Olfactory processing in bipolar disorder, major depression, and anxiety

Kamath, Vidyulata; Paksarian, Diana; Cui, Lihong; Moberg, Paul J.; Turetsky, Bruce I.; Merikangas, Kathleen R.

doi:10.1111/bdi.12625

Cited by 54 publications

(66 citation statements)

References 58 publications

(80 reference statements)

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“…Pathway analysis incorporating all nominally-significant microarray hits (including those with low differential expression) suggested that 667-Coumate may perturb olfactory transduction processes and that this perturbation may mediate drug-induced effects on postpartum maternal behaviour in the mouse; potentially, the increased prevalence of postpartum mood disorder in STS deficient women may be partially attributable to abnormalities within the olfactory system and/or its links to the limbic system. This possibility is feasible in light of the clinical observation that 667-Coumate administration can elicit taste disturbances in female patients [Stanway et al, 2006], and is consistent with an extensive literature on the importance of olfactory (and associated limbic) function in mammalian mothers [Corona and Levy, 2015], with evidence that several steroid sulfates act as ligands within the mouse accessory olfactory system [Meeks et al, 2010], with the expression of multiple olfactory receptors within human brain tissue [Flegel et al, 2013], and with recent findings that olfactory processes are perturbed in a genetic mouse model of abnormal maternal behaviour [Creeth et al, 2018] and multiple mood disorders [Kamath et al, 2018].…”

Section: Discussionsupporting

confidence: 82%

Brain gene expression in a novel mouse model of postpartum mood disorder

Humby

Davies

2019

Preprint

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Introduction: Steroid sulfatase (STS) is an enzyme which cleaves sulfate groups from a variety of steroid hormones, thereby altering their activity and solubility. The expression and activity of STS is increased in female mammalian tissues (including brain) during late pregnancy and into the postpartum period. STS-deficient human and mouse mothers (as a consequence of genetic mutation or acute pharmacological manipulation) show evidence for elevated psychopathology and abnormal behaviour respectively in the postpartum period. In mice, these behavioural effects can be partially normalised through administration of the antipsychotic ziprasidone. Methods:To explore the neurobiology underlying these postpartum behavioural effects, we compared whole brain gene expression by microarray in behaviourally-defined new mouse mothers acutely administered the STS inhibitor 667-Coumate (10mg/kg p.o.) or vehicle solution (n=12 per group); significant changes were followed-up with pathway analysis and quantitative polymerase chain reaction (qPCR). Finally, the effects of combined 667-Coumate and antipsychotic (ziprasidone) administration (0, 0.3 and 1.0mg/kg i.p.) on the brain expression of the most robustly differentially-expressed candidate genes was examined (n≥7 per group). Results: Surprisingly, no significant gene expression changes were detected between vehicle and 667-Coumate-treated brains at a False Discovery Rate (FDR) corrected p<0.1. 1,081 unique expression changes were detected at a less-stringent cut-off of p<0.05, just two top hits were verified by qPCR, and pathway analysis indicated a significant enrichment of genes involved in olfactory transduction (corrected p-value=1.8x10 -3 ). The expression of the two most robust differentially-expressed genes (Stoml3 and Cyp2g1) was not affected by ziprasidone administration. Conclusions:Behavioural abnormalities in new mothers in the postpartum period elicited as a result of STS deficiency are likely to be the culmination of many small gene expression changes. Our data are consistent with the idea that olfactory function is key to postpartum maternal behaviour in mice, and suggest that aberrant expression of olfactory system genes may partially underlie abnormal maternal behaviour in STS-deficient women.

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Section: Discussionsupporting

confidence: 82%

Brain gene expression in a novel mouse model of postpartum mood disorder

Humby

Davies

2019

Preprint

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“…The CSIT made up for the shortage of olfactory evaluation based on the Chinese population. Some experts suggested that the subjects were just the patients with MDD in previous studies, and then reached the conclusion that the lower odor identification performance belongs to these individuals with MDD 33,34 . However, mild or moderate depression do not accompany with olfactory dysfunction 7 .…”

Section: Discussionmentioning

confidence: 99%

Association between olfactory function and inhibition of emotional competing distractors in major depressive disorder

