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.

Thalamocortical connectivity in major depressive disorder

“…The predominant finding of this study was thalamo-temporal hyperconnectivity in MDD, which was also related to the severity of depression symptoms. This is in line with some other neuroimaging studies showing a positive relationship between thalamic activity and both symptoms (Milak et al, 2005) and treatment response (Yamamura et al, 2016) in MDD. However, we instead show that connectivity between thalamus and cortex is associated with severity of symptoms, and not just related to activity in thalamus, thus extending the implications of these previous studies into a network context.…”

“…Furthermore, some studies have also documented associations between thalamic activity and treatment outcomes. For example, patients with treatment resistant depression (TRD) had greater spontaneous thalamic activity compared to non-TRD patients (Yamamura et al, 2016). In this same study, a lower clinical improvement in response to antidepressants correlated with higher thalamic activity.…”

Structural and Functional Alterations in Hemodialysis Patients: A Voxel-Based Morphometry and Functional Connectivity Study

“…Furthermore, the present study revealed the presence of thalamo-temporal hypo-connectivity in hemodialysis patients, which may be due to impaired thalamo-cortical modulation underlying emotional disturbances. This is in line with previous neuroimaging studies in major depressive disorders (Milak et al, 2005;Yamamura et al, 2016). Nevertheless, thalamo-cortical networks may be a potential candidate marker for psychopathology in hemodialysis patients.…”

Subcortical Anatomy of the Default Mode Network: a functional and structural connectivity study

“…Additionally, the ventral tegmental area is connected to the nucleus accumbens through the mesolimbic system, the classical dopaminergic pathway associated with schizophrenia, and functional data shows a decrease of connectivity between VTA and several brain regions, including the thalamus, in unmedicated schizophrenic patients (Hadley et al, 2014). The pathophysiology of others diseases, such as drug addiction, depression, temporal lobe epilepsy and attention deficit and hyperactivity disorder involve modifications in the nucleus accumbens, medial septal nuclei or the thalamic nuclei that connect limbic regions as well as dysfunctional connectivity of the DMN (Table 4; Butler et al, 2013;Dinkelacker et al, 2015;Ivanov et al, 2010;Scofield et al, 2016;Vialou et al, 2010;Voets et al, 2012;Volkow et al, 2011;Yamamura et al, 2016;Zhu et al, 2016).…”