Deficits In Major Depression Research Articles

The Neural Correlates of the Recognition of Emotional Intensity Deficits in Major Depression: An ERP Study.

Deficits in facial emotional intensity recognition have been associated with social cognition in patients with major depression. The study examined multiple event-related potential (ERP) components in patients with major depression and investigated the relationships between ERPs, social cognition, and clinical features. Thirty-one patients met DSM-IV diagnosis of depression and 31 healthy participants completed the emotion intensity recognition task (EIRT), while ERPs were recorded. Data on ERP components (P100, N170, P200, and P300) were analyzed. The behavioral results showed that patients with major depression performed worse on EIRT, including all six categories of emotions (sadness, disgust, happiness, surprise, anger, and fear), compared to healthy participants. The ERP results showed that patients with major depression exhibited higher P100 amplitudes for sad and happy faces than healthy participants; P300 amplitudes induced by sad and surprise faces were also higher than in healthy participants, mainly in the central and temporal lobes. A positive correlation was found between sadness intensity scores and P100 amplitudes in patients with major depression. Patients with major depression are biased in their identification of facial expressions indicating emotional intensity. Specifically, they have emotional biases in the early and late stages of cognitive processing, mainly in the form of sensitivity to sad stimuli. It may lead to a persistent rumination of sadness that is detrimental to the remission of depression. Additionally, patients with major depression devote different amounts of cognitive resources for different intensities of sad faces during the preconscious stage of cognitive processing. The more intense their perception of sadness, the more cognitive resources they devote. Therefore, the assessment of the intensity of facial expressions is an important research topic, with clinical implications on social cognitive function in patients with major depression.

Digital Intervention for Cognitive Deficits in Major Depression: A Randomized Controlled Trial to Assess Efficacy and Safety in Adults.

The authors evaluated AKL-T03, an investigational digital intervention delivered through a video game-based interface, designed to target the fronto-parietal network to enhance functional domains for attentional control. AKL-T03 was tested in adult patients with major depressive disorder and a demonstrated cognitive impairment at baseline. Adults ages 25-55 years on a stable antidepressant medication regimen with residual mild to moderate depression and an objective impairment in cognition (as measured using the symbol coding test) were enrolled in a double-blind randomized controlled study. Participants were randomized either to AKL-T03 or to an expectation-matched digital control intervention. Participants were assessed at baseline and after completion of their 6-week at-home intervention. The primary outcome measure was improvement in sustained attention, as measured by the Test of Variables of Attention (TOVA). AKL-T03 (N=37) showed a statistically significant medium-effect-size improvement in sustained attention compared with the control intervention on the TOVA primary outcome (N=37) (partial eta-squared=0.11). Additionally, a composite score derived from all cognitive measures demonstrated significant improvement with AKL-T03 over the control intervention. Individual secondary and exploratory endpoints did not demonstrate statistically significant between-group differences. No serious adverse events were reported, and two patients (5.5%) in the AKL-T03 group reported an intervention-related adverse event (headache). Treatment with AKL-T03 resulted in significant improvement in sustained attention, as well as in cognitive functioning as a whole, compared with a control intervention. AKL-T03 is a safe digital intervention that is effective in the treatment of cognitive impairment associated with major depression. Further research will be needed to understand the clinical consequences of this treatment-induced change.

Cognitive Impairment and Neurocognitive Profiles in Major Depression-A Clinical Perspective.

