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Tryptophan rich diet is negatively associated with depression and positively linked to social cognition
Abstract
The essential amino acid tryptophan (TRP) is discussed as a potential protective factor for physical and mental health. Besides positive effects via the microbiota of the gut on many physiological processes, TRP is the precursor of the neurotransmitter serotonin (5-HT) thereby playing a role for affective disorders. The present study investigated in a population based sample the effects of a TRP rich diet on depressiveness and on one of its endophenotypes, impaired social cognition. N = 482 subjects participated in an online study assessing the ability to properly recognize emotional states from the eye region of faces (Reading the Mind in the Eye Test, RMET) and asking for subjective ratings of condemnability in a moral judgment task. Moreover, the habitual TRP intake was measured. It was hypothesized that a low TRP diet is associated with higher depressiveness and worse performance in the social cognition tasks. This could be supported, however, contrary to the expectations, the effect of TRP on social cognition was not mediated by depressiveness. Results show that a tryptophan rich diet is a potential protective factor against depression and is positively related to functioning in social cognition.
... 142 A tryptophan-rich diet has been also reported as a protective factor against depression and positively related to social cognition. 143 In a systematic review of randomized controlled trials, authors suggested that tryptophan intake may be an effective approach to decrease anxiety and increase positive mood in healthy individuals. 144 Based on these clinical trials, the authors estimated that 0.14-3 g of tryptophan per day, in addition to the usual meal, can improve mood of healthy individuals. ...
... 147 Together, these findings indicate tryptophan supplementation can produce positive effects on mood and behavior in conditions when circulating levels of tryptophan are low (Table 1). 117,118,[121][122][123][124]143,147 Sex differences have been also reported relative to the effects of tryptophan supplementation. Research has shown that the effects of tryptophan on mood and happy facial expression occur in women but not men (Table 1). ...
The importance of nutrients in our diet is becoming increasingly recognized. From the viewpoint of protein synthesis and other physiologic and metabolic functions, all amino acids are important, but some of these amino acids are not synthesized endogenously. This subset, called essential amino acids, comprise dietarily indispensable nutrients. Tryptophan, an essential amino acid, is the sole precursor of neuronal as well as peripheral serotonin (5-hydroxytryptamine). Its systemic or oral administration increases serotonin synthesis because tryptophan hydroxylase, the rate-limiting enzyme of 5-hydroxytryptamine biosynthesis, is physiologically unsaturated with its substrate. Central serotonin is implicated in a number of psychiatric illnesses, including depression, and in responses to stress. Acting peripherally, serotonin affects vasoconstriction, intestinal motility, control of T cell–mediated immunity, and liver and pancreatic functions. Depression and diabetes are 2 highly prevalent diseases that often coexist. There is evidence that occurrence of depression is 2–3 times higher in people with diabetes mellitus. A comorbid condition of diabetes and depression worsens the treatment and increases risk for death. Stress, known for its causal role in depression, can also enhance risk for diabetes. Stress-induced decreases in the circulating levels of tryptophan can impair brain and pancreatic serotonin-dependent functions to precipitate these diseases. The importance of tryptophan supplementation for improving therapeutic intervention in depression and diabetes is the focus of this article. A deficiency of this essential amino acid may enhance risk for depression as well as diabetes, and can also weaken treatment efficacy of medicinal compounds for treating these diseases. Guidelines for optimal levels of circulating tryptophan can help if supplements of this amino acid can improve treatment efficacy.
... TRP is an essential amino acid involved in the production of critical neuroactive compounds such as serotonin (5-HT), melatonin, and kynurenine (KYN), all of which play crucial roles in brain development and function [5]. ...
Autism spectrum disorder (ASD) has been associated with disruptions in tryptophan (TRP) metabolism, affecting the production of key neuroactive metabolites. Investigating these metabolic pathways could yield valuable biomarkers for ASD severity and progression. We included 44 children with ASD and 44 healthy children, members of the same family. The average age in the ASD group was 10.7 years, while the average age in the control group was 9.4 years. Urinary tryptophan metabolites were quantified via liquid chromatography—mass spectrometry operating multiple reaction monitoring (MRM). Urinary creatinine was analyzed on an Advia 2400 analyzer using the Jaffe reaction. Statistical comparisons were made between ASD subgroups based on CARS scores. Our findings indicate that children with ASD have higher TRP concentrations (19.94 vs. 16.91; p = 0.04) than their siblings. Kynurenine (KYN) was found at higher levels in children with ASD compared to children in the control group (82.34 vs. 71.20; p = 0.86), although this difference was not statistically significant. The ASD group showed trends of higher KYN/TRP ratios and altered TRP/ indole-3-acetic acid (IAA) and TRP/5-hydroxyindoleacetic acid (5-HIAA) ratios, correlating with symptom severity. Although the numbers of the two groups were different, our findings suggest that mild and severe illnesses involve separate mechanisms. However, further comprehensive studies are needed to validate these ratios as diagnostic tools for ASD.
... It was found that the deficiency of tryptophan was related to higher levels of anxiety fact, which could be related to the comorbidity with Binge Eating Disorder in people with anxiety and depression [265,266]. This is because people with mood and emotional disorders seek out food in order to reduce anxiety [267]. This amino acid releases serotonin, and it is known that a serotonin deficit will facilitate the appearance of symptoms such as sadness, anxiety and irritability [268]. ...
Mental health is an increasing topic of focus since more than 500 million people in the world suffer from depression and anxiety. In this multifactorial disorder, parameters such as inflammation, the state of the microbiota and, therefore, the patient’s nutrition are receiving more attention. In addition, food products are the source of many essential ingredients involved in the regulation of mental processes, including amino acids, neurotransmitters, vitamins, and others. For this reason, this narrative review was carried out with the aim of analyzing the role of nutrition in depression and anxiety disorders. To reach the review aim, a critical review was conducted utilizing both primary sources, such as scientific publications and secondary sources, such as bibliographic indexes, web pages, and databases. The search was conducted in PsychINFO, MedLine (Pubmed), Cochrane (Wiley), Embase, and CinAhl. The results show a direct relationship between what we eat and the state of our nervous system. The gut–brain axis is a complex system in which the intestinal microbiota communicates directly with our nervous system and provides it with neurotransmitters for its proper functioning. An imbalance in our microbiota due to poor nutrition will cause an inflammatory response that, if sustained over time and together with other factors, can lead to disorders such as anxiety and depression. Changes in the functions of the microbiota–gut–brain axis have been linked to several mental disorders. It is believed that the modulation of the microbiome composition may be an effective strategy for a new treatment of these disorders. Modifications in nutritional behaviors and the use of ergogenic components are presented as important non-pharmacological interventions in anxiety and depression prevention and treatment. It is desirable that the choice of nutritional and probiotic treatment in individual patients be based on the results of appropriate biochemical and microbiological tests.
... Additionally, tryptophan depletion has been shown to affect cognitive tasks such as response times and visual discrimination, further emphasizing its role in cognitive health (Reuter et al., 2021). ...
This study explores the interplay encompassing amino acids' roles, metabolic processes, growth, and the intricate relationships between sleep patterns, amino acid-deficient diet, and caffeine consumption, with emphasis on the vital connections between diet, oxidative stress, and cognitive health while investigating the essential role of quality sleep in maintaining cognitive function. This study investigates the intricate connections among amino acids, metabolic processes, growth, sleep patterns, amino acid-deficient diets, and caffeine consumption. Emphasizing the crucial links between diet, oxidative stress, and cognitive health, the research underscores the essential role of quality sleep in maintaining cognitive function. The bidirectional relationship between disrupted sleep and cognitive health, as well as the impact of caffeine on cognitive function, is explored. The study involved adult male Wistar rats divided into 10 groups A - J based on cage conditions and diet. Group A-E were kept in a normal cage with diets containing varying levels of tryptophan and other essential amino acids, while Group F-J underwent sleep deprivation using a disk-over-water method and received diets with varying tryptophan and other essential amino acid levels, in addition to caffeine. The experiment spanned 2 weeks, blood samples were collected on days 1,4,7, and 13 for relevant biochemical serum analyses, and the rats were sacrificed on the fourteenth day for blood sample collection, biochemical assays, and brain histology. The 2-week experiment revealed a linear decrease in melatonin and serotonin levels across all caffeine-administered groups, possibly due to stress and anxiety as compared with the reduction in these parameters observed in control rats, suggesting melatonin and serotonin as potential sleep deprivation biomarkers. Testosterone and insulin-like growth hormone assays showed a significant decrease in sleep-deprived rats with caffeine, impacting secondary sex characteristics and growth. Elevated TNF-α and interleukin-1b levels in the caffeine-administered, sleep-deprived group suggest potential health risks associated with sleep deprivation and caffeine. Serum assays for antioxidant enzymes indicated heightened oxidative stress in sleep-deprived rats with caffeine. Histopathological studies revealed cellular abnormalities in the sleep-deprived group, indicating increased cellular metabolism and potential pathological conditions. This study elucidates the complex relationships among sleep, dietary factors, and hormonal and inflammatory responses. It underscores the potential neurotoxic effects associated with caffeine consumption when coupled with sleep deprivation. These results underscore the urgent need for further investigation into dietary strategies that could alleviate these adverse effects and promote better health. Keywords: Sleep deprivation, Amino acid deficiency, Oxidative stress, Cognitive health, Caffeine
... On the other hand, tryptophan (Trp) is one of the most oxidizable amino acids and it has been proposed to be relevant for human nutrition because it is essential in the synthesis of melatonin and serotonin, as well as vitamin B3 [33]. A high signal was found for Phv26 ('Sapito'), indicating that this typical Chilean landrace has a high content of this essential amino acid, which has been discussed as a potential protective factor for physical and mental health [34]. ...
Common bean (Phaseolus vulgaris L.) is the primary grain legume cultivated worldwide for direct human consumption due to the high nutritional value of its seeds and pods. The high protein content of common beans highlights it as the most promising source of plant-based protein for the food industry. Additionally, landraces of common bean have great variability in nutritional traits, which is necessary to increase the nutritional quality of elite varieties. Therefore, the main objective of this study was to nutritionally characterize 23 Chilean landraces and 5 commercial varieties of common bean to identify genotypes with high nutritional value that are promising for the food industry and for genetic improvement programs. The landrace Phv23 (‘Palo’) was the most outstanding with high concentrations of minerals such as P (7.53 g/kg), K (19.8 g/kg), Mg (2.43 g/kg), Zn (52.67 mg/kg), and Cu (13.67 mg/kg); essential amino acids (364.8 mg/g protein); and total proteins (30.35 g/100 g seed). Additionally, the landraces Phv9 (‘Cimarrón’), Phv17 (‘Juanita’), Phv3 (‘Araucano’), Phv8 (‘Cabrita/Señorita’), and Phv4 (‘Arroz’) had a high protein content. The landrace Phv24 (‘Peumo’) stood out for its phenolic compounds (TPC = 218.1 mg GA/100 g seed) and antioxidant activity (ORAC = 22,167.9 μmol eq trolox/100 g extract), but it has moderate to low mineral and protein concentrations. In general, the concentration of nutritional compounds in some Chilean landraces was significantly different from the commercial varieties, highlighting their high nutritional value and their potential use for the food industry and for genetic improvement purposes.
... Regarding the consumption of fats, both high-fat diets and obesity are major factors that exacerbate depressive states. There are studies suggesting that the expression of the long isoform of the leptin receptor (LepRb) and the cannabinoid receptor type 1 (CNR1) is influenced, selective deletion of these receptors leading to behaviors related to depression Alternatively, a high-protein diet is linked with a reduced risk of depression, probably attributed to its rich concentration of essential amino acids such as tryptophan, a precursor to serotonin (Reuter et al., 2021). ...
