Neurogenetics of emotion processing in major depression

Die vorliegende Arbeit charakterisiert neurogenetische Mechanismen der Depression. In einer ersten Studie wurden neurobiologische Korrelate der automatischen Emotionsverarbeitung bei Depressiven mittels fMRT untersucht. Es zeigte sich, dass Depressive im Vergleich mit Gesunden eine Hyperresponsivität der Amygdala auf negative Reize zeigen, jedoch eine Hyporesponsivität auf positive Reize. In einer zweiten Studie konnte gezeigt werden, dass ein derartiges Muster mit einer genetischen Variante im Serotonintransportergen (5-HTTLPR) assoziiert ist. In einem dritten Experiment wurde eine genetische Variante im Neuropeptid Y Gen untersucht. Die depressiven Träger von Risikoallelen, die mit einem schlechten Ansprechen auf Pharmakotherapie assoziiert sind, zeigten ebenfalls ein Muster von gesteigerter Amygdalaresponsivität auf bedrohliche Gesichter. Dieser Forschungsansatz schlägt eine Brücke zwischen kleinen Effekten einzelner genetischer Varianten und komplexen psychiatrischen Phänotypen

Deepbet: Fast brain extraction of T1-weighted MRI using Convolutional Neural Networks

Brain extraction in magnetic resonance imaging (MRI) data is an important segmentation step in many neuroimaging preprocessing pipelines. Image segmentation is one of the research fields in which deep learning had the biggest impact in recent years enabling high precision segmentation with minimal compute. Consequently, traditional brain extraction methods are now being replaced by deep learning-based methods. Here, we used a unique dataset comprising 568 T1-weighted (T1w) MR images from 191 different studies in combination with cutting edge deep learning methods to build a fast, high-precision brain extraction tool called deepbet. deepbet uses LinkNet, a modern UNet architecture, in a two stage prediction process. This increases its segmentation performance, setting a novel state-of-the-art performance during cross-validation with a median Dice score (DSC) of 99.0% on unseen datasets, outperforming current state of the art models (DSC = 97.8% and DSC = 97.9%). While current methods are more sensitive to outliers, resulting in Dice scores as low as 76.5%, deepbet manages to achieve a Dice score of > 96.9% for all samples. Finally, our model accelerates brain extraction by a factor of ~10 compared to current methods, enabling the processing of one image in ~2 seconds on low level hardware

Elevated amygdala activity to sad facial expressions:a state marker of bipolar but not unipolar depression

Background - Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression. Methods - Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. Results - The BDd—relative to HC, BDr, and MDD—showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity. Conclusions - Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression

Long-Term Neuroanatomical Consequences of Childhood Maltreatment: Reduced Amygdala Inhibition by Medial Prefrontal Cortex

Similar to patients with Major depressive disorder (MDD), healthy subjects at risk for depression show hyperactivation of the amygdala as a response to negative emotional expressions. The medial prefrontal cortex is responsible for amygdala control. Analyzing a large cohort of healthy subjects, we aimed to delineate malfunction in amygdala regulation by the medial prefrontal cortex in subjects at increased risk for depression, i.e., with a family history of affective disorders or a personal history of childhood maltreatment. We included a total of 342 healthy subjects from the FOR2107 cohort (www.for2107.de). An emotional face-matching task was used to identify the medial prefrontal cortex and right amygdala. Dynamic Causal Modeling (DCM) was conducted and neural coupling parameters were obtained for healthy controls with and without particular risk factors for depression. We assigned a genetic risk if subjects had a first-degree relative with an affective disorder and an environmental risk if subjects experienced childhood maltreatment. We then compared amygdala inhibition during emotion processing between groups. Amygdala inhibition by the medial prefrontal cortex was present in subjects without those two risk factors, as indicated by negative model parameter estimates. Having a genetic risk (i.e., a family history) did not result in changes in amygdala inhibition compared to no risk subjects. In contrast, childhood maltreatment as environmental risk has led to a significant reduction of amygdala inhibition by the medial prefrontal cortex. We propose a mechanistic explanation for the amygdala hyperactivity in subjects with particular risk for depression, in particular childhood maltreatment, caused by a malfunctioned amygdala downregulation via the medial prefrontal cortex. As childhood maltreatment is a major environmental risk factor for depression, we emphasize the importance of this potential early biomarker

A Longitudinal Study

Adverse experiences interact with individual vulnerability in the etiology of mental disorders, but due to the paucity of longitudinal studies, their precise interplay remains unclear. Here, we investigated how individual differences in threat responsiveness modulated adjustments in negative affect during the COVID-19 pandemic. Participants (N = 441) underwent a fear conditioning and generalization experiment between 2013 and 2020 and were reassessed regarding anxiety and depression symptoms after the pandemic outbreak. Participants showed increased levels of negative affect following pandemic onset, which were partly modulated by laboratory measures of threat responsiveness. Decreased differentiation of threat and safety signals in participants with higher prepandemic depression and anxiety scores in the laboratory assessment were most predictive of increased symptom levels after the onset of the pandemic. However, effects were small and should be replicated in independent samples to further characterize how individual differences in threat processing interact with adverse experiences in the development of psychopathology.Peer Reviewe

Influence of Repressive Coping Style on Cortical Activation during Encoding of Angry Faces

Background: Coping plays an important role for emotion regulation in threatening situations. The model of coping modes designates repression and sensitization as two independent coping styles. Repression consists of strategies that shield the individual from arousal. Sensitization indicates increased analysis of the environment in order to reduce uncertainty. According to the discontinuity hypothesis, repressors are sensitive to threat in the early stages of information processing. While repressors do not exhibit memory disturbances early on, they manifest weak memory for these stimuli later. This study investigates the discontinuity hypothesis using functional magnetic resonance imaging (fMRI). Methods: Healthy volunteers (20 repressors and 20 sensitizers) were selected from a sample of 150 students on the basis of the Mainz Coping Inventory. During the fMRI experiment, subjects evaluated and memorized emotional and neutral faces. Subjects performed two sessions of face recognition: immediately after the fMRI session and three days later. Results: Repressors exhibited greater activation of frontal, parietal and temporal areas during encoding of angry faces compared to sensitizers. There were no differences in recognition of facial emotions between groups neither immediately after exposure nor after three days. Conclusions: The fMRI findings suggest that repressors manifest an enhanced neural processing of directly threatening facial expression which confirms the assumption of hyper-responsivity to threatening information in repression in an early processing stage. A discrepancy was observed between high neural activation in encoding-relevant brain areas in response to angry faces in repressors and no advantage in subsequent memory for these faces compared to sensitizers