Persistence of amygdala hyperactivity to subliminal negative emotion processing in the long-term course of depression.

Biased emotion processing has been suggested to underlie the etiology and maintenance of depression. Neuroimaging studies have shown mood-congruent alterations in amygdala activity in patients with acute depression, even during early, automatic stages of emotion processing. However, due to a lack of prospective studies over periods longer than 8 weeks, it is unclear whether these neurofunctional abnormalities represent a persistent correlate of depression even in remission. In this prospective case-control study, we aimed to examine brain functional correlates of automatic emotion processing in the long-term course of depression. In a naturalistic design, n = 57 patients with acute major depressive disorder (MDD) and n = 37 healthy controls (HC) were assessed with functional magnetic resonance imaging (fMRI) at baseline and after 2 years. Patients were divided into two subgroups according to their course of illness during the study period (n = 37 relapse, n = 20 no-relapse). During fMRI, participants underwent an affective priming task that assessed emotion processing of subliminally presented sad and happy compared to neutral face stimuli. A group × time × condition (3 × 2 × 2) ANOVA was performed for the amygdala as region-of-interest (ROI). At baseline, there was a significant group × condition interaction, resulting from amygdala hyperactivity to sad primes in patients with MDD compared to HC, whereas no difference between groups emerged for happy primes. In both patient subgroups, amygdala hyperactivity to sad primes persisted after 2 years, regardless of relapse or remission at follow-up. The results suggest that amygdala hyperactivity during automatic processing of negative stimuli persists during remission and represents a trait rather than a state marker of depression. Enduring neurofunctional abnormalities may reflect a consequence of or a vulnerability to depression.

Depressive symptoms and visual attention to others' eyes in healthy individuals.

BACKGROUND: Eye contact is a fundamental part of social interaction. In clinical studies, it has been observed that patients suffering from depression make less eye contact during interviews than healthy individuals, which could be a factor contributing to their social functioning impairments. Similarly, results from mood induction studies with healthy persons indicate that attention to the eyes diminishes as a function of sad mood. The present screen-based eye-tracking study examined whether depressive symptoms in healthy individuals are associated with reduced visual attention to other persons' direct gaze during free viewing. METHODS: Gaze behavior of 44 individuals with depressive symptoms and 49 individuals with no depressive symptoms was analyzed in a free viewing task. Grouping was based on the Beck Depression Inventory using the cut-off proposed by Hautzinger et al. (2006). Participants saw pairs of faces with direct gaze showing emotional or neutral expressions. One-half of the face pairs was shown without face masks, whereas the other half was presented with face masks. Participants' dwell times and first fixation durations were analyzed. RESULTS: In case of unmasked facial expressions, participants with depressive symptoms looked shorter at the eyes compared to individuals without symptoms across all expression conditions. No group difference in first fixation duration on the eyes of masked and unmasked faces was observed. Individuals with depressive symptoms dwelled longer on the mouth region of unmasked faces. For masked faces, no significant group differences in dwell time on the eyes were found. Moreover, when specifically examining dwell time on the eyes of faces with an emotional expression there were also no significant differences between groups. Overall, participants gazed significantly longer at the eyes in masked compared to unmasked faces. CONCLUSIONS: For faces without mask, our results suggest that depressiveness in healthy individuals goes along with less visual attention to other persons' eyes but not with less visual attention to others' faces. When factors come into play that generally amplify the attention directed to the eyes such as face masks or emotions then no relationship between depressiveness and visual attention to the eyes can be established.

Emotional awareness for self and others and empathic abilities in clinical depression during acute illness and recovery.

