Hippocampal shape alterations in healthy young women with familial risk for unipolar depression

Durmusoglu, Ece; Uğurlu, Onur; Akan, Şebnem; Şimşek, Fatma; Kızılateş, Gözde; Kitiş, Ömer; Özkul, Burcu; Eker, Çağdaş; Coburn, Kerry L.; Gönül, Ali Saffet

doi:10.1016/j.comppsych.2018.01.004

Cited by 11 publications

(12 citation statements)

References 68 publications

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“…Data on whether these morphological changes are present prior to the onset of disease (vulnerability factor) are more limited. In support of the vulnerability hypothesis Durmusoglu and colleagues reported contractions in the right CA1/subiculum border in young adult women at increased risk for depression by virtue of a mother with a diagnosis of recurrent depression (Durmusoglu et al, 2018). These data are similar to our own findings and provide further evidence that in some vulnerable individuals localised hippocampal atrophy precedes the onset of depression and, therefore, may be implicated in the aetiology of the disorder.…”

Section: Discussionsupporting

confidence: 89%

“…the vulnerability hypothesis (Baaré et al, 2010;Durmusoglu et al, 2018)). Support for the vulnerability hypothesis can be found across a number of studies that have demonstrated reduced hippocampal volume and/or shape differences in euthymic participants with positive family history for depression (Baaré et al, 2010;Chen, Hamilton, & Gotlib, 2010;Durmusoglu et al, 2018) and early-life adversity (Dahmen et al, 2017)two well recognised risk factors for depression. To our best knowledge, however, no one has yet investigated hippocampal volume or shape and related this to chronotype.…”

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confidence: 99%

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Exploring the effect of chronotype on hippocampal volume and shape: A combined approach

Horne

Norbury

2018

Chronobiology International

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Current evidence suggests that acute depression is associated with reduced total hippocampal volume and regional atrophy. Here, using structural magnetic resonance imaging, we assayed linear effects of chronotype on total hippocampal volume and morphology. Later chronotype was associated with localised atrophy in the subiculum region of the right hippocampus in the absence of changes in total volume. The hippocampus forms a key node in a network of brain regions implicated in emotional regulation and alterations in the structure of this region may underpin, in part, the increased vulnerability for depression in late chronotype individuals.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Exploring the effect of chronotype on hippocampal volume and shape: A combined approach

Horne

Norbury

2018

Chronobiology International

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“…In the context of classification analyses, accuracy as a measure of homogeneity, or purity of classified data, may be misleading since the primary focus is on minimizing misclassification rather than maximizing the overall accuracy of the model . Although our study is of a comparable study sample relatively to other youth‐at‐risk studies (e.g., Eggins et al ., Durmusoglu et al ., and Baglivo et al …”

Section: Discussionmentioning

confidence: 94%

“…For example, localized changes in CA1 may parallel clinical deterioration, from attenuated psychotic symptoms to syndromal psychosis with progressive pathological involvement of other hippocampal subfields . Durmusoglu and colleagues used hippocampal shape analysis on healthy young females with a high familial risk for depression and found that alterations in the CA1 region were associated with vulnerability to depression …”

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confidence: 99%

Aberrant limbic brain structures in young individuals at risk for mental illness

Nogovitsyn

Souza

Muller

et al. 2020

Psychiatry Clin Neurosci

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Aim Alterations in limbic structures may be present before the onset of serious mental illness, but whether subfield‐specific limbic brain changes parallel stages in clinical risk is unknown. To address this gap, we compared the hippocampus, amygdala, and thalamus subfield‐specific volumes in adolescents at various stages of risk for mental illness. Methods MRI scans were obtained from 182 participants (aged 12–25 years) from the Canadian Psychiatric Risk and Outcome study. The sample comprised of four groups: asymptomatic youth at risk due to family history of mental illness (Stage 0, n = 32); youth with early symptoms of distress (Stage 1a, n = 41); youth with subthreshold psychotic symptoms (Stage 1b, n = 72); and healthy comparison participants with no family history of serious mental illness (n = 37). Analyses included between‐group comparisons of brain measurements and correlational analyses that aimed to identify significant associations between neuroimaging and clinical measurements. A machine‐learning technique examined the discriminative properties of the clinical staging model. Results Subfield‐specific limbic volume deficits were detected at every stage of risk for mental illness. A machine‐learning classifier identified volume deficits within the body of the hippocampus, left amygdala nuclei, and medial‐lateral nuclei of the thalamus that were most informative in differentiating between risk stages. Conclusion Aberrant subfield‐specific changes within the limbic system may serve as biological evidence to support transdiagnostic clinical staging in mental illness. Differential patterns of volume deficits characterize those at risk for mental illness and may be indicative of a risk‐stage progression.

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“…The ventral CA1 region in particular has been implicated in this behavior by the recent finding that this region contains pyramidal neurons that generate anxiety‐like behavior, labeled “anxiety cells”, which are absent in the dorsal portion of CA1 (Jimenez et al, ). Shrinkage of the ventral CA1 has also been implicated in human mood disorders by a recent MRI study showing that women at high risk for depression had decreased hippocampal volume specific to the ventral CA1 region (Durmusoglu et al, ). The current study demonstrates that stress on a single day reduces volume in this same subregion while increasing anxiety‐like behavior.…”

Section: Discussionmentioning

confidence: 99%

New neurons restore structural and behavioral abnormalities in a rat model of PTSD

et al. 2019

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Post-traumatic stress disorder (PTSD) has been associated with anxiety, memory impairments, enhanced fear, and hippocampal volume loss, although the relationship between these changes remain unknown. Single-prolonged stress (SPS) is a model for PTSD combining three forms of stress (restraint, swim, and anesthesia) in a single session that results in prolonged behavioral effects. Using pharmacogenetic ablation of adult neurogenesis in rats, we investigated the role of new neurons in the hippocampus in the long-lasting structural and behavioral effects of SPS. Two weeks after SPS, stressed rats displayed increased anxiety-like behavior and decreased preference for objects in novel locations regardless of the presence or absence of new neurons. Chronic stress produced by daily restraint for 2 or 6 hours produced similar behavioral effects that were also independent of ongoing neurogenesis. At a longer recovery time point, one month after SPS, rats with intact neurogenesis had normalized, showing control levels of anxiety-like behavior. However, GFAP-TK rats, which lacked new neurons, continued to show elevated anxiety-like behavior and enhanced serum corticosterone response to anxiogenic experience. Volume loss in ventral CA1 paralleled increases in anxiety-like behavior, occurring in all rats exposed to SPS at the early time point and only rats lacking adult neurogenesis at the later time point. In chronic stress experiments, volume loss occurred broadly throughout the dentate gyrus and CA1 after 6-hour daily stress but was not apparent in any hippocampal subregion after 2-hr daily stress. No effect of SPS was seen on cell proliferation in the dentate gyrus, but the survival of young neurons born a week after stress was decreased. Together, these data suggest that new neurons are functionally important for recovery of normal behavior and hippocampal structure following a strong acute stress and point to the ventral CA1 region as a potential key mediator of stress-induced anxiety-like behavior.

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Hippocampal shape alterations in healthy young women with familial risk for unipolar depression

Cited by 11 publications

References 68 publications

Exploring the effect of chronotype on hippocampal volume and shape: A combined approach

Exploring the effect of chronotype on hippocampal volume and shape: A combined approach

Aberrant limbic brain structures in young individuals at risk for mental illness

New neurons restore structural and behavioral abnormalities in a rat model of PTSD

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