Neurophysiological effects of acute oxytocin administration: systematic review and meta-analysis of placebo-controlled imaging studies

Background

Oxytocin (OXT) plays a prominent role in social cognition and may have clinical applications for disorders such as autism, schizophrenia and social anxiety. The neural basis of its mechanism of action remains unclear.

Methods

We conducted a systematic literature review of placebo-controlled imaging studies using OXT as a pharmacological manipulator of brain activity.

Results

We identified a total of 21 studies for inclusion in our review, and after applying additional selection criteria, 11 of them were included in our fMRI voxel-based meta-analysis. The results demonstrate consistent alterations in activation of brain regions, including the temporal lobes and insula, during the processing of social stimuli, with some variation dependent on sex and task. The meta-analysis revealed significant left insular hyperactivation after OXT administration, suggesting a potential modulation of neural circuits underlying emotional processing.

Limitations

This quantitative review included only a limited number of studies, thus the conclusions of our analysis should be interpreted cautiously. This limited sample size precluded a more detailed exploration of potential confounding factors, such as sex or other demographic factors, that may have affected our meta-analysis.

Conclusion

Oxytocin has a wide range of effects over neural activity in response to social and emotional processing, which is further modulated by sex and task specificity. The magnitude of this neural activation is largest in the temporal lobes, and a meta-analysis across all tasks and both sexes showed that the left insula demonstrated the most robust activation to OXT administration.     

Abnormal Activation of the Social Brain Network in Children with Autism Spectrum Disorder: An fMRI Study

Objective

The aim of this study is to investigate abnormal findings of social brain network in Korean children with autism spectrum disorder (ASD) compared with typically developing children (TDC).

Methods

Functional magnetic resonance imaging (fMRI) was performed to examine brain activations during the processing of emotional faces (happy, fearful, and neutral) in 17 children with ASD, 24 TDC.

Results

When emotional face stimuli were given to children with ASD, various areas of the social brain relevant to social cognition showed reduced activation. Specifically, ASD children exhibited less activation in the right amygdala (AMY), right superior temporal sulcus (STS) and right inferior frontal gyrus (IFG) than TDC group when fearful faces were shown. Activation of left insular cortex and right IFG in response to happy faces was less in the ASD group. Similar findings were also found in left superior insular gyrus and right insula in case of neutral stimulation.

Conclusion

These findings suggest that children with ASD have different processing of social and emotional experience at the neural level. In other words, the deficit of social cognition in ASD could be explained by the deterioration of the capacity for visual analysis of emotional faces, the subsequent inner imitation through mirror neuron system (MNS), and the ability to transmit it to the limbic system and to process the transmitted emotion.     

Differential patterns of initial and sustained responses in amygdala and cortical regions to emotional stimuli in schizophrenia patients and healthy participants

Background

We sought to investigate the altered brain responses to emotional stimuli in patients with schizophrenia.

Methods

We analyzed data from 14 patients with schizophrenia and 14 healthy controls who performed an emotional face matching task. We evaluated brain activity and connectivity in the amygdala and cortical regions during the initial (first 21 seconds of each stimulation block) and sustained (last 21 seconds) stages of an emotional processing task, and we determined changes in amygdala activity across the emotional processing task.

Results

The patients with schizophrenia showed similar amygdala activation to the controls during the initial stage of processing, but their activation decreased during the sustained stage. The controls showed increasing amygdala activity across the emotional blocks, whereas activity progressively decreased in the schizophrenia group. The patients with schizophrenia showed increased cortical activity and interconnectivity in the medial frontal and inferior parietal cortex in the initial stage of emotional processing. There was increased activity in the superior temporal cortex and greater connectivity with the inferior parietal cortex in the sustained stage. Performance accuracy was lower in the schizophrenia group in the first part of the block, while their reaction time was longer in the latter part of the block.

Limitations

It was not possible to specify the moment at which the switch in amygdala response occurred.

Conclusion

Our findings suggest that patients with schizophrenia have an initial automatic emotional response but that they need to switch to a compensatory cognitive strategy to solve the task.     

Have we met before? Neural correlates of emotional learning in women with social phobia

Background

Altered memory processes are thought to be a key mechanism in the etiology of anxiety disorders, but little is known about the neural correlates of fear learning and memory biases in patients with social phobia. The present study therefore examined whether patients with social phobia exhibit different patterns of neural activation when confronted with recently acquired emotional stimuli.

