Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers

It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges. Using a high-dose carbon dioxide (CO2) challenge, we aimed to investigate the effects of acute tryptophan depletion (ATD) and acute tryptophan loading (ATL) on CO2-induced panic response in healthy volunteers. Eighteen healthy volunteers participated in a randomized, double-blind placebo-controlled study. Each subject received ATD, ATL, and a balanced condition (BAL) in separate days, and a double-breath 35% CO2 inhalation 4.5 h after treatment. Tryptophan (Trp) manipulations were obtained adding 0 g (ATD), 1.21 g (BAL), and 5.15 g (ATL) of l-tryptophan to a protein mixture lacking Trp. Assessments consisted of a visual analogue scale for affect (VAAS) and panic symptom list. A separate analysis on a sample of 55 subjects with a separate-group design has also been performed to study the relationship between plasma amino acid levels and subjective response to CO2. CO2-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p <0.05). In the separate-group analysis, Delta VAAS scores were positively correlated to the ratio Trp:I LNAA pound after treatment (r = 0.39; p <0.05). The present results are in line with preclinical data indicating a role for the serotonergic system in promoting the aversive respiratory sensations to hypercapnic stimuli (Richerson, Nat Rev Neurosci 5(6):449-461, 2004). The differences observed in our study, compared to previous findings in PD patients, might depend on an altered serotonergic modulatory function in patients compared to healthy subjects

Transcranial magnetic stimulation in the treatment of obsessive–compulsive disorder: current perspectives

Ana Lusicic,1 Koen RJ Schruers,2 Stefano Pallanti,3,4 David J Castle5,6 1PACE Clinic, Orygen Youth Health, Melbourne, VIC, Australia; 2Research Institute for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; 3Institute of Neurosciences, Florence, Italy; 4Stanford University, Palo Alto, CA, USA; 5St Vincent’s Hospital, 6University of Melbourne, Melbourne, VIC, Australia Abstract: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neurostimulation technique receiving increasing attention in the treatment of different psychiatric disorders. Evidence for rTMS use in obsessive–compulsive disorder (OCD) is accumulating and informing further developments in the neurostimulation field, the latest being deep transcranial magnetic stimulation (dTMS). dTMS allows direct stimulation of deeper subcortical structures and larger brain volume than conventional rTMS. Underlying neurobiological mechanisms related to transcranial magnetic stimulation are still under evaluation, but appear to offer a novel “third” way of addressing symptoms via localized electrical stimulation compared to pharmacotherapy and psychotherapy approaches. This systematic review focuses on the effects of rTMS and dTMS stimulation on different brain targets in OCD. Brain areas included are the dorsolateral prefrontal cortex, supplementary motor area, orbitofrontal cortex/medial prefrontal cortex, and anterior cingulate cortex (ACC). Improved understanding of the therapeutic effects of rTMS in OCD will support fine-tuning of the method and help determine how we can best optimize the approach via rTMS or dTMS to achieve clinically relevant results. Keywords: repetitive transcranial magnetic stimulation, rTMS, deep TMS, obsessive–compulsive disorder, OCD, noninvasive neurostimulatio

CO2_{2} exposure as translational cross-species experimental model for panic

The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral–emotional and bodily response to CO$_{2}$ exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO$_{2}$ exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO$_{2}$, demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies