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Objective: Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains., Method: Older adults with major depressive disorder ( N = 228, ages 65-91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning., Results: Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity., Conclusions: Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.

Objectives: Late life depression (LLD) and hoarding disorder (HD) are common in older adults and characterized by executive dysfunction and disability. We aimed to determine the frequency of co-occurring HD in LLD and examine hoarding severity as an additional contributor to executive dysfunction, disability, and response to psychotherapy for LLD., Design: Cross-sectional., Setting: Outpatient psychiatry program., Participants: Eighty-three community-dwelling adults ages 65-90 with LLD., Intervention: Problem-solving therapy., Measurements: Measures of executive function, disability, depression, and hoarding severity were completed at post-treatment. Pearson's chi-squared tests evaluated group differences in rates of cognitive impairment, disability, and depression treatment response between participants with HD (LLD+HD) and LLD only. Separate linear regressions assessed associations between hoarding severity and executive function, disability, and psychotherapy response. Covariates included age, education, gender, and depression severity., Results: 30.1% (25/83) of LLD participants met HD criteria. Relative to LLD, LLD+HD participants demonstrated greater impairment rates on measures of executive function (Letter-Number-Sequencing, X 2 (1)=4.0, p = 0.045; Stroop-Interference, X 2 (1) = 4.8, p = 0.028). Greater hoarding severity was associated with poorer executive functioning performance (Letter-Number-Sequencing (t[70] = -2.1, β = -0.05, p = 0.044), Digit-Span (t[71] = -2.4, β = -0.07, p = 0.019), Letter-Fluency (t[ 71] = -2.8, β = -0.24, p = 0.006)). Rates of disability were significantly higher for LLD+HD (88.0%) than LLD (62.3%), (X 2 [1] = 5.41, p = 0.020) and higher hoarding severity was related to greater disability (t[72] = 2.97, β = 0.13, p = 0.004). Depression treatment response rates were significantly lower for LLD+HD (24.0%) compared to LLD (48.3%), X 2 (1) = 4.26, p = 0.039, and HD status predicted psychotherapy response, t(67) = -2.15, β = -15.6, p = 0.035., Conclusions: We found 30.1% co-occurrence of HD in LLD, which was accompanied by greater executive dysfunction, disability, and poorer response to depression treatment. Results underscore the need for increased screening of hoarding behaviors in LLD and tailored interventions for this LLD+HD group., Competing Interests: DISCLOSURES The authors declare the following financial interests/personal relationships: Dr. Insel has served as a consultant for Roche; Dr. Nelson has been an advisor or consultant to Astellas, Axsome, Biohaven, Janssen, Johnson and Johnson, Novartis, Otsuka, Sunovion; Dr. Mathews serves on the Scientific Advisory Boards of the Family Foundation for OCD Research and the International OCD Foundation. Dr. Mackin has received research support from The National Institute of Mental Health and Johnson and Johnson. Drs. Kassel, Kryza-Lacombe, Rhodes, Satre, and Tosun report no conflicts to declare for this work. This manuscript is based on work supported, in part, by the Department of Veterans Affairs, but does not necessarily represent the views of the Department of Veterans Affairs or the United States Government., (Published by Elsevier Inc.)

Objectives: Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aβ) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD., Participants and Measurements: Older adults with major depression ( N = 121, Ages 65-91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical A β standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity., Results: Greater anxiety severity was associated with lower OFC volume ( β = -68.25, t = -2.18, p = .031) and greater cognitive dysfunction ( β = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aβ SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction ( β = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety., Conclusions: Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.

In a recent call to action, we described pressing issues in the health-service-psychology (HSP) internship from the perspective of interns. In our article, we sought to initiate a dialogue that would include trainees and bring about concrete changes. The commentaries on our article are a testament to the readiness of the field to engage in such a dialogue, and we applaud the actionable recommendations that they make. In our response to these commentaries, we seek to move the conversation further forward. We observe two themes that cut across these responses: the impetus to gather novel data on training (the "need to know") and the importance of taking action (the "need to act"). We emphasize that in new efforts to gather data and take policy-level action, the inclusion of trainee stakeholders (as well as others involved in and affected by HSP training) is a crucial ingredient for sustainable and equitable change., Competing Interests: Declaration of Conflicting Interests The author(s) declared that there were no conflicts of interest with respect to the authorship or the publication of this article.

