Childhood abuse and late-life depression: Mediating effects of psychosocial factors for early- and late-onset depression.

OBJECTIVE: Childhood abuse makes people vulnerable to developing depression, even in late life. Psychosocial factors that are common in late life, such as loneliness or lack of a partner, may explain this association. Our aim was to investigate whether the association between childhood abuse and depression in older adults can be explained by psychosocial factors. METHODS: Cross-sectional data were derived from the Netherlands Study of Depression in Older Persons (aged 60-93), including 132 without lifetime depression, 242 persons with an early-onset depression (<60 years), and 125 with a late-onset (≥60 years) depression. Childhood abuse (yes/no) and a frequency-based childhood abuse index were included. Multinomial regression and multivariable mediation analyses were used to examine the association between childhood abuse and the onset of depression, and the influence of loneliness, social network, and partner status. RESULTS: Multinomial regression analyses showed a significant association between childhood abuse and the childhood abuse index with early- and late-onset depression. Multivariable mediation analyses showed that the association between childhood abuse and early-onset depression was partly mediated by social network size and loneliness. This was particularly present for emotional neglect and psychological abuse, but not for physical and sexual abuse. No psychosocial mediators were found for the association between childhood abuse and late-onset depression. CONCLUSIONS: A smaller social network and feelings of loneliness mediate the association between childhood abuse and early-onset depression in older adults. Our findings show the importance of detecting childhood abuse as well as the age at depression onset and mapping of relevant psychosocial factors in the treatment of late-life depression.

Childhood Abuse and the Two-Year Course of Late-Life Depression.

OBJECTIVES: Late-life depression often has a chronic course, with debilitating effects on functioning and quality of life; there is still no consensus on important risk factors explaining this chronicity. Cross-sectional studies have shown that childhood abuse is associated with late-life depression, and in longitudinal studies with chronicity of depression in younger adults. We aim to investigate the impact of childhood abuse on the course of late-life depression. DESIGN: Two-year longitudinal cohort study. SETTING: Data were derived from the Netherlands Study of Depression in Older Persons (NESDO). PARTICIPANTS: 282 participants with a depression diagnosis in the previous 6 months (mean age: 70.6 years), of whom 152 (53.9%) experienced childhood abuse. MEASUREMENTS: Presence of childhood abuse (yes/no) and a frequency-based childhood abuse index (CAI) were calculated. Dependent variable was depression diagnosis after 2 years. RESULTS: Multivariable mediation analysis showed an association between childhood abuse and depression diagnosis at follow-up. Depression severity, age at onset, neuroticism, and number of chronic diseases were important mediating variables of this association, which then lost statistical significance. For childhood abuse (yes/no), loneliness was an additional, significant mediator. Depression severity was the main mediating variable, reducing the direct effect by 26.5% to 33.3% depending on the definition of abuse (respectively, 'yes/no" abuse and CAI). CONCLUSIONS: More depressive symptoms at baseline, lower age at depression onset, higher levels of neuroticism and loneliness, and more chronic diseases explain a poor course of depression in older adults who reported childhood abuse. When treating late-life depression it is important to detect childhood abuse and consider these mediating variables.

Early and recent psychosocial stress and telomere length in older adults.

BACKGROUND: Psychosocial stress has been associated with an increased risk for mental and somatic health problems across the life span. Some studies in younger adults linked this to accelerated cellular aging, indexed by shortened telomere length (TL). In older adults, the impact of psychosocial stress on TL may be different due to the lifetime exposure to competing causes of TL-shortening. This study aims to assess whether early and recent psychosocial stressors (childhood abuse, childhood adverse events, recent negative life events, and loneliness) were associated with TL in older adults. METHODS: Data were from the Netherlands Study of Depression in Older Persons (NESDO) in which psychosocial stressors were measured in 496 persons aged 60 and older (mean age 70.6 (SD 7.4) years) during a face-to-face interview. Leukocyte TL was determined using fasting blood samples by performing quantitative polymerase chain reaction (qPCR) and was expressed in base pairs (bp). RESULTS: Multiple regression analyses, adjusted for age, sex, and chronic diseases, showed that childhood abuse, recent negative life events and loneliness were unrelated to TL. Only having experienced any childhood adverse event was weakly but significantly negatively associated with TL. CONCLUSIONS: Our findings did not consistently confirm our hypothesis that psychosocial stress is associated with shorter TL in older adults. Healthy survivorship or other TL-damaging factors such as somatic health problems seem to dominate a potential effect of psychosocial stress on TL in older adults.

