NC Participants Research Articles

Treatment of Complicated Grief in Survivors of Suicide Loss: A HEAL Report.

Suffering associated with complicated grief (CG) is profound. Because suicide loss survivors are susceptible to developing CG, identifying effective treatments for suicide loss survivors with CG is a high priority. This report provides data on the acceptability and effectiveness of antidepressant medication and complicated grief therapy (CGT), a CG-targeted psychotherapy, for suicide loss survivors with CG identified by an Inventory of Complicated Grief score ≥ 30. This is a secondary analysis of data collected from March 2010 to September 2014 for a 4-site, double-blind, placebo-controlled randomized trial comparing the effectiveness of antidepressant medication alone or in combination with CGT for participants with CG (score ≥ 30 on the Inventory of Complicated Grief) who were bereaved by suicide (SB; n = 58), accident/homicide (A/H; n = 74), or natural causes (NC; n = 263). Using mode of death as a grouping factor, we evaluated acceptability of treatments by comparing 12-week medication and 16-session CGT completion; we evaluated effectiveness by comparing response at week 20, defined by a score of 1 or 2 on the Complicated Grief Clinical Global Impressions-Improvement scale (CG-CGI-I), and additional secondary response measures. Among participants receiving medication alone, SB medication completion rates (36%) were lower than rates for A/H (54%) and NC (68%; χ² = 11.76, P < .01). SB medication completion rates were much higher for SB individuals receiving CGT (82%; χ² = 12.45, P < .001) than for SB individuals receiving medication alone. CGT completion rates were similar in the 3 groups (SB = 74%, A/H = 64%, NC = 77%; χ² = 2.48, P = .29). For SB participants receiving CGT, CG-CGI-I response rates were substantial (64%), but lower compared to the other groups (A/H = 93%, NC = 84%; χ² = 8.00, P < .05). However, on all other outcomes, changes from baseline for SB participants were comparable to those for A/H and NC participants, including number and severity of grief symptoms, suicidal ideation, and grief-related impairment, avoidance, and maladaptive beliefs. These results raise concern about the acceptability of medication alone as a treatment for complicated grief in treatment-seeking suicide-bereaved adults. In contrast, CGT is an acceptable and promising treatment for suicide-bereaved individuals with complicated grief. ClinicalTrials.gov identifier: NCT01179568.

The Symbol-Digit Modalities Test in Mild Cognitive Impairment: Evidence from Parkinson’s Disease Patients

Background: The evaluation process of the performance of the symbol-digit modalities test (SDMT) has focused much on numerical scores paying only little attention to the qualitative aspects of performance. Incorporating the gaze analysis technique, we aimed to investigate the performance of Parkinson’s disease (PD) patients on the written SDMT task. Methods: Twelve patients with PD and normal cognition (PD-N), 11 with PD and mild cognitive impairment (PD-MCI), and 13 healthy participants (NC) controlled for age, sex and education were recruited. Results: PD-MCI participants achieved significantly lower scores than NC and PD-N participants. Eye-movement parameters, however, did not differ among the study groups, and were not correlated with task performance. Conclusions: Impaired performance on the SDMT by PD-MCI participants despite relatively preserved oculomotor performance indicates that lower SDMT scores are not due – even in part – to visuomotor impairments otherwise seen in PD patients.

18F-THK5351 PET Imaging in the Behavioral Variant of Frontotemporal Dementia.

