With the proliferation of multi-site neuroimaging studies, there is a greater need for handling non-biological variance introduced by differences in MRI scanners and acquisition protocols. Such unwanted sources of variation, which we refer to as "scanner effects", can hinder the detection of imaging features associated with clinical covariates of interest and cause spurious findings. In this paper, we investigate scanner effects in two large multi-site studies on cortical thickness measurements across a total of 11 scanners. We propose a set of tools for visualizing and identifying scanner effects that are generalizable to other modalities. We then propose to use ComBat, a technique adopted from the genomics literature and recently applied to diffusion tensor imaging data, to combine and harmonize cortical thickness values across scanners. We show that ComBat removes unwanted sources of scan variability while simultaneously increasing the power and reproducibility of subsequent statistical analyses. We also show that ComBat is useful for combining imaging data with the goal of studying life-span trajectories in the brain.

The ‘Vascular Depression’ hypothesis posits that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between late-life depression, vascular risk factors, and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in late-life depression, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression but also provide guidance on the potential repurposing of pharmacological agents that may improve late-life depression outcomes.

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Background Childhood early life stress (ELS) increases risk of adulthood Major Depressive Disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure. Methods This cross-sectional study included 64 antidepressant-free depressed and 65 never depressed individuals. Both groups reported a range of ELSs on the Early Life Stress Questionnaire, completed neuropsychological testing and 3T MRI. Neuropsychological testing assessed domains of episodic memory, working memory, processing speed and executive function. MRI measures included cortical thickness and regional gray matter volumes, with a priori focus on cingulate cortex, orbitofrontal cortex (OFC), amygdala, caudate and hippocampus. Results Of 19 ELSs, only emotional abuse, sexual abuse and severe family conflict independently predicted adulthood MDD diagnosis. The effect of total ELS score differed between groups. Greater ELS exposure was associated with slower processing speed and smaller OFC volumes in depressed subjects, but faster speed and larger volumes in nondepressed subjects. In contrast, exposure to ELSs predictive of depression had similar effects in both diagnostic groups. Individuals reporting predictive ELSs exhibited poorer processing speed and working memory performance, smaller volumes of the lateral OFC and caudate, and decreased cortical thickness in multiple areas including the insula bilaterally. Predictive ELS exposure was also associated with smaller left hippocampal volume in depressed subjects. Conclusion Findings suggest an association between childhood trauma exposure and adulthood cognitive function and brain structure. These relationships appear to differ between individuals who do and do not develop depression.

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Greater progression of WMH volume is associated with poor outcomes in geriatric depression. Future work is needed to develop means of slowing the rate of WMH progression and to determine whether this will lead to improved depression outcomes in elderly persons.

Microstructural changes in the white matter of the right superior frontal gyrus are associated with late-life depression. Further work is needed to determine how these changes contribute to depression outcomes.