Simon Surguladze

A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder

BACKGROUND Accurate recognition of facial expressions is crucial for social functioning. In depressed individuals, implicit and explicit attentional biases away from happy and toward sad stimuli have been demonstrated. These may be associated with the negative cognitions in these individuals. METHODS Using event-related functional magnetic resonance imaging (fMRI), neural responses to happy and sad facial expressions were measured in 14 healthy individuals and 16 individuals with major depressive disorder. RESULTS Healthy but not depressed individuals demonstrated linear increases in response in bilateral fusiform gyri and right putamen to expressions of increasing happiness, while depressed individuals demonstrated linear increases in response in left putamen, left parahippocampal gyrus/amygdala, and right fusiform gyrus to expressions of increasing sadness. There was a negative correlation in depressed individuals between depression severity and magnitude of neural response within right fusiform gyrus to happy expressions. CONCLUSIONS Our findings indicate preferential increases in neural response to sad but not happy facial expressions in neural regions involved in the processing of emotional stimuli in depressed individuals. These findings may be associated with the above pattern of implicit and explicit attentional biases in these individuals and suggest a potential neural basis for the negative cognitions and social dysfunction in major depression.

Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression

BACKGROUND Bipolar disorder (BD) is characterised by abnormalities in mood and emotional processing, but the neural correlates of these, their relationship to depressive symptoms, and the similarities with deficits in major depressive disorder (MDD) remain unclear. We compared responses within subcortical and prefrontal cortical regions to emotionally salient material in patients with BP and MDD using functional magnetic resonance imaging. METHODS We measured neural responses to mild and intense expressions of fear, happiness, and sadness in euthymic and depressed BD patients, healthy control subjects, and depressed MDD patients. RESULTS Bipolar disorder patients demonstrated increased subcortical (ventral striatal, thalamic, hippocampal) and ventral prefrontal cortical responses particularly to mild and intense fear, mild happy, and mild sad expressions. Healthy control subjects demonstrated increased subcortical responses to intense happy and mild fear, and increased dorsal prefrontal cortical responses to intense sad expressions. Overall, MDD patients showed diminished neural responses to all emotional expressions except mild sadness. Depression severity correlated positively with hippocampal response to mild sadness in both patient groups. CONCLUSIONS Compared with healthy controls and MDD patients, BD patients demonstrated increased subcortical and ventral prefrontal cortical responses to both positive and negative emotional expressions.

Recognition accuracy and response bias to happy and sad facial expressions in patients with major depression.

Impaired facial expression recognition has been associated with features of major depression, which could underlie some of the difficulties in social interactions in these patients. Patients with major depressive disorder and age- and gender-matched healthy volunteers judged the emotion of 100 facial stimuli displaying different intensities of sadness and happiness and neutral expressions presented for short (100 ms) and long (2,000 ms) durations. Compared with healthy volunteers, depressed patients demonstrated subtle impairments in discrimination accuracy and a predominant bias away from the identification as happy of mildly happy expressions. The authors suggest that, in depressed patients, the inability to accurately identify subtle changes in facial expression displayed by others in social situations may underlie the impaired interpersonal functioning.

Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

CONTEXT Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. OBJECTIVE To investigate the effects of 2 main psychoactive constituents of Cannabis sativa (Delta9-tetrahydrocannabinol [Delta9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. DESIGN Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. PARTICIPANTS Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. MAIN OUTCOME MEASURES Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety. RESULTS Delta9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. CONCLUSIONS Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions.

Meta-analytical Comparison of Voxel-Based Morphometry Studies in Obsessive-Compulsive Disorder vs Other Anxiety Disorders

