cortisol slopes and with less dexamethasone-related cortisol suppression for depressed women. Depression in women thus appears to be characterized by altered HPA axis functioning, as indexed by flatter diurnal cortisol slopes and an associated impaired sensitivity of cortisol to dexamethasone. Given that altered HPA axis functioning has been implicated in several somatic conditions, the present findings may be relevant for understanding the pathophysiology of both depression and depression-related physical disease.     

Serum lipid concentrations in Croatian veterans with post-traumatic stress disorder,post-traumatic stress disorder comorbid with major depressive disorder,or major depressive disorder

The aim of this study was to assess eventual differences in serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, LDL-C/HDL-C ratio between veterans with combat-related post-traumatic stress disorder (PTSD) only or comorbid with major depressive disorder (MDD), veterans with combat experiences with MDD, and healthy control group. PTSD and/ or MDD were diagnose according to structured clinical interview based on DSM-IV criteria. Additional criteria to diagnose PTSD were Clinician Administered PTSD Scale (CAPS), and to diagnose MDD Montgomery-Asberg Depression Rating Scale (MADRAS). Serum lipid concentrations were determined by using the enzyme-assay method. Veterans with combat-related PTSD as well as veterans with combat-related PTSD comorbid with MDD showed significantly higher concentrations of cholesterol (F=9.858, p<0.01), triglycerides (F=10.112, p<0.01), LDL-C (F=11.145, p<0.01), and LDL-C/HDL-C ratio (F=8.346, p<0.01) vs. veterans with MDD or healthy control group. Contrary healthy control group and veterans with MDD showed significantly higher concentrations of HDL-C (F=8.421, p<0.01), vs. veterans with PTSD or PTSD comorbid with MDD. In conclusion, there are no differences in serum lipid concentrations between veterans with combat-related PTSD and PTSD comorbid with MDD, but they have higher lipid concentrations than veterans with MDD or healthy control subjects.     

Blunted neural response to rewards prospectively predicts depression in adolescent girls

The prevalence of depression increases substantially during adolescence. Several predictors of major depressive disorder have been established, but their predictive power is limited. In the current study, the feedback negativity (FN), an event‐related potential component elicited by feedback indicating monetary gain versus loss, was recorded in 68 never‐depressed adolescent girls. Over the following 2 years, 24% of participants developed a major depressive episode (MDE); illness onset was predicted by blunted FN at initial evaluation. Lower FN amplitude predicted more depressive symptoms during the follow‐up period, even after controlling for neuroticism and depressive symptoms at baseline. This is the first prospective study to demonstrate a link between a neural measure of reward sensitivity and the first onset of an MDE. The current results suggest that low reward sensitivity may be an important factor in the development of depression.     

Depression in paranoid and nonparanoid schizophrenic patients compared with major depressive disorder

Background: Depression occurring in schizophrenia is a common problem; however, investigators have typically not studied it with the paranoid/nonparanoid dichotomy in mind. This study examines the quality as well as the severity of depression in three psychiatric groups: paranoid schizophrenia patients, nonparanoid schizophrenia patients, and nonpsychotic major depression patients. Method: Clinical and sociodemographic data were collected on 27 paranoid and 27 nonparanoid schizophrenia patients during their postpsychotic phase while they were at least mildly depressed, and a comparison group of 27 nonpsychotic patients diagnosed with major depressive disorder. The three groups were then assessed on various psychometric scales for severity of depression, profile of symptoms, suicidal risk, and anhedonia. Results: The paranoid schizophrenia patients were more depressed and more at risk for suicide than the nonparanoid schizophrenia patients, yet their depressive profiles and levels of anhedonia were similar. Conclusions: Depressed mood and anhedonia constitute serious problems for schizophrenia patients, but particularly for paranoid schizophrenia patients during the postpsychotic phase of their illnesses. Clinical implications: Schizophrenia patients, especially those with the paranoid features, should be routinely evaluated and monitored for depression. Apart from treatment with drugs, cognitive therapy may be considered a viable option, particularly for paranoid schizophrenia patients. Limitations: Gender was not matched for the two schizophrenia groups and extrapyramidal side effects were not measured.     

