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Introduction: It is well established that personality traits impact cognition, as certain personality factors are associated with performance in specific cognitive domains. However, the findings on the relationships between the Big Five traits and cognition are mixed. Additionally, few studies have explored these relationships in older adults with a history of depression. The present study aimed to (a) evaluate the impact of the Big Five personality traits in older adults with and without a lifetime history of depression; and (b) test the hypotheses that higher trait neuroticism would correlate negatively with cognitive performance, while openness to experience would correlate positively with cognition. Methods: The sample consisted of 138 participants between the ages of 55 and 78 (M = 65.56, SD = 6.36). Sixty-two participants met criteria for current or remitted Major Depressive Disorder, while 76 had no history of depression or other mental health disorders. Participants underwent comprehensive neuropsychological testing. Personality was assessed using the NEO Personality Inventory-Revised (NEO-PI-R), while depression status was determined using the Structured Clinical Interview for DSM-5 (SCID-5). Following a series of Pearson correlations of cognitive variables and the five personality factors, linear regression models were estimated for each significant correlation. Demographic variables (i.e., age, education and sex) were entered in block 1, depression status (never vs. ever) was entered in block 2, and the personality factor score, or sub-facet was entered in block 3. Results: Neuroticism was not associated with cognitive performance on any outcome measure. The facets Openness to Feelings and Openness to Values were positively related to phonemic fluency. Further Openness to Values was positively related to cognitive flexibility. Discussion: Our results suggest that older people who are (a) more capable of identifying and understanding their feelings and the feelings of others, and (b) who are more willing to re-examine social, political, and religious values perform stronger on tasks measuring verbal fluency and cognitive flexibility, which are aspects of executive functioning. Interventions that aim to enhance open mindedness in older adults may have a parallel impact on improving executive functioning, though this would need to be examined prospectively.
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BACKGROUND: Treatment resistant depression (TRD) is a subset of major depressive disorder (MDD) in which symptoms do not respond to front line therapies. In older adults, the assessment and treatment of TRD is complicated by psychosocial risk factors unique to this population, as well as a relative paucity of research. METHODS: Narrative review aimed at (1) defining TRLLD for clinical practice and research; (2) describing psychosocial risk factors; (3) reviewing psychological and non-pharmacological treatments; (4) discussing the role of clinical phenotyping for personalized treatment; and (5) outlining research priorities. RESULTS: Our definition of TRLLD centers on response to medication and neuromodulation in primary depressive disorders. Psychosocial risk factors include trauma and early life adversity, chronic physical illness, social isolation, personality, and barriers to care. Promising non-pharmacological treatments include cognitive training, psychotherapy, and lifestyle interventions. The utility of clinical phenotyping is highlighted by studies examining the impact of comorbidities, symptom dimensions (e.g., apathy), and structural/functional brain changes. LIMITATIONS: There is a relative paucity of TRLLD research. This limits the scope of empirical data from which to derive reliable patterns and complicates efforts to evaluate the literature quantitatively. CONCLUSIONS: TRLLD is a complex disorder that demands further investigation given our aging population. While this review highlights the promising breadth of TRLLD research to date, more research is needed to help elucidate, for example, the optimal timing for implementing risk mitigation strategies, the value of collaborative care approaches, specific treatment components associated with more robust response, and phenotyping to help inform treatment decisions.
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Transtorno Depressivo Resistente a Tratamento , Fenótipo , Humanos , Fatores de Risco , Transtorno Depressivo Resistente a Tratamento/terapia , Transtorno Depressivo Maior/terapia , Psicoterapia/métodos , IdosoRESUMO
This Viewpoint provides recommendations for assessment of postCOVID-19 cognitive dysfunction to improve understanding of the pathophysiology of the condition and develop appropriate interventions.
