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1.  Modality-specific alterations in the perception of emotional stimuli in Bipolar Disorder compared to Healthy Controls and Major Depressive Disorder 
Objectives
Affect identification accuracy paradigms have increasingly been utilized to understand psychiatric illness including Bipolar Disorder (BD) and Major Depressive Disorder (MDD). This investigation focused on perceptual accuracy in affect identification in both visual and auditory domains among patients with BD, relative to Healthy Controls (HC) and patients with MDD. Demographic and clinical variables, in addition to medications were also investigated.
Methods
The visual Facial Emotion Perception Test (FEPT) and auditory Emotional Perception Test (EPT) were administered to adults with BD (n = 119) and MDD (n = 78) as well as HC (n = 66).
Results
Performance on the FEPT was significantly stronger than on the EPT irrespective of group. Performance on the EPT did not significantly differentiate the groups. On the FEPT, BD samples had the greatest difficulty relative to HC in identification of sad and fearful faces. BD participants also had greater difficulty identifying sad faces relative to MDD participants though not after controlling for severity of illness factors. For the BD (but not MDD) sample several clinical variables were also correlated with FEPT performance.
Conclusions
The findings suggest that disruptions in identification of negative emotions such as sadness and fear may be a characteristic trait of BD. However, this effect may be moderated by greater illness severity found in our BD sample.
doi:10.1016/j.cortex.2011.03.017
PMCID: PMC3660134  PMID: 21683948
Bipolar Disorder; Major Depressive Disorder; Affect perception
2.  DRD2 polymorphisms modulate reward and emotion processing, dopamine neurotransmission and openness to experience 
Dopamine (DA) neurotransmission through D2 receptors (DRD2) has been implicated in the regulation of reward processing, cognition and the effects of drugs of abuse, and also has significant effects in responses to stressors and salient aversive stimuli. An examination of the influence of genetic variation across multiple psychophysical measures therefore appears critical to understand the neurobiology of DA-modulated complex personality traits and psychiatric illnesses. To examine interindividual variation in the function of DRD2 modulated mechanisms in healthy humans, we used a haplotype-based and single nucleotide polymorphism (SNP) investigation. Their effects were interrogated with functional magnetic resonance imaging (fMRI) during reward and emotional processing. We found that a haplotype block composed by two SNPs, rs4274224 and rs4581480, affected the hemodynamic responses of the dorsolateral prefrontal cortex (DLPFC) during reward expectation and the subgenual anterior cingulate cortices (sgACC) during implicit emotional processing. Exploratory analysis within the significant haplotype block revealed the same functional effects only for the SNP rs4274224. Further analysis on rs4274224 using functional connectivity and positron emission tomography (PET) measures of DA D2/3 receptor mediated neurotransmission confirmed a gene effect on the functional connectivity of the DLPFC during reward anticipation and subcortical stress induced dopamine release. At a phenotypic trait level, significant effects of genotype were obtained for the NEO PI-R “Openness to Experience” and further correlated with neuroimaging data. Overall, these results show significant neurobiological effects of genotype variation in DRD2 on multiple functional domains, such as emotional, stress and reward processing. As such, it contributes to normal variation and potentially to vulnerability to psychopathology associated with those functions, such as risk for mood and substance use disorders.
doi:10.1016/j.cortex.2012.01.010
PMCID: PMC3381848  PMID: 22424959
imaging; dopamine; DLPFC; reward; emotion
3.  Impact of Chronic Hypercortisolemia on Affective Processing 
Neuropharmacology  2011;62(1):217-225.
