Inhibitory control or regulatory difficulties have been explored in major depressive disorder (MDD) but typically in the context of affectively salient information. Inhibitory control is addressed specifically by using a task devoid of affectively-laden stimuli, to disentangle the effects of altered affect and altered inhibitory processes in MDD.
Twenty MDD and 22 control volunteer participants matched by age and gender completed a contextual inhibitory control task, the Parametric Go/No-go (PGNG) task during functional magnetic resonance imaging. The PGNG includes three levels of difficulty, a typical continuous performance task and two progressively more difficult versions including Go/No-go hit and rejection trials. After this test, 15 of 20 MDD patients completed a full 10-week treatment with s-citalopram.
There was a significant interaction among response time (control subjects better), hits (control subjects better), and rejections (patients better). The MDD participants had greater activation compared with the control group in frontal and anterior temporal areas during correct rejections (inhibition). Activation during successful inhibitory events in bilateral inferior frontal and left amygdala, insula, and nucleus accumbens and during unsuccessful inhibition (commission errors) in rostral anterior cingulate predicted post-treatment improvement in depression symptoms.
The imaging findings suggest that in MDD subjects, greater neural activation in frontal, limbic, and temporal regions during correct rejection of lures is necessary to achieve behavioral performance equivalent to control subjects. Greater activation in similar regions was further predictive of better treatment response in MDD.
Depression; executive functioning; fMRI; imaging; inhibitory control; mood disorders; SSRIs; treatment response
Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) frequently co-occur after traumatic experiences and share neurocognitive disturbances in verbal memory and executive functioning. However, few attempts have been made to systematically assess the role of a comorbid MDD diagnosis in neuropsychological studies in PTSD.
The purpose of the current study is to investigate neurocognitive deficits in PTSD patients with and without MDD. We hypothesized that PTSD patients with comorbid MDD (PTSD+MDD) would have significantly lower performance on measures of verbal memory and executive functioning than PTSD patients without MDD (PTSD–MDD).
Participants included in this study were 140 treatment-seeking outpatients who had a diagnosis of PTSD after various single traumatic events and participated in a randomized controlled trial comparing different treatment types. Baseline neuropsychological data were compared between patients with PTSD+MDD (n=84) and patients with PTSD–MDD (n=56).
The PTSD+MDD patients had more severe verbal memory deficits in learning and retrieving words than patients with PTSD alone. There were no differences between the groups in recall of a coherent paragraph, recognition, shifting of attention, and cognitive interference.
The results of this study suggest that a more impaired neurocognitive profile may be associated with the presence of comorbid MDD, with medium-sized group differences for verbal memory but not for executive functioning. From a clinical standpoint, being aware that certain verbal memory functions are more restricted in patients with comorbid PTSD and MDD may be relevant for treatment outcome of trauma-focused psychotherapy.
neuropsychology; cognitive functioning; PTSD; major depressive disorder; comorbidity
We investigated whether performance on a reward processing task differs between fully remitted patients with major depressive disorder (MDD) and healthy control subjects after catecholamine depletion.
Seventeen unmedicated subjects with remitted MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover study. The main outcome measure was the reaction time on the monetary incentive delay (MID) task.
A diagnosis × drug interaction was evident (p = .001), which was attributable to an increase in reaction time across all incentive levels after AMPT in RMDD subjects (p = .001) but no significant AMPT effect on reaction time in control subjects (p = .17). There was no drug × diagnosis interaction on control tasks involving working memory or attention. In the RMDD sample the AMPT-induced depressive symptoms correlated with AMPT-induced changes in reaction time at all incentive levels of the MID task (r values = .58 –.82, p < .002).
Under catecholamine depletion the RMDD subjects were robustly differentiated from control subjects by development of performance deficits on a reward processing task. These performance deficits correlated directly with the return of depressive symptoms after AMPT administration. The sensitivity of central reward processing systems to reductions in brain catecholamine levels thus seems to represent a trait-like marker in MDD.