Methods

Patients with social phobia and a group of healthy controls learned to associate pseudonames with pictures of persons displaying either a fearful or a neutral expression. The next day, participants read the pseudonames in the magnetic resonance imaging scanner. Afterwards, 2 memory tests were carried out.

Results

We enrolled 21 patients and 21 controls in our study. There were no group differences for learning performance, and results of the memory tests were mixed. On a neural level, patients showed weaker amygdala activation than controls for the contrast of names previously associated with fearful versus neutral faces. Social phobia severity was negatively related to amygdala activation. Moreover, a detailed psychophysiological interaction analysis revealed an inverse correlation between disorder severity and frontolimbic connectivity for the emotional > neutral pseudonames contrast.

Limitations

Our sample included only women.

Conclusion

Our results support the theory of a disturbed corticolimbic interplay, even for recently learned emotional stimuli. We discuss the findings with regard to the vigilance–avoidance theory and contrast them to results indicating an oversensitive limbic system in patients with social phobia.     

Functional connectivity between the amygdala and prefrontal cortex in medication-naive individuals with major depressive disorder

Background

Convergent evidence suggests dysfunction within the prefrontal cortex (PFC) and amygdala, important components of a neural system that subserves emotional processing, in individuals with major depressive disorder (MDD). Abnormalities in this system in the left hemisphere and during processing of negative emotional stimuli are especially implicated. In this study, we used functional magnetic resonance imaging (fMRI) to investigate amygdala–PFC functional connectivity during emotional face processing in medication-naive individuals with MDD.

Methods

Individuals with MDD and healthy controls underwent fMRI scanning while processing 3 types of emotional face stimuli. We compared the strength of functional connectivity from the amygdala between the MDD and control groups.

Results

Our study included 28 individuals with MDD and 30 controls. Decreased amygdala–left rostral PFC (rPFC) functional connectivity was observed in the MDD group compared with controls for the fear condition (p < 0.05, corrected). No significant differences were found in amygdala connectivity to any cerebral regions between the MDD and control groups for the happy or neutral conditions.

Limitations

All participants with MDD were experiencing acute episodes, therefore the findings could not be generalized to the entire MDD population.

Conclusion

Medication-naive individuals with MDD showed decreased amygdala–left rPFC functional connectivity in response to negative emotional stimuli, suggesting that abnormalities in amygdala–left rPFC neural circuitry responses to negative emotional stimuli might play an important role in the pathophysiology of MDD.     

Neural circuitry of emotional face processing in autism spectrum disorders

Background

Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces.

Methods

Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces.

Results

In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces.

Limitations

The small sample size may have affected our ability to detect additional group differences.

Conclusion

When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.     

Hippocampus and amygdala volumes in patients with borderline personality disorder with or without posttraumatic stress disorder

Background

Several studies have investigated volumetric brain changes in patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). Both groups exhibit volume reductions of the hippocampus and amygdala. Our aim was to investigate the influence of comorbid PTSD on hippocampus and amygdala volumes in patients with BPD.

Methods

We compared 2 groups of unmedicated female patients with BPD (10 with and 15 without comorbid PTSD) and 25 healthy female controls. We used T₁- and T₂-weighted magnetic resonance images for manual tracing and 3-dimensional reconstruction of the hippocampus and amygdala.

Results

Hippocampus volumes of patients with BPD and PTSD were smaller than those of healthy controls. However, there was no significant difference between patients with BPD but without PTSD and controls. Impulsiveness was positively correlated with hippocampus volumes in patients with BPD.

Limitations

Our study did not allow for disentangling the effects of PTSD and traumatization. Another limitation was the relatively small sample size.

Conclusion

Our findings highlight the importance of classifying subgroups of patients with BPD. Comorbid PTSD may be related to volumetric alterations in brain regions that are of central importance to our understanding of borderline psychopathology.     

Mood-congruent amygdala responses to subliminally presented facial expressions in major depression: associations with anhedonia

Background

Anhedonia has long been recognized as a key feature of major depressive disorders, but little is known about the association between hedonic symptoms and neurobiological processes in depressed patients. We investigated whether amygdala mood-congruent responses to emotional stimuli in depressed patients are correlated with anhedonic symptoms at automatic levels of processing.