Background and PurposeBehavioral variant frontotemporal dementia (bvFTD) is a subtype of frontotemporal dementia, which has clinical symptoms of progressive personality and behavioral changes with deterioration of social cognition and executive functions. The pathology of bvFTD is known to be tauopathy or TDP-43 equally. We analyzed the 18F-THK5351 positron emission tomography (PET) scans, which were recently developed tau PET, in patients with clinically-diagnosed bvFTD.MethodsForty-eight participants, including participants with behavioral variant frontotemporal dementia (bvFTD, n=3), Alzheimer's disease (AD, n=21) and normal cognition (NC, n=24) who completed 3T magnetic resonance images, 18F-THK5351 PET scans, and detailed neuropsychological tests were included in the study. Voxel-wise statistical analysis and region of interest (ROI)-based analyses were performed to evaluate the retention of THK in bvFTD patients.ResultsIn the voxel-based and ROI-based analyses, patients with bvFTD showed greater THK retention in the prefrontal, medial frontal, orbitofrontal, anterior cingulate, insula, anterior inferior temporal and striatum regions compared to NC participants. Left-right asymmetry was noted in the bvFTD patients. A patient with extrapyramidal symptoms showed much greater THK retention in the brainstem.ConclusionsThe distribution of THK retention in the bvFTD patients was mainly in the frontal, insula, anterior temporal, and striatum regions which are known to be the brain regions corresponding to the clinical symptoms of bvFTD. Our study suggests that 18F-THK5351 PET imaging could be a supportive tool for diagnosis of bvFTD.

IMPLEMENTING THE ATN CLASSIFICATION IN AIBL

Extending their previous two-biomarker approach, Jack and colleagues (Neurology, 2016) have proposed a new classification scheme based on: “A” (Aβ-amyloid), “T” (tau), and “N” (neuronal injury). We investigated the impact of the ATN classification on disease progression and cognitive trajectories. 624 NC participants and 142 MCI participants who underwent evaluation for A status (either 11C-PiB, 18F-florbetapir, 18F-flutemetamol, or 18F-NAV4694 PET Imaging), T status (143 by either 18F-AV1451, 18F-THK5351 or 18F-THK5317 PET Imaging and 54 CSF pTau) and N status (3D-MRI) were considered. Membership to each ATN group and the impact of ATN classification on disease progression were evaluated. 40.5% of NC, 14.3% of MCI and 14.3% of AD were ATN negative; whereas 3.0% of NC, 33.3% of MCI and 42.9% of AD were ATN positive. A linear mixed effect model of Verbal Episodic Memory in NC, identified that participants who were positive for A & N (B=-0.81; p=0.02) had a significantly worse performance at baseline compared to ATN negative, this was exacerbated in participants who were ATN positive (B=-2.45; p=0.005). The only group to have a significantly different decline from the ATN negative group were the ATN positive group (B=-0.52; p=0.00005). No other significant differences were found. The percentage of NC transitioning to MCI/AD and MCI transitioning to AD over the course of their evaluation as per ATN categories are given in Table-1. Being positive for all three categories (A, T & N) is associated with the worst prognosis in terms of risk of progression towards AD. Approximately 7% of NC who are positive for one or less categories progress to MCI or AD whereas ∼12% who are positive for two categories and 30% who are positive on all three categories progress. In MCI, it appears that being positive for A is associated with progression to AD with a higher percentage of progression in those who are also N positive or positive for all 3 categories. Increasing biomarker abnormality is associated with worse cognitive trajectories. The implementation of the ATN classification could help refine prognosis and identify those at-risk individuals more likely to progress for their inclusion in therapeutic trials.

Late-Life Body Mass Index, Rapid Weight Loss, Apolipoprotein E ε4 and the Risk of Cognitive Decline and Incident Dementia.

To examine the effect of late-life body mass index (BMI) and rapid weight loss on incident mild cognitive impairment (MCI) and Alzheimer's disease (AD). Prospective longitudinal cohort study. National Alzheimer's Coordinating Center (NACC) Uniform Data Set, including 34 past and current National Institute on Aging-funded AD Centers across the United States. 6940 older adults (n=5061 normal cognition [NC]; n=1879 MCI). BMI (kg/m2) and modified Framingham Stroke Risk Profile (FSRP) score (sex, age, systolic blood pressure, anti-hypertension medication, diabetes mellitus, cigarette smoking, prevalent cardiovascular disease, atrial fibrillation) were assessed at baseline. Cognition and weight were assessed annually. Multivariable binary logistic regression, adjusting for age, sex, race, education, length of follow-up, and modified FSRP related late-life BMI to risk of diagnostic conversion from NC to MCI or AD and from MCI to AD. Secondary analyses related late-life BMI to diagnostic conversion in the presence of rapid weight loss (>5% decrease in 12 months) and apolipoprotein E (APOE) ε4. During a mean 3.8-year follow-up period, 12% of NC participants converted to MCI or AD and 49% of MCI participants converted to AD. Higher baseline BMI was associated with a reduced probability of diagnostic conversion, such that for each one-unit increase in baseline BMI there was a reduction in diagnostic conversion for both NC (OR=0.977, 95%CI 0.958-0.996, p=0.015) and MCI participants (OR=0.962, 95%CI 0.942-0.983, p<0.001). The protective effect of higher baseline BMI did not persist in the setting of rapid weight loss but did persist when adjusting for APOE ε4. Higher late-life BMI is associated with a lower risk of incident MCI and AD but is not protective in the presence of rapid weight loss.