Anhedonia; dopamine; major depressive disorder; monetary incentive delay task; norepinephrine; reward
The objective of the present study was to evaluate memory performance in tasks with and without affective content (to confirm the mood congruency phenomenon) in acutely admitted patients with bipolar I disorder (BD) and major depression disorder (MDD) and in healthy participants. Seventy-eight participants (24 BD, 29 MDD, and 25 healthy controls) were evaluated. Three word lists were used as the memory task with affective content (positive, negative and indifferent). Psychiatric symptoms were also evaluated with rating scales (Young Mania Rating Scale for mania and Hamilton Depression Rating Scale for depression). Patients were selected during the first week of hospitalization. BD patients showed higher scores in the word span with positive tone than MDD patients and healthy controls (P = 0.002). No other difference was observed for tests with affective tone. MDD patients presented significantly lower scores in the Mini-Mental State Exam, logical memory test, visual recognition span, and digit span, while BD patients presented lower scores in the visual recognition test and digit span. Mood congruency effect was found for word span with positive tone among BD patients but no similar effect was observed among MDD patients for negative items. MDD patients presented more memory impairment than BD patients, but BD patients also showed memory impairment.
Memory; Bipolar disorder; Depression; Affect
Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories (AMs). Extensive research has examined the functional anatomical correlates of AM in healthy humans, but no studies have examined the neurophysiological underpinnings of AM deficits in individuals with MDD. The goal of the present study was to examine the differences in the hemodynamic response between MDD and healthy control (HC) participants while they engage in AM recall.
Participants (12 unmedicated MDD; 14 HCs) underwent functional MRI scanning while recalling AMs in response to positive, negative, and neutral cue words. The hemodynamic response during recall of the different memory classifications versus performing subtraction problems was compared between depressed and control samples.
Behavioral results showed that relative to controls, the MDDs had fewer specific(p=0.013), positive(p=0.030), highly arousing(p=0.036), and recent(p=0.020) AMs, and more categorical(p<0.001) AMs. During AM recall the BOLD responses in the anterior cingulate cortex, parahippocampal gyrus, and hippocampus was higher for memory recall versus subtraction in HCs and lower in MDDs. Additionally, activity in the anterior insula and lateral orbitofrontal cortex was lower in the AM task than the in subtraction task, with the magnitude of the decrement greater in MDDs.
We replicated previous findings of fewer specific and more categorical AMs in MDDs versus HCs. We found differential activity in medial temporal and prefrontal lobe structures involved in AM retrieval between MDDs and HCs as they engaged in AM recall. These neurophysiological deficits may underlie AM recall impairments seen in MDD.
Major depressive disorder (MDD), cognitive symptoms, and mild cognitive deficits commonly occur in HIV-infected individuals, despite highly active antiretroviral therapies. In this study, we compared neuropsychological performance and cognitive symptoms of 191 HIV-infected participants. Results indicated that participants with a formal diagnosis of current MDD performed significantly worse than participants without MDD in all seven neuropsychological domains evaluated, with the largest effect sizes in information processing speed, learning, and memory. In addition, a brief assessment of cognitive symptoms, derived from a comprehensive neuromedical interview, correlated significantly with neurocognitive functioning. Participants with MDD reported more cognitive symptoms and showed greater neurocognitive deficits than participants without MDD. These findings indicate that HIV-infected adults with MDD have more cognitive symptoms and worse neuropsychological performance than HIV-infected individuals without MDD. The results of this study have important implications for the diagnosis of HIV-associated neurocognitive disorders (HAND).
Depression; Cognition; Cognitive complaints; Neuropsychological tests; Acquired immunodeficiency syndrome; Mood disorders
Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories (AMs). Extensive research has examined the functional anatomical correlates of AM in healthy humans, but no studies have examined the neurophysiological underpinnings of AM deficits in MDD. The goal of the present study was to examine the differences in the hemodynamic response between patients with MDD and controls while they engage in AM recall.
