Fu L. Woon

Hippocampal and amygdala volumes in children and adults with childhood maltreatment-related posttraumatic stress disorder: a meta-analysis.

Little work has directly examined the course of hippocampal volume in children and adults with childhood maltreatment‐related posttraumatic stress disorder (PTSD). Data from adults suggest that hippocampal volume deficits are associated with PTSD, whereas findings from children with PTSD generally show no hippocampal volume deficits in PTSD. Additionally, the role of the amygdala in emotional response makes it a possible region for investigation in children and adults with childhood maltreatment‐related PTSD. The objectives of this study were 2‐fold: (1) to meta‐analytically determine whether hippocampal and amygdala volumes in children and adults with PTSD from childhood maltreatment differ from those in healthy controls, and (2) to use cross‐sectional findings performed with meta‐analyses as a proxy for longitudinal studies to estimate the course of hippocampal and amygdala volumes in child and adult subjects with PTSD from childhood maltreatment. Using electronic databases, we identified articles containing hippocampal and amygdala data for children with PTSD and adults with PTSD from childhood maltreatment. Data were extracted and effect sizes were calculated using Comprehensive Meta‐Analysis Version 2.0. Reduced bilateral hippocampal volume was found in adults with childhood maltreatment‐related PTSD compared with healthy controls, but this deficit was not seen in children with maltreatment‐related PTSD, suggesting hippocampal volume deficits from childhood maltreatment may not be apparent until adulthood. Greater left than right hippocampal volume was found in the adult healthy control group but not in the PTSD group. Amygdala volume in children with maltreatment‐related PTSD did not differ from that in healthy controls. Hippocampal volume is normal in children with maltreatment‐related PTSD but not in adults with PTSD from childhood maltreatment, suggesting an initially volumetrically normal hippocampus with subsequent abnormal volumetric development occurring after trauma exposure. However, longitudinal studies are needed to support these preliminary findings.

Hippocampal volume deficits associated with exposure to psychological trauma and posttraumatic stress disorder in adults: A meta-analysis

Trauma exposure itself in the absence of posttraumatic stress disorder (PTSD) may be associated with hippocampal volume deficits. We meta-analytically compared hippocampal volumes in PTSD subjects, in trauma-exposed subjects without PTSD, and in trauma-unexposed subjects. Using the words and phrases PTSD, neuroimaging, hippocampus, brain, violence, trauma, abuse, rape, war, combat, accident, and disaster, we searched major computerized databases to obtain candidate studies through 2008 for inclusion. We identified 39 hippocampal volumetric studies in adults with PTSD compared to control groups consisting of either trauma-exposed controls without PTSD or trauma-unexposed controls, or both. We meta-analytically compared left, right, and total hippocampal volumes between 1) PTSD subjects and a trauma-unexposed group, 2) PTSD subjects and a trauma-exposed group without PTSD, and 3) a trauma-unexposed group and a trauma-exposed group without PTSD. Hippocampal volumes were smaller in the PTSD group and trauma-exposed group without PTSD compared to the trauma-unexposed group. Further, the right hippocampus was smaller in the PTSD group compared to the trauma-exposed group without PTSD. Additionally, the right hippocampus was larger than the left in the PTSD and trauma-unexposed groups but not in the trauma-exposed group without PTSD. Hippocampal volume reduction is associated with trauma exposure independent of PTSD diagnosis, albeit additional hippocampal reduction was found in PTSD compared to the trauma-exposed group without PTSD.

Early-life stress and cognitive outcome

RationaleEarly-life stress is associated with later neuropsychiatric illness. While the association between early-life stress and brain development is well recognized, relatively few studies have examined the association between exposure to early-life stress and cognitive outcome.ObjectivesThe objective of this paper is to examine the association between early-life stress and cognitive outcome in animal models and humans.MethodsIn this article, we review alterations in cognitive function associated with early-life stress in animals and then discuss the association of early-life stress and cognitive function in humans.ResultsFindings suggest that early-life stress is associated with abnormal cognitive function in animals and humans. Furthermore, cognitive deficits associated with exposure to early-life stress in humans may persist into at least early adulthood, although animal models of enriched environments and studies of children adopted from institutionalized care into foster families suggest that certain social factors may at least partially reverse cognitive deficits following exposure to early-life stress.ConclusionsExposure to stress in early life may be associated with later deficits in cognitive function.