Increasingly, studies have investigated cognitive functioning from the perspective of acute state- to remitted phases of Major Depressive Disorder (MDD). Some cognitive deficits observed in the symptomatic phase persist in remission as traits or scars. The etiological origin and clinical consequences of the neurocognitive profiles reported in the literature are still unclear and may vary across populations. Deficits are suspected to influence the association between MDD and neurodegenerative disorders and could thus be of particular clinical consequence. The aim of this review is to describe the clinical neuropsychological profile in MDD and how it is related to research during the past decade on cognitive deficits in MDD from a state, trait, and scar perspective. This review, with a clinical perspective, investigates research from the past decade regarding cognitive functioning in MDD in a long-term perspective. We focus on the clinical manifestation of deficits, and the potential neurodegenerative consequences of the neurocognitive profile in MDD. Searches in Medline, PsycINFO and Embase were conducted targeting articles published between 2010 and 2020. Examination of the evidence for long-lasting neurocognitive deficits in major depression within the cognitive domains of Memory, Executive Functions, Attention, and Processing Speed was conducted and was interpreted in the context of the State, Scar and Trait hypotheses. Defining the neurocognitive profiles in MDD will have consequences for personalized evaluation and treatment of residual cognitive symptoms, and etiological understanding of mood disorders, and treatments could potentially reduce or delay the development of neurodegenerative disorders.

Reward-Seeking Deficits in Major Depression: Unpacking Appetitive Task Performance with Ex-Gaussian Response Time Variability Analysis.

Major depressive disorder (MDD) has extensive ties to motivation, including impaired response time (RT) performance. Average RT, however, conflates response speed and variability, so RT differences can be complex. Because recent studies have shown inconsistent effects of MDD on RT variability, the present research sought to unpack RT performance with several key improvements: (1) a sample of adults (n = 78; 18 MDD, 60 Control) free of antidepressant medication; (2) an unambiguously appetitive task with appealing incentives at stake; and (3) ex-Gaussian RT modeling, which can unconfound speed and variability by estimating parameters for the mean (Mu) and standard deviation (Sigma) of the normal component and the mean of the exponential component (Tau). The groups had comparable Mu and Sigma parameters, but the MDD group had a significantly larger Tau, reflecting greater intraindividual RT variability. The findings suggest that MDD's effect on average RT can stem from greater intraindividual variability, not from overall slowness. Possible mechanisms, such as impaired executive processes in MDD and difficulties maintaining stable mental representations of incentives, are considered.

Audiovisual emotional processing and neurocognitive functioning in patients with depression.

Alterations in the processing of emotional stimuli (e.g., facial expressions, prosody, music) have repeatedly been reported in patients with major depression. Such impairments may result from the likewise prevalent executive deficits in these patients. However, studies investigating this relationship are rare. Moreover, most studies to date have only assessed impairments in unimodal emotional processing, whereas in real life, emotions are primarily conveyed through more than just one sensory channel. The current study therefore aimed at investigating multi-modal emotional processing in patients with depression and to assess the relationship between emotional and neurocognitive impairments. Fourty one patients suffering from major depression and 41 never-depressed healthy controls participated in an audiovisual (faces-sounds) emotional integration paradigm as well as a neurocognitive test battery. Our results showed that depressed patients were specifically impaired in the processing of positive auditory stimuli as they rated faces significantly more fearful when presented with happy than with neutral sounds. Such an effect was absent in controls. Findings in emotional processing in patients did not correlate with Beck’s depression inventory score. Furthermore, neurocognitive findings revealed significant group differences for two of the tests. The effects found in audiovisual emotional processing, however, did not correlate with performance in the neurocognitive tests. In summary, our results underline the diversity of impairments going along with depression and indicate that deficits found for unimodal emotional processing cannot trivially be generalized to deficits in a multi-modal setting. The mechanisms of impairments therefore might be far more complex than previously thought. Our findings furthermore contradict the assumption that emotional processing deficits in major depression are associated with impaired attention or inhibitory functioning.

Validation of the face-name pairs task in major depression: impaired recall but not recognition

Major depression can be associated with neurocognitive deficits which are believed in part to be related to medial temporal lobe pathology. The purpose of this study was to investigate this impairment using a hippocampal-dependent neuropsychological task. The face-name pairs task was used to assess associative memory functioning in 19 patients with major depression. When compared to age-sex-and-education matched controls, patients with depression showed impaired learning, delayed cued-recall, and delayed free-recall. However, they also showed preserved recognition of the verbal and nonverbal components of this task. Results indicate that the face-name pairs task is sensitive to neurocognitive deficits in major depression.