Wang

Jin

Wang

et al. 2020

Sci Rep

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We aimed to investigate the changes of olfaction of major depressive disorder (MDD) before and after medical treatment, and to preliminarily scrutinize the association between the olfactory function and the severity of depressive symptoms, response inhibition, and emotional responding. Forty-eight medicine-naïve MDD patients plus 33 healthy controls (HC) matched on gender, ages, and level of education, were recruited in the test group. The Chinese Smell Identification Test (CSIT), Self-reported Olfactory Scale (SROS), 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), and mean reaction time/accuracy rate (ΔMRt) of emotional Stroop test were measured. The patients were assessed before the treatment (baseline) and 3 months after the treatment (follow-up). The data at the baseline level were measured then associated using multiple linear regression stepwise analysis. The MDD patients had lower scores of the CSIT and SROS and longer ΔMRt at baseline level compared to Hc while the ΔMRt of MDD patients remained longer after 3-month treatment (p's < 0.05). At the baseline level, the regression equation including age and ΔMRt of negative word-color congruent (NEG-C), was finally observed as follows: y(CSIT) = 10.676-0.063 × 1-0.002 × 2, [x 1 = the age(y), x 2 = the NEG-C (ms)]. The olfactory function of MDD appears to be correlated negatively with the age and the ΔMRT of negative stimuli before treatment. After the remission of MDD, the olfactory dysfunction was improved, which might be regarded as a responding phenotype of brain function of MDD rather than the emotional responding. Major depressive disorder (MDD) and olfaction disorder (OD) are both chronic diseases that affect human being's life quality 1. A systematic review on ten studies chosen for using the Sniffin' Sticks Test and the 40-item Smell Identification Test assessed to reveal the relationship between depression and OD. Results show that both of the olfactory threshold, olfactory discrimination, and olfactory identification were influenced by depression 2. Furthermore, symptoms of depression worsen with the severity of olfactory loss 3. It was demonstrated that olfactory bulbectomy, as a well-known method, could induce an animal model of depression in animal experiment 4. In depression-related brain areas including hippocampus, frontal cortex and hypothalamus, the turnover of serotonin and dopamine decreases in the olfactory bulbectomized rats 5. Similarly, in human studies, Cory et al. 6 found that patients with depression have decreased activities in the left medial orbitofrontal cortex (OFC) accompanied with the defect of the olfactory identification. However, Zucco et al. 7 argued that the changes mentioned above occur in patients with the MDD only, not with the mild or moderate depressive disorder. In the neural circuits involved in emotional processing 8 , these key structures such as amygdala, hippocampus, anterior cingulate cortex(ACC) and OFC, are the imperative functional regions of the human olfactory map...

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“…These data are all the more relevant given the small number of studies published to date, and the contradictory results these studies have reported. Nonetheless, the study by Kamath et al warrants further consideration.…”

mentioning

confidence: 92%

“…A recent issue of Bipolar Disorders featured a paper by Kamath et al in which they compared olfactory performance in patients with bipolar disorder, major depression, and anxiety to that in (non‐mood disorder) controls. In this paper, Kamath et al showed that individuals with major depression and bipolar disorder (with psychotic features) had poorer odor identification compared to controls, and that those with major depression demonstrated reduced accuracy in recognizing neutral odors. The authors concluded that alterations in odor identification may exist in mood disorders, particularly in bipolar patients with psychotic features, and that these disturbances are less marked than those reported for schizophrenia in which olfactory dysfunction is more global.…”

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confidence: 99%

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What can we learn about mood disorders from olfactory processes?

Henry

Dargél

2018

Bipolar Disorders

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A recent issue of Bipolar Disorders featured a paper by Kamath et al 1 in which they compared olfactory performance in patients with bipolar disorder, major depression, and anxiety to that in (non-mood disorder) controls. In this paper, Kamath et al 1 showed that individuals with major depression and bipolar disorder (with psychotic features) had poorer odor identification compared to controls, and that those with major depression demonstrated reduced accuracy in recognizing neutral odors. The authors concluded that alterations in odor identification may exist in mood disorders, particularly in bipolar patients with psychotic features, and that these disturbances are less marked than those reported for schizophrenia in which olfactory dysfunction is more global.The study by Kamath et al 1 provides an important contribution to the evidence for olfactory performance in mood disorder patients.These data are all the more relevant given the small number of studies published to date, and the contradictory results these studies F I G U R E 1 The basolateral amygdala (BLA) plays a crucial role in connecting emotional and sensory stimuli to trigger appropriate valence-specific behaviors. There is a specific anatomical connectivity and genetic identity of positive and negative value-coding BLA neurons. R-spondin 2 (Rspo2) neurons encode positive valence and project more specifically to the nucleus accumbens, whereas protein phosphatase 1 regulatory inhibitor subunit 1B (Ppp1r1B) neurons encode particularly negative valence and project to both the central amygdala and ventral hippocampus. In contrast to other sensory information, olfactory input bypasses the thalamus and reaches the amygdala directly [Colour figure can be viewed at wileyonlinelibrary.com]

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Olfactory processing in bipolar disorder, major depression, and anxiety

Abstract: Collectively, these findings indicate that odor identification difficulties may exist in mood disorders, especially when psychotic features are present. In contrast, the global olfactory dysfunction observed in schizophrenia may not be a feature of other neuropsychiatric conditions.

Cited by 54 publications

References 58 publications

Brain gene expression in a novel mouse model of postpartum mood disorder

Brain gene expression in a novel mouse model of postpartum mood disorder

Association between olfactory function and inhibition of emotional competing distractors in major depressive disorder

What can we learn about mood disorders from olfactory processes?

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