BACKGROUND: The present longitudinal investigation had two major goals. First, we intended to clarify whether depressed patients are characterized by impairments of emotional awareness for the self and the other during acute illness and whether these impairments diminish in the course of an inpatient psychiatric treatment program. Previous research based on the performance measure Levels of Emotional Awareness Scale (LEAS) provided inconsistent findings concerning emotional self-awareness in clinical depression. Second, we investigated whether cognitive and affective empathic abilities change from acute illness to recovery in depressed patients. METHODS: Fifty-eight depressed patients were tested on admission and after 6-8 weeks of inpatient psychiatric treatment. A sample of fifty-three healthy individuals were also examined twice at an interval of 6-8 weeks. The LEAS and the Interpersonal Reactivity Index (IRI) were administered to assess emotional awareness and empathic abilities. Written texts were digitalized and then analyzed using the electronic scoring program geLEAS, the German electronic Levels of Emotional Awareness Scale. RESULTS: Depressed patients reported more depressive symptoms than healthy controls and less severe depressive symptomatology at time 2 compared to time 1. Independent of time, depressed individuals tended to show lower geLEAS self scores and had lower geLEAS other scores than healthy individuals. Depressed patients showed higher personal distress scores than healthy individuals at both measurement times. No group differences were observed for the cognitive empathy scales of the IRI (perspective taking and fantasy) and empathic concern, but empathic concern decreased significantly in depressed patients from time 1 to time 2. Empathic abilities as assessed by the IRI were not significantly correlated with emotional awareness for others, neither in the whole sample, nor in the patient and control subsample. CONCLUSIONS: Depressed patients seem to be characterized by impairments in emotional awareness of others during acute illness and recovery, but they also tend to show deficits in emotional self-awareness compared to healthy individuals. Self-reported cognitive empathic abilities seem to be at normal levels in depressed patients, but their heightened self-focused affective empathy may represent a vulnerability factor for depressive disorders.

Non-conscious processing of fear faces: a function of the implicit self-concept of anxiety.

BACKGROUND: Trait anxiety refers to a stable tendency to experience fears and worries across many situations. High trait anxiety is a vulnerability factor for the development of psychopathologies. Self-reported trait anxiety appears to be associated with an automatic processing advantage for threat-related information. Self-report measures assess aspects of the explicit self-concept of anxiety. Indirect measures can tap into the implicit self-concept of anxiety. METHODS: We examined automatic brain responsiveness to non-conscious threat as a function of trait anxiety using functional magnetic resonance imaging. Besides a self-report instrument, we administered the Implicit Association Test (IAT) to assess anxiety. We used a gender-decision paradigm presenting brief (17 ms) and backward-masked facial expressions depicting disgust and fear. RESULTS: Explicit trait anxiety was not associated with brain responsiveness to non-conscious threat. However, a relation of the implicit self-concept of anxiety with masked fear processing in the thalamus, precentral gyrus, and lateral prefrontal cortex was observed. CONCLUSIONS: We provide evidence that a measure of the implicit self-concept of anxiety is a valuable predictor of automatic neural responses to threat in cortical and subcortical areas. Hence, implicit anxiety measures could be a useful addition to explicit instruments. Our data support the notion that the thalamus may constitute an important neural substrate in biased non-conscious processing in anxiety.

Alexithymia and interpersonal problems in healthy young individuals.

BACKGROUND: Alexithymia refers to a multidimensional personality trait with the facets difficulties identifying feelings (DIF), difficulties describing feelings (DDF), and externally orientated thinking (EOT). Alexithymia is a risk factor for mental and somatic disorders. Previous research with patients suffering from various disorders showed positive relationships between alexithymia and interpersonal problems. Only one study analyzed the link between alexithymic features and interpersonal difficulties in healthy individuals but yielded inconclusive findings because participants' negative affects were not controlled. A widely accepted conceptualization of interpersonal problems relies on the interpersonal circumplex, which is defined by two orthogonal dimensions, agency and communion. In the present study, we analyzed which facets of alexithymia are associated with the two interpersonal problem dimensions and the global severity of interpersonal distress, after adjusting for negative affect. METHODS: Two-hundred healthy young individuals (100 women) participated in the study. Alexithymic features were assessed using the 20-Item Toronto Alexithymia Scale (TAS-20). Interpersonal problems were measured with the Inventory of Interpersonal Problems (IIP-D). Participants' state and trait anxiety, depressive symptoms, and verbal intelligence were also assessed. RESULTS: All alexithymia scales were positively correlated with general interpersonal distress. Regression results suggested that the TAS-20 subscale DIF was the primary predictor of general interpersonal distress after controlling for negative affectivity. The scale DDF correlated negatively with the IIP-D dimension agency. According to our regression analysis, DDF was a predictor of (low) agency controlling for negative affects. Moreover, DDF correlated negatively with the IIP-D dimension communion. Our regression results indicate that DDF was a predictor of (low) communion independent of negative affect. Correlations between alexithymia facets and IIP-D subscales did not differ between genders. CONCLUSIONS: Difficulties identifying feelings seem to be linked to a high level of general interpersonal distress. Difficulties in recognizing one's feelings may disrupt emotion regulation, which could heighten the general risk of interpersonal problems. Difficulties describing feelings could be a central factor contributing to interpersonal problems related to low communion as well as low agency, since emotion expression and communication are crucial in establishing experiences of social closeness and directing other people's behavior.