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COVID-19 , Disfunção Cognitiva , Humanos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologiaRESUMO
Apathy is a neurobehavioral syndrome characterized by impaired motivation for goal-directed behaviors and cognitive activity, alongside blunted affect. Apathy is a common neuropsychiatric syndrome in Alzheimer's disease (AD), with a 5-year prevalence over 70%. Apathy also serves as a prognostic indicator, correlating with the progression of AD. Despite advances in its conceptualization and understanding of its neural basis, there is very limited empirical evidence to support the available strategies for the treatment of apathy in AD. Given its complex pathophysiology, including distinct substrates for different apathy dimensions (affective, cognitive, and behavioral), it is unlikely that a single pharmacological or nonpharmacological strategy will be effective for all cases of apathy in AD. High-quality evidence research is needed to better understand the role of specific strategies aiming at a personalized approach.
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Doença de Alzheimer , Apatia , Doença de Alzheimer/terapia , Formação de Conceito , Humanos , Transtornos do Humor , MotivaçãoRESUMO
The cognitive processes involved in inhibitory control accuracy (IC) and interference resolution speed (IR) or broadly - inhibition - are discussed in this review, and both are described within the context of a lifespan model of mood disorders. Inhibitory control (IC) is a binary outcome (success or no for response selection and inhibition of unwanted responses) for any given event that is influenced to an extent by IR. IR refers to the process of inhibition, which can be manipulated by task design in earlier and later stages through use of distractors and timing, and manipulation of individual differences in response proclivity. We describe the development of these two processes across the lifespan, noting factors that influence this development (e.g., environment, adversity and stress) as well as inherent difficulties in assessing IC/IR prior to adulthood (e.g., cross-informant reports). We use mood disorders as an illustrative example of how this multidimensional construct can be informative to state, trait, vulnerability and neuroprogression of disease. We present aggregated data across numerous studies and methodologies to examine the lifelong development and degradation of this subconstruct of executive function, particularly in mood disorders. We highlight the challenges in identifying and measuring IC/IR in late life, including specificity to complex, comorbid disease processes. Finally, we discuss some potential avenues for treatment and accommodation of these difficulties across the lifespan, including newer treatments using cognitive remediation training and neuromodulation.
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Depressão/psicologia , Inibição Psicológica , Transtornos Cognitivos/psicologia , Função Executiva , Humanos , Longevidade , Transtornos do Humor/psicologia , Testes Neuropsicológicos , Fatores de RiscoRESUMO
Memory difficulties are consistently reported in Major Depressive Disorder (MDD). Nonetheless, it has not been thoroughly investigated as to whether these deficits persist during remission from MDD. A group of 32 healthy young adults with no history of a mood disorder (Mage = 20.8, SD = 2.1) and 62 remitted depressed young adults (Mage = 21.1, SD = 1.9) completed a neuropsychological battery. The test battery included two measures of nonverbal memory, two measures of verbal memory, and a measure of performance validity. The testing session was repeated three to six weeks later to determine performance stability. No differences were found between healthy controls and remitted depressed patients in either memory domain (all ps > .05) and improvement in performance was exhibited over time for both groups (p = 0.004). Potential practice effects are examined. We found a stronger performance for women than men (p = 0.003), particularly for the Semantic List Learning Task (SLLT) (p = .047). Verbal and nonverbal memory and effort may not be impacted in those who are in a remitted state of MDD, early in the course of the illness. Women demonstrated auditory memory superiority over men, similar to prior research.
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Disfunção Cognitiva/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Transtornos da Memória/fisiopatologia , Desempenho Psicomotor/fisiologia , Adulto , Disfunção Cognitiva/etiologia , Transtorno Depressivo Maior/complicações , Feminino , Seguimentos , Humanos , Masculino , Transtornos da Memória/complicações , Indução de Remissão , Fatores Sexuais , Adulto JovemAssuntos
Transtorno Depressivo , Substância Branca , Depressão , Imagem de Tensor de Difusão , HumanosRESUMO
OBJECTIVES: The ventrolateral prefrontal cortex (vlPFC) has been speculated to play an important role in complex processes that allow emotional factors to influence human cognition. Accumulating evidence from human neuroimaging studies, in conjunction with studies of patients with lesions and animal models, shed light on the role of the vlPFC in emotion regulation (ER). This review aims to discuss and integrate recent findings related to vlPFC's role in ER in the context of aging, drawing from diverse sources, and suggest future directions for research utilizing transcranial magnetic stimulation (TMS). METHODS/DESIGN: We summarize findings from the existing literature investigating the neural basis of frontal-lobe mediated ER and then highlight major findings from recent studies directly comparing healthy younger and older adult groups. We conclude by pointing to unaddressed questions worth pursuing in future research. RESULTS AND DISCUSSION: We propose future research directions utilizing TMS to answer key unaddressed questions. Moreover, we discuss the potential advantages, challenges, and limitations of using TMS as a complement to the existing neuroimaging methods in ER.
