Translocator Protein (TSPO) Expression in Platelets of Depressed Patients Decreases during Antidepressant Therapy.

Introduction: A promising candidate in the field of pharmacological treatment options regarding major depressive disorder (MDD) is the mitochondrial translocator protein (18 kDa) (TSPO). TSPO is crucial for neurosteroid synthesis, which is in turn important for the regulation of emotions. It has already been shown that TSPO expression in platelets of depressed patients is reduced compared to healthy subjects. Methods: We measured TSPO levels in platelets of 37 depressed patients before and after 6 weeks of pharmacological treatment to test the hypotheses that i) such treatment would increase TSPO expression and ii) that this increase would be correlated with therapeutic response. Results: Surprisingly, TSPO levels in platelets of all patients were significantly reduced after 6 weeks of treatment (p=0.044). Within the responder group, a non-significant trend towards greater TSPO level reduction could be observed. Discussion: These results challenge our hypotheses that TSPO levels might increase during antidepressant therapy along with a decrease in depressive symptoms. Thus, we assume that TSPO expression in platelets is not a suitable state marker for MDD.

Enhancing neurosteroid synthesis--relationship to the pharmacology of translocator protein (18 kDa) (TSPO) ligands and benzodiazepines.

INTRODUCTION: The treatment of anxiety disorders is still a challenge; novel pharmacological approaches that combine rapid anxiolytic efficacy with fewer side effects are needed. A promising target for such compounds is the mitochondrial translocator protein (18 kDa) (TSPO). TSPO plays an important role for the synthesis of neurosteroids, known to modulate GABAA receptors, thereby exerting anxiolytic effects. METHODS: We investigated the pharmacological profile of 2 well established TSPO ligands (XBD173 and etifoxine) compared to the benzodiazepine diazepam with regard to TSPO binding affinity, TSPO expression and neurosteroidogenesis. RESULTS: In BV-2 microglia and C6 glioma cells all compounds significantly enhanced TSPO protein expression. Radioligand binding assays revealed the highest binding affinity to TSPO for XBD173, followed by diazepam and etifoxine. Pregnenolone synthesis was most potently enhanced by etifoxine. DISCUSSION: Etifoxine turned out to be the most potent enhancer of neurosteroidogenesis, although its binding affinity to TSPO was lowest. These results indicate that the efficacy of TSPO ligands to stimulate neurosteroid synthesis, thereby leading to anxiolytic effects cannot be concluded from their binding affinity to TSPO.

Oxytocin plasma levels predict the outcome of psychotherapy: A pilot study in chronic depression.

BACKGROUND: Oxytocin is associated with bonding and social deficits in psychiatric disorders and has also been discussed as a potential therapeutic intervention to augment psychotherapy. The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) is a specific form of psychotherapy for chronic depression, an illness in which interpersonal deficits play a major role. In this pilot study, we investigated whether Oxytocin plasma levels predict the clinical outcome of chronic depressive patients after CBASP. METHODS: Sixteen patients with chronic depression participated in a 10-week CBASP inpatient program. Oxytocin plasma levels were measured before and after participants played a virtual ball-tossing game (Cyberball) that mimics social exclusion. Clinical outcome after CBASP was evaluated with the Beck Depression Inventory-II (BDI-II) and the 24-item Hamilton Depression Rating Scale (HAMD-24). RESULTS: After CBASP, depressive symptoms decreased significantly: the response rates were 44% (BDI-II) and 50% (HAMD-24); and the remission rates, 38% (BDI-II) and 44% (HAMD-24). Lower oxytocin plasma levels at baseline correlated with smaller changes in BDI-II scores, but not with the change in HAMD-24 scores. LIMITATIONS: The limitations of our study were the small sample size, concomitant and non-standardized pharmacotherapy, and lack of a controlled design and a follow-up period. CONCLUSIONS: Our study provides first evidence that oxytocin plasma levels may predict the outcome of psychotherapy in chronic depression. These findings need to be replicated in larger randomized, controlled trials.

Attachment representations, patterns of emotion regulation, and social exclusion in patients with chronic and episodic depression and healthy controls.

BACKGROUND: The experience of social exclusion (ostracism) is linked to the etiology and maintenance of depression. Most individuals experience emotional stress in states of social exclusion. Insecurely attached individuals, especially with an unresolved trauma, show maladaptive coping in response to social stress. The present study examines (a) the differences with regards to attachment representations in episodic (ED) and chronic depressive (CD) inpatients and (b) how ostracism affects their emotional reactions. METHODS: Patients with CD (n=29) and ED (n=23) and healthy control subjects (n=29) were interviewed using the Adult Attachment Projective Picture System (AAP), a valid measure to assess attachment representation; and played a virtual ball tossing game simulating social exclusion (Cyberball). Multiple depression-related risk and protective factors were considered. We hypothesized that CD patients show the most severe attachment disorganization and are emotionally most affected by the social exclusion situation. Moreover, we explored the interaction between ostracism and attachment. RESULTS: Contradicting our hypotheses, ED and CD individuals were almost akin with regards to their attachment insecurity/disorganization and reactions to Cyberball. An emotionally altered reaction to social exclusion was identified in the insecure-disorganized depressive subgroup. LIMITATIONS: Small sample size hampering further subgroup analyses. The ED sample may include single CD subjects with recent manifestation. CONCLUSIONS: The pattern of emotion regulation in the depressive groups matches with findings from clinical studies, including attachment research. The relationship between attachment representations and ostracism should be further investigated in larger samples of depressive individuals.