Differential effect of quetiapine and lithium on functional connectivity of the striatum in first episode mania

Abstract

Mood disturbances seen in first-episode mania (FEM) are linked to disturbed functional connectivity of the striatum. Lithium and quetiapine are effective treatments for mania but their neurobiological effects remain largely unknown. We conducted a single-blinded randomized controlled maintenance trial in 61 FEM patients and 30 healthy controls. Patients were stabilized for a minimum of 2 weeks on lithium plus quetiapine then randomly assigned to either lithium (serum level 0.6 mmol/L) or quetiapine (dosed up to 800 mg/day) treatment for 12 months. Resting-state fMRI was acquired at baseline, 3 months (patient only) and 12 months. The effects of treatment group, time and their interaction, on striatal functional connectivity were assessed using voxel-wise general linear modelling. At baseline, FEM patients showed reduced connectivity in the dorsal (p = 0.05) and caudal (p = 0.008) cortico-striatal systems when compared to healthy controls at baseline. FEM patients also showed increased connectivity in a circuit linking the ventral striatum with the medial orbitofrontal cortex, cerebellum and thalamus (p = 0.02). Longitudinally, we found a significant interaction between time and treatment group, such that lithium was more rapid, compared to quetiapine, in normalizing abnormally increased functional connectivity, as assessed at 3-month and 12-month follow-ups. The results suggest that FEM is associated with reduced connectivity in dorsal and caudal corticostriatal systems, as well as increased functional connectivity of ventral striatal systems. Lithium appears to act more rapidly than quetiapine in normalizing hyperconnectivity of the ventral striatum with the cerebellum. The study was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12607000639426). http://www.anzctr.org.au

Three‐year longitudinal cognitive functioning in patients recently diagnosed with bipolar disorder

“…In another first‐episode mania sample, patients treated with lithium showed more improvement in verbal fluency relative to those treated with quetiapine over a one‐year period . Lithium‐treated first‐episode mania patients were also shown to have a more rapid normalization of functional connectivity abnormalities as well as slower progression of white matter loss than those treated with quetiapine. Therefore, these preliminary functional and structural brain findings in first‐episode mania converge with observations of possible detrimental effects of antipsychotics on cognition in the early course of bipolar disorder.…”

Challenging the Negative Perception of Lithium and Optimizing Its Long-Term Administration

“…There has also been data that such an approach can provide a favorable influence on the neuroprogression of the illness. Recently, it was found that, after the first episode of mania, lithium was superior to quetiapine in limiting white matter reduction and regulating neural connection between the ventral striatum and the cerebellum (Berk et al, 2017 ; Dandash et al, 2018 ).…”

Functional Connectivity of Corticostriatal Circuitry and Psychosis-Like Experiences in the General Community

“…These PET findings are complemented by studies of striatal functional connectivity, which report reduced coupling of the DLPFC with dorsal caudate and putamen in first-episode psychosis patients, their unaffected first-degree relatives, and ARMS individuals (49,50). Similar changes have been found in first-episode mania patients with psychosis (51), suggesting that dorsal CST dysfunction tracks the emergence of psychotic symptoms across diagnostic categories. Other studies focusing on thalamic connectivity support the importance of dorsal CST function in risk for psychosis (52)(53)(54).…”