Neural responses to negative feedback are related to negative emotionality in healthy adults

Prior neuroimaging and electrophysiological evidence suggests that potentiated responses in the anterior cingulate cortex (ACC), particularly the rostral ACC, may contribute to abnormal responses to negative feedback in individuals with elevated negative affect and depressive symptoms. The feedback-related negativity (FRN) represents an electrophysiological index of ACC-related activation in response to performance feedback. The purpose of the present study was to examine the FRN and underlying ACC activation using low resolution electromagnetic tomography source estimation techniques in relation to negative emotionality (a composite index including negative affect and subclinical depressive symptoms). To this end, 29 healthy adults performed a monetary incentive delay task while 128-channel event-related potentials were recorded. We found that enhanced FRNs and increased rostral ACC activation in response to negative-but not positive-feedback was related to greater negative emotionality. These results indicate that individual differences in negative emotionality-a putative risk factor for emotional disorders-modulate ACC-related processes critically implicated in assessing the motivational impact and/or salience of environmental feedback.     

Neural correlates of inhibitory deficits in depression

The present study used functional magnetic resonance imaging to examine neural correlates of inhibitory dysfunction in individuals diagnosed with major depressive disorder (MDD). Twelve MDD participants and 12 never-depressed controls completed the negative affective priming (NAP) task in the scanner. Results indicated that, in depressed participants, increased activation in the rostral anterior cingulate cortex (rACC) is associated with inhibition of negative, but not positive, words; in contrast, in nondepressed participants, inhibition of positive, but not negative, words is associated with increased activation in the rACC. These findings indicate that abnormalities in neural function, especially in the rACC, may underlie difficulties experienced by depressed individuals in inhibiting negative thoughts. These results underscore the importance of continuing to examine the relation between cognitive and neural functioning in depression in order to gain a broader and more integrative understanding of this disorder.     

Pilot study of treatment for major depression among women prisoners with substance use disorder

This study, the largest randomized controlled trial of treatment for major depressive disorder (MDD) in an incarcerated population to date, wave-randomized 38 incarcerated women (6 waves) with MDD who were attending prison substance use treatment to adjunctive group interpersonal psychotherapy (IPT) for MDD or to an attention-matched control condition. Intent-to-treat analyses found that IPT participants had significantly lower depressive symptoms at the end of 8 weeks of in-prison treatment than did control participants. Control participants improved later, after prison release. IPT's rapid effect on MDD within prison may reduce serious in-prison consequences of MDD.     

Reduced sustained brain activity during processing of positive emotional stimuli in major depression.

BACKGROUND: This study examines the directionality and temporal specificity of brain activity during sustained processing of emotional stimuli in individuals with current major depressive disorder (MDD) and nondepressed control participants. METHODS: Slow wave (SW) components of the event-related brain potential (ERP) were recorded from 16 control participants and 15 participants with MDD during a working memory task. During the task, individuals were shown a positive, neutral, or negative word and were asked to maintain it in memory for 5 sec. Participants then saw a letter and had to decide whether it was a part of the previously presented word. The ERP components were measured from nine scalp sites (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4) during the encoding of emotional words. RESULTS: Compared with control individuals, MDD participants exhibited decreased brain responses to positive relative to negative or neutral stimuli. This decrease in brain activity during processing of positive information was evident across all sites and SW components. CONCLUSIONS: Our findings suggest that cognitive deficits in MDD may stem from diminished brain responses during processing of positive information and may not be associated with an augmented response to negative stimuli.     

Major depressive disorder and attenuated negative symptoms in a child and adolescent sample with psychosis risk syndrome: the CAPRIS study