Neuroimaging, cognitive, and neurobehavioral outcomes following carbon monoxide poisoning.

Carbon monoxide is a colorless, odorless gas produced as a byproduct of combustion. Carbon monoxide is the leading cause of poisoning injury and death worldwide. Morbidity following CO poisoning includes neurologic sequelae, neuropathologic abnormalities on brain imaging, neurobehavioral changes, and cognitive impairments. It is estimated that as high as 50% of individuals with carbon monoxide poisoning will develop neurologic, neurobehavioral, or cognitive sequelae. Carbon monoxide related cognitive impairments included impaired memory, attention, executive function, motor, visual spatial, and slow mental processing speed. Given the high rate of brain related morbidity and the fact that the majority of carbon monoxide is avoidable, awareness and prevention of carbon monoxide poisoning is warranted.

Caffeine-induced psychosis

As a competitive adenosine antagonist, caffeine affects dopamine transmission and has been reported to worsen psychosis in people with schizophrenia and to cause psychosis in otherwise healthy people. We report of case of apparent chronic caffeine-induced psychosis characterized by delusions and paranoia in a 47-year-old man with high caffeine intake. The psychosis resolved within 7 weeks after lowering caffeine intake without use of antipsychotic medication. Clinicians might consider the possibility of caffeinism when evaluating chronic psychosis.

Predicting cognitive sequelae in survivors of critical illness with cognitive screening tests.

RATIONALE Survivors of critical illness have a high rate of cognitive impairments that may persist years after hospital discharge. Data are lacking regarding whether cognitive screening tests administered at hospital discharge can be used to predict which critically ill patients are likely to have long-term cognitive sequelae. OBJECTIVES This prospective study assessed whether two cognitive screening tests, the Mini-Mental State Examination (MMSE) and Mini-Cog, administered at hospital discharge, predict cognitive sequelae in survivors of critical illness 6 months after hospital discharge. METHODS Seventy critically ill patients completed the MMSE and Mini-Cog just before hospital discharge. Of these 70 patients, 53 completed a neuropsychological battery 6 months after hospital discharge. MEASUREMENTS AND MAIN RESULTS At hospital discharge, 45 patients (64%) had impaired performance on the MMSE (score < 27, mean = 24.4) and 32 (45%) on the Mini-Cog. Twenty-seven patients (39%) were impaired on both the MMSE and Mini-Cog, whereas only 20 patients (28%) had scores in the normal range on both tests. Cognitive sequelae occurred in 57% of survivors (30 of 53) at 6 months, with predominant dysfunction in the memory (38%) and executive (36%) domains. Logistic regression analyses showed that neither the MMSE nor the Mini-Cog predicted cognitive sequelae at 6 months. CONCLUSIONS A large number of critically ill survivors had cognitive impairments, as assessed by the MMSE and Mini-Cog, at hospital discharge. However, the MMSE and Mini-Cog scores did not predict long-term cognitive sequelae at 6-month follow-up and cannot be used as surrogate endpoints for long-term cognitive impairment.

Alcohol use and hippocampal volume deficits in adults with posttraumatic stress disorder: A meta-analysis

Posttraumatic stress disorder (PTSD) is associated with hippocampal volume deficits, but the effects of alcohol use on hippocampal volume in PTSD are unclear. We meta-analytically examined the relationship between alcohol use, PTSD, and hippocampal volume deficits. Studies were initially searched through electronic databases. Twelve studies reporting data for the right hippocampal volume and 11 studies with data for the left hippocampal volume met initial inclusion criteria. In the meta-analysis of the studies in which subjects had no lifetime history of alcoholism, both the left and right hippocampal volumes were smaller in PTSD subjects compared to controls. Meta-regression using a continuous trial-level covariate showed that a lifetime history of alcoholism further moderates left and right hippocampal volume in PTSD. PTSD is associated with hippocampal volume deficits independent of a lifetime history of alcoholism, but alcoholism further contributes to the hippocampal volume deficits associated with PTSD.

Does mild cognitive impairment always lead to dementia? A review

Mild cognitive impairment (MCI) has often been studied in its association with dementia, yet higher rates of reversion to normal cognition than progression to dementia suggest that MCI does not necessarily lead to dementia. Compared to the numerous studies on MCI progression, relatively few have examined reversion. This paper highlights the current literature on characteristics and predictive factors of MCI reversion, along with an overview of studies on MCI patients who remain diagnostically stable (i.e., MCI stability). Of the available studies, predictors of reversion have been noted in areas of cognitive/global functioning, demographic/genetic/biomarker data, and personality/lifestyle factors. However, there is a need for increased study of MCI reversion, considering that patients in this group can fluctuate between different trajectories of MCI (e.g., normal cognition back to MCI or even progression to dementia) within a given follow-up time period. Further examination of reversion via a longitudinal, multifactorial approach would better inform clinicians regarding the likelihood of reversion amongst MCI patients and subsequently modify treatment methods accordingly. Furthermore, researchers would have greater power in detecting treatment effects in their clinical intervention studies of early dementia by improving selection criteria to exclude MCI participants who are more likely to revert and remain cognitively normal than progress to a dementia.

Self-Reported Traumatic Brain Injury and Mild Cognitive Impairment: Increased Risk and Earlier Age of Diagnosis

This study examined whether history of traumatic brain injury (TBI) is associated with increased risk and earlier onset of mild cognitive impairment (MCI). Subjects with MCI (n = 3,187) and normal cognition (n = 3,244) were obtained from the National Alzheimers Coordinating Center database. TBI was categorized based on lifetime reported TBI with loss of consciousness (LOC) without chronic deficit. Logistic regression was used to examine TBI history as a predictor of MCI, adjusted for demographics, apolipoprotein E-ɛ4 (ApoE4), a composite vascular risk score, and history of psychiatric factors. ANCOVA was used to examine whether age at MCI diagnosis and estimated age of onset differed between those with (TBI+) and without (TBI-) a history of TBI. TBI history was a significant predictor (p <  0.01) and associated with increased odds of MCI diagnosis in unadjusted (OR = 1.25; 95% CI = 1.05-1.49) and adjusted models, accounting for age, education, ApoE4, and a composite vascular score (OR = 1.32; 95% CI = 1.10-1.58). This association, however, was largely attenuated (OR = 1.14; 95% CI = 0.94-1.37; p = 0.18) after adjustment for reported history of depression. MCI was diagnosed a mean of 2.3 years earlier (p <  0.001) in the TBI+ group, and although TBI+ subjects had an estimated mean of decline 1.7 years earlier, clinician-estimated age of onset failed to differ (p = 0.13) when gender and psychiatric factors were controlled. This is the first report of a possible role for TBI as a risk factor in MCI, but its association may be related to other factors such as gender and depression and requires further investigation.

Structural Magnetic Resonance Imaging Findings in Posttraumatic Stress Disorder and Their Response to Treatment: A Systematic Review

Since the seminal paper by Bremner et al. in 1995 reporting the findings of reduced hippocampal volumes in Vietnam combat veterans, other groups have examined brain morphology in posttraumatic stress disorder (PTSD). However, it is often difficult to com- pare these studies directly because of differences in types of trauma, length of trauma exposure, age of trauma exposure, and sex. Despite these limitations, many authors have found volume reduction in the hippocampus, suggesting that a structural brain deficit may either predispose to the development of PTSD or be the result of the disorder, or both. In fact, some findings argue that the relatively smaller hippocampal volume in patients with PTSD is a risk factor for the development of PTSD, whereas other findings suggest that hippocam- pal volume reduction may occur as a result of either stress exposure or PTSD. Regardless of the etiology of the hippocampal volume re- duction, early work hints that pharmacological intervention may alter hippocampal volume. This review evaluates and categorizes the ex- isting research of hippocampal volume reduction in patients with PTSD. Other structural brain abnormalities related to PTSD are re- viewed. Finally, clinical implications of hippocampal volume reduction in PTSD are considered, particularly the response of the hippo- campus to pharmacological intervention.