Blood Transcriptomic Markers in Patients with Late-Onset Major Depressive Disorder

Abstract

We investigated transcriptomic markers of late-onset major depressive disorder (LOD; onset age of first depressive episode ≥ 50 years) from the genes expressed in blood cells and identified state-dependent transcriptomic markers in these patients. We assessed the genes expressed in blood cells by microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD. To select potential candidates from those probes, we assessed the genes expressed in the blood of an animal model of depression, ovariectomized female mice exposed to chronic ultra-mild stress, by microarray and cross-matched the differentially expressed genes between the patients and the model mice. We identified 14 differentially expressed genes that were similarly changed in both patients and the model mice. By assessing statistical significance using real-time quantitative PCR (RT-qPCR), the following 4 genes were selected as candidates: cell death-inducing DFFA-like effector c (CIDEC), ribonuclease 1 (RNASE1), solute carrier family 36 member-1 (SLC36A1), and serine/threonine/tyrosine interacting-like 1 (STYXL1). The discriminating ability of these 4 candidate genes was evaluated in an independent cohort that was validated. Among them, CIDEC showed the greatest discriminant validity (sensitivity 91.3% and specificity 87.5%). Thus, these 4 biomarkers should be helpful for properly diagnosing LOD.

Gene expression alterations in the medial prefrontal cortex and blood cells in a mouse model of depression during menopause

“…In preclinical studies, female rodents with bilateral ovariectomies (OVXs) are frequently used as a model of menopause in women (Cho et al, 2004; Liu et al, 2004). In addition, previous reports, including ours, suggested that OVX rodents are vulnerable to stress and exhibit behavioral abnormalities similar to animal models of depression when subjected to chronic mild stress (CMS) (Lagunas et al, 2010; Miyata et al, 2016; Nakagawasai et al, 2009). Therefore, OVX rodents subjected to CMS are likely a reasonable animal model of depression during menopause.…”

“…It has been reported that the expression levels of genes associated with protein biosynthesis and energy production are altered in the prefrontal cortex of the post-mortem brains of MDD patients (Klempan et al, 2009; Sibille et al, 2004). It has also been reported that OVX induces vulnerability to stress in female rodents (Lagunas et al, 2010; Miyata et al, 2016; Nakagawasai et al, 2009). Therefore, the dysregulated pathways associated with protein biosynthesis and energy production that were observed in the mPFC in the mice in the current study may be associated with the development of stress vulnerability.…”

“…We have previously reported that OVX mice subjected to the current CMS protocol show abnormalities in emotional behavior, including a prolonged duration of immobility in forced swimming tests, a decreased amount of time spent in the center of the field during open-field tests, and a decreased time duration in the open arms in elevated plus-maze tests without a change in locomotor activity (Miyata et al, 2016). In this study, we re-analyzed the same dataset and mice.…”

“…The mice were exposed to CMS for 6 weeks in accordance with our previous report (Miyata et al, 2016). Three stressors were used in this study (Table 1).…”

Novel One-Tube-One-Step Real-Time Methodology for Rapid Transcriptomic Biomarker Detection: Signal Amplification by Ternary Initiation Complexes

“…We demonstrated the utility of the SATIC methodology for the detection of transcriptomic biomarkers 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 using the 40-mer-and 39-mer-length folding parts 50 of the RNA transcripts of the genes encoding the cell death-inducing DNA fragmentation factor-α (DFFA)-like effector C (CIDEC) 51 and adenosine diphosphate (ADP)-ribosylation factor related protein 1 (ARFRP), 52 i.e., CidR and ArfR, as target and nontarget RNAs, respectively ( Figure S11). Owing to the high G4-selective emission of ThT-HE, the positivity could clearly be recorded and displayed even with a general-purpose digital camera and without using fluorescence imaging systems with software programs for coloring and/or adjustment of the range of the fluorescence scale.…”