Efficient visual search for facial emotions in patients with major depression.

BACKGROUND: Major depressive disorder has been associated with specific attentional biases in processing emotional facial expressions: heightened attention for negative and decreased attention for positive faces. However, using visual search paradigms, previous reaction-time-based research failed, in general, to find evidence for increased spatial attention toward negative facial expressions and reduced spatial attention toward positive facial expressions in depressed individuals. Eye-tracking analyses allow for a more detailed examination of visual search processes over time during the perception of multiple stimuli and can provide more specific insights into the attentional processing of multiple emotional stimuli. METHODS: Gaze behavior of 38 clinically depressed individuals and 38 gender matched healthy controls was compared in a face-in-the-crowd task. Pictures of happy, angry, and neutral facial expressions were utilized as target and distractor stimuli. Four distinct measures of eye gaze served as dependent variables: (a) latency to the target face, (b) number of distractor faces fixated prior to fixating the target, (c) mean fixation time per distractor face before fixating the target and (d) mean fixation time on the target. RESULTS: Depressed and healthy individuals did not differ in their manual response times. Our eye-tracking data revealed no differences between study groups in attention guidance to emotional target faces as well as in the duration of attention allocation to emotional distractor and target faces. However, depressed individuals fixated fewer distractor faces before fixating the target than controls, regardless of valence of expressions. CONCLUSIONS: Depressed individuals seem to process angry and happy expressions in crowds of faces mainly in the same way as healthy individuals. Our data indicate no biased attention guidance to emotional targets and no biased processing of angry and happy distractors and targets in depression during visual search. Under conditions of clear task demand depressed individuals seem to be able to allocate and guide their attention in crowds of angry and happy faces as efficiently as healthy individuals.

Alexithymia and automatic processing of facial emotions: behavioral and neural findings.

BACKGROUND: Alexithymia is a personality trait characterized by difficulties identifying and describing feelings, an externally oriented style of thinking, and a reduced inclination to imagination. Previous research has shown deficits in the recognition of emotional facial expressions in alexithymia and reductions of brain responsivity to emotional stimuli. Using an affective priming paradigm, we investigated automatic perception of facial emotions as a function of alexithymia at the behavioral and neural level. In addition to self-report scales, we applied an interview to assess alexithymic tendencies. RESULTS: During 3 T fMRI scanning, 49 healthy individuals judged valence of neutral faces preceded by briefly shown happy, angry, fearful, and neutral facial expressions. Alexithymia was assessed using the 20-Item Toronto Alexithymia Scale (TAS-20), the Bermond-Vorst Alexithymia Questionnaire (BVAQ) and the Toronto Structured Interview for Alexithymia (TSIA). As expected, only negative correlations were found between alexithymic features and affective priming. The global level of self-reported alexithymia (as assessed by the TAS-20 and the BVAQ) was found to be related to less affective priming owing to angry faces. At the facet level, difficulties identifying feelings, difficulties analyzing feelings, and impoverished fantasy (as measured by the BVAQ) were correlated with reduced affective priming due to angry faces. Difficulties identifying feelings (BVAQ) correlated also with reduced affective priming due to fearful faces and reduced imagination (TSIA) was related to decreased affective priming due to happy faces. There was only one significant correlation between alexithymia dimensions and automatic brain response to masked facial emotions: TAS-20 alexithymia correlated with heightened brain response to masked happy faces in superior and medial frontal areas. CONCLUSIONS: Our behavioral results provide evidence that alexithymic features are related in particular to less sensitivity for covert facial expressions of anger. The perceptual alterations could reflect impaired automatic recognition or integration of social anger signals into judgemental processes and might contribute to the problems in interpersonal relationships associated with alexithymia. Our findings suggest that self-report measures of alexithymia may have an advantage over interview-based tests as research tools in the field of emotion perception at least in samples of healthy individuals characterized by rather low levels of alexithymia.