Some 70–80% of subjects with psychotic risk syndrome (PRS) have lifetime comorbidity, with depressive disorders being the most common. A high proportion of patients with PRS present nonspecific symptoms which can be confounding factors for diagnosis. Depressive and negative symptoms may be difficult to distinguish and it is important to differentiate them. The aim of this study is to assess the presence of depressive disorder in a child and adolescent sample of PRS and to examine the presence of negative symptoms and detect possible confounding characteristics between them and depressive symptoms. This is a naturalistic multi-site study with subjects who met PRS criteria. A sample of 89 PRS adolescent patients was included. Major depressive disorder (MDD) is the most prevalent comorbid disorder (34.83%). The sample was divided into patients who met criteria for MDD (PRS-MDD, n = 31) and those who did not have this disorder (PRS-ND, n = 44). We obtained significant differences in the attenuated negative symptoms (ANS) between PRS-MDD and PRS-ND (68.18 vs. 90.32%, respectively, p = 0.021). Subjects with MDD presented a higher score in ANS and Hamilton Depression Rating Scale (HDRS). Moreover, we obtained a correlation between negative symptomatology and HDRS score with a higher score on HDRS in subjects with higher negative symptom scores (r = 0.533, p < 0.001). More research is needed to fine tune differentiation between depressive and negative symptoms and learn more about the possible impact of MDD on PRS children and adolescents.

     

Functional connectivity between the amygdala and prefrontal cortex in medication-naive individuals with major depressive disorder

Background

Convergent evidence suggests dysfunction within the prefrontal cortex (PFC) and amygdala, important components of a neural system that subserves emotional processing, in individuals with major depressive disorder (MDD). Abnormalities in this system in the left hemisphere and during processing of negative emotional stimuli are especially implicated. In this study, we used functional magnetic resonance imaging (fMRI) to investigate amygdala–PFC functional connectivity during emotional face processing in medication-naive individuals with MDD.

Methods

Individuals with MDD and healthy controls underwent fMRI scanning while processing 3 types of emotional face stimuli. We compared the strength of functional connectivity from the amygdala between the MDD and control groups.

Results

Our study included 28 individuals with MDD and 30 controls. Decreased amygdala–left rostral PFC (rPFC) functional connectivity was observed in the MDD group compared with controls for the fear condition (p < 0.05, corrected). No significant differences were found in amygdala connectivity to any cerebral regions between the MDD and control groups for the happy or neutral conditions.

Limitations

All participants with MDD were experiencing acute episodes, therefore the findings could not be generalized to the entire MDD population.

Conclusion

Medication-naive individuals with MDD showed decreased amygdala–left rPFC functional connectivity in response to negative emotional stimuli, suggesting that abnormalities in amygdala–left rPFC neural circuitry responses to negative emotional stimuli might play an important role in the pathophysiology of MDD.     

MEASURING COGNITIVE FUNCTION IN MDD: EMERGING ASSESSMENT TOOLS

Cognitive impairment is emerging as an important therapeutic target in patients with psychiatric illnesses, including major depressive disorder (MDD). The objective of this general overview is to briefly review the evidence for cognitive impairment in MDD and to summarize a representative sample of cognitive assessment tools currently available to assess cognitive function in depressed patients. Study results in MDD patients with cognitive dysfunction are somewhat inconsistent, likely due to the heterogeneity of the disorder as well as the use of diverse assessment tools. Measuring cognitive changes in this population is challenging. Cognitive symptoms are typically less severe than in patients with schizophrenia and bipolar disorder, requiring greater sensitivity than afforded by existing tools. Preliminary evidence suggests antidepressant treatments may improve cognitive functioning as a direct result of ameliorating depressive symptoms; however, any procognitive effects have not been elucidated. To evaluate antidepressant efficacy in MDD patients with cognitive dysfunction, a standardized cognitive battery for use in clinical trials is essential.     

Neurocognitive impairments and quality of life in unemployed patients with remitted major depressive disorder

Quality of life (QOL) has been reported to be impaired in patients with major depressive disorder (MDD), even after remission according to symptom rating scales. Although a relationship between QOL and neurocognitive dysfunction has been reported during depressive episodes, little is known about this relationship in remitted MDD patients. The aim of the present study was to investigate the relationship between QOL and neurocognitive dysfunction in patients with remitted MDD while controlling for confounding factors. Forty-three remitted MDD patients were assessed with neuropsychological tests and QOL, which was measured by a short-form 36-item health survey. The neurocognitive performances of the patients were compared with those of 43 healthy controls. We next evaluated the relationships between neurocognitive impairments, clinical factors, and QOL. Remitted MDD patients had poorer neurocognitive performances than healthy controls for psychomotor speed, attention, and verbal memory. Residual depressive symptoms were strongly associated with QOL. Delayed verbal recall was associated with general health perceptions, which are part of the QOL assessment, even after the effects of the residual depressive symptoms were considered. The results may indicate that clinicians should try to detect neurocognitive dysfunctions that may interfere with QOL using neurocognitive assessments in their daily practice.     