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Envelhecimento/fisiologia , Ajustamento Emocional/fisiologia , Emoções/fisiologia , Córtex Pré-Frontal/fisiologia , Estimulação Magnética Transcraniana/métodos , Cognição/fisiologia , HumanosRESUMO
PURPOSE OF REVIEW: This review summarizes recent literature linking Alzheimer's disease (AD) and late life depression (LLD). It describes shared neurobiological features associated with both conditions, as well as factors that may increase resilience to onset and severity of cognitive decline and AD. Finally, we pose a number of future research directions toward improving detection, management, and treatment of both conditions. RECENT FINDINGS: Epidemiological studies have consistently shown a significant relationship between LLD and AD, with support for depression as a prodromal feature of AD, a risk factor for AD, and observation of some shared risk factors underlying both disease processes. Three major neurobiological features shared by LLD and AD include neurodegeneration, disruption to cerebrovascular functioning, and increased levels of neuroinflammation. There are also potentially modifiable factors that can increase resilience to AD and LLD, including social support, physical and cognitive engagement, and cognitive reserve. SUMMARY: We propose that, in the context of depression, neurobiological events, such as neurodegeneration, cerebrovascular disease, and neuroinflammation result in a brain that is more vulnerable to the consequences of the pathophysiological features of AD, lowering the threshold for the onset of the behavioral presentation of AD (i.e., cognitive decline and dementia). We discuss factors that can increase resilience to AD and LLD, including social support, physical and cognitive engagement, and cognitive reserve. We conclude with a discussion of future research directions.
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There is a plethora of current and emerging antidepressant therapies in the psychiatric armamentarium for the treatment of major depressive disorder. Noninvasive neuromodulation therapies are one such therapeutic category; they typically involve the transcranial application of electrical or magnetic stimulation to modulate cortical and subcortical brain activity. Although electroconvulsive therapy (ECT) has been used since the 1930s, with the prevalence of major depressive disorder and treatment-resistant depression (TRD), the past three decades have seen a proliferation of noninvasive neuromodulation antidepressant therapeutic development. The purpose of this critical review was to synthesize information regarding the clinical effects, neurocognitive effects, and possible mechanisms of action of noninvasive neuromodulation therapies, including ECT, transcranial magnetic stimulation, magnetic seizure therapy, and transcranial direct current stimulation. Considerable research has provided substantial information regarding their antidepressant and neurocognitive effects, but their mechanisms of action remain unknown. Although the four therapies vary in how they modulate neurocircuitry and their resultant antidepressant and neurocognitive effects, they are nonetheless useful for patients with acute and chronic major depressive disorder and TRD. Continued research is warranted to inform dosimetry, algorithm for administration, and integration among the noninvasive neuromodulation therapies and with other antidepressant strategies to continue to maximize their safety and antidepressant benefit.
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Emotion perception deficits could be due to disrupted connectivity of key nodes in the salience and emotion network (SEN), including the amygdala, subgenual anterior cingulate cortex (sgACC), and insula. We examined SEN resting-state (rs-)fMRI connectivity in rMDD in relation to Facial Emotion Perception Test (FEPT) performance. Fifty-two medication-free people ages 18 to 23 years participated. Twenty-seven had major depressive disorder (MDD) in remission (rMDD, 10 males), as MDD is associated with emotion perception deficits and alterations in rsfMRI. Twenty-five healthy controls (10 males) also participated. Participants completed the FEPT during fMRI, in addition to an 8-minute eyes-open resting-state scan. Seed regions of interest were defined in the amygdala, anterior insula and sgACC. Multiple regression analyses co-varied diagnostic group, sex and movement parameters. Emotion perception accuracy was positively associated with connectivity between amygdala seeds and regions primarily in the SEN and cognitive control network (CCN), and also the default mode network (DMN). Accuracy was also positively associated with connectivity between the sgACC seeds and other SEN regions, and the DMN, particularly for the right sgACC. Connectivity negatively associated with emotion perception was mostly with regions outside of these three networks, other than the left insula and part of the DMN. This study is the first to our knowledge to demonstrate relationships between facial emotion processing and resting-state connectivity with SEN nodes and between SEN nodes and regions located within other neural networks.
