Prenatal alcohol exposure results in a broad range of neuropsychological and behavioral impairments. Considering the long-lasting problems associated with fetal alcohol spectrum disorders (FASD), the development of effective treatment programs is critical. Choline, an essential nutrient, is important for healthy fetal brain development, and preclinical studies have demonstrated that choline supplementation can attenuate the severity of alcohol- related cognitive impairments. Given this evidence, this project aimed to translate preclinical findings to a clinical population to investigate if choline supplementation can ameliorate the severity of memory, executive function, and attention deficits in children with FASD. The current study was a randomized, double- blind, placebo-controlled clinical trial that explored the effectiveness of a choline intervention for children with FASD ages 5-10 years. Fifty-five children with confirmed histories of heavy prenatal alcohol exposure were randomly assigned to either the choline (n = 29) or placebo (n = 26) treatment arms. Participants in the choline group received 625 mg choline daily for 6 weeks, whereas those in the placebo group received an equivalent dose of an inactive placebo treatment. Primary outcomes were assessed at baseline and post-intervention, including performance on neuropsychological measures of memory, executive function, and attention/hyperactivity. Results indicated that participants in the choline group did not differentially improve in cognitive performance in any domain, relative to the placebo group. Dietary choline intake was a marginally significant predictor of memory performance at post-assessment, suggesting a trend towards better memory performance in participants with higher levels of dietary choline intake. Overall, the findings of the present study do not support that choline, administered at a dose of 625 mg/day for 6 weeks, is an effective intervention for children with FASD. However, this study is only one of the first to translate preclinical findings to a human clinical trial of choline supplementation in FASD. Additional studies are needed to further elucidate whether choline and other nutritional supplements may improve outcome and various parameters which may influence effective translation. Altogether, this study highlights the need for a continued understanding of the role of nutritional status and supplementation in FASD and its contributions to neurocognition

Our authors, who study successful aging and mental illnesses at the University of California, San Diego, address the often debated, complicated question that many of us have long wondered about: Does the brain improve with age?

Schizophrenia and bipolar disorder are among the leading causes of disability, morbidity, and mortality worldwide. In addition to being serious mental illnesses, these disorders are associated with considerable systemic physiological dysfunction, including chronic inflammation and elevated oxidative stress. The advent of sophisticated sequencing techniques has led to a growing interest in the potential role of gut microbiota in human health and disease. Advances in this area have transformed our understanding of a number of medical conditions and have generated a new perspective suggesting that gut microbiota might be involved in the development and maintenance of brain/mental health. Animal models have demonstrated strong though indirect evidence for a contributory role of intestinal microbiota in psychiatric symptomatology and have linked the microbiome with neuropsychiatric conditions. We present a systematic review of clinical studies of microbiome in schizophrenia and bipolar disorder. The published literature has a number of limitations; however, the investigations suggest that these disorders are associated with reduced microbial diversity and show global community differences compared to non-psychiatric comparison samples. In some reports, specific microbial taxa were associated with clinical disease characteristics, including physical health, depressive and psychotic symptoms, and sleep, but little information on the functional potential of those community changes. Studies also suggest increased intestinal inflammation and permeability, which may be among the principal mechanisms by which microbial dysbiosis impacts systemic physiological functioning. We highlight gaps in the current literature and implications for diagnosis and therapeutic interventions, and outline future directions for microbiome research in psychiatry.

BACKGROUND:Schizophrenia is associated with increased physical morbidity and early mortality, suggesting that the aging process may be accelerated in schizophrenia. However, the biological underpinnings of these alterations in aging in schizophrenia are unclear. METHOD:We conducted a detailed search of peer-reviewed empirical studies to evaluate evidence for accelerated biological aging in schizophrenia based on systemic, age-related biomarkers. We included studies that investigated differences between persons with schizophrenia and healthy comparison subjects in levels of biomarkers known to be associated with aging and examined the relationship of these biomarkers to age in the 2 groups. RESULTS:Forty-two articles that met our selection criteria were reviewed. Nearly 75% reported abnormal biomarker levels among individuals with schizophrenia, including indices of inflammation, cytotoxicity, oxidative stress, metabolic health, gene expression, and receptor/synaptic function, with medium to large effect sizes reported in many studies. Twenty-nine percent of the studies observed differential age-related decline in schizophrenia. Markers of receptor/synaptic function and gene expression were most frequently differentially related to age in schizophrenia. Schizophrenia patients with greater disease severity and longer illness duration exhibited higher levels of inflammatory and oxidative stress biomarkers and shorter telomere length. CONCLUSIONS:Most studies show biomarker abnormalities in schizophrenia, and there is some suggestion for accelerated aging. Although definitive interpretation is limited by cross-sectional design of the published reports, findings in the area of gene expression and synaptic function are promising and pave the way for future longitudinal studies needed to fully test this hypothesis.

Background

Peripheral levels of pro-inflammatory biomarkers have been shown to be altered in schizophrenia (SZ) and associated with cognitive impairments, but their relevance to specific cognitive domains remains unclear.