Cardiovascular reactivity of younger and older adults to positive-, negative-, and mixed-emotion cognitive challenge

Although aging is associated with progressive increases in blood pressure level, previous research has been inconsistent as to whether older adults show greater or lesser cardiovascular reactivity (CVR) to emotion than do younger adults. There is reason to believe that these inconsistencies could be clarified by examining age-related differences in hemodynamic profile revealed by measuring the pattern of cardiac output and total peripheral resistance associated with changes in blood pressure reactivity. Accordingly, the present study examined the performance, CVR, and hemodynamic profile of younger and older adults during encoding and recognition of word pairs involving four valence types: positive, negative, mixed (positive/negative), and neutral word pairs. Results revealed higher baseline blood pressure, increased CVR characterized by a vascular hemodynamic profile, and more rapid recovery (especially during encoding) for older than for younger participants. Results are discussed in light of research and theory on the relationship between aging and cardiovascular health.     

Memory related dysregulation of hippocampal function in major depressive disorder

Hippocampal abnormalities have frequently been associated with major depressive disorder (MDD), however evidence of a functional hippocampal deficit has remained illusive. Here, functional magnetic resonance imaging (fMRI) is employed in conjunction with an associative memory paradigm to investigate functional irregularities of the hippocampus during the encoding process. The use of a focussed analytical approach and a behavioural task targeted to hippocampal function confirmed the hypothesis that the normal modulation of hippocampal activation by encoding strength is dysregulated in MDD. Further analysis demonstrated that this impairment of function was specific to the hippocampus. A double dissociation between groups in the hippocampus and intraparietal sulcus indicates that compensatory mechanisms may exist. These results show that MDD is associated with a dysregulation of hippocampal function that cannot be explained in terms of overall brain state or motivational stance and provides an important link between memory impairments and hippocampal changes in MDD.     

Abnormal size of the amygdala predicts impaired emotional memory in major depressive disorder

BACKGROUND: Amygdala and hippocampus show significant structural abnormalities in major depressive disorder (MDD). Individuals with MDD have difficulties in emotional memory. A relationship between emotional memory deficits and structural abnormalities of amygdala and hippocampus in MDD has been proposed but not shown, yet. METHODS: The current study assessed memory for emotional faces in 21 young women with recent-onset MDD and 23 matched control subjects. All subjects underwent structural magnetic resonance imaging (3D-MRI) and a clinical and neuropsychological assessment. RESULTS: Depressive subjects had significantly enlarged amygdala size and significantly reduced hippocampal size compared with controls. Depressive subjects were significantly impaired in learning emotional facial expressions, with deficits being most pronounced for fearful, surprised and disgusted faces. Depressive subjects with amygdala volumes 1 SD or more above the mean of control subjects showed the strongest impairments. Correlation analyses revealed that larger left amygdala volumes were significantly related to worse memory performance and to higher anxiety scores of depressive subjects. Smaller left hippocampal volumes of depressive subjects were related to higher anxiety scores as well. LIMITATIONS: All MDD subjects were taking antidepressant medication at the time of the study. Longitudinal studies are needed to clarify whether the behavioral and/or volumetric abnormalities of MDD subjects can be attributed to medication or MDD or both. CONCLUSIONS: It might be speculated that amygdala enlargement in young MDD subjects is correlated with amygdalar over-activation and resolves with antidepressant treatment, as was shown for amygdalar over-activation.     

Impact of self-reported juvenile abuse on treatment outcome in patients with major depressive disorder

Background

We assessed the impact of juvenile abuse (emotional, physical, or sexual) on response to treatment in adults with major depressive disorder (MDD) suboptimally responsive to antidepressant therapy.

Methods

A post hoc analysis explored the relationship between self-reported history of juvenile abuse and response to risperidone or placebo augmentation during a 6-week double-blind study period in patients with MDD suboptimally responsive to a previous adequate trial of antidepressant monotherapy.