Participants (12 unmedicated MDD patients; 14 controls) underwent functional magnetic resonance imaging (fMRI) scanning while recalling AMs in response to positive, negative and neutral cue words. The hemodynamic response during memory recall versus performing subtraction problems was compared between MDD patients and controls. Additionally, a parametric linear analysis examined which regions correlated with increasing arousal ratings.
Behavioral results showed that relative to controls, the patients with MDD had fewer specific (p=0.013), positive (p=0.030), highly arousing (p=0.036) and recent (p=0.020) AMs, and more categorical (p<0.001) AMs. The blood oxygen level-dependent (BOLD) response in the parahippocampus and hippocampus was higher for memory recall versus subtraction in controls and lower in those with MDD. Activity in the anterior insula was lower for specific AM recall versus subtraction, with the magnitude of the decrement greater in MDD patients. Activity in the anterior cingulate cortex was positively correlated with arousal ratings in controls but not in patients with MDD.
We replicated previous findings of fewer specific and more categorical AMs in patients with MDD versus controls. We found differential activity in medial temporal and prefrontal lobe structures involved in AM retrieval between MDD patients and controls as they engaged in AM recall. These neurophysiological deficits may underlie AM recall impairments seen in MDD.
Anterior insula; autobiographical memory; depression; fMRI; hippocampus
Background: Impaired cognitive control functions have been demonstrated in both major depression (MDD) and anxiety disorder (A), but few studies have systematically examined the impact of MDD with co-morbid A (MDDA), which is the main aim of this study. Method: We compared patients with MDD with (MDDA; n = 24) and without co-morbid A (n = 37) to a group of healthy controls (HC; n = 92) on three subtests from the Cambridge Neuropsychological Test Automated Battery; intra–extra dimensional, stop signal task, and spatial working memory. These tasks correspond to a theoretical model consisting of three separable but interrelated executive control functions: Shifting, Inhibition, and Updating. A simple psychomotor speed measure was also included. Results: After controlling for age, gender, and education level, the results showed that the MDDA group displayed significantly impaired performance on the functions Shifting and Updating compared to HC. There emerged no significant differences between any of the patient groups and HC regarding Inhibition. The pure MDD group did not display dysfunctions relative to the HC group on the main executive control variables, but displayed slowed psychomotor speed. Contrary to expectation there were no significant differences between the MDDA and the MDD groups. Conclusion: Co-morbid anxiety should be taken into account when studying cognitive control functions in major depression.
unipolar major depression; co-morbid anxiety disorder; cognitive control functions; CANTAB
Major depressive disorder (MDD) is associated with action monitoring dysfunction, particularly disrupted error processing. Whether such dysregulation is further modulated by task incentives is largely unknown. The goal of this study was to investigate possible dysfunctions in error processing in MDD as a function of varying task incentives and clinical profile. To this end, we recorded the error-related negativity (ERN) and error positivity (Pe) in 18 MDD subjects and 18 healthy controls during a Stroop task that intermixed no-incentive and reward trials. Relative to controls, MDD subjects showed (1) larger ERN irrespective of task incentives, and (2) reduced Pe during reward (but not no-incentive) trials. Moreover, among MDD subjects, Pe amplitudes were negatively correlated with depression severity and clinical symptoms. The present findings highlight distinct effects of task incentives on electrophysiological components of error processing and are interpreted within current theories of action monitoring and incentive processing in depression.
ERN; Pe; Depression; Reward; Anhedonia; Action Monitoring
An intact ability to mount preparatory emotional, cognitive and bodily responses to anticipated environmental change is necessary for adaptive responding. Although abnormal insula activity during aversive anticipation has been observed in Major Depressive Disorder (MDD) individuals, the extent to which shifts in homeostatic state during anticipation affect insular activity in MDD subjects has not been reported. The aim of this study was to use functional Magnetic Resonance Imaging (fMRI) to examine how shifts in homeostatic state affect anticipatory insular activity in MDD.