Methods

Plasma levels of cytokines, chemokines, and vascular biomarkers were quantified and compared between SZ and healthy comparison (HC) groups. Cognition was assessed using the Delis-Kaplan Executive Function System Trail Making (TM) and Color Word Interference (CWI) tests. Linear regression analyses examined differential relationships of inflammatory biomarkers with executive function between groups.

Results

Plasma levels of TNFα, ICAM1, and MCP1 were higher in individuals with SZ compared to HCs. Higher level of MCP1 was associated with increased CWI Inhibition Switching Errors in SZ but not HCs.

Conclusion

Like other studies, we found evidence for increased peripheral inflammation in SZ. We also showed that SZ with particularly high MCP1 levels had poor cognitive flexibility. Interventions to reduce chemokine elevations might prove beneficial for cognitive performance.

Schizophrenia and bipolar disorder are among the leading causes of disability, morbidity, and mortality worldwide. In addition to being serious mental illnesses, these disorders are associated with considerable systemic physiological dysfunction, including chronic inflammation and elevated oxidative stress. The advent of sophisticated sequencing techniques has led to a growing interest in the potential role of gut microbiota in human health and disease. Advances in this area have transformed our understanding of a number of medical conditions and have generated a new perspective suggesting that gut microbiota might be involved in the development and maintenance of brain/mental health. Animal models have demonstrated strong though indirect evidence for a contributory role of intestinal microbiota in psychiatric symptomatology and have linked the microbiome with neuropsychiatric conditions. We present a systematic review of clinical studies of microbiome in schizophrenia and bipolar disorder. The published literature has a number of limitations; however, the investigations suggest that these disorders are associated with reduced microbial diversity and show global community differences compared to non-psychiatric comparison samples. In some reports, specific microbial taxa were associated with clinical disease characteristics, including physical health, depressive and psychotic symptoms, and sleep, but little information on the functional potential of those community changes. Studies also suggest increased intestinal inflammation and permeability, which may be among the principal mechanisms by which microbial dysbiosis impacts systemic physiological functioning. We highlight gaps in the current literature and implications for diagnosis and therapeutic interventions, and outline future directions for microbiome research in psychiatry.

Background

The ultimate goal of artificial intelligence (AI) is to develop technologies that are best able to serve humanity. This will require advancements that go beyond the basic components of general intelligence. The term "intelligence" does not best represent the technological needs of advancing society, because it is "wisdom", rather than intelligence, that is associated with greater well-being, happiness, health, and perhaps even longevity of the individual and the society. Thus, the future need in technology is for artificial wisdom (AW).

Methods

We examine the constructs of human intelligence and human wisdom in terms of their basic components, neurobiology, and relationship to aging, based on published empirical literature. We review the development of AI as inspired and driven by the model of human intelligence, and consider possible governing principles for AW that would enable humans to develop computers which can operationally utilize wise principles and result in wise acts. We review relevant examples of current efforts to develop such wise technologies.

Results

AW systems will be based on developmental models of the neurobiology of human wisdom. These AW systems need to be able to a) learn from experience and self-correct; b) exhibit compassionate, unbiased, and ethical behaviors; and c) discern human emotions and help the human users to regulate their emotions and make wise decisions.

Conclusions

A close collaboration among computer scientists, neuroscientists, mental health experts, and ethicists is necessary for developing AW technologies, which will emulate the qualities of wise humans and thus serve the greatest benefit to humanity. Just as human intelligence and AI have helped further the understanding and usefulness of each other, human wisdom and AW can aid in promoting each other's growth.

Background

Nutrition is an important factor that affects brain development. Nutritional deficiencies can exacerbate alcohol's damaging effects. Conversely, nutritional supplementation can serve a protective role against alcohol damage and may prove to be a worthwhile intervention strategy. This study investigated dietary intake in school-aged children with heavy prenatal alcohol exposure to understand their nutritional status, compared to a national sample of typically developing children and Dietary Reference Intakes.

Methods

Dietary intake data were collected from children with confirmed histories of heavy prenatal alcohol exposure (5 to 10 years, n = 55) using the Automated Self-Administered 24-Hour Dietary Recall (ASA24). Observed nutrient levels were compared to the Dietary Reference Intakes to evaluate adequacy of nutrient intake as well as to national averages for same-aged children (What We Eat in America, NHANES 2007-2008).

Results

Alcohol-exposed children exhibited poorer nutritional status compared to the typically developing NHANES sample, consuming lower levels of protein, omega-3 fatty acids, magnesium, potassium, zinc, vitamins C and K, niacin, and choline. Moreover, their diets did not meet Recommended Dietary Allowance or Adequate Intake for dietary fiber, potassium, vitamins E and K, omega-3 fatty acids, and choline.

Conclusions

The present findings are consistent with prior studies investigating nutritional intake in preschoolers with FASD, indicating that these children are vulnerable to nutritional inadequacies. Moreover, data suggest a specific profile of dietary intake in this population. As several nutrients are important for cognitive development, targeted interventions in clinical populations might be effective in boosting outcomes. Thus, further clinical investigation into the role of nutrition in improving cognitive outcomes is warranted.