Variation in the corticotropin-releasing hormone receptor 1 (CRHR1) gene influences fMRI signal responses during emotional stimulus processing

The corticotropin-releasing hormone (CRH) system coordinates neuroendocrine and behavioral responses to stress and has been implicated in the development of major depressive disorder (MDD). Recent reports suggest that GG-homozygous individuals of a single nucleotide polymorphism (rs110402) in the CRH receptor 1 (CRHR1) gene show behavioral and neuroendocrine evidence of stress vulnerability. The present study explores whether those observations extend to the neuronal processing of emotional stimuli in humans. CRHR1 was genotyped in 83 controls and a preliminary sample of 16 unmedicated patients with MDD who completed a functional magnetic resonance imaging scan while viewing blocks of positive, negative, and neutral words. In addition, potential mediating factors such as early life stress, sex, personality traits, and negative memory bias were examined. Robust differences in blood oxygenation level-dependent (BOLD) signal were found in healthy controls (A allele carriers > GG-homozygotes) in the right middle temporal/angular gyrus while subjects were viewing negative versus neutral words. Among GG-homozygotes, BOLD signal in the subgenual cingulate was greater in MDD participants (n = 9) compared with controls (n = 33). Conversely, among A-carriers, BOLD signal was smaller in MDD (n = 7) compared with controls (n = 50) in the hypothalamus, bilateral amygdala, and left nucleus accumbens. Early life stress, personality traits, and levels of negative memory bias were associated with brain activity depending on genotype. Results from healthy controls and a preliminary sample of MDD participants show that CRHR1 single nucleotide polymorphism rs110402 moderates neural responses to emotional stimuli, suggesting a potential mechanism of vulnerability for the development of MDD.     

Dysfunctional distracter inhibition and facilitation for sad faces in depressed individuals

Depression is a commonly occurring mental disorder, which is characterized by dysfunctional inhibition and facilitation for emotional stimuli. The aim of the present study was to investigate distracter inhibition and facilitation for emotional faces in depressed individuals in a negative affective priming task. Control participants who had never suffered from depression (NC), sub-clinically depressed participants, and participants diagnosed with a current major depressive disorder (MDD), Anxiety Inventory, the Hamilton Depression Rating Score were recruited using the Beck Depression Inventory, the Beck and DSM-IV as tools. Twenty-four participants in each group completed a negative affective priming task. The main finding was that there were no significant differences among the three groups in the positive and negative priming effects of happy faces. However, there were significant differences for positive and negative priming effects of sad faces between each pair of groups, with the effects being lowest for MDD and highest for NC participants. It can be concluded that depressed individuals are characterized by enhanced facilitation and deficient inhibition for negative materials, which is a stable cognitive vulnerability risk, possibly associated with the occurrence of depression. There are differences in the cognitive dysfunction for negative stimuli between clinically depressed and sub-clinically depressed individuals.     

Differences in depressive thoughts between major depressive disorder, IFN-alpha-induced depression, and depressive disorders among cancer patients

OBJECTIVE: The objective of this study is to test the hypothesis that there are differences in the distribution of negative thoughts among major depressive disorders (MDD), depressive disorders among cancer patients, and IFN-alpha-induced depression. METHODS: Twenty-three patients affected by MDD, 25 cancer patients affected by depressive disorders (20 MDD), and 19 patients affected by IFN-alpha-induced depression satisfying MDD criteria were evaluated using the 17-item Hamilton Depression Rating Scale and the 13-item Beck Depression Inventory. RESULTS: Sense of guilt was higher among MDD patients (56.5%) and was lower among cancer patients (4%) (P<.0001). Sense of failure, dissatisfaction, and self-dislike were higher among MDD patients than among IFN-alpha patients (P<.0001). CONCLUSIONS: In our study, patients affected by MDD present a different pattern of symptoms in comparison with patients affected by IFN-alpha-induced depression and depressive disorders. In particular, core depressive thoughts were less frequent in the last two conditions.     

Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression.

BACKGROUND: Bipolar disorder (BD) is characterised by abnormalities in mood and emotional processing, but the neural correlates of these, their relationship to depressive symptoms, and the similarities with deficits in major depressive disorder (MDD) remain unclear. We compared responses within subcortical and prefrontal cortical regions to emotionally salient material in patients with BP and MDD using functional magnetic resonance imaging. METHODS: We measured neural responses to mild and intense expressions of fear, happiness, and sadness in euthymic and depressed BD patients, healthy control subjects, and depressed MDD patients. RESULTS: Bipolar disorder patients demonstrated increased subcortical (ventral striatal, thalamic, hippocampal) and ventral prefrontal cortical responses particularly to mild and intense fear, mild happy, and mild sad expressions. Healthy control subjects demonstrated increased subcortical responses to intense happy and mild fear, and increased dorsal prefrontal cortical responses to intense sad expressions. Overall, MDD patients showed diminished neural responses to all emotional expressions except mild sadness. Depression severity correlated positively with hippocampal response to mild sadness in both patient groups. CONCLUSIONS: Compared with healthy controls and MDD patients, BD patients demonstrated increased subcortical and ventral prefrontal cortical responses to both positive and negative emotional expressions.     

Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls

CONTEXT: An instructive paradigm for investigating the relationship between brain serotonin function and major depressive disorder (MDD) is the response to tryptophan depletion (TD) induced by oral loading with all essential amino acids except the serotonin precursor tryptophan. OBJECTIVE: To determine whether serotonin dysfunction represents a trait abnormality in MDD in the context of specific neural circuitry abnormalities involved in the pathogenesis of MDD. DESIGN: Randomized double-blind crossover study. SETTING: Outpatient clinic. PARTICIPANTS: Twenty-seven medication-free patients with remitted MDD (18 women and 9 men; mean +/- SD age, 39.8 +/- 12.7 years) and 19 controls (10 women and 9 men; mean +/- SD age, 34.4 +/- 11.5 years). INTERVENTIONS: We induced TD by administering capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing hydrous lactose. Fluorodeoxyglucose F 18 positron emission tomography studies were performed 6 hours after TD. Magnetic resonance images were obtained for all participants. MAIN OUTCOME MEASURES: Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of sham depletion and TD. Behavioral assessments used a modified (24-item) version of the Hamilton Depression Rating Scale. RESULTS: Tryptophan depletion induced a transient return of depressive symptoms in patients with remitted MDD but not in controls (P<.001). Compared with sham depletion, TD was associated with an increase in regional cerebral glucose utilization in the orbitofrontal cortex, medial thalamus, anterior and posterior cingulate cortices, and ventral striatum in patients with remitted MDD but not in controls. CONCLUSION: The pattern of TD-induced regional cerebral glucose utilization changes in patients with remitted MDD suggests that TD unmasks a disease-specific, serotonin system-related trait dysfunction and identifies a circuit that probably plays a key role in the pathogenesis of MDD.     

Brain potentials associated with outcome expectation and outcome evaluation

Feedback-related negativity is a negative deflection in brain potentials associated with feedback indicating monetary losses or response errors. Feedback-related negativity is studied primarily in paradigms in which participants experience negative outcomes that appear to be contingent upon their previous choices. This study investigated whether feedback-related negativity can be elicited by a randomly assigned cue indicating potential monetary loss. The expected loss or win can be materialized or averted depending on participants' performance in a subsequent game. Compared with the win cue, the loss cue elicited a weak but significant feedback-related negativity-like effect. It is suggested that the anterior cingulate cortex, which generates feedback-related negativity, may function as a pre-warning system that alerts the brain to get ready for future events.     

