Orbitofrontal and Cingulate Thickness Asymmetry Associated with Depressive Symptom Dimensions.

Both clinical depression and subthreshold depressive symptoms have been associated with alterations in cortical thickness. Studies have yielded conflicting results regarding whether cortical thinning or cortical thickening best characterize the depressive state. Also unclear is whether cortical thickness differences are lateralized. This study examined the relationship between depressive symptom dimensions and cortical thickness asymmetry in cingulate and orbitofrontal regions. Fifty-four community-dwelling adults between the ages of 18 and 81 years received a 3-Tesla magnetic resonance imaging scan and completed the Center for Epidemiologic Studies Depression Scale (CES-D). Cortical thickness values were extracted for the rostral anterior cingulate, caudal anterior cingulate, posterior cingulate, isthmus cingulate, and orbitofrontal cortex. An asymmetry index was calculated for each region. Data were analyzed using separate general linear models for each region, in which the CES-D somatic symptoms, negative affect, and anhedonia subscale scores predicted the asymmetry indices, controlling for age and sex. Higher scores on the anhedonia subscale were associated with right-sided asymmetry in orbitofrontal thickness, whereas higher somatic symptom subscale scores predicted greater left-sided asymmetry in posterior cingulate thickness. Follow-up analyses showed the orbitofrontal effect was specific to the medial, not the lateral, orbitofrontal cortex. These results suggest asymmetries in cortical thickness are apparent at even subthreshold levels of depressive symptoms, as all but five participants were below the CES-D cutoff for clinical depression, and that the relationship varies for different symptom dimensions of depression. Understanding brain asymmetries across the range of depressive symptom severity is important for informing targeted depression treatment.

Be Fit, Be Sharp, Be Well: The Case for Exercise as a Treatment for Cognitive Impairment in Late-life Depression.

OBJECTIVE: To lay out the argument that exercise impacts neurobiological targets common to both mood and cognitive functioning, and thus more research should be conducted on its use as an alternative or adjunctive treatment for cognitive impairment in late-life depression (LLD). METHOD: This narrative review summarizes the literature on cognitive impairment in LLD, describes the structural and functional brain changes and neurochemical changes that are linked to both cognitive impairment and mood disruption, and explains how exercise targets these same neurobiological changes and can thus provide an alternative or adjunctive treatment for cognitive impairment in LLD. RESULTS: Cognitive impairment is common in LLD and predicts recurrence of depression, poor response to antidepressant treatment, and overall disability. Traditional depression treatment with medication, psychotherapy, or both, is not effective in fully reversing cognitive impairment for most depressed older adults. Physical exercise is an ideal treatment candidate based on evidence that it 1) is an effective treatment for depression, 2) enhances cognitive functioning in normal aging and in other patient populations, and 3) targets many of the neurobiological mechanisms that underlie mood and cognitive functioning. Results of the limited existing clinical trials of exercise for cognitive impairment in depression are mixed but overall support this contention. CONCLUSIONS: Although limited, existing evidence suggests exercise may be a viable alternative or adjunctive treatment to address cognitive impairment in LLD, and thus more research in this area is warranted. Moving forward, additional research is needed in large, diverse samples to translate the growing research findings into clinical practice.

Depression and Cognitive Control across the Lifespan: a Systematic Review and Meta-Analysis.

Depression has been shown to negatively impact neurocognitive functions, particularly those governed by fronto-subcortical networks, such as executive functions. Converging evidence suggests that depression-related executive dysfunction is greater at older ages, however, this has not been previously confirmed by meta-analysis. We performed a systematic review and meta-analysis, using three-level models, on peer-reviewed studies that examined depression-related differences in cognitive control in healthy community-dwelling individuals of any age. We focused on studies of cognitive control as defined by the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) framework, which centers on goal-directed behavior, such as goal selection (updating, representations, maintenance), response selection (inhibition or suppression), and performance monitoring. In 16,806 participants aged 7 to 97 across 76 studies, both clinical depression and subthreshold depressive symptoms were associated with cognitive control deficits (Hedges' g = -0.31). This relationship was stronger in study samples with an older mean age. Within studies with a mean age of 39 years or higher, which represents the median age in our analyses, the relationship was stronger in clinical compared to subthreshold depression and in individuals taking antidepressant medication. These findings highlight the importance of clinicians screening for cognitive control dysfunction in patients with depression, particularly in later stages of adulthood.

Rostral anterior cingulate connectivity in older adults with subthreshold depressive symptoms: A preliminary study.

Subthreshold depressive symptoms are highly prevalent among older adults and are associated with numerous health risks including cognitive decline and decreased physical health. One brain region central to neuroanatomical models of depressive disorders is the anterior cingulate cortex (ACC). The rostral portion of the ACC-comprised of the pregenual ACC and subgenual ACC-is implicated in emotion control and reward processing. The goal of the current study was to examine how functional connectivity in subregions of the rostral ACC relate to depressive symptoms, measured by the Beck Depression Inventory-Second Edition, in an ethnically diverse sample of 28 community-dwelling older adults. Based on meta-analyses of previous studies in primarily young adults with clinical depression, we hypothesized that greater depressive symptoms would be associated with primarily increased resting-state functional connectivity from both the subgenual ACC and pregenual ACC to default mode network regions and the dorsolateral PFC. We instead found that higher depressive symptoms were associated with lower functional connectivity of the ACC to the dorsolateral PFC and regions within the default mode network, including from the subgenual ACC to the dorsolateral PFC and anterior cingulate and from the pregenual ACC to the middle cingulate gyrus. This preliminary study highlights brain alterations at subthreshold levels of depressive symptoms in older adults, which could serve as targets for interventions.

Subthreshold depressive symptoms relate to cuneus structure: Thickness asymmetry and sex differences.

Despite the prominence of frontolimbic regions in depression research, recent studies also implicate posterior brain regions, including the cuneus. The current study examined the relationship between depressive symptoms and asymmetry in cuneal cortical thickness in healthy adults between the ages of 18 and 81 with primarily subthreshold levels of depressive symptoms. An asymmetry index was calculated for cortical thickness in the cuneus [(left - right) × 100/(left + right)], and regression analyses were conducted with total scores on the Center for Epidemiologic Studies Depression Scale predicting this asymmetry index, controlling for age and sex. Higher depressive symptoms were associated with a left > right asymmetry in cuneal cortical thickness, reflecting greater cortical thickness in the left hemisphere compared to right hemisphere. Follow-up analyses examining CES-D subscales showed significant effects for somatic symptoms of depression, but not negative affect or anhedonia. Analyses stratified by sex yielded significant effects in men but not in women. Results of this preliminary study further support the cuneus' role in depression and highlight the importance of examining symptom dimensions and sex differences in the neurobiology of depression.