Reduced haemodynamic response in the frontotemporal cortices of patients with major depressive disorder (MDD) has been demonstrated using functional near-infrared spectroscopy (fNIRS). Most notably, changes in cortical oxy-haemoglobin during a Japanese phonetic fluency task can differentiate psychiatric patients from healthy controls (HC). However, this paradigm has not been validated in the English language. Therefore, the present work aimed to distinguish patients with MDD from HCs, using haemodynamic response measured during an English letter fluency task. One hundred and five HCs and 105 patients with MDD took part in this study. NIRS signals during the verbal fluency task (VFT) was acquired using a 52-channel system, and changes in oxy-haemoglobin in the frontal and temporal regions were quantified. Depression severity, psychosocial functioning, pharmacotherapy and psychiatric history were noted. Patients with MDD had smaller changes in oxy-haemoglobin in the frontal and temporal cortices than HCs. In both regions of interest, oxy-haemoglobin was not associated with any of the clinical variables studied. 75.2% and 76.5% of patients with MDD were correctly classified using frontal and temporal region oxy-haemoglobin, respectively. Haemodynamic response measured by fNIRS during an English letter fluency task is a promising biomarker for MDD.
Noradrenergic A2 neurons of the nucleus of the solitary tract (NTS) have been suggested to contribute to body fluid homeostasis and cardiovascular regulation. In the present study, we investigated the effects of lesions of A2 neurons of the commissural NTS (cNTS) on the c-Fos expression in neurons of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, arterial pressure, water intake, and urinary excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats (280-320 g) received an injection of anti-dopamine-β-hydroxylase-saporin (12.6 ng/60 nl; cNTS/A2-lesion, n = 28) or immunoglobulin G (IgG)-saporin (12.6 ng/60 nl; sham, n = 24) into the cNTS. The cNTS/A2 lesions increased the number of neurons expressing c-Fos in the magnocellular PVN in rats treated with hypertonic NaCl (90 ± 13, vs. sham: 47 ± 20; n = 4), without changing the number of neurons expressing c-Fos in the parvocellular PVN or in the SON. Contrary to sham rats, intragastric 2 M NaCl also increased arterial pressure in cNTS/A2-lesioned rats (16 ± 3, vs. sham: 2 ± 2 mmHg 60 min after the intragastric load; n = 9), an effect blocked by the pretreatment with the vasopressin antagonist Manning compound (0 ± 3 mmHg; n = 10). In addition, cNTS/A2 lesions enhanced hyperosmolality-induced water intake (10.5 ± 1.4, vs. sham: 7.7 ± 0.8 ml/60 min; n = 8-10), without changing renal responses to hyperosmolality. The results suggest that inhibitory mechanisms dependent on cNTS/A2 neurons reduce water intake and vasopressin-dependent pressor response to an acute increase in plasma osmolality.