Background
Premenstrual dysphoria is characterized by the cyclical occurrence of negative mood and physical symptoms during the luteal phase of the menstrual cycle. Cardinal symptoms are irritability, depression of mood, fatigue, affective lability, and impaired impulse control, all symptoms that can be alleviated by drugs increasing serotonergic signaling. Drugs inhibiting serotonin reuptake (the SSRIs) form the most effective pharmacological treatment known today. Thus, lowered serotonergic signaling during the luteal phase might be one symptom provoking factor in premenstrual dysphoria. The aim of the study was to test the serotonin hypothesis of this disorder i.e. of an association between premenstrual decline in brain serotonin function and concomitant worsening of self-rated cardinal mood symptoms.
Method
Positron emission tomography was used to assess brain trapping of 11C-5-hydroxy-L-tryptophan, marked in the beta-position, in the follicular and premenstrual phases of the menstrual cycle in eight women with Premenstrual dysphoria. Brain trapping of this radiotracer is supposed to reflect presynaptic aromatic amino acid decarboxylase activity, the activity of the enzyme responsible for the conversion of 11C-5-hydroxy-L-tryptophan to 11C-serotonin. Region of interest analysis was performed in the following regions: dorso-lateral prefrontal cortex, medio-prefrontal cortex, the caudate nucleus, and the putamen, all on the left and right side, and in a single whole brain region of interest. Changes in mood and physical symptoms were assessed from daily VAS self-ratings.
Results
Worsening of the cardinal mood symptoms irritability and depressed mood showed significant inverse associations to changes in brain 11C-5-hydroxy-L-tryptophan trapping whereas positive mood variables all showed positive associations and physical symptoms generally displayed weak or no associations.
Conclusion
The results indicate strong inverse associations between worsening of cardinal mood symptoms of Premenstrual dysphoria and brain trapping of the serotonin precursor 11C-5-hydroxy-L-tryptophan. The results may in part support a role for serotonin in Premenstrual dysphoria and may provide a clue to the effectiveness of serotonin augmenting drugs in this disorder.