Katherine C. Hughes

Functional neuroimaging studies of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a significant problem that can affect individuals who have been exposed to a traumatic event or events, such as combat, violent crime or childhood abuse. Over the past several years, neuroimaging studies of PTSD have focused on elucidating the brain circuits that mediate this disorder. In this article, we will briefly introduce some of the methods used in functional neuroimaging studies of PTSD. We will then review functional neuroimaging studies that have reported significant findings in the amygdala, medial prefrontal cortex, hippocampus and insula. Finally, we will suggest future directions for research.

The Neural Correlates of Emotional Memory in Posttraumatic Stress Disorder

BACKGROUND Posttraumatic stress disorder (PTSD) is marked by intrusive, chronic, and distressing memories of highly emotional events. Previous research has highlighted the role of the amygdala and its interactions with the hippocampus in mediating the effect of enhanced memory for emotional information in healthy individuals. As the functional integrity of these regions may be compromised in PTSD, the current study examined the neural correlates of emotional memory in PTSD. METHODS We used functional magnetic resonance imaging and an event-related subsequent memory recognition paradigm to study amygdala and hippocampus activation in 18 individuals with PTSD and 18 trauma-exposed non-PTSD control participants. RESULTS Memory enhancement for negative, relative to neutral, pictures was found across all subjects, without significant differences between groups. Relative to the trauma-exposed non-PTSD group, the PTSD group showed exaggerated amygdala activation during the encoding of negative versus neutral pictures. This effect was even more pronounced when the analysis included data from only pictures that were subsequently remembered 1 week later. In the PTSD group, degree of amygdala activation during the encoding of negative versus neutral pictures was positively correlated with hippocampal activation and current PTSD symptom severity. The PTSD group also showed exaggerated hippocampal activation in response to negative pictures that were remembered versus forgotten. Finally, hippocampal activation associated with the successful encoding of negative relative to neutral pictures was significantly greater in the PTSD group. CONCLUSIONS Exaggerated amygdala activation during the encoding of emotionally negative stimuli in PTSD is related to symptom severity and to hippocampal activation.

The Effect of HIV-Related Immunosuppression on the Risk of Tuberculosis Transmission to Household Contacts

BACKGROUND Coinfection with human immunodeficiency virus (HIV) may modify the risk of transmitting tuberculosis. Some previous investigations suggest that patients coinfected with HIV and tuberculosis are less likely to transmit infection, whereas others do not support this conclusion. Here, we estimated the relative risk of tuberculosis transmission from coinfected patients compared to HIV-negative patients with tuberculosis. METHODS Between September 2009 and August 2012, we identified and enrolled 4841 household contacts of 1608 patients with drug-sensitive tuberculosis in Lima, Peru. We assessed the HIV status and CD4 counts of index patients, as well as other risk factors for infection specific to the index patient, the household, and the exposed individuals. Contacts underwent tuberculin skin testing to determine tuberculosis infection status. RESULTS After adjusting for covariates, we found that household contacts of HIV-infected tuberculosis patients with a CD4 count ≤250 cells/µL were less likely to be infected with tuberculosis (risk ratio = 0.49 [95% confidence interval, .24-.96]) than the contacts of HIV-negative tuberculosis patients. No children younger than 15 years who were exposed to HIV-positive patients with a CD4 count ≤250 cells/µL were infected with tuberculosis, compared to 22% of those exposed to non-HIV-infected patients. There was no significant difference in the risk of infection between contacts of HIV-infected index patients with CD4 counts >250 cells/µL and contacts of index patients who were not HIV-infected. CONCLUSIONS We found a reduced risk of tuberculosis infection among the household contacts of patients with active tuberculosis who had advanced HIV-related immunosuppression, suggesting reduced transmission from these index patients.

Diminished rostral anterior cingulate cortex activation during trauma-unrelated emotional interference in PTSD

BackgroundPrevious research suggests that individuals with posttraumatic stress disorder (PTSD) preferentially attend to trauma-related emotional stimuli and have difficulty completing unrelated concurrent tasks. Compared to trauma-exposed control groups, individuals with PTSD also exhibit lower rostral anterior cingulate cortex (rACC) activation during tasks involving interference from trauma-related stimuli. However, it is not clear whether relatively diminished rACC activation in PTSD also occurs during interference tasks involving trauma-unrelated emotional stimuli. The present study employed functional magnetic resonance imaging (fMRI) and an interference task that involves emotional facial expressions and elicits rACC activation in healthy participants.FindingsWhile performing a trauma-unrelated emotional interference task, participants with PTSD (n=17) showed less rACC activation than trauma-exposed non-PTSD (TENP; n=18) participants. In the PTSD group, rACC activation was negatively correlated with the severity of re-experiencing symptoms. The two groups did not significantly differ on behavioral measures (i.e., response times and error rates).ConclusionsThese findings suggest that relatively diminished rACC activation in PTSD can be observed in interference tasks involving trauma-unrelated emotional stimuli, indicating a more general functional brain abnormality in this disorder. Future neuroimaging studies need not employ trauma-related stimuli in order to detect rACC abnormalities in PTSD.

Intake of antioxidant vitamins and risk of parkinson's disease

Oxidative stress is proposed to be one of the potential mechanisms leading to neurodegeneration in Parkinsons disease. However, previous epidemiologic studies investigating associations between antioxidant vitamins, such as vitamins E and C and carotenoids, and PD risk have produced inconsistent results.

Appendectomy and risk of Parkinson's disease in two large prospective cohorts of men and women: Appendectomy and Parkinson's Disease

Background: Prior work on appendectomy and PD has produced mixed results. In this study we examined whether history of self‐reported appendectomy was related to risk of incident Parkinsons disease in the Nurses’ Health Study and the Health Professionals Follow‐up Study.

Interaction between caffeine and polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2) on Parkinson's disease risk: Caffeine, Grin2A, and CYP1A2 ON PD Risk

Background: Caffeine intake has been inversely associated with Parkinsons disease (PD) risk. This relationship may be modified by polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2), but the results of previous studies have been inconsistent.Background Caffeine intake has been inversely associated with Parkinson’s disease (PD) risk. This relationship may be modified by polymorphisms of GRIN2A and CYP1A2 but the results of previous studies have been inconsistent.

The association between restless legs syndrome and premotor symptoms of Parkinson's disease

BACKGROUND Previous studies regarding the association between restless legs syndrome (RLS) and Parkinsons disease (PD) have produced contradictory results. However, the time frame between them has varied across these studies, and also, the longitudinal trajectroy of RLS symptoms has not been considered. OBJECTIVE To investigate if transient or continuous/recurrent RLS identified by questionnaire are associated with the premotor symptoms of PD. METHODS The study population comprised 16,636 men in the Health Professional Follow-Up Study, who answered questions regarding RLS symptoms in both 2002 and 2008, and were not diagnosed with PD. Outcomes were self-reported constipation, possible REM sleep behavior disorder (pRBD) in 2012 and smell identification test score in 2014. RESULTS RLS was associated with increased odds of constipation, but only continuous/recurrent RLS status was associated with higher odds of having pRBD. RLS was not significantly associated with olfactory scores. CONCLUSION In this large-scale longitudinal study, we found moderate associations between the presence of RLS and increased odds of having constipation and pRBD.

Non-motor features of Parkinson’s disease in a nested case–control study of US men

Background Several non-motor features may individually contribute to identify prodromal Parkinson’s disease (PD), but little is known on how they interact. Methods We conducted a case–control study nested within the Health Professionals Follow-up Study in a large cohort of men age 40–75 at recruitment in 1986. Cases (n=120) had confirmed PD, were<85 in January 2012, returned a 2012 questionnaire with questions on probable rapid eye movement sleep behaviour disorder (RBD) and constipation sent to all cohort participants and completed in 2014 the Brief Smell Identification Test and a questionnaire assessing parkinsonism and other non-motor PD features (including depressive symptoms, excessive daytime sleepiness, impaired colour vision and body pain). Controls (n=6479) met the same criteria as cases, except for the PD diagnosis. Results Concurrent constipation, probable RBD and hyposmia were present in 29.3% of cases and 1.1% of controls, yielding an age-adjusted OR of 160(95%CI 72.8to353) for three features versus none. The odds of PD increased exponentially with additional non-motor features (OR for 6–7 features versus none: 1325; 95%CI333to5279). Among men without PD, the number of non-motor features was associated with odds of parkinsonism (OR for 6–7 features versus none: 89; 95%CI21.2to375). We estimated that in a population with a prodromal PD prevalence of 2%, concurrent constipation, probable RBD and hyposmia would have a maximum sensitivity of 29% and a positive predictive value (PPV) of 35%. The PPV could increase up to 70% by including additional features, but with sharply decreased sensitivity. Conclusions Concurrent constipation, probable RBD and hyposmia are strongly associated with PD. Because these features often precede motor symptoms and their co-occurrence could provide an efficient method for early PD identification.