Neuropsychological deficits in major depression reflect genetic/familial risk more than clinical history: A monozygotic discordant twin-pair study

Neuropsychological deficits have been associated with major depression (MD) and persist in some individuals even after symptom remission. However, it is unclear if the deficits are a consequence of MD or are pre-existing and reflect MD vulnerability. We addressed this issue by studying 117 twins from monozygotic (MZ) pairs discordant for lifetime history of DSM-III-R defined MD and 41 twins from MZ pairs in which neither twin had experienced MD. Our assessment included a structured clinical interview and measures from the WMS-III and WAIS-III. The “unaffected” twins from discordant pairs showed the same pattern of performance as their affected cotwins on measures of attention, working memory, verbal memory, and visuo-spatial processing. Compared to twins from pairs with no MD history, twins in discordant pairs had lower performance in the domains of attention, memory, visuo-spatial processing, and general knowledge. However, after adjusting for sex and age, the groups differed only on attention and general knowledge. The similar performance of twins in pairs discordant for MD suggests that familial risk for MD has a greater influence on neuropsychological functioning than individual MD history. Findings of impairment in individuals euthymic for MD are more consistent with pre-existing deficits than scarring effects of MD.

The relation between mood, cognition and psychosocial functioning in psychiatric disorders

Impairments in cognitive performance and inability to function in everyday life situations are present, in various degrees, in many severe mental illnesses, including major depressive disorder, bipolar disorder, and schizophrenia. Persistent mood symptoms (e.g., depression and mania) are associated with functional deficits in major depression and bipolar disorder, but also in conditions where mood symptoms are not the primary markers of the illness, such as in schizophrenia. While mood symptoms impact cognitive performance, both mood symptoms and cognitive deficits have a significant – and to some extent independent – impact on psychosocial functioning in psychiatric patients. Improved control of mood symptoms may represent an important strategy leading to improved functional outcomes. However, cognitive impairment may be an important independent dimension of many psychiatric disorders and such symptoms should also be considered a potential target of treatments aiming to reduce functional deficits.

Contextual recognition memory deficits in major depression are suppressed by cognitive support at encoding

ObjectivesTo investigate the effect of cognitive support (an associative orienting instruction at encoding) on contextual memory in depressed patients. MethodsSeventeen patients (age 20–40years, 14 women) diagnosed with major depressive disorder (MDD) and 22 healthy controls matched for age, gender and education completed a recognition memory task for item (object) and context (location), with or without an incidental binding cue at encoding. In addition, participants completed the vocabulary subtest of the Wechsler Adult Intelligence Scale (WAIS III) and the Wisconsin Card Sorting Test (WCST). Salivary samples were collected at 7AM, 4PM and 10PM on the day of testing for cortisol and DHEA level measurement. ResultsDepressed patients showed a deficit in contextual memory in the absence of a binding cue but did not differ from healthy controls in item memory or when a binding cue was present. Cortisol and cortisol/DHEA ratios were lower in depressed patients compared to healthy controls and correlated with memory deficits. ConclusionsContextual memory deficits in MDD patients can be reduced by providing cognitive support at encoding.

Fronto-striatal correlates of impaired implicit sequence learning in major depression: An fMRI study