The challenges observed in health service psychology (HSP) training during COVID-19 revealed systemic and philosophical issues that preexisted the pandemic, but became more visible during the global health crisis. In a position paper written by 23 trainees across different sites and training specializations, the authors use lessons learned from COVID-19 as a touchstone for a call to action in HSP training. Historically, trainee voices have been conspicuously absent from literature about clinical training. We describe longstanding dilemmas in HSP training that were exacerbated by the pandemic and will continue to require resolution after the pandemic has subsided. The authors make recommendations for systems-level changes that would advance equity and sustainability in HSP training. This article advances the conversation about HSP training by including the perspective of trainees as essential stakeholders.

Background: Mood disorders are associated with neurobiological disruptions in subliminal and supraliminal emotion processing. There may be additional variation based on sex and the presence of self-injurious thoughts and behaviors (SITBs). Examining individuals in remission allows us to understand trait-like emotion processing characteristics that persist in the absence of symptoms. This study investigates neural processing in response to supraliminal and subliminal emotional stimuli based upon mood disorder diagnosis, sex, and SITBs., Methods: Seventy-five participants with a history of any mood disorder (AMD; 52 female) and 27 healthy controls (HC; 14 female) completed a fMRI task presenting subliminal and supraliminal facial stimuli. Within the AMD group, 20 had no history of SITBs, 26 had histories of suicidal ideation only, and 27 had histories of both SI and self-injurious behavior. We examined activation of salience network regions of interest including the amygdala, insula, and subgenual anterior cingulate cortex (sgACC) during the task., Results: AMD showed greater insula activation in response to happy faces relative to sad faces, which was not seen in the HC group. Males exhibited lower insula activation in response to sad faces relative happy faces, a pattern not seen in females. Individuals with SITBs demonstrated a lack of sgACC blunting during supraliminal versus subliminal trials., Conclusions: We found different patterns of neural responses related to mood disorder status, sex, and SITBs. Findings highlight the importance of considering heterogeneity within diagnoses and examining neurobiological features in the context of remission., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Late Life Depression (LLD) is associated with persistent cognitive dysfunction even after depression symptoms improve. The present study was designed to examine cognitive outcomes associated with the pattern of depression severity change during psychotherapy intervention for LLD., Methods: 96 community-dwelling adults ages 65-91 with major depressive disorder completed 12 sessions of Problem-Solving Therapy at the University of California, San Francisco. Nonlinear trajectories of depression severity ratings using the Hamilton Depression Rating Scale were computed from multiple time points collected throughout the weekly psychotherapy intervention. Performance on measures of cognition (information processing speed, executive functioning, verbal learning, memory) was assessed at baseline and post-treatment. Linear mixed-effects models examined associations between nonlinear depression severity trajectories and post-treatment change in cognitive performance., Results: Broadly, different patterns of depression change during treatment were associated with improved cognition post-treatment. Greater and more consistent interval improvements in depression ratings were differentially associated with improvements in aspects of verbal learning, memory, and executive function post-treatment, while no associations were found with information processing speed., Conclusions: The heterogeneity of depression trajectories associated with improved cognitive outcomes suggests that the temporal pattern of depression response may impact specific cognitive processes distinctly. Results suggest that use of nonlinear depression severity trajectories may help to elucidate complex associations between the time course of depression response and cognitive outcomes of psychotherapy in LLD. These findings have important implications for identifying treatment targets to enhance clinical and cognitive outcomes of psychotherapy in LLD., (© 2022 John Wiley & Sons Ltd.)

