Increased presynaptic dopamine activity in adolescent with major depressive disorder: an ¹⁸F-FDOPA PET study

Major depressive disorder (MDD) is a prevalent mental health condition with significant impacts on adolescents, often leading to academic challenges, interpersonal conflicts, and long-term emotional difficulties. The unique symptom profile in adolescent MDD, such as increased irritability and affective reactivity, has been associated with disruptions in dopamine (DA) regulation. This study aimed to assess whether adolescents with MDD exhibit abnormal presynaptic dopamine synthesis capacity compared to healthy controls (HC) and to explore the relationship between dopamine synthesis capacity and depressive symptom severity.

19 adolescents with MDD and 14 matched HC underwent positron emission tomography (PET) using ¹⁸F-FDOPA to assess dopamine synthesis capacity. Symptoms were evaluated using the PHQ-9, SHAPS, ARI, and ASLEC. Partial correlation analyses, controlling for age, illness duration, and medication status, were used to explore the relationship between dopamine synthesis capacity and symptom severity.

Adolescents with MDD showed significantly higher ¹⁸F-FDOPA uptake in several brain regions, including the substantia nigra, brainstem, pons, frontal pole, caudate nucleus, pallidum, putamen, temporal pole, cerebellum Crus I, and inferior temporal gyrus, compared to HC. A negative correlation was found between PHQ-9 scores and dopamine synthesis capacity across widespread basal ganglia regions, including the left substantia nigra, left caudate nucleus, bilateral pallidum, and right putamen. Increased dopamine synthesis capacity in the right pons and left putamen was positively correlated with ARI scores. ASLEC scores were positively associated with dopamine synthesis capacity in the bilateral frontal poles.

These findings suggest presynaptic dopamine hyperactivity in specific brain regions is associated with emotional and stress-related symptoms in adolescent MDD, providing a potential neurobiological target for interventions.