This short overview explores the relationship between oxidative stress and mental disorders, focusing on the association with psychiatric pathologies such as Alzheimer’s disease, schizophrenia, autism, depression, and the impact of sleep deprivation. The mechanisms of mitochondrial disfunction and oxidative stress in these pathologies are described, including the physiological function of limited free radicals in signal transduction, gene transcription, neuronal plasticity and memory. Key free radicals, including hydroxyl and superoxide are highlighted, along with compounds generating free radicals. Moreover, the potential therapeutic implications of dietary supplements (zinc, selenium, magnesium, vitamin C, E, CoQ 10 ) and lifestyle interventions with antioxidant properties are presented, laying the groundwork for future research in the field of mental health.
... 113 Therefore, tryptophan can be obtained from the diet from the intake of soybeans, milk, eggs, fish and chicken. 114 Several studies have shown that a tryptophan-rich diet is negatively associated with depression, 115,116 but the mechanism of action is unclear. Animal studies reveal that a soybean diet could counteract depressive symptoms by inducing the synthesis of 5-HT. ...
Depression is a mental illness that affects the normal lives of over 300 million people. Unfortunately, about 30% to 40% of patients do not adequately respond to pharmacotherapy and other therapies. This review focuses on exploring the relationship between dietary nutrition and depression, aiming to find safer and efficient ingredients to alleviate depression. Diet can affect depression in numerous ways. These pathways include the regulation of tryptophan metabolism, inflammation, hypothalamic–pituitary–adrenal (HPA) axis, microbe–gut–brain axis, brain-derived neurotrophic factor (BDNF) and epigenetics. Furthermore, probiotics, micronutrients, and other active substances exhibit significant antidepressant effects by regulating the above pathways. These provide insights for developing antidepressant foods.
... Por otro lado, consumir alimentos de fuente animal, los cuales proporcionan vitamina B12 y omega-3, podría reducir el riesgo de depresión [13,15]. Se ha visto que un patrón de dieta alto en grasa y azúcar también se asocia a mayor riesgo de este trastorno [16] y que las dietas ricas en triptófano tienen un potencial efecto protector contra depresión [17]. ...
Introducción: Se vienen dando cambios en la alimentación en los países en vías de desarrollo como parte de la transición nutricional. Estos podrían afectar el consumo de ciertos grupos de alimentos y por lo tanto la salud mental, especialmente en los adultos mayores. El objetivo fue evaluar si existe asociación entre el consumo de ciertos grupos de alimentos (lácteos, huevos y menestras, carne, aves de corral o pescado, y frutas y/o verduras) y la presencia de síntomas depresivos en adultos mayores de pobreza y pobreza extrema en el Perú.
Metodología: Análisis secundario de un estudio de base poblacional (Encuesta de Salud y Bienestar del Adulto Mayor, en Perú) realizada en el 2012. La variable desenlace fue la presencia de síntomas depresivos, mientras que la exposición fue la frecuencia de consumo de ciertos grupos de alimentos: lácteos; huevos y menestras; carne, aves de corral o pescado; y frutas y/o verduras. Se usó modelos de regresión de Poisson, reportándose razones de prevalencia (RP) e intervalos de confianza al 95% (IC95%).
Resultados: Un total de 4214 registros fueron analizados, edad promedio de 71,2 (DE: 4,4) años, 54,2% de varones, y 61,4% de zona rural. Un total de 1621 (38,6%; IC95%: 37,1%-40,1%) adultos mayores presentaron síntomas depresivos. En modelo multivariable, la frecuencia de síntomas depresivos fue un 41% superior (IC95%: 30%-54%) entre los que no consumían huevos y menestras al menos una vez a la semana. Similarmente, se encontró asociación en aquellos que reportaron no consumir carne, aves de corral o pescado al menos tres veces por semana (18%; IC95%: 9%-28%) y los que no consumieron frutas y/o verduras al menos dos veces al día (15%; IC95%: 6%-24%).
Conclusión: Este estudio evidenció que el consumo de frutas y/o verduras, aves de corral o pescado, huevos y menestras están relacionados de manera inversa con la presencia de síntomas depresivos en el adulto mayor
... No benefit has been shown for protein intake from animal sources [47,48]. A beneficial effect of a higher supply of tryptophan in the diet has been shown to decrease the risk of depression [49][50][51]. A diet with an increased supply of protein relative to other macronutrients may have a beneficial effect on the risk of depression in adults who do not have any chronic diseases [58][59][60][61]. ...
Depression is classified as one of the most common mental disorders. Its prevalence has recently increased, becoming a growing public health threat. This review focuses on clarifying the role and importance of individual nutrients in the diet and the impact of nutrient deficiencies on the risk of depression. Deficiencies in nutrients such as protein, B vitamins, vitamin D, magnesium, zinc, selenium, iron, calcium, and omega-3 fatty acids have a significant impact on brain and nervous system function, which can affect the appearance of depressive symptoms. However, it is important to remember that diet in itself is not the only factor influencing the risk of or helping to treat depression. There are many other aspects, such as physical activity, sleep, stress management, and social support, that also play an important role in maintaining mental health. The data review observed that most of the available analyses are based on cross-sectional studies. Further studies, including prospective cohort, case-control studies, are recommended to draw more reliable conclusions.
... Tryptophan in dietary protein is a precursor for the synthesis of serotonin, and an increase in serotonin in the brain is the key to treating depression [69]. A survey by Euter et al. found that a diet low in tryptophan is associated with a higher risk of depression [70]. Subchronic tryptophan depletion is also used as an animal model of depression [71]. ...
