Biology subjects

Kolobaric, A.

Publications and source records attributed to Kolobaric, A..

4 recordsLinked to original sources

bioRxiv2025

Adolescent girls at familial risk for depression with more advanced adrenarche have altered gut microbiota

ObjectivesRates of adolescent depression are rising, especially among girls, with children of depressed parents facing a three times higher risk. Emerging evidence suggests a link between gut microbiota, neural function, and depression risk, possibly through pathways that involve brain-body interactions, including the vagus nerve. During adolescence, sex-specific changes in the microbiota align with pubertal development, although their connection to depression vulnerability remains unclear. We compared gut microbiota in adolescents at high and low familial risk for depression and explored whether differences are affected by vagal activity and pubertal stage. MethodsWe collected clinical assessments, physiological data, and stool samples from 52 adolescents (aged 9-15, including 31 females), consisting of 27 high-risk and 25 low-risk individuals. We used 16S rRNA marker gene sequencing to analyze the diversity, structure, composition, and predicted function of the microbial community. A laboratory stressor task was employed to examine changes in vagally mediated heart rate variability (stress reactivity). Regressions were used to assess the relationship between depression risk, gut microbiota, and cardiovascular stress reactivity indices. Exploratory analyses investigated the effects of sex, age, and pubertal stage (adrenarche and gonarche). ResultsHigh-risk adolescents exhibited a distinct gut microbiota profile compared to low-risk adolescents, with this effect primarily driven by female participants. This profile was characterized by a higher abundance of Prevotella, which was 2-fold higher in high-risk females, and lower levels of other beneficial genera. High-risk females were also significantly more advanced in adrenarcheal development; the link between depression risk and adrenarcheal development was mediated by gut microbiota in females. Cardiovascular stress reactivity did not differ between groups and was not linked to gut microbiota. ConclusionsOur results reveal sex-specific links between depression risk, adrenarcheal development, and gut microbiota in adolescence. The increase of Prevotella in high-risk females suggests inflammation-related pathways may connect familial vulnerability to mood disorders. Future long-term studies examining hormones, microbiota, and mood during pubertal changes are essential to determine causality and develop targeted treatments.

neuroscience↗

bioRxiv2025

Ketamine Alters Tuning of Neural and Behavioral Spatial Working Memory Precision

Deficits in working memory (WM) are a hallmark of neuropsy-chiatric disorders such as schizophrenia, yet their neurobiological basis remains poorly understood. Glutamate N-methyl-D-aspartate receptors (NMDARs) are critical for spatial WM (sWM), with NMDAR antagonist ketamine known to attenuate task-evoked activation and reduce sWM accuracy. Cortical microcircuit models hypothesize that NMDAR antagonism impairs sWM by broadening neural spatial tuning, but this mechanism has not been directly tested in humans. Using a pharmacological fMRI approach, we showed how ketamine broadened neural spatial tuning, attenuated activation across visual, parietal, and frontal areas, and worsened sWM performance in healthy humans. Ketamine-induced changes in tuning were more consistent across individuals and brain regions than changes in overall activation and correlated with individual differences in sWM performance. These findings provide empirical evidence linking NMDAR antagonism to disruptions in cortical microcircuit dynamics, the resulting neural tuning alterations, and sWM impairments, advancing frameworks for therapeutic development.

neuroscience↗

bioRxiv2024

The microbiota extends the reproductive lifespan by safeguarding the ovarian reserve

Infertility is a devastating condition affecting one in six people globally. In many cases, the underlying causes are unknown. Emerging evidence suggests that the microbiota influences reproduction, yet the mechanistic link between the microbiota, ovarian function, and length of the fertile lifespan remain unexplored. Here we report that the microbiota controls the length of the reproductive lifespan by maintaining the primordial follicle pool, a process mediated by microbiota-derived short chain fatty acids modulating gene regulatory networks crucial for the survival of the ovarian reserve. Dietary perturbation of the microbiota during a critical developmental window is sufficient to diminish the ovarian reserve, reduce oocyte retrieval, and impair preimplantation embryo viability, mirroring challenges in human fertility treatments. Targeted interventions to restore microbiota improve assisted reproductive outcomes, particularly when implemented early. These findings reveal a novel contribution of host-microbe interactions in mammalian reproduction and demonstrate that the microbiota impacts ovarian function and fertility.

developmental biology↗

bioRxiv2022

Ketamine induces multiple individually distinct whole-brain functional connectivity signatures

BackgroundKetamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamines molecular mechanisms connect to its neural and behavioral effects. MethodsWe conducted a double-blind placebo-controlled study in which 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hour). We quantified resting-state functional connectivity via data-driven global brain connectivity, related it to individual ketamine-induced symptom variation, and compared it to cortical gene expression targets. ResultsWe found that: i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; ii) ketamines data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, implicating the role of SST and PVALB interneurons in ketamines acute effects; and iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level. ConclusionsCollectively, these findings support the possibility for developing individually precise pharmacological biomarkers for treatment selection in psychiatry. FundingThis study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1-190420); Swiss Neuromatrix Foundation (Grant No. 2016-0111m Grant No. 2015 - 010); Swiss National Science Foundation under the frame-work of Neuron Cofund (Grant No. 01EW1908), Usona Institute (2015 - 2056).

neuroscience↗