Implicit affectivity in clinically depressed patients during acute illness and recovery.

BACKGROUND: Clinical depression is characterized by high levels of negative affect (NA) and attenuated positive affect (PA). Psychological and pharmacological treatments have been shown to reduce NA and to enhance PA in depressed patients. Following dual-process models, two types of affect can be distinguished: explicit (or self-reported) affect, which is formed by conscious reflections, and implicit affect, which relates to automatic affective reactions. The present study was conducted to examine, for the first time, both implicit and explicit affectivity in patients suffering from acute depression. Moreover, changes in patients' implicit and explicit affectivity were investigated over the course of inpatient treatment. METHODS: Thirty-nine patients suffering from major depression and 39 healthy individuals participated in the study. Implicit affectivity was assessed using the Implicit Positive and Negative Affect Test. The explicit state and trait affectivity were measured by the Positive and Negative Affect Schedule. The level of depressive symptoms was assessed with the Beck Depression Inventory. Tests were administered to patients after admission and after 7 weeks of therapy, whereas healthy controls were investigated only once. We examined whether either comorbidity or antidepressant medication has an effect on affectivity. RESULTS: Patients with acute depression had lower implicit and explicit PA scores and higher implicit and explicit NA scores than the healthy controls. After treatment, patients' level of depression decreased significantly. At posttreatment, patients exhibited heightened implicit and explicit PA and diminished explicit trait NA. Independent of antidepressant medication and comorbidity, no significant change in implicit NA was observed over the course of treatment. Implicit NA was correlated with explicit NA in acute depression but not during recovery. CONCLUSIONS: Acute depression appears to be characterized by decreased implicit and explicit PA and increased implicit and explicit NA. After 7 weeks of treatment, depressed patients' implicit and explicit PA increased, and explicit trait NA decreased. No decrease in implicit NA and explicit state NA occurred over the course of treatment. Finally, it seems that in the state of acute depression, the interplay between the automatic and reflective systems could be increased for negative affectivity.

Implicit and explicit self-concept of neuroticism in borderline personality disorder.

PURPOSE: In the past, research on personality in borderline personality disorder (BPD) used primarily questionnaires suggesting heightened neuroticism in BPD. Self-report instruments inform about the conscious or explicit self-concept. BPD patients are known to show negative distortion with exaggeration of negative affect in the self-report. Neuroticism represents a risk factor for mental disorders. Indirect measures are available that tap into the implicit self-concept of neuroticism. The implicit self-concept refers to individual differences in associative representations of the self. The present study examined for the first time the implicit in addition to the explicit self-concept of neuroticism in BPD. MATERIALS AND METHODS: Female BPD patients (N = 35) and healthy women (N = 39) completed an implicit association test and the NEO-FFI personality inventory. RESULTS: BPD patients showed higher implicit and explicit neuroticism compared to controls. The group difference for explicit neuroticism was four times larger than that for implicit neuroticism. Presence of comorbid depressive disorder was positively correlated with implicit neuroticism. The IAT neuroticism showed excellent split-half reliability for BPD patients. CONCLUSIONS: The present data suggest that BPD patients with comorbid clinical depression but not those without clinical depression differ from healthy individuals in their implicit self-concept of neuroticism. In the associative network, BPD patients with comorbid clinical depression exhibit stronger associations of the self with neuroticism-related characteristics, such as nervousness, fearfulness, and uncertainty than healthy individuals. Regardless of depression, BPD patients show increased explicit neuroticism. Our findings provide evidence that the IAT neuroticism can be applied reliably to BPD patients.