Depression is a common mental disorder that seriously affects the quality of life and leads to an increasing global suicide rate. Macro, micro, and trace elements are the main components that maintain normal physiological functions of the brain. Depression is manifested in abnormal brain functions, which are considered to be tightly related to the imbalance of elements. Elements associated with depression include glucose, fatty acids, amino acids, and mineral elements such as lithium, zinc, magnesium, copper, iron, and selenium. To explore the relationship between these elements and depression, the main literature in the last decade was mainly searched and summarized on PubMed, Google Scholar, Scopus, Web of Science, and other electronic databases with the keywords “depression, sugar, fat, protein, lithium, zinc, magnesium, copper, iron, and selenium”. These elements aggravate or alleviate depression by regulating a series of physiological processes, including the transmission of neural signals, inflammation, oxidative stress, neurogenesis, and synaptic plasticity, which thus affect the expression or activity of physiological components such as neurotransmitters, neurotrophic factors, receptors, cytokines, and ion-binding proteins in the body. For example, excessive fat intake can lead to depression, with possible mechanisms including inflammation, increased oxidative stress, reduced synaptic plasticity, and decreased expression of 5-Hydroxytryptamine (5-HT), Brain Derived Neurotrophic Factor (BDNF), Postsynaptic density protein 95(PSD-95), etc. Supplementing mineral elements, such as selenium, zinc, magnesium, or lithium as a psychotropic medication is mostly used as an auxiliary method to improve depression with other antidepressants. In general, appropriate nutritional elements are essential to treat depression and prevent the risk of depression.
... Considering the essential role of serotonin disregulation in psychiatric disorders, it is reasonable to suggest that contrasts in diets related to tryptophan can be associated with differences in these disorders or at least national differences in some CBPs. The impact of the tryptophan diet was, in fact, reported in association with depression in clients with neurodegenerative disease [85,86] or animal models of chronic unpredictable stress (Wang et al., 2022). As another example, soy products and the estrogen-like properties of their component, isoflavone, were noted to have an impact factor on the activity of organs that depend on estrogen, including the hypothalamus/pituitary, the other brain regions and the uterus [87]. ...
This paper reviews the principles identified in analytic neuroscience that could be used in the setup of an international project, “Hippocrates” (H-project), named after the author of the endocrine theory of temperaments. The H-project can aim to summarize the findings in functional neurochemistry of consistent behavioural patterns (CBPs) in health (such as temperament traits) and psychopathology (symptoms of psychiatric disorders); to have systematically structured neurochemical investigations; to have an analysis of CBPs that include all ranges of behavioural histories and to have these modules complemented by regional contrasts related to climate, diets and other bio-environmental factors. The review highlights the benefits of constructivism and illustrates the contrast between constructivism and current approaches in terms of analytic and methodological aspects. (1) “Where” the neurochemical biomarkers should be measured: the review expands the range of needed measurements to out-of-brain systems, including environmental factors, and explores the concept of Specialized Extended Phenotype. (2) “What” should be measured but is missing: the review points to the need for measurement of the “Throw & Catch” neurochemical relays; behavioural and neuronal events contributing to the consistency of the CBPs but not documented in measurements. (3) Structuring the H-project’s setup: the paper briefly describes a proposed earlier neurochemical framework, Functional Ensemble of Temperament that that accommodates the neurochemical continuum between temperament and symptoms of psychiatric disorders. This framework is in line with documented “Throw & Catch” neurochemical relays and can also be used to organize data about the personal and professional history of an individual.
... 113 Therefore, tryptophan can be obtained from the diet from the intake of soybeans, milk, eggs, fish and chicken. 114 Several studies have shown that a tryptophan-rich diet is negatively associated with depression, 115,116 but the mechanism of action is unclear. Animal studies reveal that a soybean diet could counteract depressive symptoms by inducing the synthesis of 5-HT. ...
Depression is a mental illness that affects the normal lives of over 300 million people. Unfortunately, about 30% to 40% of patients do not adequately respond to pharmacotherapy and other therapies. This review focuses on exploring the relationship between dietary nutrition and depression, aiming to find safer and efficient ingredients to alleviate depression. Diet can affect depression in numerous ways. These pathways include the regulation of tryptophan metabolism, inflammation, hypothalamic-pituitary-adrenal (HPA) axis, microbe-gut-brain axis, brain-derived neurotrophic factor (BDNF) and epigenetics. Furthermore, probiotics, micronutrients, and other active substances exhibit significant antidepressant effects by regulating above pathways. These provide insights for developing antidepressant foods.
... Tryptophan can be found in some foods, such as soybeans, grains, seeds, cashews, walnuts, peanuts, almonds, and salmon ( Strasser et al., 2016 ). A tryptophan-rich diet is a potential protective factor against depression and is positively related to functioning in social cognition ( Reuter et al., 2021 ). Elderly people who consumed cereals containing the higher dose in tryptophan had increased sleep efficiency, actual sleep time, and decreased total nocturnal activity ( Bravo et al., 2013 ). ...
Background:
Among breast cancer survivors, pain, fatigue, depression, anxiety, and sleep disturbance are common psychoneurological symptoms that cluster together. Inflammation-induced activation of the tryptophan-kynurenine metabolomic pathway may play an important role in these symptoms.
Aims:
This study investigated the relationship between the metabolites involved in the tryptophan-kynurenine pathway and psychoneurological symptoms among breast cancer survivors.
Design:
Cross-sectional study.
Setting:
Participants were recruited at the oncology clinic at the University of Illinois Hospital & Health Sciences System.
Participants/subjects:
79 breast cancer survivors after major cancer treatment.
Methods:
We assessed psychoneurological symptoms with the PROMIS-29 and collected metabolites from fasting blood among breast cancer survivors after major cancer treatment, then analyzed four major metabolites involved in the tryptophankynurenine pathway (tryptophan, kynurenine, kynurenic acid, and quinolinic acid). Latent profile analysis identified subgroups based on the five psychoneurological symptoms. Mann-Whitney U tests and multivariable logistic regression compared targeted metabolites between subgroups.
Results:
We identified two distinct symptom subgroups (low, 81%; high, 19%). Compared with participants in the low symptom subgroup, patients in the high symptom subgroup had higher BMI (p = .024) and were currently using antidepressants (p = .008). Using multivariable analysis, lower tryptophan levels (p = .019) and higher kynurenine/tryptophan ratio (p = .028) were associated with increased risk of being in the high symptom subgroup after adjusting for BMI and antidepressant status.
Conclusion:
The tryptophan-kynurenine pathway and impaired tryptophan availability may contribute to the development of psychoneurological symptoms.