Methods

We measured amygdala responsiveness to subliminally presented sad and happy facial expressions in depressed patients and matched healthy controls using functional magnetic resonance imaging. Amygdala responsiveness was compared between patients and healthy controls within a 2 (group) × 2 (emotion) design. In addition, we correlated patients’ amygdala responsiveness to sad and happy facial stimuli with self-report questionnaire measures of anhedonia.

Results

We included 35 patients and 35 controls in our study. As in previous studies, we observed a strong emotion × group interaction in the bilateral amygdala: depressed patients showed greater amygdala responses to sad than happy faces, whereas healthy controls responded more strongly to happy than sad faces. The lack of automatic right amygdala responsiveness to happy faces in depressed patients was associated with higher physical anhedonia scores.

Limitations

Almost all depressed patients were taking antidepressant medications.

Conclusion

We replicated our previous finding of depressed patients showing automatic amygdala mood-congruent biases in terms of enhanced reactivity to negative emotional stimuli and reduced activity to positive emotional stimuli. The altered amygdala processing of positive stimuli in patients was associated with anhedonia scores. The results indicate that reduced amygdala responsiveness to positive stimuli may contribute to an-hedonic symptoms due to reduced/inappropriate salience attribution to positive information at very early processing levels.     

Genotype over-diagnosis in amygdala responsiveness: affective processing in social anxiety disorder

Background

Although the amygdala is thought to be a crucial brain region for negative affect, neuroimaging studies do not always show enhanced amygdala response to aversive stimuli in patients with anxiety disorders. Serotonin (5-HT)–related genotypes may contribute to interindividual variability in amygdala responsiveness. The short (s) allele of the 5-HT transporter linked polymorphic region (5-HTTLPR) and the T variant of the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene have previously been associated with amygdala hyperresponsivity to negative faces in healthy controls. We investigated the influence of these polymorphisms on amygdala responsiveness to angry faces in patients with social anxiety disorder (SAD) compared with healthy controls.

Methods

We used positron emission tomography with oxygen 15-labelled water to assess regional cerebral blood flow in 34 patients with SAD and 18 controls who viewed photographs of angry and neutral faces presented in counterbalanced order. We genotyped all participants with respect to the 5-HTTLPR and TPH2 polymorphisms.

Results

Patients with SAD and controls had increased left amygdala activation in response to angry compared with neutral faces. Genotype but not diagnosis explained a significant portion of the variance in amygdala responsiveness, the response being more pronounced in carriers of s and/or T alleles.

Limitations

Our analyses were limited owing to the small sample and the fact that we were unable to match participants on genotype before enrolment. In addition, other imaging techniques not used in our study may have revealed additional effects of emotional stimuli.

Conclusion

Amygdala responsiveness to angry faces was more strongly related to serotonergic polymorphisms than to diagnosis of SAD. Emotion activation studies comparing amygdala excitability in patient and control groups could benefit from taking variation in 5-HT–related genes into account.     

Behavioural and neural correlates of self-focused emotion regulation in social anxiety disorder

Background

In healthy individuals, voluntary modification of self-relevance has proven effective in regulating subjective emotional experience as well as physiologic responses evoked by emotive stimuli. As social anxiety disorder (SAD) is characterized by both altered emotional and self-related processing, we tested if emotion regulation through self-focused reappraisal is effective in individuals with SAD.

Methods

While undergoing 3 T functional magnetic resonance imaging, individuals with SAD and matched healthy controls either passively viewed neutral and aversive pictures or actively increased or decreased their negative emotional experience through the modification of self-relevance or personal distance to aversive pictures. Participants rated all pictures with regard to the intensity of elicited emotions and self-relatedness.

Results

We included 21 individuals with SAD and 23 controls in our study. Individuals with SAD reported significantly stronger emotional intensity across conditions and showed a nonsignificant tendency to judge pictures as more self-related than controls. Compared with controls, individuals with SAD showed an overactivation in bilateral temporoparietal regions and in the posterior midcingulate cortex during the passive viewing of aversive compared with neutral pictures. During instructed emotion regulation, activation patterns normalized and no significant group differences were detected.