Amygdalar Gray Matter Volume and Social Relating in Schizophrenia.

BACKGROUND: Poor social relating is a prominent feature of schizophrenia. The amygdala has been suggested as an important node in social brain networks. METHODS: By using structural magnetic resonance imaging, this study examined, for the first time, the relationship between amygdalar gray matter (GM) volume and social relating in 35 schizophrenia patients. Social anhedonia, interaction anxiety, extraversion, and sociable tendencies were assessed as indices of social relating. RESULTS: A correlation between GM volume in the amygdala and enhanced social relating was revealed. CONCLUSION: These findings indicate that volumetric decreases in the amygdala are related to impoverished sociability in schizophrenia.

Borderline Personality Disorder and Automatic Processing of Valence and Self-Other Relevance Information.

BACKGROUND: Enhanced sensitivity to emotion stimuli and poor differentiation between self and others have been proposed to be important features of borderline personality disorder (BPD). Automatic processing of affective stimuli provides information about valence (positive vs. negative) and relevance of valence (self vs. other). The objectives of our study were to investigate the efficiency of automatic processing of valence and relevance at a semantic level in BPD compared to healthy individuals. SAMPLING AND METHODS: A masked affective priming task, varying the valence and relevance of prime and target adjectives, was administered to 33 women with BPD and 33 healthy women. The forward and backward masked primes were shown for 50 ms. Subjects had the task of evaluating target words. RESULTS: In the whole sample, a significant affective priming effect and a significant relevance priming effect occurred. BPD patients did not significantly differ from healthy individuals in affective priming or relevance priming after controlling for age, education, and intelligence. The presence of comorbid somatoform disorders was associated with increased affective priming and reduced relevance priming in BPD patients. CONCLUSIONS: The efficiency of automatic recognition and the processing of valence information at a semantic level are not impaired in BPD. Moreover, BPD patients are able to perceive and differentiate automatically self- versus other-relevance during the perception of affective information like healthy controls. Thus, there is no evidence for enhanced sensitivity to emotion stimuli or poor differentiation between self and others in BPD at a very early stage of processing. The presence of somatoform disorders appears to influence affective as well as relevance priming in BPD.

Predicting symptoms in major depression after inpatient treatment: the role of alexithymia.

Alexithymia has been considered to have a negative influence on the course of symptoms in various psychiatric disorders. Only a few studies of depressed patients have examined whether alexithymia predicts the outcome of therapeutic interventions or the course of symptoms in naturalistic settings. This prospective study investigated whether alexithymia is associated with depressive symptoms after a multimodal inpatient treatment. Forty-five inpatients suffering from acute major depression were examined in the initial phase of treatment and then again after seven weeks. Patients took part in a multimodal treatment programme comprising psychodynamic-interactional oriented individual and group therapy. The majority of patients were taking antidepressants during study participation. To assess alexithymia and depressive symptoms, the 20-item Toronto Alexithymia Scale (TAS-20), the Beck Depression Inventory II (BDI-II) and the Hamilton Depression Scale (HAMD) were administered at baseline and follow-up. When controlling for baseline depressive symptoms along with trait anxiety, high scores in the externally oriented thinking (EOT) facet of alexithymia at baseline predicted high severity of depressive symptoms at follow-up (for self-reported as well as interviewer-based scores). Inpatients suffering from major depression with a more pronounced external cognitive style might benefit less from a routine multimodal treatment approach (including psychodynamic interactional therapy, antidepressant medication, and complementary therapies). Intervention programmes might modify or account for alexithymic characteristics to improve the course of depressive symptoms in these patients.

Observer-Rated Alexithymia and its Relationship with the Five-Factor-Model of Personality.

