Biological correlates of temperament: systematic reviews, empirical studies, and a conceptual framework linking neurotransmitter signaling, intrinsic brain activity, and the hyperthymic-depressive spectrum
Hazel Tingzhu Chen, Matteo Martino, Elham Dabiri, Frans Ricardo Tamara, Lungile Sibiya, Benedetta Conio, Mario Amore, Thierry Burnouf & Paola Magioncalda
Molecular Psychiatry (2025)
Abstract
Temperament can be conceptualized as the baseline configuration of experience and behavior, contributing to individual differences in activity levels, emotional intensity, and thought patterns. This work aimed to investigate the biological correlates of temperament. First, we performed systematic reviews on the relationship of temperament with the brain’s function/structure (characterized via neuroimaging), as well as neurotransmitter signaling (measured in cerebrospinal fluid and blood). Then, we investigated the relationship of temperament with intrinsic brain activity (using resting-state functional MRI) in 122 subjects, as well as dopamine and serotonin levels (measured in platelets) in 25 subjects. The systematic reviews showed heterogeneous data. Our empirical studies showed that: the hyperthymic temperament is associated with decreased intrinsic brain activity in the medial prefrontal cortex/default-mode network, along with increased dopamine levels in platelets; conversely, the depressive temperament is associated with increased intrinsic brain activity in the medial prefrontal cortex/default-mode network, along with decreased dopamine levels in platelets. These data suggest that the hyperthymic temperament may be associated with a baseline configuration of brain activity tilted toward the sensorimotor areas at the expense of the associative areas (related to high dopamine signaling), favoring immediate interaction with the environment and a propensity for action and impulsive behavior; conversely, the depressive temperament may be associated with a baseline configuration of brain activity tilted toward the associative areas at the expense of the sensorimotor areas (related to low dopamine signaling), favoring detachment from the environment and a propensity for thinking/imagery and rumination. Accordingly, these temperaments may represent the physiological counterparts of the manic and depressive states of bipolar disorder.
