Pro- and anti-inflammatory cytokine associations with major depression in cancer patients.

OBJECTIVE: Cytokines may be linked to depression, although it has been challenging to demonstrate this association in cancer because of the overlap between depressive symptoms and other sickness behaviors. This study investigates the relationship between cytokines and depression in cancer patients, accounting for confounding clinical and methodological factors. METHODS: The GRID Hamilton Rating Scale for Depression and Neurotoxicity Rating Scale (NRS) for cytokine-induced sickness behaviors were administered to 61 cancer patients and 38 healthy controls. The cancer group was of mixed type and largely of late stage, with a recruitment rate of 35% and completion rate of 47%. Major depression was diagnosed in 19 of 61 (31%) cancer patients. Multiplexed cytokine assays for inflammatory and anti-inflammatory cytokines were conducted in plasma samples using electrochemiluminescence. RESULTS: All cancer patients had high NRS scores and elevated levels of most cytokines. Cancer patients with major depression had higher NRS scores than those without major depression. IL-1rα was positively associated with the GRID scores of depressive symptoms (regression coefficient, 3.52 ± 1.18; P = .004), but not with major depression. Major depression was negatively associated with the anti-inflammatory cytokine IL-4 (regression coefficient, -0.65 ± 0.26; P = .013), but not with IL-1rα. CONCLUSIONS: Depressive symptoms in cancer patients may represent sickness behaviors, which may have distinct cytokine associations from major depression. Sickness behaviors may be associated with an increase in inflammatory cytokines, whereas major depression may be induced by a failure to adequately resolve inflammation. Our findings suggest that cytokine-mediated interventions may be of value to treat depression in this population.

Multi-marker DNA metabarcoding detects suites of environmental gradients from an urban harbour.

There is increasing need for biodiversity monitoring, especially in places where potential anthropogenic disturbance may significantly impact ecosystem health. We employed a combination of traditional morphological and bulk macroinvertebrate metabarcoding analyses to benthic samples collected from Toronto Harbour (Ontario, Canada) to compare taxonomic and functional diversity of macroinvertebrates and their responses to environmental gradients. At the species rank, sites assessed using COI metabarcoding showed more variation than sites assessed using morphological methods. Depending on the assessment method, we detected gradients in magnesium (morphological taxa), ammonia (morphological taxa, COI sequence variants), pH (18S sequence variants) as well as gradients in contaminants such as metals (COI & 18S sequence variants) and organochlorines (COI sequence variants). Observed responses to contaminants such as aromatic hydrocarbons and metals align with known patchy distributions in harbour sediments. We determined that the morphological approach may limit the detection of macroinvertebrate responses to lake environmental conditions due to the effort needed to obtain fine level taxonomic assignments necessary to investigate responses. DNA metabarcoding, however, need not be limited to macroinvertebrates, can be automated, and taxonomic assignments are associated with a certain level of accuracy from sequence variants to named taxonomic groups. The capacity to detect change using a scalable approach such as metabarcoding is critical for addressing challenges associated with biodiversity monitoring and ecological investigations.

Positive relationships between genetic diversity and abundance in fishes.

Molecular markers, such as mitochondrial DNA and microsatellite loci, are widely studied to assess population genetics and phylogeography; however, the selective neutrality of these markers is increasingly being questioned. Given the importance of molecular markers in fisheries science and conservation, we evaluated the neutrality of both mtDNA and microsatellite loci through their associations with population size. We surveyed mtDNA and microsatellite data from the primary literature and determined whether genetic diversity increased with abundance across a total of 105 marine and freshwater fishes, with both global fisheries catch data and body size as proxies for abundance (with an additional 57 species for which only body size data were assessed). We found that microsatellite data generally yielded higher associations with abundance than mtDNA data, and within mtDNA analyses, number of haplotypes and haplotype diversity were more strongly associated with abundance than nucleotide diversity, particularly for freshwater fishes. We compared genetic diversity between freshwater and marine fishes and found that marine fishes had higher values of all measures of genetic diversity than freshwater fishes. Results for both mtDNA and microsatellites generally conformed to neutral expectations, although weaker relationships were often found between mtDNA nucleotide diversity and 'abundance' compared to any other genetic statistic. We speculate that this is because of historical events unrelated to natural selection, although a role for selection cannot be ruled out.

Historical influences dominate the population genetic structure of a sedentary marine fish, Atlantic wolffish (Anarhichas lupus), across the North Atlantic Ocean.

