Gender and Rapid Alterations of Hemispheric Dominance during Planning

Background: Mental planning and carrying out a plan provoke specific cerebral hemodynamic responses. Gender aspects of hemispheric laterality using rapid cerebral hemodynamics have not been reported. Method: Here, we applied functional transcranial Doppler sonography to examine lateralization of cerebral hemodynamics of the middle cerebral arteries of 28 subjects (14 women and 14 men) performing a standard planning task. There were easy and difficult problems, and mental planning without motor activity was separated from movement execution. Results: Difficult mental planning elicited lateralization to the right hemisphere after 2 or more seconds, a feature that was not observed during movement execution. In females, there was a dominance to the left hemisphere during movement execution. Optimized problem solving yielded an increased laterality change to the right during mental planning. Conclusions: Gender-related hemispheric dominance appears to be condition-dependent, and change of laterality to the right may play a role in optimized performance. Results are of relevance when considering laterality from a perspective of performance enhancement of higher cognitive functions, and also of psychiatric disorders with cognitive dysfunctions and abnormal lateralization patterns such as schizophrenia. Copyright (C) 2012 S. Karger AG, Base

Neuropsychodynamic Approach to Depression: Integrating Resting State Dysfunctions of the Brain and Disturbed Self-Related Processes

A mechanism-based approach was developed focusing on the psychodynamic, psychological and neuronal mechanisms in healthy and depressed persons. In this integrative concept of depression, the self is a core dimension in depression. It is attributed to negative emotions (e.g., failure, guilt). The increased inward focus in depression is connected with a decreased environmental focus. The development of neuropsychodynamic hypotheses of the altered self-reference is based on the investigation of the emotional-cognitive interaction in depressed patients. It may be hypothesized that the increased negative self-attributions—as typical characteristics of an increased self-focus in depression—may result from altered neuronal activity in subcortical-cortical midline structures in the brain, especially from hyperactivity in the cortical-subcortical midline regions and hypoactivity in the lateral regions. The increased resting state activity in depression is especially associated with an increased resting state activity in the default mode network (DMN) and a dysbalance between DMN and executive network (EN) activity. Possible therapeutic consequences of the neuropsychodynamic approach to depression involve the necessary emotional attunement in psychotherapy of depressed patients and the adequate timing of therapeutic interventions. The hypotheses which have been developed in the context of the neuropsychodynamic model of depression may be used for more specific psychotherapeutic interventions, aiming at specific mechanisms of compensation and defence, which are related to the increased resting state activity and the disturbed resting state-stimulus-interaction

The awareness of the scared - context dependent influence of oxytocin on brain function

Oxytocin is both a hormone and a neurotransmitter and has been originally recognized for its role in childbirth and lactation. Later, it became widely known as a "cuddle hormone" that induces trusting behavior towards strangers and reduces social stress and anxiety. Several studies showed that oxytocin influences empathic behavior and has prosocial effects. The anterior cingulate cortex and the anterior insula are brain regions that are active when humans observe fear in others. Therefore, the aim of this study was to investigate whether oxytocin administration affects activity in these regions depending on whether a threat is directed at another person (empathy) compared to when the threat is directed at the subject itself (fear). Our findings demonstrate increased anterior cingulate cortex activation after oxytocin administration in the fear, but not in the empathy condition. Furthermore, oxytocin administration was associated with deceased anterior insula activity in the empathy condition. However, our findings do not support the idea that oxytocin generally augments activity in brain regions associated with empathy. Thereby this study supports current research questioning that oxytocin has exclusively prosocial effects on human behavior. Rather, the effect of oxytocin depends on various contextual (e.g. presence of a familiar person) and interindividual (e.g. sex, mental disorder) factors. Therefore, to consider oxytocin an empathy inducing hormone is an oversimplification and future research should focus on factors moderating oxytocin effects

Predicting non-response to multimodal day clinic treatment in severely impaired depressed patients: a machine learning approach

A considerable number of depressed patients do not respond to treatment. Accurate prediction of non-response to routine clinical care may help in treatment planning and improve results. A longitudinal sample of N = 239 depressed patients was assessed at admission to multi-modal day clinic treatment, after six weeks, and at discharge. First, patient’s treatment response was modelled by identifying longitudinal trajectories using the Hamilton Depression Rating Scale (HDRS-17). Then, individual items of the HDRS-17 at admission as well as individual patient characteristics were entered as predictors of response/non-response trajectories into the binary classification model (eXtremeGradient Boosting; XGBoost). The model was evaluated on a hold-out set and explained in human-interpretable form by SHapley Additive explanation (SHAP) values. The prediction model yielded a multi-class AUC = 0.80 in the hold-out set. The predictive power for the binary classification yielded an AUC = 0.83 (sensitivity = .80, specificity = .77). Most relevant predictors for non-response were insomnia symptoms, younger age, anxiety symptoms, depressed mood, being unemployed, suicidal ideation and somatic symptoms of depressive disorder. Non-responders to routine treatment for depression can be identified and screened for potential next-generation treatments. Such predictors may help personalize treatment and improve treatment response

