Impaired socio-affective, but intact socio-cognitive skills in patients with treatment-resistant, recurrent depression.

BACKGROUND: Social withdrawal is a key symptom of depression. The resulting loss of social reinforcement in turn contributes to chronic, recurrent courses of the disease. However, it is not clear whether depressed patients have less motivation to socially interact, or whether their skills in doing so are impaired. The current study investigates potential skill deficits in patients with treatment-resistant depression (TRD). METHODS: 15 TRD patients and 19 age- and sex-matched healthy controls performed the EmpaToM, a paradigm which includes naturalistic video stimuli of either neutral or emotional valence and which differentiates between socio-affective (affective empathy, compassion) and socio-cognitive (theory of mind) skills. RESULTS: Controlling for the baseline affective state in neutral situations, TRD patients displayed significantly reduced affective empathy towards emotional situations compared to healthy controls. Furthermore, TRD patients were less compassionate in both neutral and emotional situations. In contrast, socio-cognitive skill performances did not differ between patients and healthy controls. LIMITATIONS: Further studies might explore socio-affective and socio-cognitive skills in TRD patients using socio-affective/-cognitive tasks involving face-to-face social interactions. CONCLUSION: Our study revealed a specific socio-affective deficit in TRD patients, while showing intact socio-cognitive skills. Patients were less able to affectively resonate with others (affective empathy) and exhibited generally reduced feelings of compassion. These deficits might interfere with providing and receiving social support. Our study contributes to a better understanding of the underlying causes of social withdrawal and stresses the need to specifically address pervasive socio-affective deficits in psychotherapy of TRD patients.

Invasive Brain Stimulation in the Treatment of Psychiatric Illness­Proposed Indications and Approaches.

BACKGROUND: Drugs, psychotherapy, and other treatment modalities are effective for many patients with mental illness. Nonetheless, many patients do not achieve a total remission with the currently available interventions, and the recurrence rates are high. As part of the ongoing search for further treatment options for refractory disorders, there is renewed interest in focal neuromodulatory techniques, including invasive ones, and deep brain stimulation (DBS) in particular. METHODS: In this review article, a group consisting of neurosurgeons, psychiatrists, and one practicing ethicist/neurologist summarizes the main aspects of the use of DBS to treat mental illness and offers recommendations on its indications and practical implementation. RESULTS: The efficacy of DBS against mental illness has not been confirmed in the randomized, controlled trials (RCTs) that have been published to date. This may be because the follow-up times were too short. In contrast to the negative RCTs, case series have indeed shown a positive effect of DBS on severe depression, but this effect can only be seen several months after the operation. CONCLUSION: DBS may be a therapeutic option for selected patients with otherwise intractable mental illness. Patients should only be treated in the setting of clinical trials. RCTs with longer follow-up times must be conducted in order to substantiate, if possible, the promising evidence that has been found in case series.

Deep Brain Stimulation in Neurological and Psychiatric Disorders.

BACKGROUND: Deep brain stimulation (DBS) is the chronic electrical stimulation of selected target sites in the brain through stereotactically implanted electrodes. More than 150 000 patients around the world have been treated to date with DBS for medically intractable conditions. The indications for DBS include movement disorders, epilepsy, and some types of mental illness. METHODS: This review is based on relevant publications retrieved by a selective search in PubMed and the Cochrane Library, and on the current guidelines of the German Neurological Society (Deutsche Gesellschaft für Neurologie, DGN). RESULTS: DBS is usually performed to treat neurological diseases, most often movement disorders and, in particular, Parkinson's disease. Multiple randomized controlled trials (RCTs) have shown that DBS improves tremor, dyskinesia, and quality of life in patients with Parkinson's disease by 25% to 50%, depending on the rating scales used. DBS for tremor usually involves stimulation in the cerebello-thalamo-cortical regulatory loop. In an RCT of DBS for the treatment of primary generalized dystonia, the patients who underwent DBS experienced a 39.3% improvement of dystonia, compared to only 4.9% in the control group. Two multicenter trials of DBS for depression were terminated early because of a lack of efficacy. CONCLUSION: DBS is an established treatment for various neurological and psychiatric diseases. It has been incorporated in the DGN guidelines and is now considered a standard treatment for advanced Parkinson's disease. The safety and efficacy of DBS can be expected to improve with the application of new technical developments in electrode geometry and new imaging techniques. Controlled trials would be helpful so that DBS could be extended to further indications, particularly psychiatric ones.