BackgroundNeural network models of major depression (MD) suggest that the striatum is involved in the pathophysiology and is linked to key cognitive and clinical features. However, functional imaging studies have largely assessed the prefrontal cortex and have utilised emotional paradigms. This study sought to probe the integrity of fronto-striatal circuits using functional magnetic resonance imaging (fMRI) in conjunction with a theoretically-driven motor sequencing implicit learning (IL) task. MethodsNineteen patients with MD (mean age=56.1years, sd=9.8) and 20 control participants (mean age=50.6years, sd=11.9) participated. A blocked fMRI paradigm was used in association with a motor sequencing task which included an IL and random sequence (baseline) condition. Although the study was hypothesis driven, within and between groups whole-brain analysis was used to examine fMRI patterns in the IL compared to BL condition. ResultsWhile both groups activated the striatum, there was no significant difference between patients and controls in striatal activation. Instead, control subjects showed significantly greater activity in the middle frontal gyrus whereas the patients exhibited greater activity in the superior temporal gyrus and cerebellum. LimitationsMost patients were receiving antidepressant medication when assessed. An event-related fMRI design would have enabled more fine-grained temporal analysis of IL related activation. ConclusionsIL deficits in MD are not due primarily to striatal dysfunction. IL performance may depend on more specific sub-components of the striatum or a more distributed neural network involving frontal, temporal and cerebellar regions.

The relation between depression, anhedonia and olfactory hedonic estimates—A pilot study in major depression

Several studies investigating olfactory hedonics in major depression have brought conflicting results and an analysis of the relation between severity of depression, anhedonia and olfactory hedonics is still lacking. In order to investigate olfactory perception in different depressive states, we carried out olfactory testing during a depressive episode ( n = 37) and in a remitted state ( n = 17). As expected, patients were significantly less depressed ( p < 0.001) and less anhedonic ( p = 0.001) in the remitted state. A comparison of olfactory perception between age- and gender-matched patients and healthy volunteers ( n = 37) controlled for intrinsic olfactory deficits in major depression. In the depressive episode, we applied regression analyses to investigate the relation of olfactory hedonics, severity of depression and anhedonia. The Sniffin’ Sticks Test extended by analogue rating scales for intensity and hedonic estimates was employed for olfactory testing. Depression severity was assessed with the Beck Depression Inventory (BDI), anhedonia with the Snaith-Hamilton-Pleasure-Scale (SHAPS). Odour identification ability was significantly reduced during the depressive state. In contrast, no significant differences in hedonic and intensity estimates could be found between the depressive and the remitted state and healthy controls. During the depressive episode, we found a significant relation only between anhedonia and olfactory hedonics. We concluded that anhedonia has potential impact on olfactory hedonics in major depression. Our results indicate the need for (1) confirmatory studies in severe melancholic depression and (2) investigation of the impact of anhedonia on olfactory hedonics in psychiatric diseases other than major depression.

Increased stress reactivity is associated with cognitive deficits and decreased hippocampal brain-derived neurotrophic factor in a mouse model of affective disorders

Cognitive deficits are a common feature of major depression (MD), with largely unknown biological underpinnings. In addition to the affective and cognitive symptoms of MD, a dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is commonly observed in these patients. Increased plasma glucocorticoid levels are known to render the hippocampus susceptible to neuronal damage. This structure is important for learning and memory, creating a potential link between HPA axis dysregulation and cognitive deficits in depression. In order to further elucidate how altered stress responsiveness may contribute to the etiology of MD, three mouse lines with high (HR), intermediate (IR), or low (LR) stress reactivity were generated by selective breeding. The aim of the present study was to investigate whether increased stress reactivity is associated with deficits in hippocampus-dependent memory tests. To this end, we subjected mice from the HR, IR, and LR breeding lines to tests of recognition memory, spatial memory, and depression-like behavior. In addition, measurements of brain-derived neurotrophic factor (BDNF) in the hippocampus and plasma of these animals were conducted. Our results demonstrate that HR mice exhibit hippocampus-dependent memory deficits along with decreased hippocampal, but not plasma, BDNF levels. Thus, the stress reactivity mouse lines are a promising animal model of the cognitive deficits in MD with the unique feature of a genetic predisposition for an altered HPA axis reactivity, which provides the opportunity to explore the progression of the symptoms of MD, predisposing genetic factors as well as new treatment strategies.

Perception of affective prosody in major depression: A link to executive functions?