CONTEXT Whether obsessive-compulsive disorder (OCD) is adequately classified as an anxiety disorder is a matter of considerable debate. OBJECTIVES To quantitatively compare structural brain changes in OCD and other anxiety disorders using novel voxel-based meta-analytical methods and to generate an online database to facilitate replication and further analyses by other researchers. DATA SOURCES The PubMed, ScienceDirect, and Scopus databases were searched between 2001 (the date of the first voxel-based morphometry study in any anxiety disorder) and 2009. All voxel-based morphometry studies comparing patients with any anxiety disorder and healthy controls were retrieved. Manual searches were also conducted. Authors were contacted soliciting additional data. STUDY SELECTION Thirty-seven data sets were identified, of which 26 (including 639 patients with anxiety disorders and 737 healthy controls) met inclusion criteria. DATA EXTRACTION Coordinates were extracted from clusters of significant gray matter difference between patients and controls. Demographic, clinical, and methodological variables were extracted from each study or obtained from the authors. DATA SYNTHESIS Patients with anxiety disorders (including OCD) showed decreased bilateral gray matter volumes in the dorsomedial frontal/anterior cingulate gyri. Individuals with OCD had increased bilateral gray matter volumes (vs healthy controls and vs individuals with other anxiety disorders) in the lenticular/caudate nuclei, while patients with other anxiety disorders (mainly panic and posttraumatic stress disorders) had decreased gray matter volumes in the left lenticular nucleus. The findings remained largely unchanged in quartile and jackknife sensitivity analyses. Controlling for potential confounders such as age or antidepressant medication had little impact on the results. CONCLUSIONS The meta-analysis consistently revealed common as well as distinct neural substrates in OCD and other anxiety disorders. These results have implications for the current debate surrounding the classification of OCD in the DSM-V.

A preferential increase in the extrastriate response to signals of danger

This study examined neural responses in nine right-handed healthy individuals while they viewed mild and intense expressions of four emotions (fear, disgust, happiness, and sadness) contrasted with neutral faces in four event-related functional magnetic resonance imaging experiments. Orthogonal polynomial trend analysis revealed a significant linear increase in the fusiform extrastriate cortical response to increasing intensities of all four emotional expressions, which was significantly greater to increasing intensities of fear and disgust than happiness and sadness, and a significant linear decrease in response to sadness in another extrastriate region. The amygdala was activated by high-intensity fearful expressions, consistent with findings from previous studies, and by low- but not high-intensity sad expressions. Significant linear increases in response to increasing intensities of fear, disgust, and happiness occurred within the hippocampus, anterior insula, and putamen, respectively. Conversely, significant linear decreases in hippocampal and putamen responses occurred to increasing intensities of sadness. We provide the first demonstration of differential increases in extrastriate and limbic responses to signals of increasing danger than to those of other emotions, and significant decreases in these responses to signals of increasing sadness in others. We suggest that this differential pattern of response to different categories of emotional signals allows the preferential direction of visual attention to signals of imminent danger than to other, less-salient emotional stimuli.

Cognitive inhibition and working memory in unipolar depression.

BACKGROUND Over the past decade, evidence has accumulated to suggest that people suffering from Major Depressive Disorder (MDD) present impairment in attention, working memory, executive function, including cognitive inhibition, problem- and task-planning. The aim of the current study was to assess inhibitory mechanisms within working memory with emotionally neutral material in a group of patients suffering from MDD. We hypothesized that impairment in cognitive inhibition is global and not only due to the emotional valence of the stimuli employed for the tasks. METHODS Twenty patients with MDD (DSM-IV) and 20 healthy controls were recruited. To assess cognitive inhibition, we used neutral material, in the form of the Prose Distraction Task (PDT) (Connelly SL, 1991), Trail Making Test (TMT), Modified Card Sorting Test (MCST), Rule Shift Cards (RSC), Stroop test and Hayling Sentence Completion test (HSC). The Modified 6 elements test, the Brixton Spatial Anticipation test, the dual task performance and the verbal fluencies test were also used to assess other executive function such as flexibility, planning tasks and memory. RESULTS Individuals with depression showed impairment in cognitive inhibition. They made more errors on the PDT, alongside slower response times. Slower response times were also observed on the Stroop, TMT and RSC. The MDD group made more errors in HSC and performed worse than controls in the semantic part of verbal fluency and Modified 6 elements tasks. The impairment of access function was significantly associated with the level of depression. CONCLUSION Depressed patients showed inability to inhibit neutral information access to working memory, restrain and delete irrelevant information. This impairment in cognitive inhibition could underlie cognitive slowness and attentional deficits in depression.