Feedback-related processes during a time-production task in young and older adults

ObjectiveWe examined whether the age-related decline in the integrity of the mid-brain dopamine system plays a role in the adaptation of precisely timed motor responses by feedback information.MethodsParticipants performed a time-production task with feedback given after each trial. They were encouraged to use the feedback for improving temporal response accuracy. Event-related potentials to the feedback were analyzed.ResultsOlder participants performed poorer than the young. Overall, high response accuracy was more favoured following positive than negative feedback. Older participants performed even worse after negative feedback than the younger. The feedback-related negativity (FRN) was of lower amplitude for older vs. young participants. FRN amplitude correlated significantly with response accuracy only for the young group.ConclusionsThe decreased response accuracy during time production of the older group may be related to a weakened fronto-striatal dopamine system and thus a reduced ability to use feedback information for improving temporal aspects of the motor response.SignificanceThe study points to difficulties especially for older participants to process error feedback, and it underlines the importance of positive feedback in order to improve temporal response accuracy. Suggestions can be drawn for the design of feedback information especially for older adults in motor learning environments.     

Italian neurologists’ perception on cognitive symptoms in major depressive disorder

The assessment of cognition is an important part of major depressive disorder (MDD) evaluation and a crucial issue is the physicians’ perception of cognitive dysfunction in MDD that remains nowadays a little known matter. The present study aims at investigating the understanding of neurologists’ perception about cognitive dysfunction in MDD. An on-line survey addressed to 85 Italian neurologists in the period between May and June 2015 was performed. The questionnaire comprised three sections: the first section collecting information on neurologists’ socio-demographic profile, the second investigating cognitive symptoms relevance in relation with different aspects and the third one explicitly focusing on cognitive symptoms in MDD. Cognitive symptoms are considered most significant among DSM-5 symptoms to define the presence of a Major Depressive Episode in a MDD, to improve antidepressant therapy adherence, patients’ functionality and concurrent neurological condition, once resolved. Furthermore, an incongruity came to light from this survey: the neurologists considered cognitive symptoms a not relevant aspect to choose the antidepressant treatment in comparison with the other DSM-5 symptoms on one side, but they declared the opposite in the third part of the questionnaire focused on cognitive symptoms. Cognitive symptoms appeared to be a relevant aspect in MDD and neurologists have a clear understanding of this issue. Nevertheless, the discrepancy between neurologists’ perception on cognitive symptoms and the antidepressant treatment highlights the feeling of an unmet need that could be filled increasing the awareness of existing drugs with pro-cognitive effects.     

Implications of the DSM's emphasis on sadness and anhedonia in major depressive disorder

At least five symptoms must occur for a DSM diagnosis of major depressive disorder (MDD), one of which must be sadness or anhedonia. The present study is the first known investigation of the implications of the presence or absence of these prioritized symptoms on symptom expression and clinical characteristics among 564 young adults with MDD. Differences in symptom expression and clinical characteristics occurred among MDD participants with sadness relative to those without sadness as well as among MDD participants with anhedonia relative to those without anhedonia. Differential symptom expression could have important implications for the etiology, prevention, and treatment of MDD.     

Symptom overlap in posttraumatic stress disorder and major depression

Over the past decade there has been consistent criticism of the diagnostic criteria of posttraumatic stress disorder (PTSD) because of its high comorbidity with other mental disorders. Part of the problem surrounding PTSD may be related to the heterogeneity of its symptoms. In fact, recent research has identified a subset of PTSD symptoms, including symptoms of numbing and dysphoria, that may explain much of the overlap between PTSD and major depressive disorder (MDD). The present study sought to extend prior work by investigating the various subsets of PTSD symptoms in individuals from all four diagnostic combinations of PTSD and MDD (no MDD-PTSD, MDD-only, PTSD-only, and comorbid MDD-PTSD). Consenting participants completed diagnostic interviews and were categorized into the four groups. Based on responses to a self-report measure of PTSD symptoms, participants with no MDD-PTSD reported the least severe symptoms while the participants with comorbid MDD-PTSD reported the most severe symptoms. Interesting, participants in the MDD-only and PTSD-only groups consistently reported similar scores across all PTSD symptom scales. These findings further highlight the problematic diagnostic criteria and comorbidity in PTSD and emphasize the need to incorporate transdiagnostic treatment practices that focus on the overlapping symptoms, rather than specific diagnostic categories.     