Major depression is associated with impairments of executive functions and affect perception deficits, both being linked to dysfunction of fronto-subcortical networks. So far, little is known about the relationship between cognitive and affective deficits in major depression. In the present investigation, affect perception and executive functions were assessed in 29 patients with a diagnosis of major depression (Dep) and 29 healthy controls (HC). Both groups were comparable on IQ, age, and gender distribution. Depressed patients showed deficits of perception of affective prosody, which were significantly related to inhibition, set shifting, and working memory. Our findings suggest a significant association between cognitive deficits and affect perception impairments in major depression, which may be of considerable clinical relevance and might be addressed in treatment approaches. Future studies are desirable to investigate the nature of the association in more detail.

Executive function, mentalizing and humor in major depression

Major depression is associated with cognitive deficits including memory, executive functions, and affect perception, which have been linked to dysfunction of fronto-subcortical networks. However, little is known about social cognition on more complex socially relevant tasks, such as humor processing. In this investigation a computerized humor-processing task was administered to 27 patients with a diagnosis of major depression (Dep) and 27 healthy controls (HC). Theory of mind (mentalizing) and executive functions were also assessed. Both groups were similar in IQ, age, and gender. Depressed patients performed below the control group with respect to both affective and cognitive aspects of humor processing, and these were related to mentalizing and executive performance. Our findings suggest social cognition deficits in major depression. Ability to process humor and appreciate mentalistic perspectives may in turn influence social interactions and should be given consideration in therapeutic approaches to depression.

Neurocognitive deficits in major depression and a new theory of ADHD: A model of impaired antagonism of cholinergic-mediated prepotent behaviours in monoamine depleted individuals

The study builds on the propositions introduced in a companion paper on the neuropharmacology of cognition and its relation to key findings in psychiatry. Cognitive inhibition is often invoked to explain performance in psychiatric illness. Yet it remains only a general conceptual model of executive dysfunction. Premotor theory proposes both neuroanatomical and neuropharmacological equivalents of conscious and unconscious processes. The interaction between monoaminergic and cholinergic neurotransmission is stated to have an inverse effect on these two fundamental psychological processes. If one conceives of cognitive inhibition as a failure to voluntarily suppress unconscious prepotent responses, then a deficit in monoaminergic antagonism of cholinergic facilitated prepotent responses accounts for the observed behavioural phenotypes. The plasticity of behaviour is further hypothesized to have an equivalent in intracellular signalling leading to plastic changes in neural networks. Apart from inhibition of prepotent responses it permits the formulation of new behavioural phenotypes. At the receptor level Gi-Gq/11 transduction coupling is proposed to mediate this effect. A hypofunctioning monoaminergic system is thought to underlie the clinical pictures of major depression and ADHD. The neurocognitive deficits of depression include memory loss, poor concentration and rumination. ADHD is characterized by inattention, impulsivity and hyperactivity. Both these syndromes effectively respond to raising serotonin and dopamine levels, respectively. The core symptoms can usefully be attributed to an imbalance between the neuromodulatory effects of monoamines and ACh. Taking the model of monoaminergic-muscarinic receptor interactions presented previously and extended here, a new hypothesis is proposed for the core symptoms of ADHD. Accordingly, impulsivity and hyperactivity result from impaired dopaminergic inhibition and remodelling of muscarinic mediated prepotent responses. The model also predicts memory impairment in major depression by proposing that low serotonin levels in the neocortex is linked to focal hippocampal dysfunction. Hippocampal theta is proposed to trigger phasic monoaminergic activation involved in encoding of cortical traces and plasticity of propotent networks. It proposes a hypothesis for the enhancement of mood and behaviour induced by antidepressants is partly a response to plasticity of neural networks, that is, remodelling of cholinergic-mediated negative habitual behaviours.

