Low serotonin levels in the brain are responsible for a greater prevalence of affective psychosis in patients with a type of Prader-Willi syndrome (PWS) known as maternal uniparental disomy PWS (mUPD PWS), according to a study.
Serotonin, a molecule found in the brain, is often referred to as a “happiness hormone” because it plays a key role in the control of emotions.
Decreased concentration of serotonin in the brains of mUPD PWS patients is associated with reduced availability of the brain-stem serotonin transporter, a protein responsible for the transport of serotonin in terminal regions of neurons, called synapses.
Findings were reported in the study, “Brain-stem serotonin transporter availability in maternal uniparental disomy and deletion Prader-Willi syndrome,” published in The British Journal of Psychiatry.
PWS is a rare genetic disorder that can be caused by either the deletion of genetic material from a paternal chromosome (del PWS) at 15q11-13 or by a maternal uniparental disomy (mUPD) — when two copies of a chromosome come from the same parent (in this case, the mother), instead of one copy from each of the parents.
PWS is not only associated with physical characteristics, including short stature, small hands and feet, and a distinctive facial appearance, but also with psychological and behavioral issues, such as mood swings, stubbornness, aggression, repetitive speech, and affective disorders.
Patients with mUPD PWS are known to be at a greater risk for developing affective psychosis than del PWS patients. However, the neurological processes behind why this occurs were not clear.
The aim of this U.K. study was to investigate if serotonin transporter (5-HTT) availability was different between these two PWS groups. In total, eight adult patients with mUPD PWS and 10 with del PWS were analyzed.
Researchers assessed 5-HTT availability and also depressive symptomatology — assessed using the Glasgow Depression Scale for people with Learning Disability (GDS-LD). Past psychotic episodes were also recorded.
Results showed that the mUPD PWS group had higher GDS-LD scores, as well as more past episodes of psychosis, compared with the del PWS group, although these differences were not particularly significant.
Researchers did find the mUPD group had significantly lower 5-HTT availability than the del group, which could explain the higher occurrence of affective psychosis in this group.
“Our findings reveal an association between PWS genotype and brain-stem 5-HTT availability. The mUPD group had lower brain-stem 5-HTT availability compared with the del group. In keeping with this, we postulate that those with mUPD have a lower synaptic serotonin concentration compared with those with del PWS, and that this may indeed account for the greater prevalence of affective psychotic illness in this population,” the researchers wrote.
The team also suggested that such lower synaptic serotonin concentration in mUPD PWS patients could explain “why drugs such as selective serotonin reuptake inhibitors are effective in treating this cohort of patients.”
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