White matter hyperintensities, suicide risk and late-onset affective disorders: an overview of the current literature
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Updated: Jun 5, 2026

Standardized Data Acquisition for Neuromelanin-Sensitive Magnetic Resonance Imaging of the Substantia Nigra
Published on: September 8, 2021
M Pompili1, G Serafini, M Innamorati
1Department of Psychiatry. Sant'Andrea Hospital, Sapienza University of Rome, Via Grottarossa, Rome, Italy. maurizio.pompili@uniroma1.it
Abstract:
White matter hyperintensities (WMHs) refer to areas of hyperintense signal on T2- or proton density-weighted brain magnetic resonance imaging. Although WMHs are a common finding in patients with bipolar disorder (BD), particularly with a later disease onset, some studies report a higher frequency of WMHs only in unipolar affective disorders. We reviewed the literature examining examining both the severity and presence of WMHs in late life and particularly in individuals with late-onset BD (LOBD). Studies investigating white matter lesions in LOBD were systematically retrieved and the reference lists of these studies were scanned for additional relevant studies of neuroimaging in LOBD. The majority of neuroimaging studies reported an association between older age and LOBD and the presence of WMHs in LOBD. Also, we found in a small sample of patients preliminary evidence of a significant relationship between older age with late-onset BD and WMHs having a higher prevalence of cardiovascular and cerebrovascular risk factors. In conclusion over 60 years older individuals with LOBD and WMHs might have a type of illness characterized by more neuropathological changes and biologically different compared to non LOBD. This is consistent with the hypothesis of vascular mania. WMHs could be a reliable biological risk marker for late onset mood disorders.
Insights
White matter hyperintensities (WMHs) are common in late-onset bipolar disorder (LOBD). These brain imaging findings may indicate more severe neuropathology and serve as a risk marker for LOBD.
Area of Science:
- Neuroimaging
- Neurology
- Psychiatry
Background:
- White matter hyperintensities (WMHs) are frequently observed in brain MRI scans.
- Their prevalence and significance in late-onset bipolar disorder (LOBD) require further investigation.
Purpose of the Study:
- To review the literature on the presence and severity of WMHs in late-life individuals with LOBD.
- To explore the association between WMHs, cardiovascular risk factors, and neuropathological changes in LOBD.
Main Methods:
- Systematic retrieval of neuroimaging studies focusing on white matter lesions in LOBD.
- Scanning reference lists for additional relevant studies.
- Analysis of preliminary data on cardiovascular and cerebrovascular risk factors in LOBD patients with WMHs.
Main Results:
- Most studies indicate a link between older age, LOBD, and the presence of WMHs.
- Preliminary evidence suggests a relationship between older age, LOBD, WMHs, and increased cardiovascular/cerebrovascular risk factors.
- Individuals over 60 with LOBD and WMHs may exhibit distinct neuropathological characteristics.
Conclusions:
- WMHs in older adults with LOBD may signify a biologically distinct illness subtype.
- This finding supports the vascular mania hypothesis.
- WMHs could serve as a valuable biological risk marker for late-onset mood disorders.
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