Higher serotonin transporter availability in early-onset obsessive-compulsive disorder patients undergoing escitalopram treatment: A [C-11]DASB PET study

Objective: Early-onset obsessive-compulsive disorder (EOCD) and late-onset obsessive-compulsive disorder (LOCD) are distinct subtypes of obsessive-compulsive disorder (OCD). OCD patients are treated with serotonin reuptake inhibitors, but the difference in serotonin transporter (SERT) availability between medicated EOCD and LOCD is unexplored yet. Methods: Six EOCD and 6 LOCD patients were enrolled. They underwent serial [C-11]DASB positron emission tomography scans during maintenance therapy with escitalopram, and their plasma concentration of escitalopram was measured simultaneously with the scan. Then, the drug-free binding potential of SERT was calculated by pharmacokinetic-pharmacodynamic modelling. Results: In comparison with LOCD patients, SERT availability was significantly higher in the putamen of EOCD patients (U = 4, p = .026), but not in the caudate nucleus (U=14, p=.589), thalamus (U = 16, p = .818), and dorsal raphe nucleus (U = 7, p = .093). Binding potential of putamen showed a negative correlation (r = -.580, p = .048) with age of onset of the disease, but not with the Yale-Brown Obsessive Compulsive Scale scores. Conclusions: These findings indicate that the earlier the age of onset of OCD, the less serotonergic pathology there is and that this difference remains even after long-term serotonin reuptake inhibitor treatment. Clinically, it might suggest that nonserotonergic treatments would be a better option for EOCD patients.N

Developmental coupling of brain iron and intrinsic activity in infants during the first 150 days

Brain iron is vital for core neurodevelopmental processes including myelination and neurotransmitter synthesis and, accordingly, iron accumulates in the brain with age. However, little is known about the association between brain iron and neural functioning and how they evolve with age in early infancy. This study investigated brain iron in 48 healthy infants (22 females) aged 64.00 ± 33.28 days by estimating R2 * relaxometry from multi-echo functional MRI (fMRI). Linked independent component analysis was performed to examine the association between iron deposition and spontaneous neural activity, as measured by the amplitude of low frequency fluctuations (ALFF) by interrogating shared component loadings across modalities. Further, findings were validated in an independent dataset (n = 45, 24 females, 77.93 ± 26.18 days). The analysis revealed developmental coupling between the global R2 * and ALFF within the default mode network (DMN). Furthermore, we observed that this coupling effect significantly increased with age (r = 0.78, p = 9.2e-11). Our results highlight the importance of iron-neural coupling during early development and suggest that the neural maturation of the DMN may correspond to growth in distributed brain iron

Data from: Altered fronto-temporal functional connectivity in individuals at ultra-high-risk of developing psychosis

Background: The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered. Methods: To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl’s gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls. Results: Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl’s gyrus seeds. From the left planum temporale seed, the FEP and UHR groups exhibited increased connectivity to the bilateral dorsolateral prefrontal cortex. In contrast, the FEP and UHR groups demonstrated decreased connectivity from the bilateral Heschl’s gyrus seeds to the dorsal anterior cingulate cortex. The enhanced connectivity between the left planum temporale and right dorsolateral prefrontal cortex was positively correlated with positive symptom severity in individuals at UHR (r = .34, p = .03). Conclusions: These findings corroborate the fronto-temporal connectivity disruption hypothesis in schizophrenia by providing evidence supporting the altered fronto-temporal intrinsic functional connection at earlier stages of psychosis. Our data indicate that subregion-specific aberrant fronto-temporal interactions exist in the STG at the early stage of psychosis, thus suggesting that these aberrancies are the neural underpinning of proneness to psychosis

Altered Fronto-Temporal Functional Connectivity in Individuals at Ultra-High-Risk of Developing Psychosis

<div><p>Background</p><p>The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered.</p><p>Methods</p><p>To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl’s gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls.</p><p>Results</p><p>Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl’s gyrus seeds. From the left planum temporale seed, the FEP and UHR groups exhibited increased connectivity to the bilateral dorsolateral prefrontal cortex. In contrast, the FEP and UHR groups demonstrated decreased connectivity from the bilateral Heschl’s gyrus seeds to the dorsal anterior cingulate cortex. The enhanced connectivity between the left planum temporale and right dorsolateral prefrontal cortex was positively correlated with positive symptom severity in individuals at UHR (<i>r</i> = .34, <i>p</i> = .03).</p><p>Conclusions</p><p>These findings corroborate the fronto-temporal connectivity disruption hypothesis in schizophrenia by providing evidence supporting the altered fronto-temporal intrinsic functional connection at earlier stages of psychosis. Our data indicate that subregion-specific aberrant fronto-temporal interactions exist in the STG at the early stage of psychosis, thus suggesting that these aberrancies are the neural underpinning of proneness to psychosis.</p></div

Connectivity maps, demographics, and clinical assessments

The zip file contains Fisher’s Z transformed connectivity map of each ROI, restricted demographics of the participants, and their clinical assessments

Associations between functional connectivity strength and symptom severity.

<p>(A) Scatterplot of the correlation between the overall positive symptom severity and altered functional connectivity of the ultra-high-risk for psychosis (UHR) subject group (<i>r</i> = .34, <i>p</i> = .03): Fisher's Z transformed connectivity strength between the left planum temporale (PT)–right dorsolateral prefrontal cortex (DLPFC) (<i>x</i> axis) and the overall positive symptom scale score of Positive and Negative Syndrome Scale (PANSS) (<i>y</i> axis). (B) Bar plot of the mean functional connectivity strength (Fisher's Z transformed) of the hallucination group (<i>n</i> = 23) and non-hallucination group (<i>n</i> = 40) among individuals in the FEP and UHR groups (<i>p</i> = .02).</p

Demographic and Clinical Characteristics.

<p><i>Note</i>: FEP, first-episode psychosis; UHR, ultra-high-risk for psychosis; HC, healthy control; IQ, Intelligence quotient. PANSS, Positive and Negative Syndrome Scale; GAF, Global Assessment of Functioning</p><p>Demographic and Clinical Characteristics.</p

Between Group Difference in Functional Connectivity of Superior Temporal Gyrus.

<p><i>Note</i>: FWE, family-wise error; FC, functional connectivity; FEP, first-episode psychosis; UHR, ultra-high-risk for psychosis; HC, healthy control</p><p>Between Group Difference in Functional Connectivity of Superior Temporal Gyrus.</p