Brain Structure and Subclinical Symptoms: A Dimensional Perspective of Psychopathology in the Depression and Anxiety Spectrum

Abstract

Human psychopathology is the result of complex and subtle neurobiological alterations. Categorial DSM or ICD diagnoses do not allow a biologically founded and differentiated description of these diverse processes across a spectrum or continuum, emphasising the need for a scientific and clinical paradigm shift towards a dimensional psychiatric nosology. The subclinical part of the spectrum is, however, of special interest for early detection of mental disorders. We review the current evidence of brain structural correlates (grey matter volume, cortical thickness, and gyrification) in non-clinical (psychiatrically healthy) subjects with minor depressive and anxiety symptoms. We identified 16 studies in the depressive spectrum and 20 studies in the anxiety spectrum. These studies show effects associated with subclinical symptoms in the hippocampus, anterior cingulate cortex, and anterior insula similar to major depression and changes in amygdala similar to anxiety disorders. Precuneus and temporal areas as parts of the default mode network were affected specifically in the subclinical studies. We derive several methodical considerations crucial to investigations of brain structural correlates of minor psycho(patho)logical symptoms in healthy participants. And we discuss neurobiological overlaps with findings in patients as well as distinct findings, e.g. in areas involved in the default mode network. These results might lead to more insight into the early pathogenesis of clinical significant depression or anxiety and need to be enhanced by multi-centre and longitudinal studies.

Subclinical Anxiety and Posttraumatic Stress Influence Cortical Thinning During Adolescence

“…There are indications in the literature that anxiety and depressive symptoms may share similar functional circuitry, though this has yet to be formally tested. 25 Prior work has largely focused on a single symptom set at a time, rather than looking at multiple symptom sets simultaneously as we did. That said, perhaps our model did not capture unique effects of anxiety and depressive symptoms on global gray matter because the symptom clusters overlapped in their effects on cortical structure.…”

“…Few studies have examined the longitudinal changes in brain structure associated with these symptom clusters, and almost no studies assess the concomitant effects of multiple symptom sets, despite the comorbid nature of depression, anxiety, and posttraumatic stress. 1,25,33,34 Moreover, there has been relatively little investigation of sex-specific patterns of neurobiological change associated with psychopathological symptoms despite evidence that male and female youth experience these symptoms at different prevalence rates. [35][36][37] Evidence suggests that male and female youth may be differentially susceptible to developing symptoms following trauma exposure depending on the timing and severity of the incident.…”

“…9,[20][21][22][23][24] Studies have generally shown that increasing anxiety or depressive symptom severity is associated with changes in gray matter, though the specific regions implicated are disparate across studies. 25 For instance, studies in adults have shown that gray matter alterations are associated with symptom severity within the amygdala, hippocampus, frontal, prefrontal, parietal, inferior temporal, anterior and posterior cingulate, and occipital cortices. 18,20,22,[26][27][28][29][30] The lack of consistent regions may suggest more systemic, global associations between symptom sets and brain morphology.…”

“…Few studies have examined the link between symptom severity and cortical structure longitudinally, a necessary endeavor to fully understand the neurodevelopmental impacts of psychopathological symptoms. 25 One such study examined changes in cortical thickness in a large study of 8-to-25 year-olds during three visits approximately two years apart, with an indepth assessment of depressive symptoms occurring only during the third visit. 32 Individuals with more depressive symptoms at the third time point had different trajectories of thinning in the orbitofrontal cortex and precentral gyrus compared to those with fewer depressive symptoms.…”

What Can Be Learned from Dimensional Perspectives on Psychiatry?

“…This psycho-logical dimension spans normality as well as several distinct psychiatric diagnoses, such as mood disorders, anxiety, and substance use disorders. Similarly, Besteher et al [6] summarized the evidence for grey matter alterations in subjects with subclinical symptoms of mood and anxiety disorders. Likewise, Geiser et al [7] reviewed insomnia across diagnoses providing an in-depth discussion of the potential application of noninvasive brain stimulation techniques.…”