Effects Of Anxiety And Depression Traits And Oxytocin On Face Processing:fMRI Studies

Face processing,especially emotional face processing,is very crucial for social interaction and communication in humans which underlines the importance of investigating the factors that influence face processing.Many previous studies have demonstrated effects of psychiatric disorder and oxytocin(OXT)treatment on behavioral and neural responses during face processing.Based on behavioral and neural evidence the current studies focused on the neural impact of psychological traits and of intranasal OXT treatment on emotional face processing.The present studies recruited healthy adults and conducted psychopharmacological functional magnetic resonance imaging(fMRI)experiments with assessment of behavioral traits using questionnaires and analysis of neuroimaging data with signal processing methods.The purpose was to explore neural biomarkers that could distinguish depression and social anxiety traits and modulatory as well as sex-dependent effects of intranasal OXT on emotional face processing.Thus the present study had the dual significance of both enriching fundamental research on face processing and brain functions and its clinical application.The first study aimed to explore the effect of depression and social anxiety traits on face processing.Major depressive disorder(MDD)and social anxiety disorder(SAD)are often co-morbid and represent the most common affective disorders where patients exhibit altered face emotional processing.To explore the specific effects of depression and social anxiety on emotional face processing and those which are contributed to by both without confounding effects of clinical symptoms and trait anxiety,we recruited 92 healthy subjects(47 males)in an fMRI study with an explicit emotional face paradigm together with questionnaire assessments using Beck Depression Inventory(BDI-?),Liebowitz Social Anxiety Scale(LSAS),and Trait subscale of State-Trait Anxiety Inventory(STAI-Trait).A control study of neutral face and house matching task was also conducted.Results showed both depression and social anxiety were positively associated with increased reactivity in left globus pallidus and putamen to negative emotions(BDI-fearful,LSAS-sad),controlling gender and trait anxiety as covariates.Further exploratory analysis on these two regions revealed that functional connectivity of left putamen – right middle cingulate cortex during sad face processing was positively associated with social anxiety,while that of the left putamen – right amygdala during fearful face processing was negatively associated with depression.Specific positive associations with depression were found on reactivity of bilateral inferior frontal gyrus,anterior cingulate cortex,and fusiform gyrus,and left inferior parietal lobule and medial prefrontal cortex,and right hippocampus to fearful faces.These are emotional-specific associations and not affected by brain structure,since there were no significant associations with gray matter volume using voxel-based morphometry(VBM)analysis,or with neural reactivity during neutral face or house recognition.The present study suggested depression and social anxiety traits had common as well as specific neural effects on negative face processing.Despite the common neural response,it also showed specific functional connectivity.These may help to serve as neural biomarkers for distinguishing depression and social anxiety disorders,thereby providing potential diagnostic and therapeutic use in psychiatric disorders.The second study explored the effects of intranasal oxytocin on emotional face processing and their sex-dependency.Previous studies found that intranasal OXT had an effect on both explicit and implicit emotional face processing,but no study to date had explored its sex-dependent effects.In line with animal models indicating sexually dimorphic effects of oxytocin on social-emotional processing,a growing number of OXT-administration studies in humans have also reported sex-dependent effects during social information processing.To explore whether sex-dependent effects already occur during early,subliminal,emotional face processing stages the present pharmacological fMRI study combined the intranasal-application of either 24 IU of OXT or placebo(n = 86,43 males)with a backward-masking emotional face paradigm.Results showed that while OXT suppressed inferior frontal gyrus,dorsal anterior cingulate and anterior insula responses to threatening face stimuli in men it increased them in women.In women increased anterior cingulate reactivity during subliminal threat processing was also positively associated with trait anxiety.O n the network level,sex-dependent effects were observed on amygdala,anterior cingulate and inferior frontal gyrus functional connectivity that were mainly driven by reduced coupling in women following O XT.Our findings demonstrate that OXT produces sex-dependent effects even at the early stages of social-emotional processing,and suggest that while it attenuates neural responses to threatening social stimuli in men it increases them in women.This finding suggests the possibility that in therapeutic context OXT may produce different effects on anxiety disorders in men and women.In sum,the present studies firstly adopted dimentional approach and found the common and specific neural effect of depression and social anxiety traits on explicit emotional face processing,which could serve as biomarkers to help improve the diagnosis and treatment for psychiatric disorders with social emotional dysfunctions.In the second study a sex-dependent effect of intranasal OXT was demonstrated in terms of the opposite neural effect in males and females during processing of masked negative face emotions.This demonstrates the importance of considering sex difference during treatment of social dysfunction psychiatric disorders using oxytocin-based interventions.