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Encéfalo/fisiologia , Transtorno Depressivo Maior/fisiopatologia , Emoções , Reconhecimento Facial , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Emoções/fisiologia , Reconhecimento Facial/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Análise de Regressão , Descanso , Adulto JovemRESUMO
OBJECTIVE: Existing cognitive and clinical predictors of treatment response to date are not of sufficient strength to meaningfully impact treatment decision making and are not readily employed in clinical settings. This study investigated whether clinical and cognitive markers used in a tertiary care clinic could predict response to usual treatment over a period of 4 to 6 months in a sample of 75 depressed adults. METHODS: Patients (N = 384) were sequentially tested in 2 half-day clinics as part of a quality improvement project at an outpatient tertiary care center between August 2003 and September 2007; additional subjects evaluated in the clinic between 2007 and 2009 were also included. Diagnosis was according to DSM-IV-TR criteria and completed by residents and attending faculty. Test scores obtained at intake visits on a computerized neuropsychological screening battery were the Parametric Go/No-Go task and Facial Emotion Perception Task. Treatment outcome was assessed using 9-item Patient Health Questionnaire (PHQ-9) self-ratings at follow-up (n = 75). Usual treatment included psychotropic medication and psychotherapy. Decline in PHQ-9 scores was predicted on the basis of baseline PHQ-9 score and education, with neuropsychological variables entered in the second step. RESULTS: PHQ-9 scores declined by 46% at follow-up (56% responders). Using 2-step multiple regression, baseline PHQ-9 score (P ≤ .05) and education (P ≤ .01) were significant step 1 predictors of percent change in PHQ-9 follow-up scores. In step 2 of the model, faster processing speed with interference resolution (go reaction time) independently explained a significant amount of variance over and above variables in step 1 (12% of variance, P < .01), while other cognitive and affective skills did not. This 2-step model accounted for 28% of the variance in treatment change in PHQ-9 scores. Processing speed with interference resolution also accounted for 12% variance in treatment and follow-up attrition. CONCLUSIONS: Use of executive functioning assessments in clinics may help identify individuals with cognitive weaknesses at risk for not responding to standard treatments.
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Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/terapia , Função Executiva , Adulto , Antidepressivos/uso terapêutico , Computadores , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/psicologia , Transtorno Depressivo Resistente a Tratamento/terapia , Feminino , Seguimentos , Humanos , Masculino , Testes Neuropsicológicos , Prognóstico , Estudos Prospectivos , Psicoterapia , Análise de Regressão , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
AIM: Impairment in neuropsychological functioning is common in major depressive disorder (MDD), but it is not clear to what degree these deficits are related to risk (e.g. trait), scar, burden or state effects of MDD. The objective of this study was to use neuropsychological measures, with factor scores in verbal fluency, processing speed, attention, set-shifting and cognitive control in a unique population of young, remitted, unmedicated, early course individuals with a history of MDD in hopes of identifying putative trait markers of MDD. METHODS: Youth aged 18-23 in remission from MDD (rMDD; n = 62) and healthy controls (HC; n = 43) were assessed with neuropsychological tests at two time points. These were from four domains of executive functioning, consistent with previous literature as impaired in MDD: verbal fluency and processing speed, conceptual reasoning and set-shifting, processing speed with interference resolution, and cognitive control. RESULTS: rMDD youth performed comparably to HCs on verbal fluency and processing speed, processing speed with interference resolution, and conceptual reasoning and set-shifting, reliably over time. Individuals with rMDD demonstrated relative decrements in cognitive control at Time 1, with greater stability than HC participants. CONCLUSION: MDD may be characterized by regulatory difficulties that do not pertain specifically to active mood state or fluctuations in symptoms. Deficient cognitive control may represent a trait vulnerability or early course scar of MDD that may prove a viable target for secondary prevention or early remediation.
