Sara L. Weisenbach

Increased Coupling of Intrinsic Networks in Remitted Depressed Youth Predicts Rumination and Cognitive Control

Objective Functional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD. Method fcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18–23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain. Results Compared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely. Conclusions Findings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.

Depression and Cognitive Impairment in Older Adults

Late life depression (LLD) is a heterogeneous illness with high rates of treatment resistance. Cognitive impairment is common in the context of LLD, and LLD may be a prodromal symptom and/or potentially a risk factor for dementia. This manuscript reviews the most recent research into the cognitive deficits associated with LLD and risk of conversion to dementia in the context of LLD. We discuss potential moderators and mediators of cognitive deficits in LLD, including demographic and clinical variables, in addition to brain structure and function. Potential interventions for cognitive symptoms of LLD are reviewed. We conclude with a discussion of the broader implications of what is now known about LLD, and how this might be applied toward improved prognosis and models for effective treatment.

The Relationship between Depressive Symptoms, Disease State, and Cognition in Amyotrophic Lateral Sclerosis

Cognitive impairment (CI) in amyotrophic lateral sclerosis (ALS) may present a serious barrier to a patient’s wellbeing and significantly decrease quality of life. Although reports of CI in ALS without frank dementia are becoming quite common, questions remain regarding the specific cognitive domains affected, as well as how other psychological and medical factors may impact cognitive functioning in these patients. Additionally, the influence of depressive symptoms on disease processes is not known. We aimed to address these questions by completing extensive neuropsychological tests with 22 patients with ALS and 17 healthy volunteers. A subgroup of these patients also completed questionnaires to measure depressive and vegetative symptoms. We tested for overall cognitive differences between groups, the influence of physical (e.g., bulbar and limb), vegetative (e.g., fatigue), and depressive symptoms on cognitive performance, and the relationship between depressive symptoms and disease severity in ALS. Overall, patients performed more poorly than healthy controls (HCs), most notably on tests of executive functioning and learning and memory. Results suggest that true cognitive performance differences exist between patients with ALS and HCs, as these differences were not changed by the presence of vegetative or depressive symptoms. There was no effect of limb or bulbar symptoms on cognitive functioning. Also, patients were not any more depressed than HCs, however increased depressive scores correlated with faster disease progression and decreased limb function. Collectively, it is suggested that translational advances in psychological intervention for those with CI and depression become emphasized in future research.

Modality-specific alterations in the perception of emotional stimuli in Bipolar Disorder compared to Healthy Controls and Major Depressive Disorder

OBJECTIVES 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. METHOD 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). RESULTS 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. CONCLUSIONS 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.

The double burden of age and disease on cognition and quality of life in bipolar disorder

Bipolar disorder (BPD) and normal aging are known to impact cognitive skills and health‐related quality of life (HRQOL). This study investigated how aging and disease interact in predicting cognitive and psychosocial outcomes.

Reduced Emotion Processing Efficiency in Healthy Males Relative to Females

This study examined sex differences in categorization of facial emotions and activation of brain regions supportive of those classifications. In Experiment 1, performance on the Facial Emotion Perception Test (FEPT) was examined among 75 healthy females and 63 healthy males. Females were more accurate in the categorization of fearful expressions relative to males. In Experiment 2, 3T functional magnetic resonance imaging data were acquired for a separate sample of 21 healthy females and 17 healthy males while performing the FEPT. Activation to neutral facial expressions was subtracted from activation to sad, angry, fearful and happy facial expressions. Although females and males demonstrated activation in some overlapping regions for all emotions, many regions were exclusive to females or males. For anger, sad and happy, males displayed a larger extent of activation than did females, and greater height of activation was detected in diffuse cortical and subcortical regions. For fear, males displayed greater activation than females only in right postcentral gyri. With one exception in females, performance was not associated with activation. Results suggest that females and males process emotions using different neural pathways, and these differences cannot be explained by performance variations.

Current Understanding of the Neurobiology and Longitudinal Course of Geriatric Depression

Late life depression is a complex disease associated with a number of contributing neurobiological factors, including cerebrovascular disease, neurodegeneration, and inflammation, which also contribute to its longitudinal prognosis and course. These factors create a context in which the brain is more vulnerable to the impact of stress, and thus, to depression. At the same time, some individuals are protected from late life depression and its consequences, even in the face of neurobiological vulnerability, through benefitting from one or more attributes associated with resilience, including social support, engagement in physical and cognitive activities, and brain reserve. Enhanced understanding of how neurobiological and environmental factors interact in predicting vulnerability and resilience is needed to predict onset and course of depression in late life and develop more effective interventions.

Age and Gender Modulate the Neural Circuitry Supporting Facial Emotion Processing in Adults with Major Depressive Disorder

OBJECTIVES Emotion processing, supported by frontolimbic circuitry known to be sensitive to the effects of aging, is a relatively understudied cognitive-emotional domain in geriatric depression. Some evidence suggests that the neurophysiological disruption observed in emotion processing among adults with major depressive disorder (MDD) may be modulated by both gender and age. Therefore, the present study investigated the effects of gender and age on the neural circuitry supporting emotion processing in MDD. DESIGN Cross-sectional comparison of fMRI signal during performance of an emotion processing task. SETTING Outpatient university setting. PARTICIPANTS One hundred adults recruited by MDD status, gender, and age. MEASUREMENTS Participants underwent fMRI while completing the Facial Emotion Perception Test. They viewed photographs of faces and categorized the emotion perceived. Contrast for fMRI was of face perception minus animal identification blocks. RESULTS Effects of depression were observed in precuneus and effects of age in a number of frontolimbic regions. Three-way interactions were present between MDD status, gender, and age in regions pertinent to emotion processing, including frontal, limbic, and basal ganglia. Young women with MDD and older men with MDD exhibited hyperactivation in these regions compared with their respective same-gender healthy comparison (HC) counterparts. In contrast, older women and younger men with MDD exhibited hypoactivation compared to their respective same-gender HC counterparts. CONCLUSIONS This the first study to report gender- and age-specific differences in emotion processing circuitry in MDD. Gender-differential mechanisms may underlie cognitive-emotional disruption in older adults with MDD. The present findings have implications for improved probes into the heterogeneity of the MDD syndrome.

Auditory memory decrements, without dissimulation, among patients with major depressive disorder

Questions have been raised about whether poor performance on memory tasks by individuals with major depressive disorder (MDD) might be the result of poor or variable effort or disease-related disruption of neural circuits supporting memory functions. The present study examined performance on a measure of task engagement and on an auditory memory task among 45 patients with MDD (M age = 47.82, SD = 19.55) relative to 32 healthy controls (HC; M age = 51.03, SD = 22.09). One-hundred percent of HC and MDD volunteers performed above the threshold for adequate effort on a formal measure of task engagement. The MDD subjects performed significantly more poorly than the HC subjects on an auditory learning and memory test. The present results suggest that auditory memory difficulties do occur among those with MDD and that decrements in performance in this group may be related to factors other than lack of effort.

Domain-specific impairment in cognitive control among remitted youth with a history of major depression

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.