Reductions in anti-inflammatory gut bacteria are associated with depression in a sample of young adults

We assessed the gut microbiota of 90 American young adults, comparing 43 participants with major depressive disorder (MDD) and 47 healthy controls, and found that the MDD subjects had significantly different gut microbiota compared to the healthy controls at multiple taxonomic levels. At the phylum level, participants with MDD had lower levels of Firmicutes and higher levels of Bacteroidetes, with similar trends in the at the class (Clostridia and Bacteroidia) and order (Clostridiales and Bacteroidales) levels. At the genus level, the MDD group had lower levels of Faecalibacterium and other related members of the family Ruminococcaceae, which was also reduced relative to healthy controls. Additionally, the class Gammaproteobacteria and genus Flavonifractor were enriched in participants with MDD. Accordingly, predicted functional differences between the two groups include a reduced abundance of short-chain fatty acid production pathways in the MDD group. We also demonstrated that the magnitude of taxonomic changes was associated with the severity of depressive symptoms in many cases, and that most changes were present regardless of whether depressed participants were taking psychotropic medications. Overall, our results support a link between MDD and lower levels of anti-inflammatory, butyrate-producing bacteria, and may support a connection between the gut microbiota and the chronic, low-grade inflammation often observed in MDD patients.     

Deficient inhibition of return for emotional faces in depression

Depression is a commonly-occurred mental disorder. Researchers have highlighted the attentional bias of depressive disorders, although results have been mixed. The cue-target task has often been used to explore attentional bias; a particular phenomenon revealed by such studies is the inhibition of return (IOR). However, cue-target task has seldom been used so far in the study of depressed patients. The aim of the present study was to investigate the IOR phenomenon in depressed individuals in cue-target task using emotional faces as cues.Control participants who had never suffered depression (NC), participants who had experienced at least two depressive episodes in their lives but were currently remitted (RMD), and participants diagnosed with a current major depressive disorder (MDD), were recruited using BDI, BAI, HDRS and DSM-IV as tools. Seventeen participants in each group completed a cue-target task in a behavioral experiment that comprised three kinds of experimental condition, two cue types and four face types. Each participant also completed a simpler cue-target task in an event-related potential (ERP) experiment. In cue-target task, a target appeared after a cue and the participant responded to its location.In the behavioral experiment, it was found that when the stimulus onset asynchrony (SOA) was 14 ms, the NC and RMD participants had IOR effects for all faces and MDD participants for angry and sad faces. When the SOA was 250 ms, all three groups all had cue validity for sad faces but the effect was much more marked for the MDD group. When the SOA was 750 ms, the NC participants had an IOR effect for sad faces, the RMD participants had cue validity for angry, happy and sad faces, and the MDD participants had cue validity for sad faces and an IOR effect for angry faces. In the ERP experiment, the NC participants showed bigger P3 amplitude for happy cue compared with the other groups, smaller P1 amplitude for happy faces in the invalid cue condition than for other faces, smaller P1 amplitude for sad faces in the valid cue condition than for happy faces, bigger P3 amplitude for happy faces in the valid cue condition compared with MDD participants, and bigger P3 amplitude for sad faces in the invalid cue condition compared with other groups. The RMD participants had larger P3 amplitude for sad cue than for other faces, larger P3 amplitude for happy faces in the valid cue condition compared with MDD participants, and smaller P3 amplitude for sad faces in the invalid cue condition compared with NC participants. The MDD participants had larger P1 amplitude for sad cue compared with other groups, larger P3 amplitude for sad cue than for other face cues, smaller P3 amplitude for sad faces in the invalid cue condition compared with NC participants, and smaller P3 amplitude for happy faces in the valid cue condition compared with other groups.It can be concluded that the MDD participants had cue validity and deficient IOR for negative stimuli. The deficient inhibition of negative stimuli renders them unable to eliminate the interference of negative stimuli and causes the maintenance and development of depression. The RMD participants had cue validity and deficient IOR for both positive and negative stimuli, which enables them to perceive positive and negative stimuli sufficiently and to maintain emotional balance.