Results

Overall, only one clinical measure showed a small, but statistically significant difference in outcome between patients with abuse versus without abuse (HRSD-17). In patients reporting abuse (n=141), improvement with risperidone versus placebo augmentation was greater on several measures: HRSD-17 total and 2 subscale scores, responder rates, Q-LES-Q, and PaRTS-D. In patients without abuse (n=127), only two measures showed significant improvement: HRSD-17 subscale and PaRTS-D. Responder rates (HRSD-17) were: 40.9% (risperidone) versus 23.1% (placebo; p=0.01; odds ratio=2.7) in those with abuse, and 41.0% versus 34.4% (p=0.39; odds ratio=1.4) in those without. Adverse events rates were: 37.0% (risperidone) and 54.4% (placebo) in patients with abuse, and 56.3% and 55.6% in those without.

Limitations

Analysis not preplanned. Validated questionnaire not used to determine abuse status.

Conclusions

Self-reported juvenile abuse history may impact response to risperidone augmentation therapy in adults with MDD suboptimally responsive to antidepressants. Abuse status may reduce placebo response and reporting of adverse events.     

Cognitive control adjustments and conflict adaptation in major depressive disorder

Individuals with major depressive disorder (MDD) show alterations in the cognitive control function of conflict processing. We examined the influence of these deficits on behavioral and event‐related potential (ERP) indices of conflict adaptation, a cognitive control process wherein previous‐trial congruency modulates current‐trial performance, in 55 individuals with MDD and 55 matched controls. ERPs were calculated while participants completed a modified flanker task. There were nonsignificant between‐groups differences in response time, error rate, and N2 indices of conflict adaptation. Higher depressive symptom scores were associated with smaller mean N2 conflict adaptation scores for individuals with MDD and when collapsed across groups. Results were consistent when comorbidity and medications were analyzed. These findings suggest N2 conflict adaptation is associated with depressive symptoms rather than clinical diagnosis alone.     

Sleep deprivation alters pupillary reactivity to emotional stimuli in healthy young adults

The aim of this pilot study was to quantify the impact of sleep deprivation on psychophysiological reactivity to emotional stimuli. Following an adaptation night of sleep in the lab, healthy young adults were randomly assigned to either one night of total sleep deprivation or to a normal sleep control condition. The next afternoon, responses to positive, negative, and neutral picture stimuli were examined with pupillography, an indicator of cognitive and affective information processing. Only the sleep-deprived group displayed significantly larger pupil diameter while viewing negative pictures compared to positive or neutral pictures. The sleep-deprived group also showed anticipatory pupillary reactivity during blocks of negative pictures. These data suggest that sleep deprivation is associated with increased reactions to negative emotional information. Such responses may have important implications for psychiatric disorders, which may be triggered or characterized by sleep disturbances.     

Duloxetine for the treatment of major depressive disorder in women ages 40 to 55 years

The efficacy of duloxetine in the treatment of major depressive disorder in women of approximately perimenopausal age (40-55 years; 62 placebo subjects and 55 subjects taking duloxetine, 60 mg/day) was compared with that observed in cohorts of younger (<40 years, 94 placebo subjects and 85 duloxetine subjects) and older (>55 years, 26 placebo subjects and 25 duloxetine subjects) women. Women (ages 40-55 years) receiving duloxetine demonstrated significantly greater improvement in total scores on the 17-item Hamilton Rating Scale for Depression compared with placebo at the study endpoint (week 9). Significant advantages for duloxetine over placebo were observed on 17-item Hamilton depression scale subscales (core, Maier, anxiety, retardation, and sleep), in addition to the Clinical Global Impression severity and Patient Global Impression of Improvement Scale, the Quality of Life in Depression Scale, and Visual Analog Scales assessing pain severity. The magnitude of duloxetine's treatment effect in women ages 40-55 years was similar to that observed in younger (age <40 years) and older (age >55 years) female patients. In the placebo treatment groups, however, mean changes differed substantially by age group with the smallest placebo responses observed in the 40-55 age group. Duloxetine (60 mg/day) was demonstrated to be an effective treatment for major depressive disorder in this cohort of women ages 40-55 years.