Limitations

As no positive pictures were presented, results might be limited to the regulation of negative emotion.

Conclusion

During passive viewing of aversive images, individuals with SAD showed evidence of neural hyperreactivity that may be interpreted as increased bodily self-consciousness and heightened perspective-taking. During voluntary increase and decrease of negative emotional intensity, group differences disappeared, suggesting self-focused reappraisal as a successful emotion regulation strategy for individuals with SAD.     

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

Background

Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure.

Methods

Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD.

Results

Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC.

Limitations

Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD.

Conclusion

These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.     

DNA methylation of the serotonin transporter gene (SLC6A4) is associated with brain function involved in processing emotional stimuli

Background

The aim of the present study was to investigate the association of fMRI blood oxygen–level dependent (BOLD) reactivity with the level of epigenetic methylation of SLC6A4 in blood DNA from a sample of healthy participants and patients with major depressive disorder (MDD).

Methods

We investigated patients with MDD and healthy controls using fMRI and an emotional attention-shifting task. We assessed site-specific DNA methylation of a previously characterized SLC6A4 region in peripheral blood DNA using pyrosequencing.

Results

Our study involved 25 patients with MDD and 35 healthy controls. Activation in the anterior insula elicited by negative emotional content was significantly positively associated with the degree of SLC6A4 methylation. Significantly negative associations were observed between activation in the posterior insula and the degree of SLC6A4 methylation when judging the geometry of pictures after seeing negative in contrast to positive emotional stimuli. Healthy controls with a high degree of SLC6A4 methylation depicted significantly more activity elicited by positive stimuli in limbic regions and more activity elicited by negative stimuli in limbic as well as cognitive control regions than those with a low degree of SLC6A4 methylation.

Limitations

It is impossible to measure methylation directly in the brain and thus we assessed peripheral methylation of SLC6A4. Since the association was cross-sectional, no conclusion about cause and effect can be drawn.

Conclusion

Our study provides further support to the hypothesis that particular DNA methylation states that are associated with brain function during emotion processing are detectable in the periphery.     

Reduced amygdalar and hippocampal size in adults with generalized social phobia

Background

Structural and functional brain imaging studies suggest abnormalities of the amygdala and hippocampus in posttraumatic stress disorder and major depressive disorder. However, structural brain imaging studies in social phobia are lacking.

Methods

In total, 24 patients with generalized social phobia (GSP) and 24 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical investigation.

Results

Compared with controls, GSP patients had significantly reduced amygdalar (13%) and hippocampal (8%) size. The reduction in the size of the amygdala was statistically significant for men but not women. Smaller right-sided hippocampal volumes of GSP patients were significantly related to stronger disorder severity.

Limitations

Our sample included only patients with the generalized subtype of social phobia. Because we excluded patients with comorbid depression, our sample may not be representative.

Conclusion

We report for the first time volumetric results in patients with GSP. Future assessment of these patients will clarify whether these changes are reversed after successful treatment and whether they predict treatment response.     

Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies

Background

Most of our social interactions involve perception of emotional information from the faces of other people. Furthermore, such emotional processes are thought to be aberrant in a range of clinical disorders, including psychosis and depression. However, the exact neurofunctional maps underlying emotional facial processing are not well defined.

Methods

Two independent researchers conducted separate comprehensive PubMed (1990 to May 2008) searches to find all functional magnetic resonance imaging (fMRI) studies using a variant of the emotional faces paradigm in healthy participants. The search terms were: “fMRI AND happy faces,” “fMRI AND sad faces,” “fMRI AND fearful faces,” “fMRI AND angry faces,” “fMRI AND disgusted faces” and “fMRI AND neutral faces.” We extracted spatial coordinates and inserted them in an electronic database. We performed activation likelihood estimation analysis for voxel-based meta-analyses.

