Incorporation coefficients ( K* ) of arachidonic acid (AA) in the brain are increased in a rat model of neuroinflammation, as are other markers of AA metabolism. Data also indicate that neuroinflammation contributes to Alzheimer's disease (AD). On the basis of these observations, K* for AA was hypothesized to be elevated in patients with AD. Methods: A total of 8 patients with AD with an average (±SD) Mini-Mental State Examination score of 14.7 ± 8.4 (mean age, 71.7 ± 11.2 y) and 9 controls with a normal Mini-Mental State Examination score (mean age, 68.7 ± 5.6 y) were studied. Each subject received a 15O-water PET scan of regional cerebral blood flow, followed after 15 min by a 1-11C-AA scan of regional K* for AA. Results: In the patients with AD, compared with control subjects, global gray matter K* for AA (corrected or uncorrected for the partial-volume error [PVE]) was significantly elevated, whereas only PVE-uncorrected global cerebral blood flow was reduced significantly ( P < 0.05). A false-discovery-rate procedure indicated that PVE-corrected K* for AA was increased in 78 of 90 identified hemispheric gray matter regions. PVE-corrected regional cerebral blood flow, although decreased in 12 regions at P < 0.01 by an unpaired t test, did not survive the false-discovery-rate procedure. The surviving K* increments were widespread in the neocortex but were absent in caudate, pallidum, and thalamic regions. Conclusion: These preliminary results show that K* for AA is widely elevated in the AD brain, particularly in regions reported to have high densities of senile (neuritic) plaques with activated microglia. To the extent that the elevations represent upregulated AA metabolism associated with neuroinflammation, PET with 1-11C-AA could be used to examine neuroinflammation in patients with AD and other brain diseases.
Preclinical evidence indicates that the κ-opioid receptor (KOR)/dynorphin pathway is implicated in depressive-like behaviors. Ketamine is believed to partly exert its antidepressant effects by modulating the opioid system. This post hoc study examined the following research questions: (1) at baseline, were there differences in KOR or dynorphin plasma levels between individuals with major depressive disorder (MDD) and healthy volunteers (HVs) or between men and women? (2) in individuals with MDD, did KOR or dynorphin baseline plasma levels moderate ketamine's therapeutic effects or adverse effects? and (3) in individuals with MDD, were KOR or dynorphin plasma levels affected after treatment with ketamine compared with placebo?
The age at which a parent has a child impacts the child's cognition and risk for mental illness. It appears that this risk is curvilinear, with both age extremes associated with lower intelligence and increased prevalence of some neuropsychiatric disorders. Little is known of the neural mechanisms underpinning this phenomenon. We extracted lobar volumes, surface areas, and cortical thickness from 489 neuroanatomic magnetic resonance images acquired on 171 youth. Using linear mixed model regression, we determined the association between parental age and offspring's neuroanatomy, adjusting for offspring's age, sex, intelligence, and parental socioeconomic class. For gray matter volumes, quadratic paternal and maternal age terms contributed significantly (maternal quadratic age effect: t = -2.2, P = 0.03; paternal quadratic age effect: t = -2.4, P = 0.02) delineating an inverted "U" relationship between parental age and gray matter volume. Cortical volume increased with both advancing paternal and maternal age until around the early 30s after which it fell. Paternal age effects were more pronounced on cortical surface area, whereas maternal age impacted more on cortical thickness. There were no significant effects of parental age on white matter volumes. These parental age effects on cerebral morphology may form part of the link between parental age extremes and suboptimal neurocognitive outcomes.
This study sought to examine the association between prospective suicidal behavior and variability, intensity, and persistence of suicidal ideation (SI) in bipolar disorder (BD).Data were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a naturalistic study of 4360 outpatients 15 years or older with BD. In separate models, logistic regressions with suicidal behavior (first attempt or death by suicide) as the outcome variable and SI variability (fluctuating levels of SI over time, measured as ordinal dispersion of SI score), intensity (median SI score over time in study), or persistence (number of visits with reported SI) as the explanatory variables were used to examine the relationship between SI characteristics and odds of future suicidal behavior events.After adjusting for possible confounders, the odds of prospective suicidal behavior were 1.2 times greater per 10% increase in SI variability. SI persistence was not associated with suicidal behavior. For SI intensity, a median SI score of 'rare/fleeting' or 'several days' of SI was not associated with suicidal behavior, but the odds of prospective suicidal behavior were nearly five times greater for participants with the highest observed median SI intensity score of 'nearly every day'.The findings suggest that, in BD participants, monitoring SI variability may be clinically useful for assessing suicide risk.
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