title: 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.
abstract: 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 (HRSD17) 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 HRSD17 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.
authors.affiliation: Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamamura
authors.affiliation: Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Okada
authors.affiliation: Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takaishi
authors.affiliation: Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takamura
authors.affiliation: Mantani Mental Clinic, Hiroshima, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Mantani
authors.affiliation: Department of Psychiatry, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kurata
authors.affiliation: Kyobashi Shinryo Clinic, Hiroshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Otagaki
authors.affiliation: Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamawaki
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology; D061218:Depressive Disorder, Treatment-Resistant / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000000981:diagnostic imaging* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000503:physiopathology; D013788:Thalamus / Q000000981:diagnostic imaging* / Q000503:physiopathology
chemical_list: D000928:Antidepressive Agents