Effects of Psychotherapy on Glutamatergic Neurotransmission

Introduction: Psychodynamic psychotherapy is an effective and widely used treatment for major depressive disorder (MDD); however, little is known about neurobiological changes associated with induced symptom improvement. Methods: Proton magnetic resonance spectroscopy with a two-dimensional J-resolved sequence served to test the relationship between glutamate (Glu) and glutamine (Gln) levels, measured separately in pregenual anterior cingulate cortex (pgACC) and the anterior midcingulate cortex (aMCC) as a control region, with change in depression symptoms after 6 months of weekly psychodynamic psychotherapy sessions in MDD patients. Depressed (N = 45) and healthy (N = 30) subjects participated in a baseline proton magnetic resonance spectroscopy measurement and a subgroup of MDD subjects (N = 21) then received once-a-week psychodynamic psychotherapy and participated in a second proton magnetic resonance spectroscopy measurement after 6 months. Change in depression symptoms was assessed using the Hamilton Depression Rating Scale (HAMD). Results: Higher pretreatment pgACC Gln concentrations in MDD patients compared to healthy controls were associated with symptom severity. Patients and controls did not differ regarding Gln levels in aMCC nor regarding Glu levels in both regions. The association of pgACC Gln concentration and severity of depressive symptoms was reversed after 6 months of psychotherapy in MDD subjects. Regarding Gln in aMCC as well as Glu in both regions, there were no significant associations with improvement of depressive symptoms in the course of psychotherapy. Discussion: Findings indicate specific regional effects of psychodynamic psychotherapy on glutamatergic neurotransmission and thereby highlight the key role of the pgACC in both depression pathophysiology and recovery

Differential Alterations in Resting State Functional Connectivity Associated with Depressive Symptoms and Early Life Adversity

Depression and early life adversity (ELA) are associated with aberrant resting state functional connectivity (FC) of the default mode (DMN), salience (SN), and central executive networks (CEN). However, the specific and differential associations of depression and ELA with FC of these networks remain unclear. Applying a dimensional approach, here we analyzed associations of FC between major nodes of the DMN, SN, and CEN with severity of depressive symptoms and ELA defined as childhood abuse and neglect in a sample of 83 healthy and depressed subjects. Depressive symptoms were linked to increased FC within the SN and decreased FC of the SN with the DMN and CEN. Childhood abuse was associated with increased FC within the SN, whereas childhood neglect was associated with decreased FC within the SN and increased FC between the SN and the DMN. Our study thus provides evidence for differential associations of depressive symptoms and ELA with resting state FC and contributes to a clarification of previously contradictory findings. Specific FC abnormalities may underlie specific cognitive and emotional impairments. Future research should link specific clinical symptoms resulting from ELA to FC patterns thereby characterizing depression subtypes with specific neurobiological signatures

Effects of psychotherapy on glutamatergic neurotransmission

Introduction: Psychodynamic psychotherapy is an effective and widely used treatment for major depressive disorder (MDD); however, little is known about neurobiological changes associated with induced symptom improvement. Methods: Proton magnetic resonance spectroscopy with a two-dimensional J-resolved sequence served to test the relationship between glutamate (Glu) and glutamine (Gln) levels, measured separately in pregenual anterior cingulate cortex (pgACC) and the anterior midcingulate cortex (aMCC) as a control region, with change in depression symptoms after 6 months of weekly psychodynamic psychotherapy sessions in MDD patients. Depressed (N = 45) and healthy (N = 30) subjects participated in a baseline proton magnetic resonance spectroscopy measurement and a subgroup of MDD subjects (N = 21) then received once-a-week psychodynamic psychotherapy and participated in a second proton magnetic resonance spectroscopy measurement after 6 months. Change in depression symptoms was assessed using the Hamilton Depression Rating Scale (HAMD). Results: Higher pretreatment pgACC Gln concentrations in MDD patients compared to healthy controls were associated with symptom severity. Patients and controls did not differ regarding Gln levels in aMCC nor regarding Glu levels in both regions. The association of pgACC Gln concentration and severity of depressive symptoms was reversed after 6 months of psychotherapy in MDD subjects. Regarding Gln in aMCC as well as Glu in both regions, there were no significant associations with improvement of depressive symptoms in the course of psychotherapy. Discussion: Findings indicate specific regional effects of psychodynamic psychotherapy on glutamatergic neurotransmission and thereby highlight the key role of the pgACC in both depression pathophysiology and recovery

Differential alterations in resting state functional connectivity associated with depressive symptoms and early life adversity

Depression and early life adversity (ELA) are associated with aberrant resting state functional connectivity (FC) of the default mode (DMN), salience (SN), and central executive networks (CEN). However, the specific and differential associations of depression and ELA with FC of these networks remain unclear. Applying a dimensional approach, here we analyzed associations of FC between major nodes of the DMN, SN, and CEN with severity of depressive symptoms and ELA defined as childhood abuse and neglect in a sample of 83 healthy and depressed subjects. Depressive symptoms were linked to increased FC within the SN and decreased FC of the SN with the DMN and CEN. Childhood abuse was associated with increased FC within the SN, whereas childhood neglect was associated with decreased FC within the SN and increased FC between the SN and the DMN. Our study thus provides evidence for differential associations of depressive symptoms and ELA with resting state FC and contributes to a clarification of previously contradictory findings. Specific FC abnormalities may underlie specific cognitive and emotional impairments. Future research should link specific clinical symptoms resulting from ELA to FC patterns thereby characterizing depression subtypes with specific neurobiological signatures