SSRI Treatment Response Prediction in Depression Based on Brain Activation by Emotional Stimuli.

Introduction: The prediction of antidepressant treatment response may improve outcome. Functional magnetic resonance imaging (fMRI) of emotion processing in major depressive disorder (MDD) may reveal regional brain function serving as predictors of response to treatment with selective serotonin reuptake inhibitor (SSRI). Methods: We examined the association between pre-treatment neural activity by means of fMRI during the perception of emotional stimuli in 22 patients with MDD and the treatment outcome after 6 weeks' medication with an SSRI. A whole brain correlation analysis with Beck Depression Inventory (BDI) change between pre- to post-treatment was conducted to identify neural regions associated with treatment response. Results: During the perception of positive stimuli, responders were characterized by more activation in posterior cingulate cortex (PCC), medial prefrontal cortex, and thalamus as well as middle temporal gyrus. During perception of negative stimuli, PCC, and pregenual anterior cingulate cortex showed the highest correlation with treatment response. Furthermore, responders exhibited higher activation to emotional stimuli than to neutral stimuli in all the above-mentioned regions, while non-responders demonstrated an attenuated neural response to emotional compared to neutral stimuli. Conclusion: Our data suggest that the activity of distinct brain regions is correlated with SSRI treatment outcome and may serve as treatment response predictor. While some regions, in which activity was correlated with treatment response, can be assigned to networks that have been implied in the pathophysiology of depression, most of our regions of interest could also be matched to the default mode network (DMN). Higher DMN activity has been associated with increased rumination as well as negative self-referential processing in previous studies. This may suggest our responders to SSRI to be characterized by such dysregulations and that SSRIs might modify the function associated with this network.

The fear of being laughed at as additional diagnostic criterion in social anxiety disorder and avoidant personality disorder?

Social anxiety disorder (SAD) is the most common anxiety disorder and has considerable negative impact on social functioning, quality of life, and career progression of those affected. Gelotophobia (the fear of being laughed at) shares many similarities and has therefore been proposed as a subtype of SAD. This hypothesis has, however, never been tested in a clinical sample. Thus, the relationship between gelotophobia, SAD and avoidant personality disorder (APD) was investigated by examining a sample of 133 participants (64 psychiatric patients and 69 healthy controls matched for age and sex) using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (4th edition) and an established rating instrument for gelotophobia (GELOPH<15>). As expected, gelotophobia scores and the number of gelotophobic individuals were significantly higher among patients with SAD (n = 22) and APD (n = 12) compared to healthy controls and other psychiatric patients. Furthermore, gelotophobia scores were highest in patients suffering from both SAD and APD. In fact, all patients suffering from both disorders were also suffering from gelotophobia. As explained in the discussion, the observed data did not suggest that gelotophobia is a subtype of SAD. The findings rather imply that the fear of being laughed at is a symptom characteristic for both SAD and APD. Based on that, gelotophobia may prove to be a valuable additional diagnostic criterion for SAD and APD and the present results also contribute to the ongoing debate on the relationship between SAD and APD.

Uncontrollable and unpredictable stress interacts with subclinical depression and anxiety scores in determining anxiety response.

According to learned helplessness theory, uncontrollable stress is assumed to be a critical etiological factor in the pathogenesis of depression. In contrast, unpredictability of stressors is assumed to facilitate the development of sustained anxiety. Despite the frequent co-morbidity of depression and anxiety disorders, these two factors have rarely been studied simultaneously in humans. Therefore, we investigated whether there are interaction effects of uncontrollability and unpredictability on anxiety response in healthy participants. Seventy-nine healthy participants performed a visual dot probe task with emotional faces, while receiving mild electrical shocks in four different conditions (2 × 2 factorial design). In (un)controllable conditions, participants were (not) able to attenuate shock intensity. In (un)predictable conditions, participants were (not) able to anticipate shock occurrence. Before the experiment, participants' subclinical depression and anxiety scores were measured using the Beck Depression and Anxiety Inventories (BDI/BAI). During the experiment, continuous skin conductance and self-reported state anxiety were assessed and attentional biases towards angry faces were calculated. As expected, participants showed greater anxiety in uncontrollable compared to controllable and in unpredictable compared to predictable conditions. Additionally, anxiety decreased within the test sessions in participants with low BDI/BAI scores but not in participants with higher BDI/BAI scores. Most importantly, controllability and predictability interacted with each other and with BDI/BAI scores with regard to anxiety. Our results provide evidence that uncontrollability and unpredictability of stressors not only have separate but also interaction effects on several anxiety measures in susceptible individuals and may provide insights into the psychological mechanisms underlying a depressive/anxiety co-morbidity.