ow levels and could be synthesized via the deacetylation of melatonin in the pineal gland and contribute to production of 5-MTPOL, and is also involved in the regulation of the hormonal axis,. These observations along with the findings of this study suggest that methoxyindoles could be involved in pathogenesis of depression and its treatment outcomes. Circadian rhythm dysfunction is linked to depressive states,, and SSRIs modify circadian locomotor activity rhythms. The relationship between perturbations in the circadian cycle, depression, sleep pattern changes, production of methoxyindoles and regulation of the hormonal axis remains to be further explored. Limitations of this study include a relatively small sample size and relatively short duration of treatment. Longer treatment periods should help to determine which changes occur earlier, better define the relation between response and biochemical changes, and better discern the ability 
of early changes to predict latter outcomes. In future studies we will focus on effects of SSRIs and placebo on other pathways, this should extend findings reported and explain variability that exists between responders and non-responders in more details. Additionally correlations between peripheral and central metabolic changes induced by drug and placebo should be investigated. This can lead to the identification of peripheral biomarkers that are disease related and that can be more easily measured. Additionally, a potential limitation of this study is lack of the group of MDD patients without any treatment. While without such group of subjects the possibility still exists 8866946 that response to placebo could not be distinguished from spontaneous recovery, justification of such clinical trial design could be problematic due to the ethical concerns; future studies are necessary to address this question. In conclusion, our results suggest a potential role for methoxyindoles in mechanisms of recovery from depressed state, a finding that needs to be followed upon where samples should be collected during the day and night hours to define how the circadian cycle, production of methoxyindoles, changes in sleep patterns and hormonal axis are modified in responders and non-responders to SSRIs and to placebo. Atherosclerotic stenosis of large arteries at the base of the brain or intracranial large order SKI II artery disease is a major cause of stroke especially in Asians, Hispanics and Africans, and is possibly the most common vascular lesion in the world. It affects the middle cerebral artery, intracranial portion of the internal carotid 19497313 artery, vertebrobasilar artery and the posterior and anterior cerebral arteries. ICLAD carries a poor prognosis in terms of subsequent vascular event and death, and there is 25 30% incidence of recurrence in the 2 years after stroke. The disease is also prevalent among 53% of vascular dementia and 18% of Alzheimer’s disease patients of Asian ethnicity. The risk factors for ICLAD include hypertension, diabetes, hypercholesterolemia and cigarette smoking, and a strong association is found between asymptomatic ICLAD presenting as intracranial stenosis or calcification with large artery stiffness, and patients with untreated hypertension. Arterial stiffness is a major determinant of increased systolic blood pressure, and is associated with lesions in intracranial arteries. Prolonged elevation of blood pressure leads to reduction in vessel cross sectional area, increased wall thickness and accele