Cortical Amyloid Burden Differences Across Empirically-Derived Mild Cognitive Impairment Subtypes and Interaction with APOE ɛ4 Genotype.

We examined cortical amyloid-β (Aβ) levels and interactions with apolipoprotein (APOE) ɛ4 genotype status across empirically-derived mild cognitive impairment (MCI) subgroups and cognitively normal older adults. Participants were 583 ADNI participants (444 MCI, 139 normal controls [NC]) with baseline florbetapir positron emission tomography (PET) amyloid imaging and neuropsychological testing. Of those with ADNI-defined MCI, a previous cluster analysis [1] classified 51% (n = 227) of the current sample as amnestic MCI, 8% (n = 37) as dysexecutive/mixed MCI, and 41% (n = 180) as cluster-derived normal (cognitively normal). Results demonstrated that the dysexecutive/mixed and amnestic MCI groups showed significantly greater levels of amyloid relative to the cluster-derived normal and NC groups who did not differ from each other. Additionally, 78% of the dysexecutive/mixed, 63% of the amnestic MCI, 42% of the cluster-derived normal, and 34% of the NC group exceeded the amyloid positivity threshold. Finally, a group by APOE genotype interaction demonstrated that APOE ɛ4 carriers within the amnestic MCI, cluster-derived normal, and NC groups showed significantly greater amyloid accumulation compared to non-carriers of their respective group. Such an interaction was not revealed within the dysexecutive/mixed MCI group which was characterized by both greater cognitive impairment and amyloid accumulation compared to the other participant groups. Our results from the ADNI cohort show considerable heterogeneity in Aβ across all groups studied, even within a group of robust NC participants. Findings suggest that conventional criteria for MCI may be susceptible to false positive diagnostic errors, and that onset of Aβ accumulation may occur earlier in APOE ɛ4 carriers compared to non-carriers.

The Vanderbilt Memory & Aging Project: Study Design and Baseline Cohort Overview.

Vascular health factors frequently co-occur with Alzheimer's disease (AD). A better understanding of how systemic vascular and cerebrovascular health intersects with clinical and pathological AD may inform prevention and treatment opportunities. To establish the Vanderbilt Memory & Aging Project, a case-control longitudinal study investigating vascular health and brain aging, and describe baseline methodology and participant characteristics. From September 2012 to November 2014, 335 participants age 60- 92 were enrolled, including 168 individuals with mild cognitive impairment (MCI, 73±8 years, 41% female) and 167 age-, sex-, and race-matched cognitively normal controls (NC, 72±7 years, 41% female). At baseline, participants completed a physical and frailty examination, fasting blood draw, neuropsychological assessment, echocardiogram, cardiac MRI, and brain MRI. A subset underwent 24-hour ambulatory blood pressure monitoring and lumbar puncture for cerebrospinal fluid (CSF) collection. As designed, participant groups were comparable for age (p = 0.31), sex (p = 0.95), and race (p = 0.65). MCI participants had greater Framingham Stroke Risk Profile scores (p = 0.008), systolic blood pressure values (p = 0.008), and history of left ventricular hypertrophy (p = 0.04) than NC participants. As expected, MCI participants performed worse on all neuropsychological measures (p-values < 0.001), were more likely to be APOEɛ4 carriers (p = 0.02), and had enhanced CSF biomarkers, including lower Aβ42 (p = 0.02), higher total tau (p = 0.004), and higher p-tau (p = 0.02) compared to NC participants. Diverse sources of baseline and longitudinal data will provide rich opportunities to investigate pathways linking vascular and cerebrovascular health, clinical and pathological AD, and neurodegeneration contributing to novel strategies to delay or prevent cognitive decline.

