Table 2.
DTI and fMRI studies of DUP.
| Author | Year | n | Dx | Clinical severity and/or phase of illness | Mean age (SD) years | % Male | AP N/F/M | AP Tx length | Mean DUP/DUI (SD) months | Imaging measure | Magnet strength | Result |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Collinson | 2014 | 113 | SCZ | 65 first-episode SCZ; 48 chronic SCZ; all in a state psychiatric hospital; minimal symptoms based on the PANSS | 29.3 (7.0) in the first-episode group; 37.0 (9.0) in the chronic group | 74 | 0/0/113 | NR | 18.6 (25.1) first-episode group; 14.2 (14.6) in the chronic group | DTI | 3T | No relationship between DUP and corpus callosum volume or fractional anisotropy measures in corpus callosum |
| Filippi | 2014 | 43 | SCZ | First-contact SCZ; moderately to severely symptomatic based on the PANSS | 29.3 (7.4) | 56 | 43/0/0 | NA | 7.9 (9.7) | DTI | 1.5T | Negative relationship between DUP and MD values of the cerebral peduncles, pons and medulla oblongata, middle cingulum, parahippocampal tracts and inferior longitudinal fasciculi bilaterally, and right posterior limb of the internal capsule, right thalamic radiations, right inferior fronto-occipital, and right uncinate fasciculi as well as a positive relationship between DUP and FA values of the posterior limb of the internal capsule, superior longitudinal and inferior fronto-occipital fasciculi bilaterally, and the right uncinate fasciculi |
| Guo | 2012 | 20 | SCZ | First-episode paranoid SCZ; mildly to moderately symptomatic based on the PANSS | 24.0 (4.9) | 45 | 20/0/0 | NA | 6.6 (3.1) | DTI | 1.5T | No relationship between DUP and FA in right superior longitudinal fasciculus II, the right fornix, the right internal capsule, and the right external capsule |
| Kraguljac | 2020 | 66 | FEP | FEP; inpatients, outpatients, emergency rooms; moderately symptomatic based on the BPRS | 23.8 (6.2) | 65 | 55/NR/NR | <5 days | 20.6 (38.9) | DWI | 3T | DUP was negatively correlated with whole-brain fractional anisotropy and axial diffusivity compared to controls. No relationship between DUP and mean and radial diffusivity |
| Lee | 2018 | 95 | FEP | FEP; moderately symptomatic based on the SANS and SAPS | 33.5 (11.9) | 33 | NR | 8.2 (9.4) days | 3.3 (5.0) | DTI | NR | Fractional anisotropy values of left tapetum (part of splenium of corpus callosum) were significantly inversely correlated with DUP |
| Liu | 2013 | 17 | SCZ | Chronic SCZ | 38.5 (3.9) | 41 | 17/0/0 | NA | 184.9 (76.0) | DTI | 3T | No relationships between DUP and FA in left inferior longitudinal fasciculus (ILF) and left inferior fronto-occipital fasciculus (IFOF) |
| Liu | 2021 | 153 | SCZ | SCZ; inpatients or outpatients; moderately symptomatic based on the PANSS | 27.1 (11.4) | 48 | 153/0/0 | NA | 41.2 (88.4) | DTI, rsfMRI | 3T | No significant associations between DUP and amplitude of low-frequency fluctuations, gray matter-white matter functional synchrony, and fractional anisotropy |
| Luck | 2010 | 32 | SCZ | First-episode SCZ; mildly to moderately symptomatic based on the PANSS | 23.6 (0.7) | 69 | NR/NR/27 | 157.3 (22.0) days | 2.4 (1.1) | DTI | 1.5T | No relationships between DUP and FA in left or right fornix |
| Luck | 2011 | 44 | FEP | FEP | 23.3 (0.5) | 70 | NR/NR/36 | NR | 3.5 (1.5) | DTI | 1.5T | No relationships between DUP and uncinate or superior longitudinal fasciculi |
| Mandl | 2013 | 16 | FEP | First episode; mildly symptomatic based on the PANSS | 23.4 (3.5) | 81 | 16/0/0 | NA | 22.2 (35.6) | DTI | 1.5T | There was a positive relationship between a combination of fractional anisotropy, mean diffusivity, and magnetization transfer ratio in the genu of the corpus callosum |
| Zeng | 2021 | 56 | SCZ | First-episode SCZ; moderately symptomatic based on the PANSS | 24.2 (7.7) good outcome patients; 24.4 (10.0) bad outcome patients | 45 | 56/0/0 | NA | 1.75 (1, 12; IQR) good outcome patients; 6 (1, 23; IQR) bad outcome patients | DTI | 3T | No relationship between DUP and fractional anisotropy and DUP did not aid in separate good versus poor outcome patients |