Opposing effects of oxytocin on moral judgment in males and females.

Current perspectives on the evolutionary roots of human morality suggest it arose to incentivize social cooperation by promoting feelings of disgust toward selfish behavior, although the underlying neural mechanisms remain unclear. To investigate whether the ancient mammalian neuropeptide oxytocin (OXT) influences self-referential processing in the domains of emotion evaluation and moral decision making, we conducted a pharmaco-functional magnetic resonance imaging (fMRI) and a behavioral experiment involving 157 healthy women and men who were treated with either OXT (24 IU) or placebo (PLC) intranasally. Our results show that OXT facilitated cortical midline responses during self-processing of disgust and selectively promoted self-interest moral judgments in men. In contrast, in women OXT increased the reaction time difference between accepted and rejected moral dilemmas and led them to suppress their self-interest and respond more altruistically for the benefit of others. Taken together, these findings suggest an OXT-related sexual dimorphism in human moral behavior which evolved adaptively to optimize both protection and nurturing of offspring by promoting selfish behavior in men and altruistic behavior in women.

An oxytocin-induced facilitation of neural and emotional responses to social touch correlates inversely with autism traits.

Social communication through touch and mutual grooming can convey highly salient socio-emotional signals and has been shown to involve the neuropeptide oxytocin (OXT) in several species. Less is known about the modulatory influence of OXT on the neural and emotional responses to human interpersonal touch. The present randomized placebo (PLC)-controlled within-subject pharmaco-functional magnetic resonance imaging (fMRI) study was designed to test the hypothesis that a single intranasal dose of synthetic OXT (24 IU) would facilitate both neural and emotional responses to interpersonal touch in a context- (female vs male touch) and trait- (autistic trait load) specific manner. Specifically, the experimental rationale was to manipulate the reward value of interpersonal touch independent of the intensity and type of actual cutaneous stimulation administered. Thus, 40 heterosexual males believed that they were touched by either a man or a woman, although in fact an identical pattern of touch was always given by the same female experimenter blind to condition type. Our results show that OXT increased the perceived pleasantness of female, but not male touch, and associated neural responses in insula, precuneus, orbitofrontal, and pregenual anterior cingulate cortex. Moreover, the behavioral and neural effects of OXT were negatively correlated with autistic-like traits. Taken together, this is the first study to show that the perceived hedonic value of human heterosexual interpersonal touch is facilitated by OXT in men, but that its behavioral and neural effects in this context are blunted in individuals with autistic traits.

Modeling a negative response bias in the human amygdala by noradrenergic-glucocorticoid interactions.

An emerging theme in the neuroscience of emotion is the question of how acute stress shapes, and distorts, social-emotional behavior. The prevailing neurocircuitry models of social-emotional behavior emphasize the central role of the amygdala. Acute stress leads to increased central levels of norepinephrine (NE) and cortisol (CORT), and evidence suggests that these endogenous neuromodulators synergistically influence amygdala responses to social-emotional stimuli. We therefore hypothesized that amygdala responses to emotional facial expressions would be susceptible to pharmacologically induced increases in central NE and CORT levels. To specifically test this hypothesis, we measured amygdala activation to emotional faces using functional magnetic resonance imaging in 62 healthy subjects under four pharmacological conditions: (1) single oral dose of placebo, (2) 4 mg of the selective NE-reuptake inhibitor reboxetine (RBX), (3) 30 mg of hydrocortisone, or (4) both drugs in combination. We found that a decrease in amygdala activation to positive facial emotion was coupled with an increase in amygdala activation to negative facial emotion in the RBX-CORT combined challenge condition. In conclusion, a pharmacologically induced elevation of central NE and CORT levels in healthy subjects created a negative response bias in the amygdala that did not exist at baseline. Our results implicate a causative role of NE-CORT interactions in the emergence of a negative bias of cognitive and emotional functions which is germane in stress-related affective spectrum disorders.