Genetic variation was assessed in Atlantic wolffish, Anarhichas lupus, across the North Atlantic Ocean using microsatellite and amplified fragment length polymorphism (AFLP) markers. Despite unusual life history attributes such as large benthic eggs, large larvae, a limited pelagic stage and relatively sedentary adults, which suggest potential for strong population structure, range-wide FST values were comparable to other marine fishes (≤0.035). Nevertheless, both significant genetic differentiation among regions and isolation by distance were observed, suggesting limited dispersal in this species. AFLP loci, evaluated on a subset of samples, revealed slightly higher FST values, but similar patterns of differentiation and isolation-by-distance estimates, compared to microsatellites. The genetic structure of Atlantic wolffish has likely been shaped by its post-glacial history of recolonization, North Atlantic current patterns and continuity of habitat on continental shelves.

Phylogeography of 3 North Atlantic Wolffish species (Anarhichas spp.) with phylogenetic relationships within the family Anarhichadidae.

Phylogenetic analyses of all 4 wolffish species (Atlantic, Spotted, Northern, and Bering wolffishes) and the Wolfeel were assessed with both mitochondrial (D-loop and ND1) and nuclear (amplified fragment length polymorphism) DNA to resolve relationships within the family Anarhichadidae. Species-specific mitochondrial DNA (mtDNA) mutation rates were estimated based on 2 possible dates of divergence between the Pacific and Atlantic lineages. Phylogeographic patterns within each of the 3 North Atlantic wolffishes were investigated with Markov chain Monte Carlo simulations based on mtDNA to determine whether population size changes occurred following the last glaciation and where wolffishes likely survived glaciation. All 3 species of North Atlantic wolffishes showed evidence of postglacial expansion but did not show evidence of persistence in multiple refugia in both the eastern and western Atlantic Ocean. Rather, the data supported persistence in a single refuge, with postglacial expansion into the rest of the range. Nucleotide diversity, in particular, was low in wolffishes compared with other marine fishes, possibly related to reductions in population sizes during the last glaciation.

Nonesterified Fatty Acids and Depression in Cancer Patients and Caregivers.

BACKGROUND: Nonesterified fatty acids (NEFAs) are known to have inflammatory effects. The inflammatory hypothesis of depression suggests that omega-3 (ω-3) and omega-6 (ω-6) fatty acids might be negatively and positively correlated with depression, respectively. OBJECTIVE: An exploratory study was conducted to determine the association between dietary free fatty acids and depressive symptoms in cancer patients and caregivers. METHODS: Associations between depression and the NEFA pool were investigated in 56 cancer patients and 23 caregivers using a combination of nonparametric tests and regularized regression. Plasma NEFAs were measured using thin layer and gas chromatography with flame ionization detection. Depression was characterized both as a continuous severity score using the GRID-Hamilton Depression Rating Scale (GRID Ham-D), and as a categorical diagnosis of major depression by structured clinical interview. RESULTS: Initial hypotheses regarding the relation between depression and omega-3 or omega-6 fatty acids were not well supported. However, elaidic acid, a trans-unsaturated fatty acid found in hydrogenated vegetable oils, was found to be negatively correlated with continuous depression scores in cancer patients. No significant associations were found in caregivers. CONCLUSIONS: An unexpected negative association between elaidic acid and depression was identified, supporting recent literature on the role of G protein-coupled receptors in depression. Further research is needed to confirm this result and to evaluate the potential role of G protein agonists as therapeutic agents for depression in cancer patients.

Cytokines and depression in cancer patients and caregivers.

OBJECTIVE: A better understanding of the biobehavioral mechanisms underlying depression in cancer is required to translate biomarker findings into clinical interventions. We tested for associations between cytokines and the somatic and psychological symptoms of depression in cancer patients and their healthy caregivers. PATIENTS AND METHODS: The GRID Hamilton Rating Scale for Depression (Ham-D) was administered to 61 cancer patients of mixed type and stage, 26 primary caregivers and 38 healthy controls. Concurrently, blood was drawn for multiplexed plasma assays of 15 cytokines. Multiple linear regression, adjusted for biobehavioral variables, identified cytokine associations with the psychological (Ham-Dep) and somatic (Ham-Som) subfactors of the Ham-D. RESULTS: The Ham-Dep scores of cancer patients were similar to their caregivers, but their Ham-Som scores were significantly higher (twofold, p=0.016). Ham-Som was positively associated with IL-1ra (coefficient: 1.27, p≤0.001) in cancer patients, and negatively associated with IL-2 (coefficient: -0.68, p=0.018) in caregivers. Ham-Dep was negatively associated with IL-4 (coefficient: -0.67, p=0.004) in cancer patients and negatively associated with IL-17 (coefficient: -1.81, p=0.002) in caregivers. CONCLUSION: The differential severity of somatic symptoms of depression in cancer patients and caregivers and the unique cytokine associations identified with each group suggests the potential for targeted interventions based on phenomenology and biology. The clinical implication is that depressive symptoms in cancer patients can arise from biological stressors, which is an important message to help destigmatize the development of depression in cancer patients.