Cued hot and warm stimuli were delivered while subjects either passively viewed a fixation cross or performed an attentional task during fMRI. The task was designed so that anticipatory brain activation related to the following three types of shifts could be measured: (1) anticipatory shifts in stimulus intensity, (2) anticipatory shifts in cognitive demand, (3) dual anticipatory shifts (i.e., shifts in both stimulus intensity and cognitive demand). Brain activation related to each of these three contrasts was compared between 15 (12F) unmedicated subjects with current MDD and 17 (10F) age- and education-comparable healthy control (HC) subjects.
MDD versus HC subjects showed lower right anterior insula activity related to anticipatory shifts in stimulus intensity, and altered brain activation during anticipatory shifts in cognitive demand and dual anticipatory shifts.
These results indicate that MDD individuals show altered brain responses to shifts in homeostatic state during anticipation, and may suggest that MDD is associated with an impaired ability to effectively prepare for changes in the environment.
Homeostatsis; emotion; interoception; fmri; emotional allodynia; heat; pain
Individuals with major depressive disorder (MDD) process information with a bias towards negative stimuli. However, little is known on the link between vulnerability to MDD and brain functional anomalies associated with stimulus bias.
A cohort of 38 subjects, of which 14 were patients with acute MDD and 24 were healthy controls (HC), were recruited and compared. The HC group included 10 healthy participants with a first degree family history of depression (FHP) and 14 volunteers with no family history of any psychiatric disease (FHN). Blood oxygen level dependence signals were acquired from functional magnetic resonance imaging (fMRI) during performance in a dot-probe task using fearful and neutral stimuli. Reaction times and the number of errors were also obtained.
Although MDD patients and HC showed no behavioral difference, the MDD group exhibited smaller activation in the left middle cingulum. The MDD group also showed smaller activation in the left insula when compared to the HC group or the FHN group. Finally, FHP participants exhibited higher activation in the right Heschl's gyrus compared to FHN participants.
The present study shows that family risk for MDD is associated with increased activation in the Heschl's gyrus. Our results also suggest that acute MDD is linked to reduced activation in the insula and anterior cingulate cortex during processing of subliminal, not recognizable, masked fearful stimuli. Further research should confirm these results in a larger cohort of participants.
Verbal and visuospatial working memory (WM) impairment is a well-documented finding in psychiatric patients suffering from major psychoses such as schizophrenia or bipolar affective disorder. However, in major depression (MDD) the literature on the presence and the extent of WM deficits is inconsistent. The use of a multitude of different WM tasks most of which lack process-specificity may have contributed to these inconsistencies. Eighteen MDD patients and 18 healthy controls matched with regard to age, gender and education were tested using process- and circuit-specific WM tasks for which clear brain-behaviour relationships had been established in prior functional neuroimaging studies. Patients suffering from acute MDD showed a selective impairment in articulatory rehearsal of verbal information in working memory. By contrast, visuospatial WM was unimpaired in this sample. There were no significant correlations between symptom severity and WM performance. These data indicate a dysfunction of a specific verbal WM system in acutely ill patients with MDD. As the observed functional deficit did not correlate with different symptom scores, further, longitudinal studies are required to clarify whether and how this deficit is related to illness acuity and clinical state of MDD patients.
Major depression; Neurocognition; Cognitive endophenotype; Psychosis; Brain imaging
Data are reviewed on the societal costs of major depressive disorder (MDD). Early-onset MDD is found to predict difficulties in subsequent role transitions, including low educational attainment, high risk of teen child-bearing, marital disruption, and unstable employment. Among people with specific social and productive roles, MDD is found to predict significant decrements in role functioning (e.g., low marital quality, low work performance, low earnings). MDD is also associated with elevated risk of onset, persistence, and severity of a wide range of chronic physical disorders as well as with increased early mortality due to an even wider range of physical disorders and to suicide. Although effectiveness trials show that expanded MDD treatment can reverse many of these adverse effects, only a minority of people with MDD receives treatment and the quality of treatment is unacceptably low among the majority of those in treatment.
