Hippocampal and parahippocampal volume and function predict antidepressant response in patients with major depression: A multimodal neuroimaging study.

BACKGROUND: For many patients with major depressive disorder (MDD) adequate treatment remains elusive. Neuroimaging techniques received attention for their potential use in guiding and predicting response, but were rarely investigated in real-world psychiatric settings. AIMS: To identify structural and functional Magnetic Resonance Imaging (MRI) biomarkers associated with antidepressant response in a real-world clinical sample. METHODS: We studied 100 MDD inpatients admitted to our psychiatric ward, treated with various antidepressants upon clinical need. Hamilton Depression Rating Scale percentage decrease from admission to discharge was used as a measure of response. All patients underwent 3.0 T MRI scanning. Grey matter (GM) volumes were investigated both in a voxel-based morphometry (VBM), and in a regions of interest (ROI) analysis. In a subsample of patients, functional resting-state connectivity patterns were also explored. RESULTS: In the VBM analysis, worse response was associated to lower GM volumes in two clusters, encompassing the left hippocampus and parahippocampal gyrus, and the right superior and middle temporal gyrus. Investigating ROIs, lower bilateral hippocampi and amygdalae volumes predicted worse treatment outcomes. Functional connectivity in the right temporal and parahippocampal gyrus was also associated to response. CONCLUSION: Our results expand existing literature on the relationship between the structure and function of several brain regions and treatment response in MDD. While we are still far from routine use of MRI biomarkers in clinical practice, we confirm a possible role of these techniques in guiding treatment choices and predicting their efficacy.

Neutrophil to lymphocyte ratio and antidepressant treatment response in patients with major depressive disorder: Effect of sex and hippocampal volume.

Several factors may affect response to treatment in Major Depressive Disorder (MDD) including immune/inflammatory alterations and regional brain volumes, particularly in hippocampal regions which have shown to be influenced by inflammatory status. Neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker found to be elevated in depressed women in large population studies. Here we investigate the effect of NLR on treatment response in MDD patients, and the role of sex and hippocampal volume on influencing this relationship. A sample of 124 MDD depressed inpatients (F = 80) underwent MRI acquisition, admission NLR was calculated by dividing absolute neutrophil by absolute lymphocyte counts and depression severity was assessed at admission and discharge via the Hamilton Depression Rating Scale (HDRS). As a measure of treatment response, delta HDRS was calculated. We found a significant moderation effect of sex on the relationship between NLR and Delta HDRS: a negative relation was found in females and a positive one in males. NLR was found to negatively affect hippocampal volumes in females. Both left and right hippocampal volume positively associated with Delta HDRS. Finally, left hippocampal volume mediated the effect of NLR on Delta HDRS in females. Sex moderated the relation between inflammation and treatment response in line with previous reports linking inflammation to hampered antidepressant effect in females. Further, this effect is partially mediated by hippocampal volume, suggesting that antidepressant response may be hampered by the detrimental effect of inflammation on the brain.

Long-term effect of childhood trauma: Role of inflammation and white matter in mood disorders.

Bipolar disorder (BD) and major depressive disorder (MDD) are severe psychiatric illnesses that share among their environmental risk factors the exposure to adverse childhood experiences (ACE). Exposure to ACE has been associated with long-term changes in brain structure and the immune response. In the lasts decades, brain abnormalities including alterations of white matter (WM) microstructure and higher levels of peripheral immune/inflammatory markers have been reported in BD and MDD and an association between inflammation and WM microstructure has been shown. However, differences in these measures have been reported by comparing the two diagnostic groups. The aim of the present study was to investigate the interplay between ACE, inflammation, and WM in BD and MDD. We hypothesize that inflammation will mediate the association between ACE and WM and that this will be different in the two groups. A sample of 200 patients (100 BD, 100 MDD) underwent 3T MRI scan and ACE assessment through Childhood Trauma Questionnaire. A subgroup of 130 patients (75 MDD and 55 BD) underwent blood sampling for the assessment of immune/inflammatory markers. We observed that ACE associated with higher peripheral levels of IL-2, IL-17, bFGF, IFN-γ, TNF-α, CCL3, CCL4, CCL5, and PDGF-BB only in the BD group. Further, higher levels of CCL3 and IL-2 associated with lower FA in BD. ACE were found to differently affect WM microstructure in the two diagnostic groups and to be negatively associated with FA and AD in BD patients. Mediation analyses showed a significant indirect effect of ACE on WM microstructure mediated by IL-2. Our findings suggest that inflammation may mediate the detrimental effect of early experiences on brain structure and different mechanisms underlying brain alterations in BD and MDD.

Sex Hormones, Sleep, and Memory: Interrelationships Across the Adult Female Lifespan.

As the population of older adults grows, so will the prevalence of aging-related conditions, including memory impairments and sleep disturbances, both of which are more common among women. Compared to older men, older women are up to twice as likely to experience sleep disturbances and are at a higher risk of cognitive decline and Alzheimer's disease and related dementias (ADRD). These sex differences may be attributed in part to fluctuations in levels of female sex hormones (i.e., estrogen and progesterone) that occur across the adult female lifespan. Though women tend to experience the most significant sleep and memory problems during the peri-menopausal period, changes in memory and sleep have also been observed across the menstrual cycle and during pregnancy. Here, we review current knowledge on the interrelationships among female sex hormones, sleep, and memory across the female lifespan, propose possible mediating and moderating mechanisms linking these variables and describe implications for ADRD risk in later life.