Obsessive-Compulsive Disorder (OCD) is a debilitating disorder causing marked distress and functional impairment. While advances in behavioral and pharmacotherapies have been effective for a majority of patients with OCD, 10-30% remain treatment refractory and severely impaired. For a subset of treatment-resistant individuals with the most severe and disabling (intractable) illness, gamma ventral capsulotomy (GVC) appears effective in reducing OCD symptoms and functional impairment. However, the effects of the ventral internal capsule lesion via GVC surgery on executive function in everyday life have been minimally investigated. Examining behavioral outcomes of GVC also provides a rare opportunity to probe the functional importance of the ventral prefrontal-subcortical connections of the internal capsule white matter tract in a relatively homogenous sample of patients with comparable white matter lesions. The present study investigated changes in frontally-mediated behaviors, measured by the Frontal Systems Behavior Scale (FrSBe), following GVC in 45 individuals with severe and otherwise intractable OCD, as rated by patients themselves and family members. Linear mixed effects models revealed a significant improvement in patient self-ratings on the FrSBe after surgery, while family ratings did not significantly change. Interestingly, improvement on the FrSBe for both self and family raters was significantly correlated with improvement in OCD symptomatology post-surgery, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). At the group level, we found no evidence of decline in frontally-mediated behaviors assessed by the FrSBe as a result of focal white matter disconnection via GVC. However, we cannot rule out the possibility that placebo effects or compromised patient self-awareness or insight contributed to the significant improvement in self ratings. Our measures may also have limited sensitivity to more selective impairments that could result from a small lesion to the ventral internal capsule. The present study demonstrates the need for detailed investigation of cognitive and behavioral changes as important factors when considering GVC as a viable treatment option for patients with refractory OCD., (Published by Elsevier Ltd.)

Trait markers, or intermediate phenotypes linking different units of analysis (self-report, performance) from the Research Domain Criteria (RDoC) matrix across populations is a necessary step in identifying at-risk individuals. In the current study, 150 healthy controls (HC) and 456 individuals with bipolar disorder (BD) Type I or II, NOS (not otherwise specified) or Schizoaffective BD completed self-report neuropsychological tests of inhibitory control (IC) and executive functioning. Bifactor analyses were used to examine the factor structure of these measures and to evaluate for invariance across groups. Bifactor analyses found modest convergence of items from neuropsychological tests and self-report measures of IC among HC and BD. The factor scores showed evidence of a general IC construct (i.e., subdomain) across measures. Importantly, invariance testing indicated that the same construct was measured equally well across groups. Groups differed on the general factor for three of the four scales. Convergence on a general IC factor and invariance across diagnosis supports the use of combined dimensional measures to identify clinical risk and highlights how prospective RDoC studies might integrate units of analysis.

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 ( M age  = 20.8, SD  = 2.1) and 62 remitted depressed young adults ( M age  = 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.

Altered HPA-axis functioning is a hypothesized mechanism for worsened cognition in depression. The current study examines the indirect effects of depression on processing speed, executive functioning, and memory as a function of the HPA-axis. 38 individuals with a depression diagnosis and 50 healthy controls (HCs) aged 18-86 underwent neuropsychological testing and at-home diurnal salivary cortisol collection. Depression was assessed via structured clinical interviews and rating scales. Cognitive composite scores were derived from factor analysis. Daytime cortisol exposure was estimated using area under the curve (AUC). Depression was associated with higher cortisol levels and slower processing speed . A significant suppression effect of AUC was present on the relationship between depression and processing speed. Limitations include the cross-sectional design and limited sample heterogeneity. Though poorly modulated HPA-axis is one proposed mechanism of cognitive alterations in depression, our results did not support this conclusion for processing speed. Alternative mechanisms should be considered to inform interventions to target cognitive alterations in depression.