... As is well known, dysregulation of the serotonin systems, contributing to the occurrence of depression (Deakin 1991), is a primary target for the most commonly used antidepressants (Smith et al. 2021). Tryptophan is a precursor of serotonin (Zadori et al. 2018), and tryptophan-rich diet is positively related to the function in social cognition, which is a potential protective factor against depression (Reuter et al. 2021). Tryptophan metabolism has an important role in the regulation of MGB axis. ...
Rationale
Depression is a serious mood disorder, and crocetin has a variety of pharmacological activities, including antidepressant effect. The alterations of intestinal flora have a significant correlation with depression, and crocetin can alter the composition of intestinal flora in mice with depression-like behaviors.
Objective
This study investigated the underlying antidepressant mechanisms of crocetin through multi-omics coupled with biochemical technique validation.
Methods
Chronic unpredictable stress (CUMS) was used to induce mice model of depression to evaluate the antidepressant effect of crocetin through behavioral tests, and the metagenomic and metabolomic were used to explore the potential mechanisms involved. In order to verify its underlying mechanism, western blot (WB), Elisa, immune histological and HPLC techniques were used to detect the level of inflammatory cytokines and the level of metabolites/proteins related to tryptophan metabolism in crocetin-treated mice.
Results
Crocetin ameliorated depression-like behaviors and increased mobility in depressive mice induced by CUMS. Metagenomic results showed that crocetin regulated the structure of intestinal flora, as well as significantly regulated the function gene related to derangements in energy metabolism and amino acid metabolism in mice with depression-like behaviors. Metabolomic results showed that the tryptophan metabolism, arginine metabolism and arachidonic acid metabolism played an essential role in exerting antidepressant-like effect of crocetin. According to multi-omics approaches and validation results, tryptophan metabolism and inflammation were identified and validated as valuable biological processes involved in the antidepressant effects of crocetin. Crocetin regulated the tryptophan metabolism in mice with depression-like behaviors, including increased aryl hydrocarbon receptor (AhR) expression, reduced indoleamine 2,3-dioxygenase 1 (IDO1) and serotonin transporter (SERT) expression in the hippocampus, elevated the content of 5-HT, kynurenic acid in serum and 5-HT, tryptophan in hippocampus. In addition, crocetin also attenuated inflammation in mice with depression-like behaviors, which presented with reducing the production of inflammatory cytokines in serum and colon. Meanwhile, crocetin up-regulated the expression of zonula occludens 1 (ZO-1) and occludin in ileum and colon to repair the intestinal barrier for preventing inflammation transfer.
Conclusion
Our findings clarify that crocetin exerted antidepressant effects through its anti-inflammation, repairment of intestinal barrier, modulatory on the intestinal flora and metabolic disorders, which further regulated tryptophan metabolism and impacted mitogen-activated protein kinase (MAPK) signaling pathway to enhance neural plasticity, thereby protect neural.
... A cross-sectional study of 4272 first-year female dietetic students in a university, college, or vocational school and 3651 of their mothers in Japan showed that higher tryptophan intake was significantly inversely related to the prevalence of depressive symptoms based on CES-D [5]. Although tryptophan intake itself was not assessed, there were significant correlations between habitual consumption levels of 29 tryptophan-rich foods (whey products, mozzarella, cheddar, cocoa, cashew, chia seeds, linseed, sesame, pumpkin seeds, sunflower seeds, pistachios, almonds, hemp seeds, wheat bran, oat bran, Kellogg's All Bran, kidney beans, white beans, soy, eggs, salmon, halibut, crayfish, shrimps, crabs, lobster, turkey, pancreas, and liver) and depressive symptoms assessed using Beck's Depression Inventory II in an online cross-sectional study of 462 German participants aged 18 to 72 years [28]. An intervention study of 35 volunteers (26 females and 9 males) aged 55-75 years with normal weight who suffered from sleep difficulties found that, after one week of ingesting 30 g of tryptophan-enriched cereals (containing 60 mg tryptophan) at breakfast and dinner, their Beck's Depression Inventory scores decreased significantly compared with the control week (diet with standard cereals and 22.5 mg of tryptophan per dose) [29]. ...
Objective
Tryptophan is an essential amino acid wholly derived from diet. While the majority of tryptophan is degraded through the kynurenine pathway into neuroactive metabolites like quinolinic acid and kynurenic acid, a small proportion of ingested tryptophan is metabolized into the neurotransmitter serotonin. The current cross-sectional study in Japan examined the association between tryptophan intake and depressive symptoms during pregnancy.
Methods
Study subjects were 1744 pregnant women. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. Depressive symptoms were defined as a score ≥ 16 on the Center for Epidemiologic Studies Depression Scale. Adjustment was made for age, gestation, region of residence, number of children, family structure, history of depression, family history of depression, smoking, secondhand smoke exposure at home and at work, employment, household income, education, body mass index, and intake of saturated fatty acids, eicosapentaenoic acid plus docosahexaenoic acid, calcium, vitamin D, and isoflavones.
Results
The prevalence of depressive symptoms during pregnancy was 19.2%. After adjustment for confounding factors, higher tryptophan intake was independently inversely associated with the prevalence of depressive symptoms during pregnancy: the adjusted prevalence ratios (95% confidence intervals) for depressive symptoms during pregnancy in the first, second, third, and fourth quartiles of tryptophan intake were 1 (reference), 0.99 (0.76−1.28), 0.94 (0.71−1.25), and 0.64 (0.44−0.93), respectively (p for trend = 0.04).
Conclusions
Higher estimated tryptophan intake was cross-sectionally independently associated with a lower prevalence of depressive symptoms during pregnancy in Japanese women.
... The opposite effect, worse emotion recognition after TRP depletion, was found before 53 but for the present whole sample, the positive effect of TRP on emotion recognition was not significant. In a larger sample habitual TRP consumption was related to emotion recognition 54 . Importantly, in line with our hypotheses and research proposing an altered serotonin metabolism in higher age 37 , we found age to be a significant contributing factor to TRP and 5-HTP effects. ...