Neural response to specific components of fearful faces in healthy and schizophrenic adults

Perception of fearful faces is associated with functional activation of cortico-limbic structures, which has been found altered in individuals with psychiatric disorders such as schizophrenia, autism and major depression. The objective of this study was to isolate the brain response to the features of standardized fearful faces by incorporating principal component analysis (PCA) into the analysis of neuroimaging data of healthy volunteers and individuals with schizophrenia. At the first stage, the visual characteristics of morphed fearful facial expressions (FEEST, Young et al., 2002) were classified with PCA, which produced seven orthogonal factors, with some of them related to emotionally salient facial features (eyes, mouth, brows) and others reflecting non-salient facial features. Subsequently, these PCA-based factors were included into the functional magnetic resonance imaging (fMRI) analysis of 63 healthy volunteers and 32 individuals with schizophrenia performing a task that involved implicit processing of FEEST stimuli. In healthy volunteers, significant neural response was found to visual characteristics of eyes, mouth or brows. In individuals with schizophrenia, PCA-based analysis enabled us to identify several significant clusters of activation that were not detected by the standard approach. These clusters were implicated in processing of visual and emotional information and were attributable to the perception of eyes and brows. PCA-based analysis could be useful in isolating brain response to salient facial features in psychiatric populations.

What are the effects of group cognitive behaviour therapy for voices? A randomised control trial

BACKGROUND Little evidence exists for the effects of psychological treatment on voices even though it is clear that CBT does affect delusions and symptoms overall. This study tested whether a group based on cognitive behavioural principles could produce beneficial effects on hallucinations. AIM To test the effectiveness of group CBT on social functioning and severity of hallucinations. METHOD Participants were included if they had a diagnosis of schizophrenia and experienced distressing auditory hallucinations (rated on the PANSS). They were randomly allocated to group CBT (N = 45) or a control group who received treatment as usual (N = 40). The two main outcomes were social functioning as measured by the Social Behaviour Schedule and the severity of hallucinations as measured by the total score on the Hallucinations Scale of PSYRATS. Assessments were carried out at baseline, 10 weeks (post therapy) and 36 weeks (six months following therapy). RESULTS Mixed random effects models revealed significant improvement in social functioning (effect size 0.63 six months after the end of therapy). There was no general effect of group CBT on the severity of hallucinations. However, there was a large cluster effect of therapy group on the severity of hallucinations such that they were reduced in some but not all of the therapy groups. Improvement in hallucinations was associated with receiving therapy early in the trial and having very experienced therapists (extensive CBT training which included expert supervision for a series of individual cases for at least a year following initial training). CONCLUSION Group CBT does improve social functioning but unless therapy is provided by experienced CBT therapists hallucinations are not reduced.

A Reversal of the Normal Pattern of Parahippocampal Response to Neutral and Fearful Faces Is Associated with Reality Distortion in Schizophrenia

BACKGROUND Individuals with schizophrenia demonstrate impaired recognition of facial expressions and may misattribute emotional salience to otherwise nonsalient stimuli. The neural mechanisms underlying this deficit and the relationship with different symptoms remain poorly understood. METHODS We used event-related functional magnetic resonance imaging to measure neural responses to neutral, mildly fearful, and prototypically fearful facial expressions. The sample included 15 medicated individuals with chronic schizophrenia (SZ) and 11 healthy control individuals (CON), matched for gender (all male), age, and years of education. RESULTS A repeated measures 3 x 2 analysis of variance (ANOVA) revealed a significant interaction between expression intensity and group in right parahippocampal gyrus (p < .01). Individuals with chronic schizophrenia demonstrated a decrease, whereas CON showed an increase, in right parahippocampal gyrus response to increasingly fearful expressions. Between-group comparison revealed greater activation in SZ than CON in right parahippocampal gyrus to neutral faces. The reality distortion dimension, but not neuroleptic medication dose, was positively associated with the right parahippocampal gyral and right amygdalar response to neutral faces in SZ. CONCLUSIONS An abnormally increased parahippocampal response to neutral faces was positively associated with reality distortion in SZ. This may underlie the previously reported finding of a misattribution of emotional salience to nonsalient social stimuli in schizophrenia.