Background: Decreased volume and disrupted function in neural structures essential for memory formation (e.g. medial temporal lobe and prefrontal cortex) are common among individuals with depression. Hypothalamic-pituitary-axis function, as reflected by measurement of cortisol levels, is linked to neural activity during memory encoding in healthy people. However, it is not as well understood whether cortisol is associated with alterations in fronto-temporal recruitment during memory encoding in depression., Methods: In this pilot study, we evaluated associations between cortisol and neural activation during memory encoding in 62 adults (18-65 years) with mood disorders (MD; n = 39, 66.7% female), including major depression (n = 28) and bipolar I disorder (n = 11), and healthy controls (HC; n = 23, 43.5% female). Participants provided salivary cortisol samples before and after completing a semantically-cued list-learning task during 3-Tesla fMRI. Links between pre-scan cortisol (and cortisol change) and activation during encoding were evaluated using block and event-related models., Results: Overall, pre-scan cortisol level was positively associated with greater engagement of fronto-limbic activation during the encoding block. However, in MD, pre-scan cortisol was associated with attenuated activation during encoding in medial frontal, superior and middle temporal gyri, insula, lingual gyrus, and claustrum relative to HCs. Cortisol-related attenuation of activation in MD was also observed during encoding of words subsequently recalled in the ventral anterior cingulate, hypothalamus, and middle temporal gyrus. By and large, cortisol change (pre/post scan) predicted the same pattern of findings in both block and event-related contrasts., Limitations: Although analyses accounted for variations in scanner time of day, circadian alterations in cortisol may have introduced variability into the results., Conclusions: Pre-scan cortisol may selectively interfere with recruitment of important fronto-temporal memory circuitry in mood disorders. The inverted associations between cortisol and neural function in MD relative to HC also elucidate potentially unique pathophysiological markers of mood disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This didactic aims of this review are to demonstrate the advantages of examining the entire reaction time (RT) distribution to better realize the efficacy of mental speed assessment in clinical neuropsychology. RT distributions are typically non-normal, requiring consideration of a host of statistical issues. Specifically, the appropriate model of the mental speed task's distribution (e.g., ex-Gaussian, Weibull, Normal-Gaussian, etc.) must be determined to know what parameters can be used to characterize test performance. While RT mean and standard deviation are typically used to characterize clinical performance, these parameters are usually inappropriate because RT performance rarely conforms to a normal-Gaussian distribution. For illustrative purposes, a tutorial for examining the entire RT distribution is provided that demonstrates differences between an Attention Deficit/Hyperactivity and a neurotypical group of college students. While such analyses are descriptive, it is important to characterize test performance in the context of a theoretical model of RT performance. Therefore, the tutorial includes interpretation that uses the Diffusion model (Ratcliff Psychological Review, 85, 59-108, 1978), which assumes an ex-Gaussian distribution. It is concluded that current results conform to a large literature demonstrating a more nuanced understanding of cognition afforded by non-Gaussian analysis of RT. This literature is compelling neuropsychology to enlarge assessment technology beyond the limitations of paper-and-pencil instruments.

Background: Sex differences in emotion processing may play a role in women's increased risk for Major Depressive Disorder (MDD). However, studies of sex differences in brain mechanisms involved in emotion processing in MDD (or interactions of sex and diagnosis) are sparse., Methods: We conducted an event-related fMRI study examining the interactive and distinct effects of sex and MDD on neural activity during a facial emotion perception task. To minimize effects of current affective state and cumulative disease burden, we studied participants with remitted MDD (rMDD) who were early in the course of the illness. In total, 88 individuals aged 18-23 participated, including 48 with rMDD (32 female) and 40 healthy controls (HC; 25 female)., Results: fMRI revealed an interaction between sex and diagnosis for sad and neutral facial expressions in the superior frontal gyrus and left middle temporal gyrus. Results also revealed an interaction of sex with diagnosis in the amygdala., Limitations: Data was from two sites, which might increase variability, but it also increases power to examine sex by diagnosis interactions., Conclusions: This study demonstrates the importance of taking sex differences into account when examining potential trait (or scar) mechanisms that could be useful in identifying individuals at-risk for MDD as well as for evaluating potential therapeutic innovations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (© 2015 Wiley Publishing Asia Pty Ltd.)