Absenteeism; costs of illness; disability; illness burden; impairment; major depressive disorder
Anhedonia is a core feature of major depressive disorder (MDD), but the precise nature of anhedonic symptoms is unknown. While anhedonia has traditionally been viewed as a deficit in the experience of pleasure, more recent evidence suggests that reduced anticipation and motivation may also be a core feature of this symptom. Here, we provide data from a study in MDD patients and healthy controls using a translational measure of reward motivation, the Effort Expenditure for Rewards Task (EEfRT or “effort”). This task offers subjects a series of trials where they may choose to expend more or less effort for the opportunity to win varying amounts of monetary rewards. We found that MDD patients were less willing to expend effort for rewards than controls. Additionally, we observed that patients were less able to effectively use reward information about magnitude and probability of rewards to guide their choice behavior. Finally, within the MDD patient group, duration of the current episode was a significant negative predictor of EEfRT task performance. These findings offer novel support for theoretical models proposing that anhedonia in MDD may reflect specific impairments in motivation and reward-based decision-making.
Major depressive disorder (MDD) has been associated with both dysfunction of the central serotonergic system and abnormal responses to emotional stimuli. We used acute tryptophan depletion (ATD) to investigate the effect of temporarily reducing brain serotonin synthesis on neural and behavioural responses to emotional stimuli in remitted MDD subjects (rMDD) and healthy controls.
Twenty controls and 23 rMDD subjects who had been unmedicated and in remission for ≥3 months completed the study. Following tryptophan or sham depletion, participants performed an emotional-processing task during functional magnetic resonance imaging. In addition, resting-state regional blood-flow was measured using arterial spin labelling.
Neither group exhibited significant mood-change following ATD. However, tryptophan depletion differentially affected the groups in terms of hemodynamic responses to emotional words in a number of structures implicated in the pathophysiology of MDD, including medial thalamus and caudate. These interactions were driven by increased responses to emotional words in the controls, with little effect in the patients under the ATD condition. Following ATD, habenula blood-flow increased significantly in the rMDD subjects relative to the controls, and increasing amygdala blood-flow was associated with more negative emotional bias score across both groups.
These data provide evidence for elevated habenula blood-flow and alterations in the neural processing of emotional stimuli following ATD in rMDD subjects, even in the absence of overt mood-change. However, further studies are required to determine whether these findings represent mechanisms of resilience or vulnerability to MDD.
Depression; Serotonin; Acute Tryptophan Depletion; Functional Magnetic Resonance Imaging (fMRI); Emotional Processing; Affective Go/No-go (AGNG)
Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) are frequently co-morbid, and dysfunctional frontal-striatal circuits have been implicated in both disorders. Neurobiological distinctions between OCD and MDD are insufficiently clear, and comparative neuroimaging studies are extremely scarce. OCD and MDD may be characterized by cognitive rigidity at the phenotype level, and frontal-striatal brain circuits constitute the neural substrate of intact cognitive flexibility. In the present study, 18 non-medicated MDD-free patients with OCD, 19 non-medicated OCD-free patients with MDD, and 29 matched healthy controls underwent functional magnetic resonance imaging during performance of a self-paced letter/digit task switching paradigm. Results showed that both patient groups responded slower relative to controls during repeat events, but only in OCD patients slowing was associated with decreased error rates. During switching, patients with OCD showed increased activation of the putamen, anterior cingulate and insula, whereas MDD patients recruited inferior parietal cortex and precuneus to a lesser extent. Patients with OCD and MDD commonly failed to reveal anterior prefrontal cortex activation during switching. This study shows subtle behavioral abnormalities on a measure of cognitive flexibility in MDD and OCD, associated with differential frontal-striatal brain dysfunction in both disorders. These findings may add to the development of biological markers that more precisely characterize frequently co-morbid neuropsychiatric disorders such as OCD and MDD.