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Transtornos Cognitivos/psicologia , Transtorno Depressivo Maior/psicologia , Adolescente , Adulto , Atenção , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Função Executiva , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Adulto JovemRESUMO
OBJECTIVE: Depression and bipolar disorder (negative mood disorders, NMD) are associated with dysregulated hypothalamic-pituitary-adrenal (HPA)-axis function and disrupted emotion processing. The neural networks involved in attenuation of HPA-axis reactivity overlap with the circuitry involved in perception and modulation of emotion; however, direct links between these systems are understudied. This study investigated whether cortisol activity prior to undergoing fMRI was related to neural processing of emotional information in participants with NMD. METHODS: Forty-one adults (Mage=40.33, SD=15.57) with major depression (n=29) or bipolar disorder (n=12) and 23 healthy control comparisons (Mage=36.43, SD=17.33) provided salivary cortisol samples prior to completing a facial emotion perception test during 3-Tesla fMRI. RESULTS: Overall, pre-scan cortisol level was positively associated with greater engagement of the dorsal anterior cingulate (dACC), inferior parietal lobule, insula, putamen, precuneus, middle and medial frontal and postcentral gyri, posterior cingulate, and inferior temporal gyrus during emotion processing of all faces. NMD status moderated this effect; in NMD participants' pre-scan cortisol was associated with attenuated activation of the insula, postcentral gyrus, precuneus, and putamen for fearful faces and the medial frontal gyrus for angry faces relative to HCs. Cortisol-related attenuation of activation among NMD participants was also observed for facial identification in the dACC, putamen, middle temporal gyrus, precuneus, and caudate. CONCLUSIONS: Across all participants, cortisol was associated with greater activation in several regions involved in the perception and control of emotion. However, cortisol responsivity was associated with hypoactivation of several of these regions in the NMD group, suggesting that HPA-axis activity may selectively interfere with the potentially adaptive recruitment of circuits supporting emotion perception, processing and/or regulation in mood disorders.
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Transtorno Bipolar/fisiopatologia , Córtex Cerebral/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Emoções/fisiologia , Expressão Facial , Reconhecimento Facial/fisiologia , Hidrocortisona/metabolismo , Neostriado/fisiopatologia , Percepção Social , Adulto , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/metabolismo , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neostriado/diagnóstico por imagemRESUMO
OBJECTIVES: There is a well-known association between memory impairment and major depressive disorder (MDD). Additionally, recent studies are also showing resting-state functional magnetic resonance imaging (rsMRI) abnormalities in active and remitted MDD. However, no studies to date have examined both rs connectivity and memory performance in early course remitted MDD, nor the relationship between connectivity and semantically cued episodic memory. METHODS: The rsMRI data from two 3.0 Tesla GE scanners were collected from 34 unmedicated young adults with remitted MDD (rMDD) and 23 healthy controls (HCs) between 18 and 23 years of age using bilateral seeds in the hippocampus. Participants also completed a semantically cued list-learning test, and their performance was correlated with hippocampal seed-based rsMRI. Regression models were also used to predict connectivity patterns from memory performance. RESULTS: After correcting for sex, rMDD subjects performed worse than HCs on the total number of words recalled and recognized. rMDD demonstrated significant in-network hypoactivation between the hippocampus and multiple fronto-temporal regions, and multiple extra-network hyperconnectivities between the hippocampus and fronto-parietal regions when compared to HCs. Memory performance negatively predicted connectivity in HCs and positively predicted connectivity in rMDD. Conclusions Even when individuals with a history of MDD are no longer displaying active depressive symptoms, they continue to demonstrate worse memory performance, disruptions in hippocampal connectivity, and a differential relationship between episodic memory and hippocampal connectivity.