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 (M age =40.33, SD=15.57) with major depression (n=29) or bipolar disorder (n=12) and 23 healthy control comparisons (M age =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., Competing Interests: M. G. M. is on the Speakers Bureau for Merck Pharmaceuticals., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We present neuroimaging markers of the remitted state of major depressive disorder (rMDD) during facial emotion perception in 84 individuals during fMRI. Participants comprised 47 individuals (aged 18-23) diagnosed with rMDD and 37 healthy controls (HCs). Participants classified emotional faces or animals (control condition) in the Facial Emotion Perception Test (FEPT) during fMRI. Behavioural performance on the FEPT did not differ significantly between groups. During fMRI, both groups demonstrated significant blood oxygen level-dependent (BOLD) activity in bilateral inferior frontal gyri for the faces minus animals (F-A) contrast. The rMDD group additionally showed BOLD activity during F-A in numerous regions, including the bilateral paracingulate gyri, middle temporal gyri and right amygdala. The rMDD group exhibited significantly greater activity than the HC group in regions including the bilateral middle temporal gyri and left superior frontal gyrus. Although the rMDD group did not manifest the behavioural performance deficits on facial emotion recognition tasks that have been observed in actively depressed individuals, the rMDD group nevertheless showed increased BOLD activity compared with never-depressed controls during F-A in multiple posterior brain regions, suggesting that persistent effects of illness or possible trait vulnerabilities may distinguish individuals with rMDD from never-depressed controls., (© The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits., Methods: Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models., Results: MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD., Conclusions: Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD.

Poor cognitive control (CC) is common among older individuals with major depressive disorder (OMDD). At the same time, studies of CC in OMDD with fMRI are relatively limited and often have small samples. The present study was conducted to further examine poor CC in OMDD with early onset depression, as well as to investigate the interactive effects of MDD and aging on cognitive control. Twenty OMDD, 17 older never-depressed comparisons (ONDC), 16 younger adults with MDD (YMDD), and 18 younger never-depressed comparisons (YNDC) participated. All participants completed the Go level of the Parametric Go/No-Go Test, which requires sustained attention and inhibitory control while undergoing functional MRI (fMRI). YNDC were faster in reaction times (RTs) to go targets relative to the other 3 groups, and the YMDD group was faster than the OMDD group. fMRI effects of both age and diagnosis were present, with greater activation in MDD, and in aging. Additionally, the interaction of age and MDD was also significant, such that OMDD exhibited greater recruitment of fronto-subcortical regions relative to older comparisons. These results are consistent with prior research reporting that OMDD recruit more fronto-striatal regions in order to perform at the same level as their never-depressed peers, here on a task of sustained attention and inhibitory control. There may be an interaction of cognitive aging and depression to create a double burden on the CC network in OMDD, including possible fronto-striatal compensation during CC that is unique to OMDD, as younger MDD individuals do not show this pattern., ((c) 2015 APA, all rights reserved.)

Major depressive disorder and bipolar disorder share symptoms that may reflect core mood disorder features. This has led to the pursuit of intermediate phenotypes and a dimensional approach to understand neurobiological disruptions in mood disorders. Executive dysfunction, including cognitive control, may represent a promising intermediate phenotype across major depressive disorder and bipolar disorder. This study examined dimensions of cognitive control in women with major depressive disorder or bipolar disorder in comparison to healthy control subjects using two separate, consecutive experiments. For Experiment 1, participants completed a behavioural cognitive control task (healthy controls = 150, major depressive disorder = 260, bipolar disorder = 202; age range 17-84 years). A sample of those participants (healthy controls = 17, major depressive disorder = 19, and bipolar disorder = 16) completed a similar cognitive control task in an event-related design functional magnetic resonance imaging protocol for Experiment 2. Results for Experiment 1 showed greater impairments on the cognitive control task in patients with mood disorders relative to healthy controls (P < 0.001), with more of those in the mood disorder group falling into the 'impaired' range when using clinical cut-offs (<5th percentile). Experiment 2 revealed only a few areas of shared activation differences in mood disorder greater than healthy controls. Activation analyses using performance as a regressor, irrespective of diagnosis, revealed within and extra-network areas that were more active in poor performers. In summary, performance and activation during cognitive control tasks may represent an intermediate phenotype for mood disorders. However, cognitive control dysfunction is not uniform across women with mood disorders, and activation is linked to performance more so than disease. These findings support subtype and dimensional approaches to understanding risk and expression of mood disorders and are a promising area of inquiry, in line with the Research Domain Criteria initiative of NIMH., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Imaging techniques are increasingly being used to examine the neural correlates of stress and emotion processing; however, relations between the primary stress hormone cortisol, the functional magnetic resonance imaging (fMRI) environment, and individual differences in response to emotional challenges are not yet well studied. The present study investigated whether cortisol activity prior to, and during, an fMRI scan may be related to neural processing of emotional information., Methods: Twenty-six healthy individuals (10 female) completed a facial emotion perception test during 3-tesla fMRI., Results: Prescan cortisol was significantly correlated with enhanced amygdala, hippocampal, and subgenual cingulate reactivity for facial recognition. Cortisol change from pre- to postscanning predicted a greater activation in the precuneus for both fearful and angry faces. A negative relationship between overall face accuracy and activation in limbic regions was observed., Conclusion: Individual differences in response to the fMRI environment might lead to a greater heterogeneity of brain activation in control samples, decreasing the power to detect differences between clinical and comparison groups. © 2015 S. Karger AG, Basel.