To examine cardiovascular reactivity and recovery to laboratory stress among a naturalistic sample of individuals diagnosed with major depressive disorder (MDD) and healthy control participants. Prospective evidence suggests that MDD confers risk for cardiovascular disease equal to or greater than the risk associated with depressed mood. Enhanced cardiovascular reactivity has been proposed as a mechanism explaining increased risk, but data are inconsistent as to whether depressed individuals exhibit enhanced or attenuated reactivity. Further, few studies have examined appraisal and recovery differences.
Participants diagnosed with MDD (N = 25) and healthy control participants (N = 25) engaged in a cardiovascular reactivity protocol including two tasks, each followed by a brief recovery period.
Main outcome measures
Blood pressure, heart rate, pre-ejection period, cardiac output and total peripheral resistance were assessed. Appraisals of tasks were assessed prior to each task.
Depressed participants exhibited significantly less systolic blood pressure, heart rate and cardiac output reactivity during speech, less heart rate reactivity during mirror tracing and less heart rate recovery after speech and mirror tracing than controls. Depressed participants appraised the tasks as more demanding, threatening, and stressful and reported being less able to cope than controls. Appraisals were related to heart rate reactivity, but appraisals did not mediate the relationship between depression group and reactivity.
Impaired recovery rather than exaggerated cardiovascular reactivity may partially explain the increased prospective cardiovascular disease risk in depressed individuals.
Depression; cardiovascular reactivity; recovery; cognitive appraisals
Individuals with major depressive disorder (MDD) often exhibit impaired executive function, particularly in experimental tasks that involve response conflict and require adaptive behavioral adjustments. Prior research suggests that these deficits might be due to dysfunction within frontocingulate pathways implicated in response conflict monitoring and the recruitment of cognitive control. However, the temporal unfolding of conflict monitoring impairments in MDD remains poorly understood. To address this issue, we recorded 128-channel event-related potentials while 20 unmedicated participants with MDD and 20 demographically matched, healthy controls performed a Stroop task. Compared to healthy controls, MDD subjects showed larger Stroop interference effects and reduced N2 and N450 amplitudes. Source localization analyses at the time of maximal N450 activity revealed that MDD subjects had significantly reduced dorsal anterior cingulate cortex (dACC; Brodmann area 24/32) and left dorsolateral prefrontal cortex (Brodmann area 10/46) activation to incongruent relative to congruent trials. Consistent with the heterogeneous nature of depression, follow-up analyses revealed that depressed participants with the lowest level of conflict-related dACC activation 620 ms post-stimulus were characterized by the largest Stroop interference effects (relatively increased slowing and reduced accuracy for incongruent trials). Conversely, MDD participants with relatively stronger dACC recruitment did not differ from controls in terms of interference effects. These findings suggest that for some, but not all individuals, MDD is associated with impaired performance in trials involving competition among different response options, and reduced recruitment of frontocingulate pathways implicated in conflict monitoring and cognitive control.
Depression; Action Monitoring; Anterior Cingulate Cortex; Dorsolateral Prefrontal Cortex; Cognitive Control; Executive Function
Generalized anxiety disorder (GAD) and major depressive disorder (MDD) frequently co-occur, yet the reasons for their comorbidity remain poorly understood. In the present experiment, we tested whether a tendency to engage in negative, repetitive thinking constitutes a common risk process for the two disorders. A mixed sample of adults with comorbid GAD-MDD (n = 50), GAD only (n = 35), MDD only (n = 34), or no lifetime psychopathology (n = 35) was administered noncontingent failure and success feedback on consecutive performance tasks. Perseverative thought (PT), measured by negative thought intrusions during a baseline period of focused breathing, emerged as a powerful prospective predictor of responses to this experimental challenge. Participants reporting more frequent negative thought intrusions at baseline, irrespective of thought content or diagnostic status, exhibited a stronger negative response to failure that persisted even after subsequent success. Higher PT over the course of the experiment was associated with later behavioral avoidance, with negative affect and other traits closely linked to anxiety and depression, and with the presence and severity of GAD and MDD. These findings provide evidence for a broadly-defined PT trait that is shared by GAD and MDD and contributes to adverse outcomes in these disorders.