Understanding of emotions and intentions are key processes in social cognition at which serotonin is an important neuromodulator. Its precursor is the essential amino acid tryptophan (TRP). Reduced TRP availability leads to weaker impulse control ability and higher aggression, while TRP supplementation promotes confidence. In a double-blind placebo-controlled fMRI study with 77 healthy adults, we investigated the influence of a 4 week TRP enriched diet and an acute 5-hydroxytryptophan (5-HTP) intake on two social-cognitive tasks, a moral evaluation and an emotion recognition task. With 5-HTP, immoral behavior without negative consequences was rated as more reprehensible. Additionally, during story reading, activation in insula and supramarginal gyrus was increased after TRP intake. No significant effects of TRP on emotion recognition were identified for the whole sample. Importantly, emotion recognition ability decreased with age which was for positive emotions compensated by TRP. Since the supramarginal gyrus is associated with empathy, pain and related information integration results could be interpreted as reflecting stricter evaluation of negative behavior due to better integration of information. Improved recognition of positive emotions with TRP in older participants supports the use of a TRP-rich diet to compensate for age related decline in social-cognitive processes.
... A 2015 study in 25 healthy young adults demonstrated that consuming more dietary tryptophan resulted in less depressive symptoms and decreased anxiety [94]. A tryptophan-rich diet is not only a potential protective factor against depression but also positively related to functioning in social cognition [95]. Particularly in the elderly, mild and moderate depression may be associated with a lower intake of tryptophan [96]. ...
Purpose of Review
The SARS-CoV-2-pandemic has caused mortality and morbidity at an unprecedented global scale. Many patients infected with SARS-CoV-2 continue to experience symptoms after the acute phase of infection and report fatigue, sleep difficulties, anxiety, and depression as well as arthralgia and muscle weakness. Summarized under the umbrella term “long-COVID,” these symptoms may last weeks to months and impose a substantial burden on affected individuals. Dietary approaches to tackle these complications have received comparably little attention. Although plant-based diets in particular were shown to exert benefits on underlying conditions linked to poor COVID-19 outcomes, their role with regard to COVID-19 sequelae is yet largely unknown. Thus, this review sought to investigate whether a plant-based diet could reduce the burden of long-COVID.
Recent Findings
The number of clinical trials investigating the role of plant-based nutrition in COVID-19 prevention and management is currently limited. Yet, there is evidence from pre-pandemic observational and clinical studies that a plant-based diet may be of general benefit with regard to several clinical conditions that can also be found in individuals with COVID-19. These include anxiety, depression, sleep disorders, and musculoskeletal pain. Adoption of a plant-based diet leads to a reduced intake in pro-inflammatory mediators and could be one accessible strategy to tackle long-COVID associated prolonged systemic inflammation.
Summary
Plant-based diets may be of general benefit with regard to some of the most commonly found COVID-19 sequelae. Additional trials investigating which plant-based eating patterns confer the greatest benefit in the battle against long-COVID are urgently warranted.
... As mentioned above, ACE inhibitory tripeptides prefer C-terminal W. Therefore, a W-rich diet is more likely to reduce blood pressure. Chia seeds, edible seeds of chia plant, have a high concentration of W (440 mg/100 g)(Kałużna- Czaplińska et al., 2019;Reuter et al., 2021). Some studies have shown a promising potential of chia seeds to inhibit the activity of ACE. ...
Food‐derived angiotensin I‐converting enzyme (ACE) inhibitory peptides represent a potential source of new antihypertensive. However, their characteristics and binding mechanisms were not well understood. In this study, novel energy calculation and experimentation were combined to elucidate the characteristics and mechanisms of ACE inhibitory tripeptides. ACE inhibitory activity of all 8,000 tripeptides was investigated by in silico experiments. IC50 values of the five top‐rated tripeptides ranged from 5.86 to 21.84 μM. Five hundred top‐ranked tripeptides were chosen for detailed structure–activity analysis, and a significant preference for aromatic amino acids at both C‐ and N‐terminus was found. By binding free energy analysis of nine representative tripeptides via MM/GBSA, electrostatic energy was found to be the leading energy that contributed to the binding of ACE with its high affinity tripeptides. Besides, S355, V380, and V518, three residues positioned around the classical binding pockets of ACE, also played a key role in ACE's binding. Therefore, for tripeptides, their binding pockets in ACE were redefined. In conclusion, the characteristics of ACE inhibitory peptides were more deeply illustrated by the thorough analysis of all tripeptides. The energy analysis allows a better understanding of the binding mechanisms of ACE inhibitory peptides, which could be used to redesign the ACE inhibitors for stronger inhibitory activity. The characteristics of C‐ and N‐terminus of ACE inhibitory tripeptides were investigated. Electrostatic energy contributed to the binding of ACE with its high affinity tripeptides. S355, V380, and V518 played a key role ACE’s binding with tripeptides.
Over the last decade there has been increasing interest in the links between the consumption of ultra-processed foods and various neuropsychiatric disorders, aggression, and antisocial behavior. Neurolaw is an interdisciplinary field that seeks to translate the rapid and voluminous advances in brain science into legal decisions and policy. An enhanced understanding of biophysiological mechanisms by which ultra-processed foods influence brain and behavior allows for a historical reexamination of one of forensic neuropsychiatry’s most famous cases—The People v. White and its associated ‘Twinkie Defense’. Here in this Viewpoint article, we pair original court transcripts with emergent research in neurolaw, including nutritional neuroscience, microbiome sciences (legalome), pre-clinical mechanistic research, and clinical intervention trials. Advances in neuroscience, and related fields such as the microbiome, are challenging basic assumptions in the criminal justice system, including notions of universal free will. Recent dismissals of criminal charges related to auto-brewery syndrome demonstrate that courts are open to advances at the intersection of neuromicrobiology and nutritional neuroscience, including those that relate to criminal intent and diminished capacity. As such, it is our contention that experts in the neurosciences will play an increasing role in shaping research that underpins 21st-century courtroom discourse, policy, and decision-making.
