Longitudinal Structural MRI Findings in Individuals at Genetic and Clinical High Risk for Psychosis: A Systematic Review

Background: Several cross-sectional studies report brain structure differences between healthy volunteers and subjects at genetic or clinical high risk of developing schizophrenia. However, longitudinal studies are important to determine whether altered trajectories of brain development precede psychosis onset. Methods: We conducted a systematic review to determine if brain trajectories differ between (i) those with psychotic experiences (PE), genetic (GHR) or clinical high risk (CHR), compared to healthy volunteers, and (ii) those who transition to psychosis compared to those who do not. Results: Thirty-eight studies measured gray matter and 18 studies measured white matter in 2,473 high risk subjects and 990 healthy volunteers. GHR, CHR, and PE subjects show an accelerated decline in gray matter primarily in temporal, and also frontal, cingulate and parietal cortex. In those who remain symptomatic or transition to psychosis, gray matter loss is more pronounced in these brain regions. White matter volume and fractional anisotropy, which typically increase until early adulthood, did not change or reduced in high risk subjects in the cingulum, thalamic radiation, cerebellum, retrolenticular part of internal capsule, and hippocampal–thalamic tracts. In those who transitioned, white matter volume and fractional anisotropy reduced over time in the inferior and superior fronto-occipital fasciculus, corpus callosum, anterior limb of the internal capsule, superior corona radiate, and calcarine cortex. Conclusion: High risk subjects show deficits in white matter maturation and an accelerated decline in gray matter. Gray matter loss is more pronounced in those who transition to psychosis, but may normalize by early adulthood in remitters

Association of blood lead level with neurological features in 972 children affected by an acute severe lead poisoning outbreak in Zamfara State, northern Nigeria.

BACKGROUND: In 2010, Médecins Sans Frontières (MSF) investigated reports of high mortality in young children in Zamfara State, Nigeria, leading to confirmation of villages with widespread acute severe lead poisoning. In a retrospective analysis, we aimed to determine venous blood lead level (VBLL) thresholds and risk factors for encephalopathy using MSF programmatic data from the first year of the outbreak response. METHODS AND FINDINGS: We included children aged ≤5 years with VBLL ≥45 µg/dL before any chelation and recorded neurological status. Odds ratios (OR) for neurological features were estimated; the final model was adjusted for age and baseline VBLL, using random effects for village of residence. 972 children met inclusion criteria: 885 (91%) had no neurological features; 34 (4%) had severe features; 47 (5%) had reported recent seizures; and six (1%) had other neurological abnormalities. The geometric mean VBLLs for all groups with neurological features were >100 µg/dL vs 65.9 µg/dL for those without neurological features. The adjusted OR for neurological features increased with increasing VBLL: from 2.75, 95%CI 1.27-5.98 (80-99.9 µg/dL) to 22.95, 95%CI 10.54-49.96 (≥120 µg/dL). Neurological features were associated with younger age (OR 4.77 [95% CI 2.50-9.11] for 1-<2 years and 2.69 [95%CI 1.15-6.26] for 2-<3 years, both vs 3-5 years). Severe neurological features were seen at VBLL <105 µg/dL only in those with malaria. INTERPRETATION: Increasing VBLL (from ≥80 µg/dL) and age 1-<3 years were strongly associated with neurological features; in those tested for malaria, a positive test was also strongly associated. These factors will help clinicians managing children with lead poisoning in prioritising therapy and developing chelation protocols

Neurological status categories and definitions.

<p>*Noted abnormalities were hypo-reflexia, inconsolable crying, agitation, and decreased mobility.</p><p>“Any neurological features”  =  categories 1+2+3.</p

Final multi-level logistic regression model to assess factors associated with having any neurological features at time of first-ever pre-chelation VBLL.

<p>*P-value from the Wald test of no association of the attribute with the outcome adjusted for the other variables in the model. VBLL = venous blood lead level. OR = odds ratio. (n = 972).</p

Characteristics by neurological status in children ≤5 years, with first-ever pre-chelation VBLL ≥45 µg/dL from 1 June 2010 to 30 June 2011.

<p>*Malaria test performed only on symptomatic children, but no result in database not confirmation that asymptomatic.</p>†<p>p-values only given when <20% data missing. VBLL = venous blood lead level. RDT = rapid diagnostic test. MUAC = mid upper-arm circumference. Mod = moderately. m = months. y = years. ALT = alanine transaminase.</p

Distribution of VBLL by neurological status in children ≤5 years, with first-ever pre-chelation VBLL ≥45 µg/dL.

<p>VBLL tested from 1 June 2010 to 30 June 2011. VBLL = venous blood lead level.</p

First-ever pre-chelation VBLL test (in categories, µg/dL) by age group (number and % of row).

<p>VBLL = venous blood lead level.</p