Introduction: List learning tasks are powerful clinical tools for studying memory, yet have been relatively underutilized within the functional imaging literature. This limits understanding of regions such as the Papez circuit that support memory performance in healthy, nondemented adults., Method: The current study characterized list learning performance in 40 adults who completed a semantic list learning task (SLLT) with a Brown-Peterson manipulation during functional magnetic resonance imaging (fMRI). Cued recall with semantic cues and recognition memory were assessed after imaging. Internal reliability, convergent, and discriminant validity were evaluated., Results: Subjects averaged 38% accuracy in recall (62% for recognition), with primacy but no recency effects observed. Validity and reliability were demonstrated by showing that the SLLT was correlated with the California Verbal Learning Test (CVLT), but not with executive functioning tests, and by high intraclass correlation coefficient across lists for recall (.91). fMRI measurements during encoding (vs. silent rehearsal) revealed significant activation in bilateral hippocampus, parahippocampus, and bilateral anterior and posterior cingulate cortex. Post hoc analyses showed increased activation in anterior and middle hippocampus, subgenual cingulate, and mammillary bodies specific to encoding. In addition, increasing age was positively associated with increased activation in a diffuse network, particularly frontal cortex and specific Papez regions for correctly recalled words. Gender differences were specific to left inferior and superior frontal cortex., Conclusions: This is a clinically relevant list learning task that can be used in studies of groups for which the Papez circuit is damaged or disrupted, in mixed or crossover studies at imaging and clinical sites.

Objective: Verbal memory difficulties are common among individuals with late-life depression (LLD), though there is limited knowledge about disruptions to underlying cerebral circuitry. The purpose of this study is to examine aberrations to cerebral networks implicated in encoding novel verbal semantic material among older adults with LLD., Methods: Twenty-four older adults with early-onset LLD and 23 non-depressed comparisons participated in the study. Participants completed a word list-learning task while undergoing functional magnetic resonance imaging., Results: In the context of equivalent recall and recognition of words following scanning and similar hippocampal volumes, patients with LLD exhibited less activation in structures known to be relevant for new learning and memory, including hippocampus, parahippocampal gyrus, insula, and cingulate, relative to non-ill comparisons. An important region in which the LLD group displayed greater activation than the non-depressed comparison group was in left inferior frontal gyrus, an area involved in cognitive control and controlled semantic/phonological retrieval and analysis; this region may be critical for LLD patients to consolidate encoded words into memory., Conclusions: Functional irregularities found in LLD patients may reflect different modes of processing to-be-remembered information and/or early changes predictive of incipient cognitive decline. Future studies might consider mechanisms that could contribute to these functional differences, including hypothalamic-pituitary-adrenal axis functioning and vascular integrity, and utilize longitudinal designs in order to understand whether functional changes are predictive of incipient cognitive decline., (Copyright © 2014 John Wiley & Sons, Ltd.)