Selektiva serotoninåterupptagshämmare fungerar på ett speciellt vis vid premenstruellt dysforiskt syndrom jämfört med depressivitet: varför?

Tidsperiod: 2016-01-01 till 2018-12-31

Projektledare: Erica Comasco, Erika Comasco

Finansiär: Vetenskapsrådet

Bidragstyp: Bidrag för anställning eller stipendier

Budget: 5 834 778 SEK

Sex and gonadal hormones affect mental health in a profound manner. Their role in modulation of emotional circuits is presumably critical to differences in prevalence, aetiology, course, and treatment outcome of depression and anxiety symptoms. Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific psychiatric disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. PMDD as well as depression and anxiety disorders are characterized by emotional distress and dysregulation. All three are treated with serotonergic antidepressants, however efficacy in PMDD reaches almost 90% and is immediate, while is much lower and delayed for depression and anxiety. The aim of the present study is to investigate the psycho-neurobiological mechanisms and effects of hormonal and sex specific serotonergic antidepressants efficacy in PMDD patients. This cross-over, double-blind, randomized, placebo controlled, longitudinal, study will investigate women with a diagnosis of Premenstrual Dysphoric Disorder as well as healthy subjects. The methods comprise: antidepressant treatment or placebo, emotion processing psychological tasks, pharmaco-neuroimaging scanning, hormone measurements and blood omic analyses.The present study will address the following questions: what are the neural substrates of negative bias in emotion processing in women´s experience of negative mood states during the luteal phase of the menstrual cycle? Do and, if yes, how selective serotonin reuptake inhibitor treatment and its efficacy affect functional and structural neural substrates and emotion processing? Is there an effect of placebo? What are the differences at the neural level between PMDD patients and healthy subjects at different phases of the menstrual cycle? Can objective biological intermediate phenotypes of PMDD be identified?The study offers the opportunity to get insights on the psycho-neurobiological mechanisms behind hormonal and sex specific serotonergic antidepressants efficacy in patients with Premenstrual Dysphoric Disorder. The results will provide unique data relevant to the neuroscience and psychiatry fields which are hampered by the inaccessibility of the brain in living humans, and which have overlooked psychological and neural correlates of antidepressants treatment and different hormonal states. Additionally, the findings will be of clinical utility for the treatment of depression and anxiety which are disorders characterized by sex differences and emotion dysregulation, and whose treatment with the usual first-choice serotonergic antidepressant drugs is at present associated with 40-60% non-response and only 30% remittance. Finally, as negative bias in emotion processing is also the target of cognitive behavioural therapy, increased knowledge of the psycho-neurological underpinnings of symptoms relief will further understanding of psychological therapy for depression and anxiety symptoms.