Inclusion of an informant yields strong associations between cognitive complaint and longitudinal cognitive outcomes in non-demented elders.

The relation between the source of cognitive complaint and objective cognitive performance is not well understood. Examine self and informant cognitive complaint as predictors of objective cognitive and functional trajectory in non-demented elders. Participants from the National Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC; n = 6133, 72±8 years, 68% female) or mild cognitive impairment (MCI; n = 3010, 74±8 years, 55% female). Four independent groups defined cognitive complaint: no complaint, self-only complaint, informant-only complaint, or mutual complaint (both self and informant complaint). Linear mixed model regression analyses related complaint status (referent was no complaint) to cognitive and functional trajectories, adjusting for age, sex, race, education, and follow-up period. Among NC participants, mutual complaint related to faster decline in global cognition (p < 0.0001), language (all p-values <0.0001), processing speed (p = 0.0002), and executive functioning (p = 0.0006). Informant-only complaint related to faster decline in global cognition (p = 0.0001) and processing speed (p = 0.0001). Self-only complaint related to greater decline in immediate (p < 0.0001) and delayed (p = 0.0005) episodic memory. In MCI, mutual complaint related to faster decline in global cognition (p < 0.0001), verbal episodic memory (all p-values <0.0001), language (all p-values <0.0001), and processing speed(all p-values <0.0006). Informant-only or self-only complaint associations with cognitive trajectory did not survive correction factor for multiple comparisons.Conclusion: Cognitive complaint appears to have clinical significance, as it is related to declines in objective cognitive performance over time. Mutual complaint was associated with the worst cognitive trajectory in both NC and MCI elders, highlighting the importance of incorporating an informant into evaluation of elders whenever feasible.

Variables associated with hippocampal atrophy rate in normal aging and mild cognitive impairment

The goal of this study was to identify factors contributing to hippocampal atrophy rate (HAR) in clinically normal older adults (NC) and participants with mild cognitive impairment (MCI). Longitudinal HAR was measured on T1-weighted magnetic resonance imaging, and the contribution of age, gender, apolipoprotein E (ApoE) ε4 status, intracranial volume, white matter lesions, and β-amyloid (Aβ) levels to HAR was determined using linear regression. Age-related effects of HAR were compared in Aβ positive (Aβ+) and Aβ negative (Aβ−) participants. Age and Aβ levels had independent effects on HAR in NC, whereas gender, ApoE ε4 status, and Aβ levels were associated with HAR in MCI. In multivariable models, Aβ levels were associated with HAR in NC; ApoE ε4 and Aβ levels were associated with HAR in MCI. In MCI, age was a stronger predictor of HAR in Aβ− versus Aβ+ participants. HAR was higher in Aβ+ participants, but most of the HAR was because of factors other than Aβ status. Age-related effects on HAR did not differ between NC versus MCI participants with the same Aβ status. Therefore, we conclude that even when accounting for other covariates, Aβ status, and not age, is a significant predictor of HAR; and that most of the HAR is not accounted for by Aβ status in either NC or MCI.

