Dataset Information

Neurite Orientation Dispersion and Density Imaging (NODDI) and Duration of Untreated Psychosis in Antipsychotic Medication-Naive First Episode Psychosis Patients.

ABSTRACT:

Background

Diffusion tensor imaging suggests that white matter alterations are already evident in first episode psychosis patients (FEP) and may become more prominent as the duration of untreated psychosis (DUP) increases. But because the tensor model lacks specificity, it remains unclear how to interpret findings on a biological level. Here, we used a biophysical diffusion model, Neurite Orientation Dispersion and Density Imaging (NODDI), to map microarchitecture in FEP, and to investigate associations between DUP and microarchitectural integrity.

Methods

We scanned 78 antipsychotic medication-naïve FEP and 64 healthy controls using a multi-shell diffusion weighted sequence and used the NODDI toolbox to compute neurite density (ND), orientation dispersion index (ODI) and extracellular free water (FW) maps. AFNI's 3dttest++ was used to compare diffusion maps between groups and to perform regression analyses with DUP.

Results

We found that ND was decreased in commissural and association fibers but increased in projection fibers in FEP. ODI was largely increased regardless of fiber type, and FW showed a mix of increase in decrease across fiber tracts. We also demonstrated associations between DUP and microarchitecture for all NODDI indices.

Conclusions

We demonstrated that complex microarchitecture abnormalities are already evident in antipsychotic-naïve FEP. ND alterations are differentially expressed depending on fiber type, while decreased fiber complexity appears to be a uniform marker of white matter deficit in the illness. Importantly, we identified an empirical link between longer DUP and greater white matter pathology across NODDI indices, underscoring the critical importance of early intervention in this devastating illness.

SUBMITTER: Kraguljac NV

PROVIDER: S-EPMC10038586 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neurite Orientation Dispersion and Density Imaging (NODDI) and Duration of Untreated Psychosis in Antipsychotic Medication-Naïve First Episode Psychosis Patients.

Kraguljac Nina Vanessa NV Monroe William Stonewall WS Anthony Thomas T Jindal Ripu Daman RD Hill Harrison H Lahti Adrienne Carol AC

Neuroimage. Reports 20210304 1

<h4>Background</h4>Diffusion tensor imaging suggests that white matter alterations are already evident in first episode psychosis patients (FEP) and may become more prominent as the duration of untreated psychosis (DUP) increases. But because the tensor model lacks specificity, it remains unclear how to interpret findings on a biological level. Here, we used a biophysical diffusion model, Neurite Orientation Dispersion and Density Imaging (NODDI), to map microarchitecture in FEP, and to investig ...[more]

PMID: 36969709

Similar Datasets

Project description:ImportanceDuration of untreated psychosis (DUP) has been associated with poor outcomes in schizophrenia, but the mechanism responsible for this association is not known.ObjectivesTo determine whether hippocampal volume loss occurs during the initial 8 weeks of antipsychotic treatment and whether it is associated with DUP, and to examine molecular biomarkers in association with hippocampal volume loss and DUP.Design, setting, and participantsA naturalistic longitudinal study with matched healthy controls was conducted at Shanghai Mental Health Center. Between March 5, 2013, and October 8, 2014, 71 medication-naive individuals with nonaffective first-episode psychosis (FEP) and 73 age- and sex-matched healthy controls were recruited. After approximately 8 weeks, 31 participants with FEP and 32 controls were reassessed.ExposuresThe participants with FEP were treated according to standard clinical practice with second-generation antipsychotics.Main outcomes and measuresHippocampal volumetric integrity (HVI) (an automated estimate of the parenchymal fraction in a standardized hippocampal volume of interest), DUP, 13 peripheral molecular biomarkers, and 14 single-nucleotide polymorphisms from 12 candidate genes were determined.ResultsThe full sample consisted of 71 individuals with FEP (39 women and 32 men; mean [SD] age, 25.2 [7.7] years) and 73 healthy controls (40 women and 33 men; mean [SD] age, 23.9 [6.4] years). Baseline median left HVI was lower in the FEP group (n = 57) compared with the controls (n = 54) (0.9275 vs 0.9512; difference in point estimate, -0.020 [95% CI, -0.029 to -0.010]; P = .001). During approximately 8 weeks of antipsychotic treatment, left HVI decreased in 24 participants with FEP at a median annualized rate of -.03791 (-4.1% annualized change from baseline) compared with an increase of 0.00115 (0.13% annualized change from baseline) in 31 controls (difference in point estimate, -0.0424 [95% CI, -0.0707 to -0.0164]; P = .001). The change in left HVI was inversely associated with DUP (r = -0.61; P = .002). Similar results were found for right HVI, although the association between change in right HVI and DUP did not achieve statistical significance (r = -0.35; P = .10). Exploratory analyses restricted to the left HVI revealed an association between left HVI and markers of inflammation, oxidative stress, brain-derived neurotrophic factor, glial injury, and markers reflecting dopaminergic and glutamatergic transmission.Conclusions and relevanceAn association between longer DUP and accelerated hippocampal atrophy during initial treatment suggests that psychosis may have persistent, possibly deleterious, effects on brain structure. Additional studies are needed to replicate these exploratory findings of molecular mechanisms by which untreated psychosis may affect hippocampal volume and to determine whether these effects account for the known association between longer DUP and poor outcome.