The influence of childhood abuse on cortisol levels and the cortisol awakening response in depressed and nondepressed older adults.

OBJECTIVES: Childhood abuse has been associated with depression in later life. This may be related to hypothalamic-pituitary-adrenal (HPA) axis functioning. Therefore we aimed to examine the impact of childhood abuse and its interaction with depression on cortisol levels in older adults. METHODS: Data from 418 participants (mean age 70.8 years) in the Netherlands Study of Depression in Older Persons (NESDO) were used; 187 participants experienced childhood abuse; 309 participants had a diagnosis of depression. Diurnal cortisol levels were determined using six saliva samples from every participant. Multiple regression analyses were performed. RESULTS: Significant negative associations between childhood abuse and morning cortisol levels were found. In nondepressed persons, both psychological and sexual abuse were associated with greater dynamics of the HPA axis in response to awakening. CONCLUSIONS: Childhood abuse is associated with lower basal cortisol levels at awakening irrespective of major depressive disorder (MDD). Higher reactivity of the HPA axis during the hour after awakening was found in nondepressed participants only, which might suggest that late-life depression modifies the effect of childhood abuse on the HPA axis. Older adults with a history of childhood abuse may be more negatively affected by stress or stressful events and this is reflected in dysregulation of the HPA axis.

Neurosurgical targets for compulsivity: what can we learn from acquired brain lesions?

Treatment efficacy of deep brain stimulation (DBS) and other neurosurgical techniques in refractory obsessive-compulsive disorder (OCD) is greatly dependent on the targeting of relevant brain regions. Over the years, several case reports have been published on either the emergence or resolution of obsessive-compulsive symptoms due to neurological lesions. These reports can potentially serve as an important source of insight into the neuroanatomy of compulsivity and have implications for targets of DBS. For this purpose, we have reviewed all published case reports of patients with acquired or resolved obsessive-compulsive symptoms after brain lesions. We found a total of 37 case reports describing 71 patients with acquired and 6 with resolved obsessive-compulsive symptoms as a result of hemorrhaging, infarctions or removal of tumors. Behavioral symptoms following brain lesions consisted of typical obsessive-compulsive symptoms, but also symptoms within the compulsivity spectrum. These data suggests that lesions in the cortico-striato-thalamic circuit, parietal and temporal cortex, cerebellum and brainstem may induce compulsivity. Moreover, the resolution of obsessive-compulsive symptoms has been reported following lesions in the putamen, internal capsule and fronto-parietal lobe. These case reports provide strong evidence supporting the rationale for DBS in the ventral striatum and internal capsule for treatment of compulsivity and reveal the putamen and fronto-parietal cortex as promising new targets.

Improved sensitivity to cerebral white matter abnormalities in Alzheimer's disease with spherical deconvolution based tractography.

Diffusion tensor imaging (DTI) based fiber tractography (FT) is the most popular approach for investigating white matter tracts in vivo, despite its inability to reconstruct fiber pathways in regions with "crossing fibers." Recently, constrained spherical deconvolution (CSD) has been developed to mitigate the adverse effects of "crossing fibers" on DTI based FT. Notwithstanding the methodological benefit, the clinical relevance of CSD based FT for the assessment of white matter abnormalities remains unclear. In this work, we evaluated the applicability of a hybrid framework, in which CSD based FT is combined with conventional DTI metrics to assess white matter abnormalities in 25 patients with early Alzheimer's disease. Both CSD and DTI based FT were used to reconstruct two white matter tracts: one with regions of "crossing fibers," i.e., the superior longitudinal fasciculus (SLF) and one which contains only one fiber orientation, i.e. the midsagittal section of the corpus callosum (CC). The DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD), obtained from these tracts were related to memory function. Our results show that in the tract with "crossing fibers" the relation between FA/MD and memory was stronger with CSD than with DTI based FT. By contrast, in the fiber bundle where one fiber population predominates, the relation between FA/MD and memory was comparable between both tractography methods. Importantly, these associations were most pronounced after adjustment for the planar diffusion coefficient, a measure reflecting the degree of fiber organization complexity. These findings indicate that compared to conventionally applied DTI based FT, CSD based FT combined with DTI metrics can increase the sensitivity to detect functionally significant white matter abnormalities in tracts with complex white matter architecture.