Volumetric brain differences in clinical depression in association with anxiety: a systematic review with meta-analysis

Abstract

Background: Structural differences associated with depression have not been confirmed in brain regions apart from the hippocampus. Comorbid anxiety has been inconsistently assessed, and may explain discrepancies in previous findings. We investigated the link between depression, comorbid anxiety and brain structure. Methods: We followed Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42018089286). We searched the Cochrane Library, MEDLINE, PsycInfo, PubMed and Scopus, from database inception to Sept. 13, 2018, for MRI case–control studies that reported brain volumes in healthy adults and adults with clinical depression. We summarized mean volumetric differences using meta-analyses, and we assessed demographics, depression factors and segmentation procedure as moderators using meta-regressions. Results: We included 112 studies in the meta-analyses, assessing 4911 healthy participants and 5934 participants with depression (mean age 49.8 yr, 68.2% female). Volume effects were greater in late-onset depression and in multiple episodes of depression. Adults with depression and no comorbidity showed significantly lower volumes in the putamen, pallidum and thalamus, as well as significantly lower grey matter volume and intracranial volume; the largest effects were in the hippocampus (6.8%, p < 0.001). Adults with depression and comorbid anxiety showed significantly higher volumes in the amygdala (3.6%, p < 0.001). Comorbid anxiety lowered depression effects by 3% on average. Sex moderated reductions in intracranial volume. Limitations: High heterogeneity in hippocampus effects could not be accounted for by any moderator. Data on symptom severity and medication were sparse, but other factors likely made significant contributions. Conclusion: Depression-related differences in brain structure were modulated by comorbid anxiety, chronicity of symptoms and onset of illness. Early diagnosis of anxiety symptomatology will prove crucial to ensuring effective, tailored treatments for improving long-term mental health and mitigating cognitive problems, given the effects in the hippocampus.

Associations of subclinical cerebral small vessel disease and processing speed in non-demented subjects: A 7-year study

“…Further, it should be noted that the depressive symptoms used in this study are not a clinical diagnosis, but a self-reported symptom in a questionnaire. In our analyses, subjects with depressive symptoms showed less BPV at baseline (very weak effect size), which is consistent with previous studies ( Espinoza Oyarce et al, 2020 , Kumar et al, 1998 , Lebedeva et al, 2018 , Nunes et al, 2018 ). On the other hand, our subjects with depressive symptoms showed a decrease in dWMH over time (weak effect size), while several other previous studies have, in a clinical context, associated depression with higher WMH load ( Krishnan et al, 2006 , Nebes et al, 2002 , Teodorczuk et al, 2007 ).…”

Association Between Amygdala Volume and Trajectories of Neuropsychiatric Symptoms in Alzheimer's Disease and Dementia With Lewy Bodies

“…Nevertheless, conflicting results also reported an opposite direction for this relationship ( 53 ). Large meta-analyses concluded that a direct association between amygdala volume and major depression was particularly observed in depressed patients with comorbid anxiety ( 10 ), or those who were under antidepressive treatment ( 13 ). In AD, the presence of concomitant Lewy pathology in the amygdala increases the risk for major depression ( 54 ).…”

“…Importantly, the amygdala is an essential structure for emotion regulation and is part of the salience neural network (9). Of note, several systematic reviews and meta-analyses have linked amygdala structure and function with psychiatric disorders such as major depressive disorder, depression with comorbid anxiety, schizophrenia, and bipolar disorder (10)(11)(12)(13). However, the role of the amygdala as a potential marker of neuropsychiatric symptoms (NPS) during the course of dementia remains elusive.…”

Coping Strategies, Neural Structure, and Depression and Anxiety During the COVID-19 Pandemic: A Longitudinal Study in a Naturalistic Sample Spanning Clinical Diagnoses and Subclinical Symptoms

“…Structural integrity of the brain regions involved in emotional processing of stressful events has been demonstrated to play a role in the development of symptoms. For example, studies have reported altered gray matter volume and cortical thickness in the amygdala, anterior cingulate cortex (ACC), insula, and hippocampus of individuals with symptoms of anxiety and depression ( 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ). Specifically, there is evidence of amygdala gray matter volume reductions ( 21 , 23 , 24 , 25 ) and increases ( 27 ), as well as gray matter reductions in the hippocampus ( 21 , 22 , 23 , 29 , 32 ).…”

“…For example, studies have reported altered gray matter volume and cortical thickness in the amygdala, anterior cingulate cortex (ACC), insula, and hippocampus of individuals with symptoms of anxiety and depression ( 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ). Specifically, there is evidence of amygdala gray matter volume reductions ( 21 , 23 , 24 , 25 ) and increases ( 27 ), as well as gray matter reductions in the hippocampus ( 21 , 22 , 23 , 29 , 32 ). In addition, reduced cortical thickness of the insula ( 21 , 23 , 32 , 33 , 34 ) and ACC ( 21 , 23 , 25 , 26 , 32 ) have been implicated in depression and anxiety.…”