Project description:The NODDI-DTI signal model is a modification of the NODDI signal model that formally allows interpretation of standard single-shell DTI data in terms of biophysical parameters in healthy human white matter (WM). The NODDI-DTI signal model contains no CSF compartment, restricting application to voxels without CSF partial-volume contamination. This modification allowed derivation of analytical relations between parameters representing axon density and dispersion, and DTI invariants (MD and FA) from the NODDI-DTI signal model. These relations formally allow extraction of biophysical parameters from DTI data. NODDI-DTI parameters were estimated by applying the proposed analytical relations to DTI parameters estimated from the first shell of data, and compared to parameters estimated by fitting the NODDI-DTI model to both shells of data (reference dataset) in the WM of 14 in vivo diffusion datasets recorded with two different protocols, and in simulated data. The first two datasets were also fit to the NODDI-DTI model using only the first shell (as for DTI) of data. NODDI-DTI parameters estimated from DTI, and NODDI-DTI parameters estimated by fitting the model to the first shell of data gave similar errors compared to two-shell NODDI-DTI estimates. The simulations showed the NODDI-DTI method to be more noise-robust than the two-shell fitting procedure. The NODDI-DTI method gave unphysical parameter estimates in a small percentage of voxels, reflecting voxelwise DTI estimation error or NODDI-DTI model invalidity. In the course of evaluating the NODDI-DTI model, it was found that diffusional kurtosis strongly biased DTI-based MD values, and so, making assumptions based on healthy WM, a novel heuristic correction requiring only DTI data was derived and used to mitigate this bias. Since validations were only performed on healthy WM, application to grey matter or pathological WM would require further validation. Our results demonstrate NODDI-DTI to be a promising model and technique to interpret restricted datasets acquired for DTI analysis in healthy white matter with greater biophysical specificity, though its limitations must be borne in mind.

Project description:BackgroundThe neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression - how age affects clinical presentation in first-episode psychosis - has not been thoroughly investigated.MethodsUsing generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals with first-episode psychosis (N = 340, 12-40 years, 1-12 visits), collected at the University of Pittsburgh from 1990 to 2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We tested for age-associated effects on change in positive or negative symptom severity following baseline assessment and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development.ResultsPerceptual positive symptom severity significantly decreased with increasing age (F = 7.0, p = 0.0007; q = 0.003) while non-perceptual positive symptom severity increased with age (F = 4.1, p = 0.01, q = 0.02). Anhedonia severity increased with increasing age (F = 6.7, p = 0.00035; q = 0.0003), while flat affect decreased in severity with increased age (F = 9.8, p = 0.002; q = 0.006). Findings remained significant when parental SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p > 0.25). Beginning at age 18, there was a statistically significant association between severity of non-perceptual and perceptual symptoms. This relationship increased in strength throughout adulthood.ConclusionsThese findings suggest that as maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced. Findings underscore how pathological brain-behavior relationships vary as a function of development.