Chronic stress induces upregulation of brain-derived neurotrophic factor (BDNF) mRNA and integrin α5 expression in the rat pineal gland

Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. Moreover, stress induces deleterious actions on the epithalamic pineal organ, a gland involved in a wide range of physiological functions. The aim of this study was to investigate whether the stress effects on the pineal gland are related with changes in the expression of neurotrophic factors and cell adhesion molecules. Using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, we analyzed the effect of chronic immobilization stress on the BDNF mRNA and integrin α5 expression in the rat pineal gland. We found that BDNF is produced in situ in the pineal gland. Chronic immobilization stress induced upregulation of BDNF mRNA and integrin α5 expression in the rat pineal gland but did not produce changes in β-actin mRNA or in GAPDH expression. Stressed animals also evidenced an increase in anxiety-like behavior and acute gastric lesions. These results suggest that BDNF and integrin α5 may have a counteracting effect to the deleterious actions of immobilization stress on functionally stimulated pinealocytes. Furthermore, this study proposes that the pineal gland may be a target of glucocorticoid damage during stress.

Chronic stress impairs acoustic conditioning more than visual conditioning in rats: Morphological and behavioural evidence

Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. The aim of this study was to determine the effect of chronic immobilization stress on the auditory and visual mesencephalic regions in the rat brain. We analyzed in Golgi preparations whether stress impairs the neuronal morphology of the inferior (auditory processing) and superior colliculi (visual processing). Afterward, we examined the effect of stress on acoustic and visual conditioning using an avoidance conditioning test. We found that stress induced dendritic atrophy in inferior colliculus neurons and did not affect neuronal morphology in the superior colliculus. Furthermore, stressed rats showed a stronger impairment in acoustic conditioning than in visual conditioning. Fifteen days post-stress the inferior colliculus neurons completely restored their dendritic structure, showing a high level of neural plasticity that is correlated with an improvement in acoustic learning. These results suggest that chronic stress has more deleterious effects in the subcortical auditory system than in the visual system and may affect the aversive system and fear-like behaviors. Our study opens a new approach to understand the pathophysiology of stress and stress-related disorders such as major depression.

Cognitive deficits in major depression

Major depression is a mood disorder that is often accompanied by the impairment of cognitive functions. Although suggestive, the large range of existing neuropsychological, neuropsychiatric, and, lately, neuroimaging investigations have not yet given a consistent picture of the psychological and biological disturbances involved in this psychiatric disorder. The present study of the cognitive functions in depression was part of an extensive investigation, including neuropsychological testing, psychiatric examination, and neuroimaging. A representative sample of 40 severely depressed hospitalized patients and a group of 49 closely matched control subjects were tested with an extensive neuropsychological test battery. Results, corrected for various confounding factors, confirmed the current notion that depressed patients suffer from wide-spread cognitive impairments. The group analysis did not allow any hypothesis on a possible pattern to the dysfunctions, but heterogeneity in the test performances calls for further analysis of the data in patient subgroups in relation to neuroimaging results.

Executive deficits in major depression.

Clinically depressed patients and control subjects were examined by means of different tests to assess executive functions (the Wisconsin Card Sorting Test, the Stroop Color Word Test and a test of verbal fluency). The results indicate that the depressed patients were generally slower than the controls, as reflected by longer retrieval times for both words and colours. Furthermore, the depressed patients showed impairment with regard to altering behaviour appropriately in response to feedback. However, there were no depression-related increases in perseverative responses, and the ability to inhibit irrelevant information was unaffected by depression. No relationship was found between specific depressive symptoms or the severity of depression and cognitive performance. The overall pattern of results suggests that depression may affect various executive functions in a differentiated manner.

Impaired effortful cognition in depression

Depressed patients have been reported to have deficits in “effortful,” but not effortless, cognitive functions compared to healthy volunteers. To test the hypothesis that the effortful cognitive deficits in major depression are not simply a function of psychiatric illness or hospitalization, we administered both effort-demanding and effortless cognitive tasks to 17 inpatients with major affective disorder and 17 hospitalized psychiatric controls. The depressed patients performed significantly more poorly than the controls on the effort-demanding task. The groups did not differ on the effortless task. These findings suggest that depressed patients are impaired in performing effort-demanding cognitive tasks compared to nondepressed psychiatric patients.