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Objectives Sexual dysfunction is a prominent feature of Major Depressive Disorder (MDD), which affects depressed women more frequently and more pronounced compared to men. Reduced sexual desire might reflect overall anhedonia, a core symptom of MDD, which is putatively related to disturbed reward processing. Here, we aim to illuminate plausible underlying neurobiology of sexual dysfunction and in particular sexual desire in women with depression. We map associations between serotonin 4 receptor (5-HT4R) brain binding in the striatum, a key hub of the reward circuitry, and self-reported sexual function, where we focused on sexual desire, in the unmedicated depressed state. In addition, within women, we evaluate if pre-treatment sexual desire score predicted treatment outcome after eight weeks of treatment. Methods From the NeuroPharm study, we had access to brain scans of 5-HT4R binding and self-reports on sexual functioning (CSFQ-14 F&M) from 85 untreated MDD patients (71% women) who underwent eight weeks of antidepressant drug treatment. Whether pre-treatment sexual desire score predicted treatment outcome was evaluated using the area under the ROC curve (AUC). Treatment outcome was dichotomized as 50% or more reduction in Hamilton Depression Rating Scale 6-item (HDRS6) or not at 8 weeks clinical follow-up. Results We found a positive association between sexual desire and 5-HT4R binding in women (b=0.07, 95%CI [0.02:0.13], p.adj=0.024), but not in men (b=0.05, 95%CI [-0.05:0.15], p.adj=0.62). We did not find an association between overall sexual functioning and serotonin 4 receptor binding neither in women nor in men. Sexual desire at baseline did not predict treatment outcome i.e. ≥50% reduction in HDRS6 from baseline to week 8 (AUC=51.7% [36%:67%]). Conclusions Taken together, we find evidence for an association between low sexual desire and low striatal 5-HT4R agonist capacity in depressed women. Interestingly, this

Objectives Sexual dysfunction is a prominent feature of Major Depressive Disorder (MDD), which affects depressed women more frequently and more pronounced compared to men. Reduced sexual desire might reflect overall anhedonia, a core symptom of MDD, which is putatively related to disturbed reward processing. Here, we aim to illuminate plausible underlying neurobiology of sexual dysfunction and in particular sexual desire in women with depression. We map associations between serotonin 4 receptor (5-HT4R) brain binding in the striatum, a key hub of the reward circuitry, and self-reported sexual function, where we focused on sexual desire, in the unmedicated depressed state. In addition, within women, we evaluate if pre-treatment sexual desire score predicted treatment outcome after eight weeks of treatment. Methods From the NeuroPharm study, we had access to brain scans of 5-HT4R binding and self-reports on sexual functioning (CSFQ-14 F&M) from 85 untreated MDD patients (71% women) who underwent eight weeks of antidepressant drug treatment. Whether pre-treatment sexual desire score predicted treatment outcome was evaluated using the area under the ROC curve (AUC). Treatment outcome was dichotomized as 50% or more reduction in Hamilton Depression Rating Scale 6-item (HDRS6) or not at 8 weeks clinical follow-up. Results We found a positive association between sexual desire and 5-HT4R binding in women (b=0.07, 95%CI [0.02:0.13], p.adj=0.024), but not in men (b=0.05, 95%CI [-0.05:0.15], p.adj=0.62). We did not find an association between overall sexual functioning and serotonin 4 receptor binding neither in women nor in men. Sexual desire at baseline did not predict treatment outcome i.e. ≥50% reduction in HDRS6 from baseline to week 8 (AUC=51.7% [36%:67%]). Conclusions Taken together, we find evidence for an association between low sexual desire and low striatal 5-HT4R agonist capacity in depressed women. Interestingly, this

Major achievements have been made recently regarding the tephrochronology of the North Atlantic area. For the first time a tephra-based correlation between marine cores from the North Atlantic and a terrestrial site on the Faroe Islands of Eemian age (OIS 5e) have been achieved (Wastegård et al., 2005). This is the first time that tephrochronology has been used in order to correlate between marine and terrestrial archives older than OIS 4 in the North Atlantic region. Several new tephras from OIS 5-2 have been identified in North Atlantic sediments and the geochemical composition and distribution of the well-known North Atlantic Ash Zone II (ca 54 ka cal BP) has been refined (Wastegård et al., 2006). The known geographical distribution of other significant tephra strata have been outlined and, as a result, have established important tie-points between diverse palaeoarchives during the last glacial cycle. One important step forward was the identification of the Fugloyarbanki tephra in the NGRIP ice core, where it is dated to 26,740 ± 390 b2k according to the new Greenland Ice Core Chronology (GICC05). This widespread marker horizon has previously been reported in marine cores from the northern North Atlantic Sea and the Labrador Sea (Wastegård et al., 2006). Detection of this tephra for the first time within the NGRIP ice-core provides a pivotal link between marine and ice-core records during the transition between OIS 3/2, enabling an unprecedented insight into the spatial complexity of rapid climatic changes during this time (Davies et al., submitted). Recently another link between marine and ice-core records was established. The FMAZ III ash zone has been described in cores from the Faroe Islands area (c. 33,000 14C years BP), slightly above Heinrich layer 4, and close to the onset of GIS8. An equivalent tephra was recently identified in NGRIP where it is situated right at the peak of GIS8. References Davies, S.M., Wastegård, S., Rasmussen, T.L., Johnsen, S.J., St

Tephrochronology has recently become a key technique for the precise correlation of Late Quaternary records in the North Atlantic region. Recent developments have extended the geographical distribution of significant tephra strata and, as a result, have established important tie-points between diverse palaeoarchives during the last glacial cycle. We will report on the work being undertaken to identify, date and geochemically characterise tephra horizons in marine cores from the Faroe Islands region and the Greenland ice-cores. Four ash zones including the widespread North Atlantic Ash Zone II (NAAZ II; 52-53 ka BP) and three mainly basaltic ash zones here referred to as the Faroe Marine Ash Zones (FMAZ) I (ca 15.4 14C ka BP), II/Fugloyarbanki Tephra (ca 23-24 14C ka BP) and III (ca 33 14C ka BP) occur in several cores from the Faroe Islands margin. Detailed investigations of NAAZ II in high-resolution cores show that two separate layers can be distinguished; a lower mixed alkalic basalt and rhyolitic layer and an upper predominantly tholeiitic basalt tephra, separated by as much as 1500 years. FMAZ III is a thick and relatively scattered basaltic ash zone found in three cores from the Faroe area. It has not been directly dated, but extrapolation of AMS radiocarbon dates from all cores suggest an age of c. 33,000 14C years BP, slightly above Heinrich layer 4, and close to the onset of GIS8. An equivalent tephra was recently identified in NGRIP where it is situated right at the peak of GIS8. The FMAZ II/Fugloyarbanki tephra occurs in all analysed marine cores in the Faroe Islands region and in NGRIP. It is dated to 26,740 ± 390 b2k according to the Greenland Ice Core Chronology (GICC05). This tephra falls right after the warmest peak of GIS3 in both the NGRIP and marine records and provides another important tie-point. Other tephras identified within the ice-core material have revealed the presence of previously unreported tephra horizons of Icelandic origin, thus, ad