Results

Of the originally identified studies, 105 met our inclusion criteria. The overall database consisted of 1785 brain coordinates that yielded an overall sample of 1600 healthy participants. Quantitative voxel-based meta-analysis of brain activation provided neurofunctional maps for 1) main effect of human faces; 2) main effect of emotional valence; and 3) modulatory effect of age, sex, explicit versus implicit processing and magnetic field strength. Processing of emotional faces was associated with increased activation in a number of visual, limbic, temporoparietal and prefrontal areas; the putamen; and the cerebellum. Happy, fearful and sad faces specifically activated the amygdala, whereas angry or disgusted faces had no effect on this brain region. Furthermore, amygdala sensitivity was greater for fearful than for happy or sad faces. Insular activation was selectively reported during processing of disgusted and angry faces. However, insular sensitivity was greater for disgusted than for angry faces. Conversely, neural response in the visual cortex and cerebellum was observable across all emotional conditions.

Limitations

Although the activation likelihood estimation approach is currently one of the most powerful and reliable meta-analytical methods in neuroimaging research, it is insensitive to effect sizes.

Conclusion

Our study has detailed neurofunctional maps to use as normative references in future fMRI studies of emotional facial processing in psychiatric populations. We found selective differences between neural networks underlying the basic emotions in limbic and insular brain regions.     

Multisensory integration of emotionally valenced olfactory–visual information in patients with schizophrenia and healthy controls

Background

Patients with schizophrenia frequently have deficits in social cognition, and difficulties in the discrimination of emotional facial expressions have been discussed as an important contributing factor. We investigated whether this impairment is aggravated by difficulties relating the observed facial expression to contextual information, as is often provided by emotionally valenced crossmodal stimulation.

Methods

We investigated the effects of odorant primes on the accuracy and speed of emotional face recognition. Healthy controls and patients with schizophrenia were exposed to 2-second odorant stimuli: vanillin (pleasant), ambient air (neutral) and hydrogen sulfide (unpleasant). The odours were followed by an emotional face recognition task, in which participants determined if a face showed happiness, disgust or neutral affect.

Results

Controls showed improved performance in the categorization of disgusted faces after all types of odour stimulation irrespective of the emotional valence. However, in controls, the response time for happy faces was slower after presentation of any odour. Schizophrenia patients showed an attenuated effect of olfactory priming on disgust recognition, which resulted in the increased performance differences between the groups. This effect was particularly strong for the unpleasant odour.

Limitations

The study design did not allow us to fully differentiate between the effects of perceived odour intensity and valence. A possible contribution of cognitive deficits on the observed effects should be investigated in future studies.

Conclusion

Our results provide novel evidence for a special connection between the presentation of odorant cues and the accuracy of recognition of disgusted faces in healthy controls. This recognition advantage is disturbed in patients with schizophrenia and appears to contribute to the observed deficit in emotional face recognition.     

Sustained anxiety increases amygdala–dorsomedial prefrontal coupling: a mechanism for maintaining an anxious state in healthy adults

Background

Neuroimaging research has traditionally explored fear and anxiety in response to discrete threat cues (e.g., during fear conditioning). However, anxiety is a sustained aversive state that can persist in the absence of discrete threats. Little is known about mechanisms that maintain anxiety states over a prolonged period. Here, we used a robust translational paradigm (threat of shock) to induce sustained anxiety. Recent translational work has implicated an amygdala–prefrontal cortex (PFC) circuit in the maintenance of anxiety in rodents. To explore the functional homologues of this circuitry in humans, we used a novel paradigm to examine the impact of sustained anticipatory anxiety on amygdala–PFC intrinsic connectivity.

Methods

Task-independent fMRI data were collected in healthy participants during long-duration periods of shock anticipation and safety. We examined intrinsic functional connectivity.

Results

Our study involved 20 healthy participants. During sustained anxiety, amygdala activity was positively coupled with dorsomedial PFC (DMPFC) activity. High trait anxiety was associated with increased amygdala–DMPFC coupling. In addition, induced anxiety was associated with positive coupling between regions involved in defensive responding, and decreased coupling between regions involved in emotional control and the default mode network.

Limitations

Inferences regarding anxious pathology should be made with caution because this study was conducted in healthy participants.

Conclusion

Findings suggest that anticipatory anxiety increases intrinsic amygdala–DMPFC coupling and that the DMPFC may serve as a functional homologue for the rodent prefrontal regions by sustaining anxiety. Future research may use this defensive neural context to identify bio-markers of risk for anxious pathology and target these circuits for therapeutic intervention.     

Brain structural plasticity in survivors of a major earthquake

Background

Stress responses have been studied extensively in animal models, but effects of major life stress on the human brain remain poorly understood. The aim of this study was to determine whether survivors of a major earthquake, who were presumed to have experienced extreme emotional stress during the disaster, demonstrate differences in brain anatomy relative to individuals who have not experienced such stressors.

Methods

Healthy survivors living in an area devastated by a major earthquake and matched healthy controls underwent 3-dimentional high-resolution magnetic resonance imaging (MRI). Survivors were scanned 13–25 days after the earthquake; controls had undergone MRI for other studies not long before the earthquake. We used optimized voxel-based morphometry analysis to identify regional differences of grey matter volume between the survivors and controls.

Results

We included 44 survivors (17 female, mean age 37 [standard deviation (SD) 10.6] yr) and 38 controls (14 female, mean age 35.3 [SD 11.2] yr) in our analysis. Compared with controls, the survivors showed significantly lower grey matter volume in the bilateral insula, hippocampus, left caudate and putamen, and greater grey matter volume in the bilateral orbitofrontal cortex and the parietal lobe (all p < 0.05, corrected for multiple comparison).

Limitations

Differences in the variance of survivor and control data could impact study findings.

Conclusion

Acute anatomic alterations could be observed in earthquake survivors in brain regions where functional alterations after stress have been described. Anatomic changes in the present study were observed earlier than previously reported and were seen in prefrontal–limbic, parietal and striatal brain systems. Together with the results of previous functional imaging studies, our observations suggest a complex pattern of human brain response to major life stress affecting brain systems that modulate and respond to heightened affective arousal.     

Analysis of Altered Baseline Brain Activity in Drug-Naive Adult Patients with Social Anxiety Disorder Using Resting-State Functional MRI

Objective

We hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD.

Methods

We investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-naïve adult SAD patients and 19 healthy controls. Voxels were used to analyze the ALFF values using one- and two-sample t-tests. A post-hoc correlation of clinical symptoms was also performed.

Results

Our findings show decreased ALFF in the bilateral insula, left medial superior frontal gyrus, left precuneus, left middle temporal gyrus, right middle temporal pole, and left fusiform gyrus of the SAD group. The SAD patients exhibited significantly increased ALFF in the right inferior temporal gyrus, right middle temporal gyrus, bilateral middle occipital gyrus, orbital superior frontal gyrus, right fusiform gyrus, right medial superior frontal gyrus, and left parahippocampal gyrus. Moreover, the Liebowitz Social Anxiety Scale results for the SAD patients were positively correlated with the mean Z values of the right middle occipital and right inferior occipital but showed a negative correlation with the mean Z values of the right superior temporal gyrus and right medial superior frontal gyrus.

Conclusion

These results of the altered regional baseline brain function in SAD suggest that the regions with abnormal spontaneous activities are involved in the underlying pathophysiology of SAD patients.     

Reduced amygdala and hippocampus size in trauma-exposed women with borderline personality disorder and without posttraumatic stress disorder

Background

Individuals with posttraumatic stress disorder (PTSD) display reduced hippocampus size and impaired cognition. However, studies on individuals with borderline personality disorder (BPD) are rare, and studies on trauma-exposed patients with BPD but without PTSD are lacking.

Methods

Twenty-four trauma-exposed women with BPD (10 with PTSD and 14 without) and 25 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical and neuropsychological investigation.

Results

Compared with controls, patients with BPD and PTSD displayed significantly reduced amygdala (34%) and hippocampus (12%) size and significantly impaired cognition. Trauma-exposed patients with BPD but without PTSD also showed significantly reduced amygdala (22%) and hippocampus (11%) size but normal cognition. Amygdala and hippocampus size did not differ significantly between patients with and without PTSD.

Limitations

The sample sizes of trauma-exposed groups are relatively small. A larger sample size may have revealed statistically significant differences in amygdala size between those with and without PTSD.

Conclusion

Our results demonstrate strong amygdala size reduction in trauma-exposed patients with BPD with or without PTSD, much exceeding that reported for trauma-exposed individuals without BPD. Our data suggest that BPD is associated with small amygdala size. Furthermore, evidence is increasing that amygdala and hippocampus size reduction is not only due to PTSD, but also to traumatic exposure.