BackgroundPrevious research has documented reduced heart rate and blood pressure variability in major depressive disorder (MDD), suggesting a limited capacity for cardiovascular regulation and diminished homeostatic resources in the disorder. This study aimed to complement this knowledge by investigating short-term cerebral blood flow (CBF) variability in MDD. MethodsUsing transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries of both hemispheres were recorded in 35 MDD patients and 35 healthy controls, at rest and during serial subtraction task-induced mental stress. CBF variability was represented by the root mean square of successive differences (RMSSD) in the beat-to-beat mean, systolic and diastolic flow velocity. ResultsPatients, as compared to controls, exhibited smaller mean and diastolic blood flow variability in MCA both at rest and during mental stress. Mean, systolic and diastolic blood flow variability were greater during the task than at rest. CBF variability did not differ between patient subgroups composed according to medication use. LimitationsPotential effects of blood pressure and respiration on CBF variability could not be investigated. ConclusionsThe study revealed evidence of reduced short-term CBF variability in MDD. The task-induced CBF variability increase may be ascribed to neural activity associated with arithmetic processing. Lower blood pressure variability and deficient autonomic cardiovascular control may contribute to the reduction of short-term CBF variability seen in MDD. Short-term CBF variability reflects preserved interplay of regulatory mechanisms ensuring optimal blood and energy supply to the brain. Therefore, the results suggest impaired cerebroprotective mechanisms, associated with suboptimal cerebral performance.