Speaker: Gitte Moos Knudsen, Denmark

s | 31 non-pharmacologic treatments have been shown to result in rapid symptom resolution (defined as a sizeable and statistically significant treatment effect versus placebo that is apparent as early as 24 to 72 hours post-initiation of therapy), despite the tremendous need for rapid antidepressant therapies that would allow for meaningful clinical improvements within the context of very short hospital admissions for TRD patients. The goal of the NIMH-funded RAPID (rapidly acting treatments for major depressive disorder) program is explore treatments that could meet this need. This lecture will review current options for treatment-resistant depression, as well as the rational and structure of the RAPID program and its components. PL04 Imaging: Multimodal human brain imaging of the serotonergic transmitter system Chair: Siegfried Kasper, Austria Speaker: Gitte Moos Knudsen, Denmark Abstract Over the last decade, the availability of suitable Positron Emission Tomography (PET) radioligands has enabled vivo neuroimaging of the serotonin (5-HT) system in humans. The combination of high-resolution PET and structural magnetic resonance brain imaging (MRI) with novel quantification methods (1) allows for generation of population based brain atlases showing the 5-HT receptors and transporters in the brain in great detail. Access to such an atlas provides exciting opportunities for exploring the 5-HT function in relation to, e.g., pharmacological interventions. Pharmacological magnetic resonance imaging (phMRI), is a promising way to assess the impact of pharmacological challenges on blood oxygenation level dependent (BOLD) contrast based fMRI and it allows one to localize the temporal and spatial pharmacological actions in the brain. The simultaneous acquisition of neurotransmission data with PET generates, on the other hand, important information about how the pharmacologically induced hemodynamic effects are induced by neurochemical changes, in particular regional neurotransmitter release. An example of how multimodality imaging approaches can benefit science will be given here: Healthy volunteers underwentOver the last decade, the availability of suitable Positron Emission Tomography (PET) radioligands has enabled vivo neuroimaging of the serotonin (5-HT) system in humans. The combination of high-resolution PET and structural magnetic resonance brain imaging (MRI) with novel quantification methods (1) allows for generation of population based brain atlases showing the 5-HT receptors and transporters in the brain in great detail. Access to such an atlas provides exciting opportunities for exploring the 5-HT function in relation to, e.g., pharmacological interventions. Pharmacological magnetic resonance imaging (phMRI), is a promising way to assess the impact of pharmacological challenges on blood oxygenation level dependent (BOLD) contrast based fMRI and it allows one to localize the temporal and spatial pharmacological actions in the brain. The simultaneous acquisition of neurotransmission data with PET generates, on the other hand, important information about how the pharmacologically induced hemodynamic effects are induced by neurochemical changes, in particular regional neurotransmitter release. An example of how multimodality imaging approaches can benefit science will be given here: Healthy volunteers underwent three-week intervention with either placebo or the selective serotonin reuptake inhibitor (SSRI) fluoxetine and were scanned before and after with fMRI and the 5-HT4 receptor radioligand [11C]SB207145 PET. The intervention did not result in any significant group-differences in emotional face processing with fMRI. This, however, changed when taking the SSRI intervention associated changes in central 5-HT levels, as measured with the 5-HT4 receptor radioligand [11C]SB207145 PET (2), into account: The greater the increase in central 5-HT levels, the lower the threat-related amygdala reactivity (3). This provides direct evidence that individual changes in brain 5-HT levels are linked to threat-related amygdala reactivity. Although historically mostly being used separately, magnetic resonance imaging (MRI) and positron emission tomography (PET) offer two complementary techniques for in vivo investigation of the brain. With the recent development of combined MR-PET equipment that allows for simultaneous acquisition of the signals, a powerful tool has been made available to tap different physio-chemical properties of the brain condition. This is particularly promising assessment of pharmacological or nonpharmacological interventions because one can then assess the regional and temporal effects of, e.g., hemodynamics and neurotransmitter related outcome measures. Simultaneous fMRI-PET studies have captured effects of regional differences in pharmacologically induced endogenous brain neurotransmitter levels of dopamine (4) or pain induced changes in opioids (5) corresponding to observed changes in regional cerebral blood flow. The relationship between pharmacologically induced changes in receptor occupancies and regional blood flow changes remains, however, to be better understood. In conclusion, a particular promising exploitation of simultaneous PET-MRI is its ability to capture neurotransmission specific networks within the brain and to investigate how those are related to the associated changes in regional metabolism and blood flow. This presents a completely novel opportunity to assess pharmacological effects on the human brain in vivo.