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- Sodergren, Erica, et al.
(author)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Journal article (peer-reviewed)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 2. |
- Henje Blom, Eva, 1962-, et al.
(author)
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Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.
- 2015
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 5
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Journal article (peer-reviewed)abstract
- Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.
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| 4. |
- Lindqvist, Daniel, et al.
(author)
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Oxidative stress, inflammation and treatment response in major depression
- 2016
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In: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 76, s. 197-205
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Increased inflammation and oxidative stress have been shown in Major Depressive Disorder (MDD), although there is significant heterogeneity across studies. Whether markers of inflammation and oxidative stress are associated with antidepressant treatment response in MDD is currently unclear. The goals of the present study are to investigate markers of inflammation and oxidative stress in unmedicated MDD subjects and controls and test the relationship between these markers and antidepressant response in MDD subjects.METHODS: Interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein, F2-isoprostanes, 8-OH 2-deoxyguanosine (8-OHdG), glutathione peroxidase, glutathione, and vitamin C were quantified in blood samples from 50 unmedicated MDD subjects and 55 healthy controls. Depression symptom severity was rated with the 17-item Hamilton Depression Rating Scale (HDRS). All subjects were somatically healthy and free from medications that could interfere with inflammation and oxidative stress markers. A subgroup of 22 MDD subjects underwent open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment for eight weeks, after which blood sampling and the HDRS were repeated. Antidepressant treatment "response" was defined as ≥50% decrease in HDRS ratings over 8 weeks of treatment.RESULTS: After controlling for the effects of age, sex, body mass index and smoking, MDD subjects had significantly higher levels of IL-6 (p<0.001), TNF-α (p<0.001), 8-OHdG (p=0.018), and F2-isoprostanes (p=0.012). Compared to Responders, Non-responders to SSRI antidepressant treatment had higher levels of F2-isoprostanes at baseline (p=0.006), and after eight weeks of treatment (p=0.031). Non-responders showed a significant increase in 8-OHdG over the course of treatment (p=0.021), whereas Responders showed a significant decrease in IL-6 over the course of treatment (p=0.019).CONCLUSION: Our results are in line with previous reports of increased levels of markers of inflammation and oxidative stress in MDD. Moreover, poorer antidepressant treatment response was related to higher baseline levels of the major oxidative stress marker, F2-isoprostanes, in vivo. Further, antidepressant response was associated with changes in oxidative (8-OHdG) and inflammatory (IL-6) markers.
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| 7. |
- Steenkamp, Lisa R., et al.
(author)
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Severity of anxiety– but not depression– is associated with oxidative stress in Major Depressive Disorder
- 2017
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In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327. ; 219, s. 193-200
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Journal article (peer-reviewed)abstract
- Background Oxidative stress is implicated in both depression and anxiety, but it is currently unclear whether this relates to syndromal diagnoses or trans-diagnostic dimensional symptoms. We examined the relationship between oxidative stress and severity of depression and anxiety symptoms in individuals with Major Depressive Disorder (MDD). Methods Plasma oxidative stress markers F2-isoprostanes and oxidized glutathione (GSSG), and the antioxidant reduced glutathione (GSH), were assessed in 69 physically healthy, medication-free MDD subjects. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety (HAM-A) and Hamilton Depression (HAM-D) Rating Scales. Total HAM-A and HAM-D scores, along with “core” anxiety and depression subscales, and individual HAM-D items “psychic anxiety” and “depressed mood,” were related to oxidative stress markers. Analyses controlled for age, sex, BMI, and smoking. Results Total HAM-A ratings were positively associated with F2-isoprostanes (β=.26, p=.042) and GSSG (β=.25, p=.049), but not GSH (β=.05, p=.711). Core anxiety severity was positively associated with F2-isoprostanes (β=.34, p=.012) and GSSG, although this did not reach significance (β=.24, p=.074). None of the biological markers were significantly associated with total HAM-D or core depression ratings (all p>.13). Subjects scoring high on “psychic anxiety” had elevated F2-isoprostanes (p=.030) and GSSG (p=.020). This was not seen with “depressed mood” scores (all p>.12). Limitations We assessed peripheral oxidative markers, but their relationship to the brain is unclear. Conclusions Oxidative stress is more closely related to anxiety than depression symptoms in MDD. This highlights the importance of relating oxidative stress to specific symptoms and could provide new insights into the biological correlates of affective disorders.
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| 8. |
- Hough, Christina M., et al.
(author)
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Pre-treatment allostatic load and metabolic dysregulation predict SSRI response in major depressive disorder : A preliminary report
- 2021
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In: Psychological Medicine. - 0033-2917. ; 51:12, s. 125-2117
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Journal article (peer-reviewed)abstract
- BackgroundMajor depressive disorder (MDD) is associated with increased allostatic load (AL; a measure of physiological costs of repeated/chronic stress-responding) and metabolic dysregulation (MetD; a measure of metabolic health and precursor to many medical illnesses). Though AL and MetD are associated with poor somatic health outcomes, little is known regarding their relationship with antidepressant-treatment outcomes.MethodsWe determined pre-treatment AL and MetD in 67 healthy controls and 34 unmedicated, medically healthy MDD subjects. Following this, MDD subjects completed 8-weeks of open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment and were categorized as 'Responders' (≥50% improvement in depression severity ratings) or 'Non-responders' (<50% improvement). Logistic and linear regressions were performed to determine if pre-treatment AL or MetD scores predicted SSRI-response. Secondary analyses examined cross-sectional differences between MDD and control groups.ResultsPre-treatment AL and MetD scores significantly predicted continuous antidepressant response (i.e. absolute decreases in depression severity ratings) (p = 0.012 and 0.014, respectively), as well as post-treatment status as a Responder or Non-responder (p = 0.022 and 0.040, respectively), such that higher pre-treatment AL and MetD were associated with poorer SSRI-treatment outcomes. Pre-treatment AL and MetD of Responders were similar to Controls, while those of Non-responders were significantly higher than both Responders (p = 0.025 and 0.033, respectively) and Controls (p = 0.039 and 0.001, respectively).ConclusionsThese preliminary findings suggest that indices of metabolic and hypothalamic-pituitary-adrenal-axis dysregulation are associated with poorer SSRI-treatment response. To our knowledge, this is the first study to demonstrate that these markers of medical disease risk also predict poorer antidepressant outcomes.
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| 9. |
- Lindqvist, Daniel, et al.
(author)
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Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging.
- 2015
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In: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634. ; 55:May 18, s. 333-364
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Research review (peer-reviewed)abstract
- Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets.
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