Perseveration; Worry; Rumination; Generalized Anxiety Disorder; Major Depression; Comorbidity
Depression predicts fall risk among older adults, and this relationship may be partially explained by depression-associated executive dysfunction, relevant to navigating demanding environments. This pilot study examined timed stepping accuracy under simple and complex dual-task conditions, using an instrumented walkway based on the Trail Making Test. Participants were balance-impaired older adults, either with (n = 8; major depressive disorder [MDD]) or without (n = 8; nondepressed [ND]) MDD. After accounting for comfortable gait speed and age, the MDD group was significantly slower than the ND group on the walkway with the highest cognitive demand and demonstrated greater dual-task cost, both of which were correlated with performance on traditional measures of executive functioning. No group differences were observed on the walkway with the least cognitive demand. Balance-impaired older adults with MDD demonstrate increased stepping accuracy time under cognitively demanding conditions, reflecting executive dysfunction and an additional contribution to increased fall risk.
late life depression; dual task; gait
The aims of this study was to clarify how accurate the depressed patients perceive their cognitive symptoms, and verify the appropriateness of the depressive rating scales in evaluating cognitive deficits in major depressive disorder (MDD) patients.
The subjects consisted of 19 well-characterized medication-free patients with MDD and 19 healthy volunteers. The clinical and neuropsychological assessments, including Hamilton Rating Scale for Depression (HAM-D), Taiwanese Depression Questionnaire (TDQ), Finger Tapping Test, Wechsler Memory Scale-Revised, Stroop Color-Word Test, and Continuous Performance Test, were administered at the time of recruitment and repeated six months after treatment.
Depressed patients exhibited significant impairment in several neurocognitive domains. Neurocognitive impairment was correlated with both the affective and somatic factors, but not with the cognitive factors of TDQ. The similar results were shown after 6-month treatment.
Our results suggest that the MDD patients do not perceive their cognitive dysfunction correctly. The depression rating scales, especially the patient-administered scale, need to be validated for measuring neurocognitive deficits of MDD patients in the future, if cognitive component is suspected as one of the major domains of self-rating scale.
Major depressive disorder; Cognitive deficits; Depression rating scale
Unipolar major depressive disorder (MDD) is characterized by impaired cognitive control in affective contexts, but the potential for psychotherapy to affect the neural correlates of these functions has not been evaluated.
Twelve adults with and 15 adults without MDD participated in two identical functional magnetic resonance imaging (fMRI) scans that utilized a task requiring cognitive control in both sad and neutral contexts. Between scans, MDD outpatients received Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with positive stimuli and reduce avoidance behaviors.
Seventy-five percent of adults with MDD were treatment responders, achieving post-treatment Hamilton Rating Scale for Depression score of six or below. Consistent with predictions, psychotherapy resulted in decreased activation in response to cognitive control stimuli presented within a sad context in prefrontal structures, including the paracingulate gyrus, the right orbital frontal cortex, and the right frontal pole. Furthermore, the magnitude of pretreatment activation in the paracingulate gyrus cluster responsive to psychotherapy predicted the magnitude of depressive symptom change after psychotherapy.
Replication with larger samples is needed, as are follow-up studies that involve placebo control groups, wait-list control groups, and alternative forms of antidepressant intervention.
Behavioral Activation Therapy for Depression improves depressive symptoms and concomitantly influences brain systems mediating cognitive control in affective contexts.
Unipolar Depression; Target Detection; Cognitive Control; Functional Magnetic Resonance Imaging; Psychotherapy; Prefrontal Cortex; Paracingulate Gyrus
Affect identification accuracy paradigms have increasingly been utilized to understand psychiatric illness including Bipolar Disorder (BD) and Major Depressive Disorder (MDD). This investigation focused on perceptual accuracy in affect identification in both visual and auditory domains among patients with BD, relative to Healthy Controls (HC) and patients with MDD. Demographic and clinical variables, in addition to medications were also investigated.