Cushing syndrome (CS) is the classic condition of cortisol dysregulation, and cortisol dysregulation is the prototypic finding in Major Depressive Disorder (MDD). We hypothesized that subjects with active CS would show dysfunction in frontal and limbic structures relevant to affective networks, and also manifest poorer facial affect identification accuracy, a finding reported in MDD.Twenty-one patients with confirmed CS (20 ACTH-dependent and 1 ACTH-independent) were compared to 21 healthy controlsubjects. Identification of affective facial expressions (Facial Emotion Perception Test) was conducted in a 3 Tesla GE fMRI scanner using BOLD fMRI signal. The impact of disease (illness duration, current hormone elevation and degree of disruption of circadian rhythm), performance, and comorbid conditions secondary to hypercortisolemia were evaluated.CS patients made more errors in categorizing facial expressions and had less activation in left anterior superior temporal gyrus, a region important in emotion processing. CS patients showed higher activation in frontal, medial, and subcortical regions relative to controls. Two regions of elevated activation in CS, left middle frontal and lateral posterior/pulvinar areas, were positively correlated with accuracy in emotion identification in the CS group, reflecting compensatory recruitment. In addition, within the CSgroup, greater activation in left dorsal anterior cingulatewas related to greater severity of hormone dysregulation. In conclusion, cortisol dysregulation in CS patients is associated with problems in accuracy of affective discrimination and altered activation of brain structures relevant to emotion perception, processing and regulation, similar to the performance decrements and brain regions shown to be dysfunctional in MDD.
doi:10.1016/j.neuropharm.2011.07.006
PMCID: PMC3196277  PMID: 21787793
HPA; cortisol; ACTH; emotion; affect; fMRI; Cushings
4.  The Relationship between Depressive Symptoms, Disease State, and Cognition in Amyotrophic Lateral Sclerosis 
Cognitive impairment (CI) in amyotrophic lateral sclerosis (ALS) may present a serious barrier to a patient’s wellbeing and significantly decrease quality of life. Although reports of CI in ALS without frank dementia are becoming quite common, questions remain regarding the specific cognitive domains affected, as well as how other psychological and medical factors may impact cognitive functioning in these patients. Additionally, the influence of depressive symptoms on disease processes is not known. We aimed to address these questions by completing extensive neuropsychological tests with 22 patients with ALS and 17 healthy volunteers. A subgroup of these patients also completed questionnaires to measure depressive and vegetative symptoms. We tested for overall cognitive differences between groups, the influence of physical (e.g., bulbar and limb), vegetative (e.g., fatigue), and depressive symptoms on cognitive performance, and the relationship between depressive symptoms and disease severity in ALS. Overall, patients performed more poorly than healthy controls (HCs), most notably on tests of executive functioning and learning and memory. Results suggest that true cognitive performance differences exist between patients with ALS and HCs, as these differences were not changed by the presence of vegetative or depressive symptoms. There was no effect of limb or bulbar symptoms on cognitive functioning. Also, patients were not any more depressed than HCs, however increased depressive scores correlated with faster disease progression and decreased limb function. Collectively, it is suggested that translational advances in psychological intervention for those with CI and depression become emphasized in future research.
doi:10.3389/fpsyg.2012.00542
PMCID: PMC3571885  PMID: 23411492
ALS; motor neuron disease; neuropsychology; depression; ALSFRS-r; cognition; limb symptoms
5.  Auditory Memory Decrements, Without Dissimulation, among Patients with Major Depressive Disorder 
Questions have been raised about whether poor performance on memory tasks by individuals with major depressive disorder (MDD) might be the result of poor or variable effort or disease-related disruption of neural circuits supporting memory functions. The present study examined performance on a measure of task engagement and on an auditory memory task among 45 patients with MDD (M age = 47.82, SD = 19.55) relative to 32 healthy controls (HC; M age = 51.03, SD = 22.09). One-hundred percent of HC and MDD volunteers performed above the threshold for adequate effort on a formal measure of task engagement. The MDD subjects performed significantly more poorly than the HC subjects on an auditory learning and memory test. The present results suggest that auditory memory difficulties do occur among those with MDD and that decrements in performance in this group may be related to factors other than lack of effort.
doi:10.1093/arclin/acr041
PMCID: PMC3201698  PMID: 21593060
Depression; Malingering/symptom validity testing; Learning and memory

Results 1-5 (5)