Incidence of cerebral microbleeds in preclinical Alzheimer disease

We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with (11)C-Pittsburgh compound B (PiB) PET imaging. One hundred seventy-four participants from the observational Australian Imaging, Biomarkers and Lifestyle Study of Ageing (97 with normal cognition [NC], 37 with mild cognitive impairment [MCI], and 40 with Alzheimer disease [AD] dementia) were assessed at 3 time points over 3 years with 3-tesla susceptibility-weighted MRI and (11)C-PiB PET. MRIs were inspected for microbleeds, siderosis, infarction, and white matter hyperintensity severity, blind to clinical and PiB findings. Neocortical PiB standardized uptake value ratio, normalized to cerebellar cortex, was dichotomized as positive or negative (PiB+/-, standardized uptake value ratio >1.5). Annualized LMB incidence was calculated, and logistic regression was used to determine the association of incident LMBs with PiB, APOE ε4+ status, and cerebrovascular disease. LMBs were present in 18.6% of NC, 24.3% of MCI, and 40% of AD participants (p < 0.05 vs NC). LMB incidence was 0.2 ± 0.6 per year in NC participants, 0.2 ± 0.5 in MCI, and 0.7 ± 1.4 in AD (p < 0.03 vs NC) and was 6-fold higher in PiB+ than PiB-NC. Incident LMBs were associated with age, APOE ε4+, PiB+, and baseline LMBs. Incidence of multiple LMBs was also associated with lacunar infarction and white matter hyperintensity severity. Older age, baseline LMBs, higher β-amyloid burden, and concomitant cerebrovascular disease may all confer higher risk of incident LMBs. This should be considered when designing protocols for amyloid-modifying clinical trials.

The source of cognitive complaints predicts diagnostic conversion differentially among nondemented older adults

ObjectiveThe objective of this study was to compare whether different sources of cognitive complaint (i.e., subjective and informant) predict diagnostic conversion in nondemented older adults. MethodsParticipants from the National Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC; n = 4414; mean age, 73 ± 8 years; 69% female) or mild cognitive impairment (MCI; n = 1843; mean age, 74 ± 8 years; 52% female). Multinomial logistic regression related baseline cognitive complaint (no complaint, self only, informant only, or both self and informant) to diagnostic outcome (reversion, stable, or conversion). ResultsAt follow-up, 14% of NC participants converted to MCI/dementia (3.5 ± 1.8 years), and 41% of MCI participants converted to dementia (3.0 ± 1.6 years). Among NC participants, self complaint only (odds ratio [OR], 2.1; 99% confidence interval (CI),1.5–2.9; P < .001), informant complaint only (OR, 2.2; 99% CI, 1.2–3.9; P < .001), and both self and informant complaint (OR, 4.2; 99% CI, 2.9–6.0; P < .001) were associated with diagnostic conversion compared with no complaint. Among participants with MCI—compared with no complaint, informant complaint only (OR, 2.2; 99% CI, 1.2–4.3, P = .002), and both self and informant complaint (OR, 2.9; 99% CI, 1.8–4.8; P < .001)—were associated with conversion. ConclusionsCognitive complaints are related to conversion among nondemented older adults. Complaint from both (i.e. mutual complaint) sources was most predictive of diagnostic outcome, followed by informant complaint, highlighting the need for obtaining informant corroboration to enhance prognosis and distinguish underlying pathological processes from normal cognitive aging. Self complaint was related inconsistently to diagnostic outcome.

Does Guasha Offer Hepatoprotective Effect to Chronic Inactive Hepatitis B Carriers? A Built-in Design to Control Subject Expectation

A previous case study showed that Guasha, an ancient manual therapeutic technique, could exert hepatoprotective effect in a human chronic active hepatitis B carrier (active-CHB) by modulating the liver enzymes, cytokines, and heme oxygenase-1 (HO-1). The present study serves as a control to the aforementioned case report. The controls were chronic inactive carriers (inactive-CHB) and noncarriers of hepatitis B (NCs). Besides showing a difference in biochemical markers between controls and the previously reported active-CHB case, the asymptomatic condition in both inactive- and active-CHB offers an excellent control for the patient's expectation about Guasha's efficacy. The purpose of this case study was to investigate whether hepatoprotective biochemical markers previously measured in active-CHB in response to Guasha were also present in controls. Four inactive-CHB and nine NC participants were included. Each participant received a 15-minute Guasha treatment. Blood samples were obtained immediately before Guasha (day 0) and after Guasha (days 2, 5, and 7). Biochemistry values for liver function, HO-1, and T-helper (Th) cytokines were determined from blood tests. Neither the participants nor the investigator who administered Guasha were aware of the blood test results until after all data were collected for all participants. In both inactive-CHB and NC participants, liver function, serum HO-1, and Th1/Th2 cytokines did not significantly differ before and after Guasha. In contrast to results in active-CHB patients, Guasha did not induce any significant modulation of liver enzymes, HO-1, or cytokines in inactive-CHB and NC participants. The current results suggest that a Guasha-induced hepatoprotective effect depends on the inflammatory event or clinical stage of chronic hepatitis B. Because both active and inactive carriers were completely unaware of their liver status at the time of receiving Guasha, the research protocol is effective in discounting the model that attributes the Guasha therapeutic efficacy to a placebo effect due to participants' expectations.