Health and general well-being have been related to good nutrition and diet. More in-depth review will be given in this chapter to the pathways and mechanisms relating nutrition and diet to mental illness, going further than the generally known diet-related problems. While traditional associations with obesity, heart disease, and diabetes are recognized, many recent scientific evidences back up the concept that diet strongly affects the state of mental well-being, including depression, anxiety, and cognitive function. This review delves into key pathways implicated in the diet-mental illness connection, emphasizing the roles of the gut microbiome, inflammation, oxidative stress, nutrient deficiencies, food sensitivities, disrupted energy metabolism, and neurotransmitter pathways.
Acknowledging the complexity of mental illnesses influenced by genetic, environmental, and lifestyle factors, the chapter highlights the evolving role of diet in mental health research. Current knowledge on how diet influences pathways associated with mental health is critically examined, with a focus on the integration of dietary approaches in neurology and psychiatry. The chapter underscores the recognition of food as a potential modulator of mood and neurological conditions, offering insights into the preventive and therapeutic implications for mental illness.
Despite the fact that tryptophan (Trp) is an essential amino acid that humans typically obtain through diet, there are several interesting tryptophan dynamics at play in the body. Quantifying and understanding these dynamics are crucial in studies of depression, autism spectrum disorder, and other disorders that involve neurotransmitters directly synthesized from tryptophan. Here we detail the optimization of waveform parameters in fast scan cyclic voltammetry at carbon fiber microelectrodes to yield four-fold higher sensitivity and six-fold higher selectivity compared to previously reported methods. We demonstrate the utility of our method in measuring (1) exogenous Trp dynamics from administration of Trp to PC-12 cells with and without overexpression of tryptophan hydroxylase-2 and (2) endogenous Trp dynamics in pinealocyte cultures with and without stimulation via norepinephrine. We observed interesting differences in Trp dynamics in both model systems, which demonstrate that our method is indeed sensitive to Trp dynamics in different applications.
The number of individuals experiencing mental disorders (e.g., anxiety and depression) has significantly risen in recent years. Therefore, it is essential to seek prevention and treatment strategies for mental disorders. Several gut microbiota, especially Firmicutes and Bacteroidetes, are demonstrated to affect mental health through microbiota-gut-brain axis, and the gut microbiota dysbiosis can be related to mental disorders, such as anxiety, depression, and other mental disorders. On the other hand, dietary components, including probiotics (e.g., Lactobacillus and Bifidobacterium), prebiotics (e.g., dietary fiber and alpha-lactalbumin), synbiotics, postbiotics (e.g., short-chain fatty acids), dairy products, spices (e.g., Zanthoxylum bungeanum, curcumin, and capsaicin), fruits, vegetables, medicinal herbs, and so on, could exert protective effects against mental disorders by enhancing beneficial gut microbiota while suppressing harmful ones. In this paper, the mental disorder-associated gut microbiota are summarized. In addition, the protective effects of dietary components on mental health through targeting the gut microbiota are discussed. This paper can be helpful to develop some dietary natural products into pharmaceuticals and functional foods to prevent and treat mental disorders.
Increasing evidence indicates that tryptophan (Trp) metabolism disturbance controls hippocampal 5-hydroxytryptamine (5-HT) and thereby affecting depression-like behavior, in which the gut microbiota (GM) might be involved. This study investigated the effect of Trp-rich whey protein isolate (WPI) on depressive-like behavior in 4T1 tumor-bearing mice. Female BALB/c mice were subcutaneously inoculated with murine 4T1 mammary carcinoma cells and received 2 g/kg of WPI by gavage daily for 21 days. The results showed that WPI exerted no significant effects on tumor weight and volume, but abrogated tumor-induced depression-like behavior, as evidenced by remarkably increased time and distance in the center of the open-field test, decreased immobility time in the tail suspension test, increased time and number of entries to the open arms in the elevated plus maze and sucrose preference. Moreover, WPI promoted the hippocampal Trp, 5-hydroxytryptophan (5-HTP), 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) levels and inhibited kynurenine (Kyn) through up-regulating serotonin transporter (SERT) and down-regulating indoleamine 2, 3-dioxygenase (IDO). WPI showed an enriched microbial diversity indicated by increased Shannon index and decreased Simpson index, reduced the abundances of Proteobacteria, Rikenellaceae_RC9_gut_group, Alloprevotella and Prevotellaceae_UCG-001, and increased the abundance of unclassified_k__norank_d__Bacteria in tumor-bearing mice (P < 0.05). At level 3, WPI enhanced the function of microbial gene related to Trp metabolism in the KEGG pathways (P < 0.05). Our results suggest that WPI exhibits a potent antidepressant-like effect via the regulation of hippocampal Trp metabolism and alteration of GM composition and function, and it may be an effective prevention for cancer-related depression.
The elderly often suffer from sleep disorders and depression, which contribute to mood disorders. In our previous work, we showed that elderly individuals with mood disorders had a lower intake of TRP and recommended a TRP-based dietary intervention to improve the mental state of such individuals. In this work, we assessed the impact of a TRP-rich diet on the mental state of, and TRP metabolism in, elderly individuals with mood disorders. Forty elderly individuals with depression and sleep disorders and an equal number of elderly subjects without mood disorders were enrolled in this study. TRP intake was evaluated with the nutrition calculator. Patients with mood disorders had a lower TRP intake than their normal counterparts and received a TRP-rich diet with TRP content of 25 mg per kilogram of the body per day for 12 weeks. The mental state was assessed before and after this dietary intervention with the Hamilton Depression Rating Scale (HAM-D) and the Insomnia Severity Index (ISI). At those times, urinary levels of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), L-kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) were determined by liquid chromatography with tandem mass spectrometry and related to creatinine level. After TRP-based dietary intervention, the score of ISI and HAM-D decreased by more than half. A correlation analysis reveals that TRP, 5-HIAA, and KYNA might have anti-depressive action, while KYN and QA—pro-depressive. The levels of TRP, 5-HIAA, and KYNA in urine of mood disorder patients increased, while the levels of KYN and QA decreased. In conclusion, dietary consumption of adequate amount of tryptophan has a beneficial effect on mental health of the elderly with mood disorders and improves metabolism of this amino acid. Therefore, a TRP-enriched diet may be considered as a component of the treatment of elderly individuals with mood disorders.