The visual Facial Emotion Perception Test (FEPT) and auditory Emotional Perception Test (EPT) were administered to adults with BD (n = 119) and MDD (n = 78) as well as HC (n = 66).
Performance on the FEPT was significantly stronger than on the EPT irrespective of group. Performance on the EPT did not significantly differentiate the groups. On the FEPT, BD samples had the greatest difficulty relative to HC in identification of sad and fearful faces. BD participants also had greater difficulty identifying sad faces relative to MDD participants though not after controlling for severity of illness factors. For the BD (but not MDD) sample several clinical variables were also correlated with FEPT performance.
The findings suggest that disruptions in identification of negative emotions such as sadness and fear may be a characteristic trait of BD. However, this effect may be moderated by greater illness severity found in our BD sample.
Bipolar Disorder; Major Depressive Disorder; Affect perception
Depression is characterized by executive dysfunctions and abnormal reactions to errors; however, little is known about the brain mechanisms that underlie these deficits.
To examine whether abnormal reactions to errors in patients with major depressive disorder (MDD) are associated with exaggerated paralimbic activation and/or a failure to recruit subsequent cognitive control to account for mistakes in performance.
Between February 15, 2005, and January 19, 2006, we recorded 128-channel event-related potentials while study participants performed a Stroop task, modified to incorporate performance feedback.
Patients with MDD and healthy comparison subjects were recruited from the general community.
Study participants were 20 unmedicated patients with MDD and 20 demographically matched comparison subjects.
Main Outcome Measures
The error-related negativity and error positivity were analyzed through scalp and source localization analyses. Functional connectivity analyses were conducted to investigate group differences in the spatiotemporal dynamics of brain mechanisms that underlie error processing.
Relative to comparison subjects, patients with MDD displayed significantly lower accuracy after incorrect responses, larger error-related negativity, and higher current density in the rostral anterior cingulate cortex (ACC) and medial prefrontal cortex (PFC) (Brodmann area 10/32) 80 milliseconds after committing an error. Functional connectivity analyses revealed that for the comparison subjects, but not the patients with MDD, rostral ACC and medial PFC activation 80 milliseconds after committing an error predicted left dorsolateral PFC (Brodmann area 8/9) activation 472 milliseconds after committing an error.
Unmedicated patients with MDD showed reduced accuracy and potentiated error-related negativity immediately after committing errors, highlighting dysfunctions in the automatic detection of unfavorable performance outcomes. New analytic procedures allowed us to show that abnormal reaction to committing errors was accompanied by hyperactivation in rostral ACC and medial PFC regions 80 milliseconds after committing errors and a failure to recruit dorsolateral PFC-based cognitive control. Future studies are warranted to investigate whether these dysfunctions might foster the emergence and maintenance of negative processing biases and thus increase vulnerability to depression.
Dysfunction of serotonergic neurotransmission has been implicated in the etiopathogenesis of major depression (MDD) and alcohol use disorders (AUD). To compare serotonin function in MDD with co-occurring AUD (MDD/AUD), MDD without co-occurring AUD (MDD only) and healthy controls (HC) we sought to study differences in prolactin responses to fenfluramine administration in patients with MDD/AUD, patients with MDD only and HC. In all, 169 subjects (62 MDD/AUD, 75 MDD only, and 32 HC) were entered into the study. Controlling for gender, prolactin responses were lower in the MDD/AUD group compared to the MDD only or the HC group. Controlling for gender and aggression, prolactin responses in the MDD/AUD group remained significantly lower compared to the HC group but the difference between the MDD/AUD and the MDD only groups disappeared. The difference in prolactin responses between MDD/AUD and MDD only could be attributed to higher aggression scores in the MDD/AUD group compared to the MDD group.
Serotonin; Prolactin; Fenfluramine; Depression; Alcohol; Aggression