Yes/No Versus Forced-Choice Recognition Memory in Mild Cognitive Impairment and Alzheimer's Disease: Patterns of Impairment and Associations with Dementia Severity

Memory tests are sensitive to early identification of Alzheimer's disease (AD) but less useful as the disease advances. However, assessing particular types of recognition memory may better characterize dementia severity in later stages of AD. We sought to examine patterns of recognition memory deficits in individuals with AD and mild cognitive impairment (MCI). Memory performance and global cognition data were collected from participants with AD (n = 37), MCI (n = 37), and cognitively intact older adults (normal controls, NC; n = 35). One-way analyses of variance (ANOVAs) examined differences between groups on yes/no and forced-choice recognition measures. Individuals with amnestic MCI performed worse than NC and nonamnestic MCI participants on yes/no recognition, but were comparable on forced-choice recognition. AD patients were more impaired across yes/no and forced-choice recognition tasks. Individuals with mild AD (≥120 Dementia Rating Scale, DRS) performed better than those with moderate-to-severe AD (<120 DRS) on forced-choice recognition, but were equally impaired on yes/no recognition. There were differences in the relationships between learning, recall, and recognition performance across groups. Although yes/no recognition testing may be sensitive to MCI, forced-choice procedures may provide utility in assessing severity of anterograde amnesia in later stages of AD. Implications for assessment of insufficient effort and malingering are also discussed.

Biased attention towards negative schematic expression in abstinent heroin abusers

Background and objectivesDrug dependents exhibit biases when evaluating emotional facial expressions; however little is known about their emotional biases appearing at the pre-awareness stage. The present study examined whether abstinent heroin abusers preferentially attended to facial expressions with particular emotion type. MethodThirty-seven abstinent heroin abusers (AH participants), twenty normal healthy controls (NC participants), and nineteen individuals with moderate anxiety/depression disorders (PC participants) were included in the study. Participants searched displays containing a varying number of schematic neutral faces for a unique schematic face expressing either a positive or a negative emotion. ResultsResults revealed that AH participants had generally shallower search slopes for locating the negative target face than those for locating the positive one, whereas no such difference was found on NC participants or PC participants. ConclusionIt suggested that abstinent heroin abusers are biased to attend to negative expression more effectively than attend to positive expression. We proposed that this may result from abstinent heroin abusers’ repeated exposure to people’s negative expressions in their living environment or a pre-existing emotional processing deficit which could initiate the development of drug abuse behaviour.

Dysexecutive functioning in mild cognitive impairment: derailment in temporal gradients.

Libon et al. (2010) provided evidence for three statistically determined clusters of patients with mild cognitive impairment (MCI): amnesic (aMCI), dysexecutive (dMCI), and mixed (mxMCI). The current study further examined dysexecutive impairment in MCI using the framework of Fuster's (1997) derailed temporal gradients, that is, declining performance on executive tests over time or test epoch. Temporal gradients were operationally defined by calculating the slope of aggregate letter fluency output across 15-s epochs and accuracy indices for initial, middle, and latter triads from the Wechsler Memory Scale-Mental Control subtest (Boston Revision). For letter fluency, slope was steeper for dMCI compared to aMCI and NC groups. Between-group Mental Control analyses for triad 1 revealed worse dMCI performance than NC participants. On triad 2, dMCI scored lower than aMCI and NCs; on triad 3, mxMCI performed worse versus NCs. Within-group Mental Control analyses yielded equal performance across all triads for aMCI and NC participants. mxMCI scored lower on triad 1 compared to triads 2 and 3. dMCI participants also performed worse on triad 1 compared to triads 2 and 3, but scored higher on triad 3 versus triad 2. These data suggest impaired temporal gradients may provide a useful heuristic for understanding dysexecutive impairment in MCI.

