Elevated serum chemokine CCL22 levels in first-episode psychosis: associations with symptoms, peripheral immune state and in vivo brain glial cell function

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p < 0.0001; Cohen's d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (rho = 0.20) and disorganization (rho = 0.23), and with worse verbal performance (rho = -0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [C-11]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (V-T) of [C-11]PBR28 was lower in patients compared to controls (p = 0.026; Cohen's d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells

Nest-mate recognition cues are not used during or influenced by mating in the antFormica exsecta

A wide range of mating isolating mechanisms has evolved to avoid mating with close relatives. In mating aggregations that commonly occur in social insects (bees, wasps and ants) sexuals from the same colony can potentially be present, so some type of colony-recognition system would be useful to avoid inbreeding. In the ant Formica exsecta, colony-specific (Z)9-alkene profiles are used by workers to distinguish nest-mates from non-nest-mates, so this information has the potential to be employed in mating behaviour, i.e. to recognise potential mates, avoid inbreeding and indicate mating status. However, in F. exsecta queens, we found no consistent quantitative or qualitative differences in the cuticular hydrocarbon (CHC) profiles between males and queens, or any changes associated with mating in queens. Neither did the (Z)9-alkene recognition profile appear to be acting as a pre-mating barrier, since successful mating occurred across a wide range of CHC profiles. The main pre-mating barrier in F. exsecta appears to be the sequential production of males followed by queens coupled with a long mating period, a strategy adopted by many social insects

Nest-mate recognition cues are not used during or influenced by mating in the antFormica exsecta

A wide range of mating isolating mechanisms has evolved to avoid mating with close relatives. In mating aggregations that commonly occur in social insects (bees, wasps and ants) sexuals from the same colony can potentially be present, so some type of colony-recognition system would be useful to avoid inbreeding. In the ant Formica exsecta, colony-specific (Z)9-alkene profiles are used by workers to distinguish nest-mates from non-nest-mates, so this information has the potential to be employed in mating behaviour, i.e. to recognise potential mates, avoid inbreeding and indicate mating status. However, in F. exsecta queens, we found no consistent quantitative or qualitative differences in the cuticular hydrocarbon (CHC) profiles between males and queens, or any changes associated with mating in queens. Neither did the (Z)9-alkene recognition profile appear to be acting as a pre-mating barrier, since successful mating occurred across a wide range of CHC profiles. The main pre-mating barrier in F. exsecta appears to be the sequential production of males followed by queens coupled with a long mating period, a strategy adopted by many social insects

Mating for convenience or genetic diversity? Mating patterns in the polygynous ant Plagiolepis pygmaea

Several genetic and nongenetic benefits have been proposed to explain multiple mating (polyandry) in animals, to compensate for costs associated with obtaining additional mates. The most prominent hypotheses stress the benefits of increased genetic diversity. In social insects, queens of most species mate only once or have effective mating frequencies close to one. Yet, in a few species of ants, bees, and wasps, polyandry is the rule. In these species, colonies are usually headed by a single queen, whereas multiple queening adds diversity in several of the remaining species, especially in ants. Here we investigated mating frequency, inbreeding and relatedness between the queens and their mates in the polygynous ant Plagiolepis pygmaea, and the effect of polyandry on the genetic diversity as a function of the effective population size of individual colonies. Our results show that polyandry occurs frequently in the species. However, queens are frequently inseminated by close relatives, and additional sires add little genetic diversity among offspring of individual queens. In addition, the increase in diversity at the colony level is only marginal. Hence, contrary to established notions, polyandry in P. pygmaea seems not to be driven by substantial benefits of genetic diversity. Nonetheless, very small or as yet unidentified genetic benefits to one party (males, workers, queens) in conjunction with low costs of mating may favor polyandry. Alternatively, nongenetic factors, such as convenience polyandry, may be more important than genetic factors in promoting polyandry in P. pygmaea. Copyright 2007, Oxford University Press.

Elevated serum chemokine CCL22 levels in first-episode psychosis : associations with symptoms, peripheral immune state and in vivo brain glial cell function

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p <0.0001; Cohen's d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (rho = 0.20) and disorganization (rho = 0.23), and with worse verbal performance (rho = -0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [C-11]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (V-T) of [C-11]PBR28 was lower in patients compared to controls (p = 0.026; Cohen's d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.Peer reviewe

Expression patterns of NKCC1 in neurons and non-neuronal cells during cortico-hippocampal development

The Na-K-2Cl cotransporter NKCC1 is widely expressed in cells within and outside the brain. However, our understanding of its roles in brain functions throughout development, as well as in neuropsychiatric and neurological disorders, has been severely hindered by the lack of reliable data on its developmental and (sub)cellular expression patterns. We provide here the first properly controlled analysis of NKCC1 protein expression in various cell types of the mouse brain using custom-made antibodies and an NKCC1 knock-out validated immunohistochemical procedure, with parallel data based on advanced mRNA approaches. NKCC1 protein and mRNA are expressed at remarkably high levels in oligodendrocytes. In immature neurons, NKCC1 protein was located in the somata, whereas in adult neurons, only NKCC1 mRNA could be clearly detected. NKCC1 immunoreactivity is also seen in microglia, astrocytes, developing pericytes, and in progenitor cells of the dentate gyrus. Finally, a differential expression of NKCC1 splice variants was observed, with NKCC1a predominating in non-neuronal cells and NKCC1b in neurons. Taken together, our data provide a cellular basis for understanding NKCC1 functions in the brain and enable the identification of major limitations and promises in the development of neuron-targeting NKCC1-blockers.Peer reviewe

Inbreeding and kinship in the ant Plagiolepis pygmaea

In ants the presence of multiple reproductive queens (polygyny) decreases the relatedness among workers and the brood they rear, and subsequently dilutes their inclusive fitness benefits from helping. However, adoption of colony daughters, low male dispersal in conjunction with intranidal (within nest) mating and colony reproduction by budding may preserve local genetic differences, and slow down the erosion of relatedness. Reduced dispersal and intranidal mating may, however, also lead to detrimental effects owing to competition and inbreeding. We studied mating and dispersal patterns, and colony kinship in three populations of the polygynous ant Plagiolepis pygmaea using microsatellite markers. We found that the populations were genetically differentiated, but also a considerable degree of genetic structuring within populations. The genetic viscosity within populations can be attributed to few genetically homogeneous colony networks, which presumably have arisen through colony reproduction by budding. Hence, selection may act at different levels, the individuals, the colonies and colony networks. All populations were also significantly inbred (F=0.265) suggesting high frequencies of intranidal mating and low male dispersal. Consequently the mean regression relatedness among workers was significantly higher (r = 0.529-0.546) than would be expected under the typically reported number (5-35) of queens in nests of the species. Furthermore, new queens were mainly recruited from their natal or a neighbouring related colony. Finally, the effective number of queens coincided with that found upon excavation, suggesting low reproductive skew.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe