A Pilot Study of Neuroplasticity Based Cognitive Remediation in Early Onset Psychosis

Introduction – Neuroplasticity based auditory and visual training programs appear to improve neurocognitive function in adults with schizophrenia, but use in younger individuals has not been determined. We hypothesized that adolescents might play more often and respond better than adults to training using a game-like laptop in their home environment. Methods -- Youth 10-19 years with Early Onset Psychosis (EOP) were provided a laptop and randomly assigned to play games to enhance basic auditory, visual and social processing neuroplasticity games (NPG) or assigned to control games with cognitive components, such as Sudoku or hangman or (CG). All received neurocognitive assessments at baseline, intervention completion and 4 months post treatment. Results — 12 youth (15.5 +3.2 yrs) were assigned to NPG and 10 participants (16.2 +2.1 years) were assigned to CG. More NPG than CG participants completed the prescribed hours of game play (block 1 - 92% vs. 70% over the first 40 hours), with both groups engaged less over time. Although most neurocognitive functions did not change, the NPG group did show improvements in WRAML Visual Learning, WISC Digit Span Forward, Spatial Span Backwards and CPT omission errors. Surprisingly, satisfaction was lower for NPG than CG. Conclusions — Groups were well matched for baseline illness characteristics. On the global measures of cognition, both EOP groups showed improvement over time but those improvements were generally greater in the CG than in the NPG group, with potentially significant differences favoring the CG evident in the neurocognitive composite score (p=0.072) and BRIEF metacognition (p=.117). Youth did not play as frequently or as long as requested despite providing a laptop for their home use and stipends for playing

Interactions between Bifidobacterium and Bacteroides and human milk oligosaccharides and their associations with infant cognition

While ample research on independent associations between infant cognition and gut microbiota composition and human milk (HM) oligosaccharides (HMOs) has been reported, studies on how the interactions between gut microbiota and HMOs may yield associations with cognitive development in infancy are lacking. We aimed to determine how HMOs and species of Bacteroides and Bifidobacterium genera interact with each other and their associations with cognitive development in typically developing infants. A total of 105 mother-infant dyads were included in this study. The enrolled infants [2.9–12 months old (8.09 ± 2.48)] were at least predominantly breastfed at 4 months old. A total of 170 HM samples from the mothers and fecal samples of the children were collected longitudinally. Using the Mullen Scales of Early Learning to assess cognition and the scores as the outcomes, linear mixed effects models including both the levels of eight HMOs and relative abundance of Bacteroides and Bifidobacterium species as main associations and their interactions were employed with adjusting covariates; infant sex, delivery mode, maternal education, site, and batch effects of HMOs. Additionally, regression models stratifying infants based on the A-tetrasaccharide (A-tetra) status of the HM they received were also employed to determine if the associations depend on the A-tetra status. With Bacteroides species, we observed significant associations with motor functions, while Bif. catenulatum showed a negative association with visual reception in the detectable A-tetra group both as main effect (value of p = 0.012) and in interaction with LNFP-I (value of p = 0.007). Additionally, 3-FL showed a positive association with gross motor (p = 0.027) and visual reception (p = 0.041). Furthermore, significant associations were observed with the interaction terms mainly in the undetectable A-tetra group. Specifically, we observed negative associations for Bifidobacterium species and LNT [breve (p = 0.011) and longum (p = 0.022)], and positive associations for expressive language with 3′-SL and Bif. bifidum (p = 0.01), 6′-SL and B. fragilis (p = 0.019), and LNFP-I and Bif. kashiwanohense (p = 0.048), respectively. Our findings suggest that gut microbiota and HMOs are both independently and interactively associated with early cognitive development. In particular, the diverse interactions between HMOs and Bacteroides and Bifidobacterium species reveal different candidate pathways through which HMOs, Bifidobacterium and Bacteroides species potentially interact to impact cognitive development in infancy

Joint analyses of human milk fatty acids, phospholipids, and choline in association with cognition and temperament traits during the first 6 months of life

Early dietary exposure via human milk nutrients offers a window of opportunity to support cognitive and temperament development. While several studies have focused on associations of few pre-selected human milk nutrients with cognition and temperament, it is highly plausible that human milk nutrients synergistically and jointly support cognitive and behavioral development in early life. We aimed to discern the combined associations of three major classes of human milk nutrients with cognition and temperament during the first 6 months of life when human milk is the primary source of an infant’s nutrition and explore whether there were persistent effects up to 18 months old. The Mullen Scales of Early Learning and Infant Behavior Questionnaires—Revised were used to assess cognition and temperament, respectively, of 54 exclusively/predominantly breastfed infants in the first 6 months of life, whose follow-ups were conducted at 6–9, 9–12, and 12–18 months old. Human milk samples were obtained from the mothers of the participants at less than 6 months of age and analyzed for fatty acids [total monounsaturated fatty acids, polyunsaturated fatty acid, total saturated fatty acid (TSFA), arachidonic acid (ARA), docosahexaenoic acid (DHA), ARA/DHA, omega-6/omega-3 polyunsaturated fatty acids ratio (n-6/n-3)], phospholipids [phosphatidylcholine, phosphatidylethanolamine (PE), phosphatidylinositol (PI), sphingomyelin], and choline [free choline, phosphocholine (PCho), glycerophosphocholine]. Feature selection was performed to select nutrients associated with cognition and temperament. The combined effects of selected nutrients were analyzed using multiple regression. A positive association between the arachidonic acid (ARA) and surgency was observed (p = 0.024). A significant effect of DHA, n-6/n-3, PE, and TSFA concentrations on receptive language (R2 = 0.39, p = 0.025) and the elevated ARA, PCho, and PI with increased surgency (R2 = 0.43, p = 0.003) was identified, suggesting that DHA and ARA may have distinct roles for temperament and language functions. Furthermore, the exploratory association analyses suggest that the effects of human milk nutrients on R.L. and surgency may persist beyond the first 6 months of life, particularly surgency at 12–18 months (p = 0.002). Our study highlighted that various human milk nutrients work together to support the development of cognition and temperament traits during early infancy

Plant extracts as natural photosensitizers in photodynamic therapy: in vitro activity against human mammary adenocarcinoma MCF-7 cells

Objective: To examine three plant extracts [Lumnitzera racemosa (Combretaceae) (L. racemosa), Albizia procera (Fabaceae) (A. procera) and Cananga odorata (Annonaceae)] for their potential as source of photosensitizers in photodynamic therapy. Methods: Human mammary adenocarcinoma (MCF-7) cells were treated with the plant extracts, which were irradiated with 5.53 mW and 0.553 mW broadband light. Cell viability was assessed using MTT assay and induction of apoptosis was determined using terminal deoxynucleotidyl transferase-dUTP nick end labeling assay. Results: The crude ethanolic extracts, independently, were nontoxic against cancer and non-cancer cells but when irradiated with 5.53 mW broadband light, L. racemosa and A. procera extracts were cytotoxic against MCF-7 with IC50 of 11.63 μg/mL and 10.73 μg/mL, respectively. With 0.553 mW broadband light, the IC50 values were higher at 17.14 μg/mL and 19.59 μg/mL, respectively. Photoactivated L. racemosa and A. procera extracts were found to be more cytotoxic against MCF-7 than the non-cancer cell line, human dermal fibroblast-neonatal. Moreover, the cytotoxicity of the extracts was mediated by apoptosis. Conclusions: Two of the plant extracts used, L. racemosa and A. procera were toxic and induced apoptosis to mammary cell adenocarcinoma, MCF-7 when photoactivated. These extracts were also more toxic to human cancer than non-cancer cell lines