Studies examining the relationship between alexithymia and personality exclusively employed self-report measures of alexithymia. In the present study, we examined the relationship of both observer-rated and self-reported alexithymia with the Big Five personality dimensions. We administered the Toronto Structured Interview for Alexithymia (TSIA) as an interview-based measure of alexithymia and, in addition, two self-report questionnaires, the 20-item Toronto Alexithymia Scale (TAS-20) and the Bermond-Vorst Alexithymia Questionnaire (BVAQ). Fifty-one university students were interviewed and completed the alexithymia scales and the NEO Five-Factor Inventory. In contrast to TAS-20 and BVAQ, the Difficulty identifying feelings (DIF) scale of the TSIA was found to be unrelated to neuroticism, suggesting that the frequently reported association between DIF and neuroticism could be due to the use of self-report scales. In contrast, the affective dimension of alexithymia, measured by the BVAQ, was even negatively related with neuroticism. Thus, a paucity of fantasy and little emotional arousal goes together with increased emotional stability. Furthermore, we revealed negative correlations between interview-based alexithymia scores and openness to experience and agreeableness, which cross-validated the self-report findings. Finally, extraversion and conscientiousness each showed only one negative correlation, namely with subscales of the BVAQ. Taken together, our findings show that on the basis of interviews there is no evidence for a relation of DIF with neuroticism, while associations of alexithymia with low openness to experience and low agreeableness emerged irrespective of assessment approach. The relations of alexithymia with personality are discussed in the light of different measurement approaches.

Associations between childhood maltreatment and emotion processing biases in major depression: results from a dot-probe task.

BACKGROUND: Childhood maltreatment is considered an important risk factor for the development of major depression. Research indicates an association between childhood adversity and altered emotion processing. Depression is characterized by mood-congruent cognitive biases, which play a crucial role in symptom persistence and recurrence. However, whether attentional biases in adult major depression are associated with experienced childhood neglect or abuse remains unclear. METHODS: A sample of 45 patients suffering from major depression were recruited to examine correlations between maltreatment experienced during childhood and attentional biases to sad and happy facial expressions. Attention allocation was assessed using the dot-probe task and a history of childhood maltreatment was measured by means of the 25-item Childhood Trauma Questionnaire (CTQ). RESULTS: Our results indicate an association between childhood maltreatment and sustained attention toward sad facial expressions. This relationship was not confounded by severity of symptoms, age, verbal intelligence or more recent stressful experiences. CONCLUSIONS: Our findings confirm the hypothesis that a mood-congruent bias in emotion processing observed in major depression is related to early traumatic experiences.

Automatic processing of facial affects in patients with borderline personality disorder: associations with symptomatology and comorbid disorders.

BACKGROUND: Instability of affects and interpersonal relations are important features of borderline personality disorder (BPD). Interpersonal problems of individuals suffering from BPD might develop based on abnormalities in the processing of facial affects and high sensitivity to negative affective expressions. The aims of the present study were to examine automatic evaluative shifts and latencies as a function of masked facial affects in patients with BPD compared to healthy individuals. As BPD comorbidity rates for mental and personality disorders are high, we investigated also the relationships of affective processing characteristics with specific borderline symptoms and comorbidity. METHODS: Twenty-nine women with BPD and 38 healthy women participated in the study. The majority of patients suffered from additional Axis I disorders and/or additional personality disorders. In the priming experiment, angry, happy, neutral, or no facial expression was briefly presented (for 33 ms) and masked by neutral faces that had to be evaluated. Evaluative decisions and response latencies were registered. Borderline-typical symptomatology was assessed with the Borderline Symptom List. RESULTS: In the total sample, valence-congruent evaluative shifts and delays of evaluative decision due to facial affect were observed. No between-group differences were obtained for evaluative decisions and latencies. The presence of comorbid anxiety disorders was found to be positively correlated with evaluative shifting owing to masked happy primes, regardless of baseline-neutral or no facial expression condition. The presence of comorbid depressive disorder, paranoid personality disorder, and symptoms of social isolation and self-aggression were significantly correlated with response delay due to masked angry faces, regardless of baseline. CONCLUSIONS: In the present affective priming study, no abnormalities in the automatic recognition and processing of facial affects were observed in BPD patients compared to healthy individuals. The presence of comorbid anxiety disorders could make patients more susceptible to the influence of a happy expression on judgment processes at an automatic processing level. Comorbid depressive disorder, paranoid personality disorder, and symptoms of social isolation and self-aggression may enhance automatic attention allocation to threatening facial expressions in BPD. Increased automatic vigilance for social threat stimuli might contribute to affective instability and interpersonal problems in specific patients with BPD.

Implicit affectivity and rapid processing of affective body language: An fMRI study.

Previous research has revealed affect-congruity effects for the recognition of affects from faces. Little is known about the impact of affect on the perception of body language. The aim of the present study was to investigate the relationship of implicit (versus explicit) affectivity with the recognition of briefly presented affective body expressions. Implicit affectivity, which can be measured using indirect assessment methods, has been found to be more predictive of spontaneous physiological reactions than explicit (self-reported) affect. Thirty-four healthy women had to label the expression of body postures (angry, fearful, happy, or neutral) presented for 66 ms and masked by a neutral body posture in a forced-choice format while undergoing functional magnetic resonance imaging (fMRI). Participants' implicit affectivity was assessed using the Implicit Positive and Negative Affect Test. Measures of explicit state and trait affectivity were also administered. Analysis of the fMRI data was focused on a subcortical network involved in the rapid perception of affective body expressions. Only implicit negative affect (but not explicit affect) was correlated with correct labeling performance for angry body posture. As expected, implicit negative affect was positively associated with activation of the subcortical network in response to fearful and angry expression (compared to neutral expression). Responses of the caudate nucleus to affective body expression were especially associated with its recognition. It appears that processes of rapid recognition of affects from body postures could be facilitated by an individual's implicit negative affect.

RGS2 ggenetic variation: association analysis with panic disorder and dimensional as well as intermediate phenotypes of anxiety.

Accumulating evidence from mouse models points to the G protein-coupled receptor RGS2 (regulator of G-protein signaling 2) as a promising candidate gene for anxiety in humans. Recently, RGS2 polymorphisms were found to be associated with various anxiety disorders, e.g., rs4606 with panic disorder (PD), but other findings have been negative or inconsistent concerning the respective risk allele. To further examine the role of RGS2 polymorphisms in the pathogenesis of PD, we genotyped rs4606 and five additional RGS2 tag single nucleotide polymorphisms (SNPs; rs16834831, rs10801153, rs16829458, rs1342809, rs1890397) in two independent PD samples, comprising 531 matched case/control pairs. The functional SNP rs4606 was nominally associated with PD when both samples were combined. The upstream SNP rs10801153 displayed a Bonferroni-resistant significant association with PD in the second and the combined sample (P = 0.006 and P = 0.017). We furthermore investigated the effect of rs10801153 on dimensional anxiety traits, a behavioral avoidance test (BAT), and an index for emotional processing in the respective subsets of the total sample. In line with categorical results, homozygous risk (G) allele carriers displayed higher scores on the Agoraphobic Cognitions Questionnaire (ACQ; P = 0.015) and showed significantly more defensive behavior during fear provoking situations (P = 0.001). Furthermore, significant effects on brain activation in response to angry (P = 0.013), happy (P = 0.042) and neutral faces (P = 0.032) were detected. Taken together, these findings provide further evidence for the potential role of RGS2 as a candidate gene for PD.

Amygdala excitability to subliminally presented emotional faces distinguishes unipolar and bipolar depression: an fMRI and pattern classification study.

BACKGROUND: Bipolar disorder and Major depressive disorder are difficult to differentiate during depressive episodes, motivating research for differentiating neurobiological markers. Dysfunctional amygdala responsiveness during emotion processing has been implicated in both disorders, but the important rapid and automatic stages of emotion processing in the amygdala have so far never been investigated in bipolar patients. METHODS: fMRI data of 22 bipolar depressed patients (BD), 22 matched unipolar depressed patients (MDD), and 22 healthy controls (HC) were obtained during processing of subliminal sad, happy and neutral faces. Amygdala responsiveness was investigated using standard univariate analyses as well as pattern-recognition techniques to differentiate the two clinical groups. Furthermore, medication effects on amygdala responsiveness were explored. RESULTS: All subjects were unaware of the emotional faces. Univariate analysis revealed a significant group × emotion interaction within the left amygdala. Amygdala responsiveness to sad>neutral faces was increased in MDD relative to BD. In contrast, responsiveness to happy>neutral faces showed the opposite pattern, with higher amygdala activity in BD than in MDD. Most of the activation patterns in both clinical groups differed significantly from activation patterns of HC--and therefore represent abnormalities. Furthermore, pattern classification on amygdala activation to sad>happy faces yielded almost 80% accuracy differentiating MDD and BD patients. Medication had no significant effect on these findings. CONCLUSIONS: Distinct amygdala excitability during automatic stages of the processing of emotional faces may reflect differential pathophysiological processes in BD versus MDD depression, potentially representing diagnosis-specific neural markers mostly unaffected by current psychotropic medication.

Serotonin transporter gene methylation is associated with hippocampal gray matter volume.

BACKGROUND: The serotonin transporter (5-HTT) and the 5-HTTLPR/rs25531 polymorphisms in its gene (SLC6A4) have been associated with depression, increased stress-response, and brain structural alterations such as reduced hippocampal volumes. Recently, epigenetic processes including SLC6A4 promoter methylation were shown to be affected by stress, trauma, or maltreatment and are regarded to be involved in the etiology of affective disorders. However, neurobiological correlates of SLC6A4 promoter methylation have never been studied or compared to genotype effects by means of human neuroimaging hitherto METHODS: Healthy subjects were recruited in two independent samples (N = 94, N = 95) to obtain structural gray matter images processed by voxel-based morphometry (VBM8), focusing on hippocampal, amygdala, and anterior cingulate gyrus gray matter structure. SLC6A4 promoter methylation within an AluJb element and 5-HTTLPR/rs25531 genotypes were analyzed in view of a possible impact on local gray matter volume RESULTS: Strong associations of AluJb methylation and hippocampal gray matter volumes emerged within each sample separately, which in the combined sample withstood most conservative alpha-corrections for the entire brain. The amygdala, insula, and caudate nucleus showed similar associations. The 5-HTTLPR/rs25531 showed no main effect on gray matter, and the effect of methylation rates on hippocampal structure was comparable among the genotype groups CONCLUSIONS: Methylation within the AluJb appears to have strong effects on hippocampal gray matter volumes, indicating that epigenetic processes can alter brain structures crucially involved in stress-related disorders. Different ways of regulating SLC6A4 expression might involve exonization or transcription factor binding as potentially underlying mechanisms, which, however, is speculative and warrants further investigation.

Alexithymia and the labeling of facial emotions: response slowing and increased motor and somatosensory processing.

BACKGROUND: Alexithymia is a personality trait that is characterized by difficulties in identifying and describing feelings. Previous studies have shown that alexithymia is related to problems in recognizing others' emotional facial expressions when these are presented with temporal constraints. These problems can be less severe when the expressions are visible for a relatively long time. Because the neural correlates of these recognition deficits are still relatively unexplored, we investigated the labeling of facial emotions and brain responses to facial emotions as a function of alexithymia. RESULTS: Forty-eight healthy participants had to label the emotional expression (angry, fearful, happy, or neutral) of faces presented for 1 or 3 seconds in a forced-choice format while undergoing functional magnetic resonance imaging. The participants' level of alexithymia was assessed using self-report and interview. In light of the previous findings, we focused our analysis on the alexithymia component of difficulties in describing feelings. Difficulties describing feelings, as assessed by the interview, were associated with increased reaction times for negative (i.e., angry and fearful) faces, but not with labeling accuracy. Moreover, individuals with higher alexithymia showed increased brain activation in the somatosensory cortex and supplementary motor area (SMA) in response to angry and fearful faces. These cortical areas are known to be involved in the simulation of the bodily (motor and somatosensory) components of facial emotions. CONCLUSION: The present data indicate that alexithymic individuals may use information related to bodily actions rather than affective states to understand the facial expressions of other persons.