Olfactory sulcus morphology in patients with current and past major depression
Introduction
Several lines of evidence have suggested that olfactory function is involved in emotional regulation, with common underlying neural substrates (Soudry et al., 2011, Takahashi et al., 2015). Although not consistently, patients with major depressive disorder (MDD) have been reported to have olfactory deficits, especially for olfactory sensitivity (reviewed by Burón and Bulbena, 2013, Kohli et al., 2016, Schablitzky and Pause, 2014), which are associated with the severity of depressive symptoms and at least partly persist even after the clinical improvement (Naudin et al., 2012). These previous findings implicate a role for the olfactory system in the pathogenesis of depression (Yuan and Slotnick, 2014).
The depth of the olfactory sulcus, which appears in the fetal forebrain at around 16 weeks gestation (Chi et al., 1977), relates to olfactory function in healthy subjects and is usually deeper on the right hemisphere in association with functional lateralization in the olfactory system (Hummel et al., 2003). Regarding psychiatric disorders, an abnormally shallow olfactory sulcus has been reported in schizophrenia (Takahashi et al., 2013, Turetsky et al., 2009), supporting the notion that olfactory dysfunction may represent a marker of early neurodevelopmental abnormalities related to vulnerability to psychosis (Brewer et al., 2001, Brewer et al., 2003, Kamath et al., 2014). On the other hand, several magnetic resonance imaging (MRI) studies in MDD have provided evidence for trait- and vulnerability-related alterations in volume (Lorenzetti et al., 2009b, 2010; Opel et al., 2016, Takahashi et al., 2010) or surface morphology (Peng et al., 2015) of limbic and cortical structures, suggesting neurodevelopmental pathology in depressive disorders (Ansorge et al., 2007). Interestingly, Zhang et al. (2009) found decreased cortical gyrification in MDD, which may reflect neural underdevelopment during gestation, predominantly in the olfactory system structures (i.e., cingulate, insula, and orbitofrontal regions). Also, Negoias et al., 2010, Negoias et al., 2016 have reported that reduced volume of the olfactory bulb (OB), which is the first relay in the olfactory system and has strong projections into amygdala and other olfactory structures (Soudry et al., 2011), is related to olfactory sensitivity and symptom severity of depression. However, it remains largely unknown whether MDD patients exhibit morphologic changes of the olfactory sulcus.
This MRI study investigated the length and depth of the olfactory sulcus in current depressed patients (cMDD), individuals with a history of major depression but who are currently in remission (rMDD), and healthy comparison subjects. This approach enabled us to examine whether abnormalities of the olfactory sulcus in MDD, if present, reflect state or trait markers of the disorder. On the basis of enduring olfactory deficits in MDD patients observed during episodes and after remission (Naudin et al., 2012), as well as the potential role of olfactory sulcus depth as a neurodevelopmental marker, we predicted that both cMDD and rMDD patients would have shallower olfactory sulci compared with controls, representing a trait-related feature of MDD. We also examined the influence of severity of depressive symptoms and subtypes of depression (e.g., co-morbid anxiety disorder, melancholic versus non-melancholic) on olfactory sulcus morphology in the MDD patients.
Section snippets
Subjects
Eighty-nine subjects were recruited in the study, of which 29 received a current diagnosis of major depressive disorder (cMDD), 27 were currently medically and psychiatrically well individuals with a previous history of major depressive disorder (rMDD), and 33 were healthy controls (Table 1). Seven rMDD patients had a total Beck Depression Inventory (BDI; Beck and Steer, 1987) score >18, but did not fulfill the criteria of MDD by the Structured Clinical Interview for DSM-IV (SCID-IV-TR; First
Demographic and clinical data
Comparison of the groups revealed no significant differences in age, gender, and intelligence but, as expected, measures of depressive and anxiety symptoms were significantly different between groups (Table 1). The cMDD patients, as compared to rMDD patients, had an earlier age of onset, a higher proportion of participants on medication in the previous 6 months, and a higher rate of co-morbid anxiety disorder.
Depth and length of the olfactory sulcus
ANCOVA and post-hoc analyses showed that both cMDD and rMDD patients had significantly
Discussion
To our knowledge, this is the first MRI study to report morphologic changes of the olfactory sulcus in MDD patients. In this study, both current and remitted MDD patients had significantly shallower olfactory sulci as compared with healthy controls. The right sulcus depth was negatively correlated with number of depressive episodes in the depressed patients, which may reflect vulnerability to relapse, and with degree of residual depressive symptoms in the remitted patients. These findings
Contributors
In this work, Drs. Yücel and Allen conceived the idea and methodology of the study. Dr. Nishikawa and Lorenzetti managed the literature searches and analyses. Drs. Takahashi, Nishikawa, and Sasabayashi analyzed MRI data. Dr. Takahashi undertook the statistical analysis and wrote the first draft of the manuscript. Drs. Yücel, Suzuki, Walterfang, Whittle, Allen and Pantelis provided supervision on interpretation of data and contributed in revising the manuscript. All authors contributed to and
Conflict of interest
None.
Acknowledgements
This research was supported in part by Grants-in-Aid for Scientific Research (C) (No. 26461739) and Grants-in-Aid for Scientific Research (B) (No. 24390281) from the Japanese Society for the Promotion of Science, and Health and Labour Sciences Research Grants for Comprehensive Research on Persons with Disabilities from Japan Agency for Medical Research and Development (AMED). MY was supported by a National Health and Medical Research Council of Australia (NHMRC) Fellowship (#APP1021973). SW was
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