Dysfunctional distracter inhibition and facilitation for sad faces in depressed individuals

Depression is a commonly occurring mental disorder, which is characterized by dysfunctional inhibition and facilitation for emotional stimuli. The aim of the present study was to investigate distracter inhibition and facilitation for emotional faces in depressed individuals in a negative affective priming task. Control participants who had never suffered from depression (NC), sub-clinically depressed participants, and participants diagnosed with a current major depressive disorder (MDD), Anxiety Inventory, the Hamilton Depression Rating Score were recruited using the Beck Depression Inventory, the Beck and DSM-IV as tools. Twenty-four participants in each group completed a negative affective priming task. The main finding was that there were no significant differences among the three groups in the positive and negative priming effects of happy faces. However, there were significant differences for positive and negative priming effects of sad faces between each pair of groups, with the effects being lowest for MDD and highest for NC participants. It can be concluded that depressed individuals are characterized by enhanced facilitation and deficient inhibition for negative materials, which is a stable cognitive vulnerability risk, possibly associated with the occurrence of depression. There are differences in the cognitive dysfunction for negative stimuli between clinically depressed and sub-clinically depressed individuals.

What goes up can come down? A preliminary investigation of emotion reactivity and emotion recovery in bipolar disorder

How is emotion disrupted in bipolar disorder? Two studies are presented that adopt a multi-method approach to investigate emotion reactivity and emotion recovery in bipolar I disorder. Across both studies, individuals with inter-episode bipolar disorder and healthy controls were shown three emotion-eliciting films (neutral, happy, and sad) and experiential and physiological responses were measured. In Study 1, bipolar (BD; n=23) and non-clinical control (NC; n=24) participants' emotional reactivity during film clips was assessed. In Study 2, a separate sample of BD (n=23) and NC (n=25) participants' emotion recovery was assessed after the film clips were assessed. Results indicated that the BD group exhibited increased self-reported positive emotion and respiratory sinus arrhythmia across all films compared to the NC group. There were no group differences in emotion recovery. Taken together, these results suggest that bipolar disorder is associated with increased positive emotion reactivity, but not emotion recovery, across contexts.

Deficient distracter inhibition and enhanced facilitation for emotional stimuli in depression: An ERP study

The aim of the present study was to investigate distracter inhibition ability for emotional faces in depression using a negative affective priming (NAP) task combined with event-related potentials (ERP). The reaction times and the ERP amplitudes were recorded during the task. In a first behavioral experiment, control participants (NC), participants who were currently remitted (RMD), and participants diagnosed with a current major depressive disorder (MDD), performed a modified NAP task. The main finding was that compared with the NC group, MDD participants had enhanced positive priming and less inhibition of sad faces. RMD individuals were characterized by general inhibitory impairments for all emotional faces and a facilitation for sad faces compared with NC individuals. In a second experiment combing the modified NAP task with ERP, the MDD participants had a larger P1 and P3 amplitude for sad faces in the positive priming condition compared with the other groups, and smaller P3 amplitude for sad faces in negative priming condition compared with other faces. Interestingly, RMD participants showed a distinct pattern of results compared with NC and MDD participants. Across the experiments, it can be concluded that MDD participants have deficient distracter inhibition and excessive facilitation for negative stimuli. The RMD participants show a mixed pattern of deficient distracter inhibition and excessive facilitation for both positive and negative stimuli. The results are in line with the idea that impaired distracter inhibition of emotional material is a cognitive risk factor of depression.

