Association of thalamic hyperactivity with treatment-resistant depression and poor response in early treatment for major depression: a resting-state fMRI study using fractional amplitude of low-frequency fluctuations

• Published in: Translational psychiatry Vol. 6; no. 3; p. e754
• Main Authors: Yamamura, T, Okamoto, Y, Okada, G, Takaishi, Y, Takamura, M, Mantani, A, Kurata, A, Otagaki, Y, Yamashita, H, Yamawaki, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.03.2016; Nature Publishing Group
• Subjects: 59/36; 631/378; Adult; Antidepressive Agents - therapeutic use; Behavioral Sciences; Biological Psychology; Brain - diagnostic imaging; Brain - physiopathology; Case-Control Studies; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - physiopathology; Depressive Disorder, Treatment-Resistant - diagnostic imaging; Depressive Disorder, Treatment-Resistant - drug therapy; Depressive Disorder, Treatment-Resistant - physiopathology; Female; Functional Neuroimaging; Humans; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Middle Aged; Neurosciences; Original; original-article; Parietal Lobe - diagnostic imaging; Parietal Lobe - physiopathology; Pharmacotherapy; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - physiopathology; Psychiatry; Thalamus - diagnostic imaging; Thalamus - physiopathology
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/tp.2016.18

Despite novel antidepressant development, 10–30% of patients with major depressive disorder (MDD) have antidepressant treatment-resistant depression (TRD). Although new therapies are needed, lack of knowledge regarding the neural mechanisms underlying TRD hinders development of new therapeutic options. We aimed to identify brain regions in which spontaneous neural activity is not only altered in TRD but also associated with early treatment resistance in MDD. Sixteen patients with TRD, 16 patients with early-phase non-TRD and 26 healthy control (HC) subjects underwent resting-state functional magnetic resonance imaging. To identify brain region differences in spontaneous neural activity between patients with and without TRD, we assessed fractional amplitude of low-frequency fluctuations (fALFF). We also calculated correlations between the percent change in the Hamilton Rating Scale for Depression (HRSD 17 ) scores and fALFF values in brain regions with differing activity for patients with and without TRD. Patients with TRD had increased right-thalamic fALFF values compared with patients without TRD. The percent change in HRSD 17 scores negatively correlated with fALFF values in patients with non-TRD. In addition, patients with TRD showed increased fALFF values in the right inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and vermis, compared with patients with non-TRD and HC subjects. Our results show that spontaneous activity in the right thalamus correlates with antidepressant treatment response. We also demonstrate that spontaneous activity in the right IFG, IPL and vermis may be specifically implicated in the neural pathophysiology of TRD.