Widespread white matter (WM) abnormalities may offer new insight into hoarding disorder (HD).
In a neuroimaging study, investigators led by Taro Mizobe, Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, compared brain scans of individuals with and without HD.
Results showed that compared with healthy family members, participants with HD had anatomically widespread abnormalities in WM tracts.
In particular, a broad range of alterations were found in frontal WM related to HD symptom severity, as well as cortical regions involved in cognitive dysfunction.
“The finding of a characteristic association between alterations in the prefrontal WM tract, which connects cortical regions involved in cognitive function and the severity of hoarding symptoms, could provide new insights into the neurobiological basis of HD,” the researchers write.
The findings were published online January 18 in the Journal of Psychiatric Research.
“Although there are no clear neurobiological models of HD, several neuroimaging studies have found specific differences in specific brain regions” between patients with and without HD, the investigators write.
Structural MRI studies and voxel-based morphometry have shown larger volumes of gray matter in several regions of the brain in patients with HD. However, there have been no reports on alterations in the WM tracts — and studies of patients with OCD and hoarding symptoms have yielded only “limited information” regarding WM tracts, the researchers note.
Diffusion tensor imaging (DTI) studies have yielded “inconsistent” findings, “therefore little is known about the microstructure of WM in the brains of patients with HD,” they add.
The current study was designed “to investigate microstructural alterations in the WM tracts of individuals with HD” by using tract-based spatial statistics — a model typically used for whole-brain, voxel-wise analysis of DTI measures.
DTI neuroimaging can assess the microstructure of WM. In the current study, the investigators focused on the three measures yielded by DTI: fractional anisotropy (FA), which is an index of overall WM integrity; axial diffusivity (AD); and radial diffusivity (RD).
Participants underwent MRI and DTI scans. Brain images of 25 individuals with hoarding disorder (mean age, 43 years; 64% women; 96% right-handed) were compared with those of 36 healthy controls matched for age, sex, and handedness.
Participants with HD had higher scores on the Hamilton Rating Scales for depression and anxiety than those without HD (P .001 for both).
Of the patients with HD, 10 were taking psychiatric medications such as antidepressants, tranquilizers, or nonstimulant agents for attention deficit hyperactivity disorder (ADHD).
Most (n = 18) were concurrently diagnosed with other psychiatric conditions, including ADHD, anxiety disorder, major depressive disorder, posttraumatic stress disorder, or obsessive-compulsive disorder.
The researchers also conducted a post hoc analysis of regions of interest “to detect correlations with clinical features.”
Compared with healthy controls, patients with hoarding disorder showed decreased FA and increased RD in anatomically widespread WM tracts.
Decreased FA areas included the left superior longitudinal fasciculus (SLF), left uncinate fasciculus, left inferior fronto-occipital fasciculus (IFOF), left anterior thalamic radiation (ATR), left corticospinal tract, and left anterior limb of the internal capsule (ALIC).
Increased RD areas included the bilateral SLF, right IFOF, bilateral anterior and superior corona radiata, left posterior corona radiata, right ATR, left posterior thalamic radiation, right external capsule, and right ALIC.
Post hoc analyses of “regions of interest,” revealed “significant negative correlation” between the severity of hoarding symptoms and FA, particularly in the left anterior limb of the internal capsule, and a positive correlation between HD symptom severity and radial diffusivity in the right anterior thalamic radiation.
Those with HD also showed “a broad range of alterations” in the frontal WM tracts, including the frontothalamic circuit, frontoparietal network, and frontolimbic pathway.
“We found anatomically widespread decreases in FA and increases in WD in many major WM tracts and correlations between the severity of hoarding symptoms and DTI parameters (FA and RD) in the left ALIC and right ATR, which is part of the frontothalamic circuit,” the investigators write.
These findings “suggest that patients with HD have microstructural alterations in the prefrontal WM tracts,” they add.
The researchers say that, to their knowledge, this is the first study to find major abnormalities in WM tracts within the brain and correlations between DTI indices and clinical features in patients with HD.
The frontothalamic circuit is “thought to play an important role in executive functions, including working memory, attention, reward processing, and decision-making,” the investigators write.
Previous research implied that frontothalamic circuit-related cognitive functions are “impaired in patients with HD” and suggested that these impairments “underlie hoarding symptoms such as acquiring, saving, and cluttering relevant to HD.”
The decreased FA in the left SLF “reflects alterations in WM in the frontoparietal network in these patients and may be associated with cognitive impairments, such as task switching and inhibition, as shown in previous studies,” the researchers write.
Additionally, changes in FA and RD often “indicate myelin pathology,” which suggest that HD pathophysiology “may include abnormalities of myelination.”
However, the investigators cite several study limitations, including the “relatively small” sample size, which kept the DTI analysis from being “robust.” Moreover, many patients with HD had comorbid psychiatric disorders, which have also been associated with microstructural abnormalities in WM, the researchers note.
Commenting for Medscape Medical News, Michael Stevens, PhD, director, CNDLAB, Olin Neuropsychiatry Research Center, and adjunct professor of psychiatry at Yale University School of Medicine, New Haven, Connecticut, said the study “provides useful new clues for understanding HD neurobiology” because of its novel approach in assessing microstructural properties of major WM tracts.
The study’s “main contribution is to identify specific WM pathways between brain regions as worth looking at closely in the future. Some of these regions already have been implicated by brain function neuroimaging as abnormal in patients who compulsively hoard,” said Stevens, who was not involved in the research.
He noted that when WM pathway integrity is affected, “it is thought to have an impact on how well information is communicated” between the brain regions.
“So once these specific findings are replicated in a separate study, they hopefully can guide researchers to ask new questions to learn exactly how these WM tracts might contribute to hoarding behavior,” Stevens said.
The study had no specific funding. The investigators and Stevens have disclosed no relevant financial relationships.
J Psychiatr Res. Published online January 18, 2022. Abstract