| Guo | 2014b | 49 | SCZ | Inpatients with first-episode paranoid SCZ; moderately symptomatic based on the PANSS | 22.7 (4.6) | 61 | 49/0/0 | NA | 22.5 (6.7) | rsfMRI | 3T | No relationship between DUP and alterations of the network homogeneity of the default mode network |
| Guo | 2014a | 49 | SCZ | Inpatients with first-episode paranoid SCZ; moderately symptomatic based on the PANSS | 22.7 (4.6) | 61 | 49/0/0 | NA | 22.5 (6.7) | rsfMRI | 3T | No relationship between DUP and voxel-mirrored homotopic connectivity in the precuneus, the precentral gyrus, the superior temporal gyrus, the middle occipital gyrus, and the fusiform gyrus/cerebellum lobule VI |
| Manivannan | 2019 | 37 | SCZ, SAD, SPD, PNOS | FEP; mildly symptomatic based on the BPRS | 22.2 (5.1) | 70 | 11/0/26 | <2 months | 34.7 | fMRI | 3T | No relationship between DUP and visuospatial working memory performance or activation in the dorsolateral prefrontal cortex (DLPFC), DUP was associated with decreased frontostriatal functional connectivity in a cluster of voxels within the DLPFC |
| Maximo | 2020 | 55 | FEP | FEP; inpatient and outpatient and emergency room; mildly symptomatic based on the BPRS | 24.2 (6.3) | 62 | 24/31/0 | <5 days | 19.7 (39.4) | rsfMRI and morphometry | 3T | DUP was negatively correlated with functional connectivity in the default mode network (DFM), salience network (SN), and central executive network (CEN), and surface area in the SN and CEN. DUP was positively correlated with cortical thickness in the DMN and SN. |
| Niendam | 2018 | 87 | SCZ, SAD, or SPD | SCZ, SAD, SPD | 19.6 (3.0) | 84 | NR/NR/61 | NR | 4.9 (4.5) | fMRI | 1.5T | No relationship between DUP and performance or activation in DLPFC |
| Ren | 2013 | 100 | SCZ | First episode; moderately to severely symptomatic based on the PANSS | 24.3 (7.5) | 41 | 100/0/0 | NA | 6.3 (11.0) | Volumetry and rsfMRI | 3T | No differences in volumetry or rsfMRI between groups with short (<1 year) or long (>1 year) DUP |
| Sarpal | 2017 | 83 | SCZ, SPD, SAD, PNOS | Mildly to moderately symptomatic based on the BPRS | 21.9 (6.0) RD group 21.2 (3.7) NRD group |
73 | 31/NR/NR | 15 (59) days | 23.8 (18.0) | rsfMRI | 3T | Lower functional connectivity was associated with greater DUP between striatum and cortex that overlapped in several regions, including the supramarginal gyrus, middle frontal gyrus, and cingulate gyrus. Positive relationship between increasing DUP and functional connectivity between the ventral striatum/nucleus accumbens and the subcallosal cortex/orbitofrontal cortex, and medial frontal pole |
| Zhang | 2019 | 60 | SCZ | First-episode SCZ; mildly to moderately symptomatic based on the BPRS | 25.6 (7.0) | 40 | 60/0/0 | NA | 8.0 (8.8) | rsfMRI | 3T | DUP was associated with decreased functional network connectivity in select sensory-motor subnetworks (left/right upper limb—trunk), but not others (auditory—head/face) |
Dx diagnosis, Tx treatment, AP N/F/M antipsychotic naive/free/medicated, FEP first episode of psychosis, SCZ schizophrenia, SAD schizoaffective disorder, SPD schizophreniform disorder, PNOS psychosis NOS, SDUP short duration of untreated psychosis, LDUP long duration of untreated psychosis, DUP duration of untreated psychosis, CT computed tomography, MRI magnetic resonance imaging, fMRI functional magnetic resonance imaging, rsfMRI resting-state functional magnetic resonance imaging, NIRS near-infrared spectroscopy, MRS magnetic resonance spectroscopy, STEAM stimulated echo acquisition mode, PRESS point-resolved spectroscopy, DTIL diffusion tensor imaging, FA fractional anisotropy, EEG electroencephalogram, PET positron emission tomography, T Tesla, NA not applicable, NR not reported, RD responder, NRD non-responder, BPRS Brief Psychiatric Rating Scale, PANSS Positive and Negative Syndrome Scale.