Deficient Inhibition of Return for Emotional Faces in Depression

Depression is a commonly-occurred mental disorder. Researchers have highlighted the attentional bias of depressive disorders,although results have been mixed. The cue-target task has often been used to explore attentional bias; a particular phenomenon revealed by such studies is the inhibition of return (IOR). However,cue-target task has seldom been used so far in the study of depressed patients. The aim of the present study was to investigate the IOR phenomenon in depressed individuals in cue-target task using emotional faces as cues. Control participants who had never suffered depression (NC),participants who had experienced at least two depressive episodes in their lives but were currently remitted (RMD),and participants diagnosed with a current major depressive disorder (MDD),were recruited using BDI,SDS,HAMD and CCMD-3 as tools. Seventeen participants in each group completed a cue-target task in a behavioral experiment that comprised three kinds of experimental condition,two cue types and four face types. Each participant also completed a simpler cue-target task in an event-related potential (ERP) experiment. In this task,a target appeared after a cue and the participant responded to its location. In the behavioral experiment,it was found that when the stimulus onset asynchrony (SOA) was 14 ms,the NC and RMD participants had IOR effects for all faces and MDD participants for angry and sad faces. When the SOA was 250 ms,all three groups all had cue validity for sad faces but the effect was much more marked for the MDD group. When the SOA was 750 ms,the NC participants had an IOR effect for sad faces,the RMD participants had cue validity for angry,happy and sad faces,and the MDD participants had cue validity for sad faces and an IOR effect for angry faces. In the ERP experiment,the NC participants showed a bigger P3 amplitude for happy cue than the other groups,a smaller P1 amplitude for happy faces in the invalid cue condition than for other faces,a smaller P1 amplitude for sad faces in the valid cue condition than for other faces,a bigger P3 amplitude for happy faces in the valid cue condition compared with MDD participants,and a bigger P3 amplitude for sad faces in the invalid cue condition compared with other groups. The RMD participants had larger P3 amplitude for sad cue than for other faces,larger P3 amplitude for happy faces in the valid cue condition compared with MDD participants,and smaller P3 amplitude for sad faces in the invalid cue condition compared with NC participants. The MDD participants had a larger P1 amplitude for sad cue compared with other groups,a larger P3 amplitude for sad cue than for other face cues,a smaller P3 amplitude for sad faces in the invalid cue condition compared with NC participants,and a smaller P3 amplitude for happy faces in the valid cue condition compared with other groups. It can be concluded that the MDD participants had cue validity and deficient IOR for negative stimuli. The deficient inhibition of negative stimuli renders them unable to eliminate the interference of negative stimuli and causes the maintenance and development of depression. The RMD participants had cue validity and deficient IOR for both positive and negative stimuli,which enables them to perceive positive and negative stimuli sufficiently and to maintain emotional balance.

Self-paced timing detects and tracks change in prodromal Huntington disease.

This study compares self-paced timing performance (cross-sectionally and longitudinally) between participants with prodromal Huntington's disease (pr-HD) and a comparison group of gene non-expanded participants from affected families (NC). Participants (747 pr-HD: 188 NC) listened to tones presented at 550-ms intervals, matched that pace by tapping response keys and continued the rhythm (self-paced) after the tone had stopped. Standardized cross-sectional and longitudinal linear models examined the relationships between self-paced timing precision and estimated proximity to diagnosis, and other demographic factors. Pr-HD participants showed significantly less timing precision than NC. Comparison of pr-HD and NC participants showed a significant performance difference on two task administration conditions (dominant hand: p < .0001; alternating thumbs: p < .0001). Additionally, estimated proximity to diagnosis was related to timing precision in both conditions, (dominant hand: t = -11.14, df = 920, p < .0001; alternating thumbs: t = -11.32, df = 918, p < .0001). Longitudinal modeling showed that pr-HD participants worsen more quickly at the task than the NC group, and rate of decline increases with estimated proximity to diagnosis in both conditions (dominant hand: t = -2.85, df = 417, p = .0045; alternating thumbs: t = -3.56, df = 445, p = .0004). Effect sizes based on adjusted mean annual change ranged from -0.34 to 0.25 in the longitudinal model. The self-paced timing paradigm has potential for use as a screening tool and outcome measure in pr-HD clinical trials to gauge therapeutically mediated improvement or maintenance of function.