Increases in Amplitude of Low-Frequency Fluctuations in Left Fronto-Parietal Area After Duloxetine Therapy in First-Episode, Drug-Naïve, Major Depressive Disorder With Panic Disorder Patients

To the Editor: The amplitude of low-frequency fluctuations (ALFF) is a way to measure resting functional magnetic resonance imaging (RFMRI), which reflects cortical functioning. We present data showing that five remitted, first-episode, drug-naïve, major depressive disorder with panic disorder (FEMDDPD) patients had increases of ALFF in the left fronto-parietal area after duloxetine therapy within 6 weeks.

Case Series

Five patients (three women, two men; 26.6 [SD: 4.56] years old) were enrolled. Their baseline rating data were as follows: Hamilton Rating Scale for Depression (Ham-D): 28.8 (4.6) and Panic Disorder Severity Scale (PDSS): 19.8 (4.32). No specific physical illness, psychotic features, past manic episodes, nonpsychiatric medication use, or substance abuse were mentioned. Duloxetine 30 mg/day was initiated and then titrated to 60 mg within 2 weeks without any significant side effects except mild nausea and sedation. After a 6-week course of therapy, their FEMDDPD symptoms responded to duloxetine (Ham-D: 8.2 [3.83]; PDSS: 3.4 [1.67]).

RFMRI scans were obtained with a 3T GE Version scanner housed at Buddhist Tzu Chi Hospital, Taipei Branch. Echo planar imaging (EPI) sequences were acquired in 20 axial slices (TR: 2,000 msec., TE: 40 msec., flip angle: 90°, FOV: 24 cm.; 5-mm. thickness, and 1-mm gap; 400 sec. for each subject) at baseline and 6th-week visit. ALFF was calculated by REST software (Resting State FMRI Data Analysis Toolkit, Version 1.4), using the preprocessed RFMRI data with default mask. The ALFF of each voxel was calculated within the brain and divided by global ALFF value. The standardized ALFF should have a value of approximately 1, and then be modulated for the following group comparison. The baseline and posttreatment-modulated ALFF maps were processed by the paired t-test function of REST software with production of T-statistic image (statistic threshold: p<0.00005; cluster size >270 mm³, rmm: 4; surface-connected hypothesis). Increased ALFF was observed in left fronto-parietal regions (left middle frontal gyrus [MFG]: −48, 12, 38 and inferior parietal lobe [IPL]: −48, −50, 43]), and decreased ALFF was found in left thalamus and left lingual gyrus (LG) after duloxetine therapy.

Discussion

MFG activity is a state-dependent marker for executive functions of depressive patients. IPL activity is also altered in depressive patients, which is possibly a disease-related impact.¹ MFG activity is also correlated with its cortical thickness and important in the executive attention network.² The IPL is also a part of attention and adaptive control in the intrinsic functional organization of depression. The network abnormalities probably contribute to emotional processing bias for prolonged negative emotional impacts in depression.³ The increase of ALFF in MFG and IPL probably improved cognition and emotion through the modulation of these networks. The thalamus is associated with expected unpleasant experiences and also a part of the “pessimistic” attitude in depression.⁴ The LG is also a part of structural deficits in our published study of FEMDDPD patients, and it is important for visual processing in anxiety and depression.⁵ The decrease of ALFF in these regions suggested inhibition of the limbic-visual system.