(1). An essential component of any treatment for patients with irritable bowel syndrome (IBS) is an adequate diet. Currently, a low FODMAP diet is recommended as a first-line therapy, but it does not relieve abdominal discomfort in all patients, and alternative nutritional treatment is required. The purpose of this study was to evaluate the effect of a tryptophan-lowering diet (TRP) on abdominal and mental symptoms in patients with irritable bowel syndrome with predominant diarrhea (IBS-D). (2). The study included 40 patients with IBS-D, and 40 healthy subjects served as a baseline for IBS-D patients, after excluding comorbidities. The TRP intake was calculated using the nutritional calculator. The severity of abdominal symptoms was assessed using the gastrointestinal symptom rating scale (GSRS-IBS). Mental state was assessed using the Hamilton anxiety rating scale (HAM-A), the Hamilton depression rating scale (HAM-D), and the insomnia severity index (ISI). The serum levels of serotonin and melatonin and the urinary excretion of their metabolites 5-hydroxyindoleacetic acid (5-HIAA) and 6-sulfatoxymelatonin (aMT6) were determined by the ELISA method. The severity of symptoms and laboratory data were analyzed before and after a 12 week diet with tryptophan restricted to a daily dose 10 mg per kilogram body weight. (3). Compared to the control group, patients with IBS-D had a higher serum level of serotonin (198.2 ± 38.1 vs. 142.3 ± 36.4 ng/mL; p < 0.001) but a similar level of melatonin (8.6 ± 1.1 vs. 9.4 ± 3.0 pg/mL; p > 0.05). The urinary excretion of 5-HIAA was also higher in patients with IBS-D patients (7.7 ± 1.5 vs. 6.0 ± 1.7 mg/24 h; p < 0.001). After nutritional treatment, both the serum serotonin level and the urinary 5-HIAA excretion significantly decreased (p < 0.001). The severity of the abdominal symptoms and anxiety also decreased, while the HAM-D score and the ISI score remained unchanged (4). Lowering the dietary intake of tryptophan may reduce abdominal complaints and does not alter the mental state of IBS-D patients.
The intestine has a major role in the digestion and absorption of nutrients, and gut barrier is the first defense line against harmful pathogens. Alteration of the intestinal barrier is associated with enhanced intestinal permeability and development of numerous pathological diseases including gastrointestinal and cardiometabolic diseases. Among the metabolites that play an important role within intestinal health, L Tryptophan (Trp) is one of the nine essential amino acids supplied by diet, whose metabolism appears as a key modulator of gut microbiota, with major impacts on physiological, and pathological pathways. Recently, emerging evidence showed that the Trp catabolism through one major enzyme indoleamine 2,3-dioxygenase 1 (IDO1) expressed by the host affects Trp metabolism by gut microbiota to generate indole metabolites, thereby altering gut function and health in mice and humans. In this mini review, I summarize the most recent advances concerning the role of Trp metabolism in host–microbiota cross-talk in health, and metabolic diseases. This novel aspect of IDO1 function in intestine will better explain its complex roles in a broad range of disease states where the gut function affects local as well as systemic health, and will open new therapeutic strategies.
In 21st-century public health, rapid urbanization and mental health disorders are a growing global concern. The relationship between diet, brain function and the risk of mental disorders has been the subject of intense research in recent years. In this review, we examine some of the potential socioeconomic and environmental challenges detracting from the traditional dietary patterns that might otherwise support positive mental health. In the context of urban expansion, climate change, cultural and technological changes and the global industrialization and ultraprocessing of food, findings related to nutrition and mental health are connected to some of the most pressing issues of our time. The research is also of relevance to matters of biophysiological anthropology. We explore some aspects of a potential evolutionary mismatch between our ancestral past (Paleolithic, Neolithic) and the contemporary nutritional environment. Changes related to dietary acid load, advanced glycation end products and microbiota (via dietary choices and cooking practices) may be of relevance to depression, anxiety and other mental disorders. In particular, the results of emerging studies demonstrate the importance of prenatal and early childhood dietary practices within the developmental origins of health and disease concept. There is still much work to be done before these population studies and their mirrored advances in bench research can provide translation to clinical medicine and public health policy. However, the clear message is that in the midst of a looming global epidemic, we ignore nutrition at our peril.
Melatonin and serotonin rhythms, which exhibit a close association with the endogenous circadian component of sleep, are attenuated with increasing age. This decrease seems to be linked to sleep alterations in the elderly. Chrononutrition is a field of chronobiology that establishes the principle of consuming foodstuffs at times of the day when they are more useful for health, improving, therefore, biorhythms and physical performance. Our aim was to analyze whether the consumption of cereals enriched with tryptophan, the precursor of both serotonin and melatonin, may help in the reconsolidation of the sleep/wake cycle and counteract depression and anxiety in 35 middle-aged/elderly (aged 55-75 year) volunteers in a simple blind assay. Data were collected for 3 weeks according to the following schedule: The control week participants consumed standard cereals (22.5 mg tryptophan in 30 g cereals per dose) at breakfast and dinner; for the treatment week, cereals enriched with a higher dose of tryptophan (60 mg tryptophan in 30 g cereals per dose) were eaten at both breakfast and dinner; the posttreatment week volunteers consumed their usual diet. Each participant wore a wrist actimeter that logged activity during the whole experiment. Urine was collected to analyze melatonin and serotonin urinary metabolites and to measure total antioxidant capacity. The consumption of cereals containing the higher dose in tryptophan increased sleep efficiency, actual sleep time, immobile time, and decreased total nocturnal activity, sleep fragmentation index, and sleep latency. Urinary 6-sulfatoxymelatonin, 5-hydroxyindoleacetic acid levels, and urinary total antioxidant capacity also increased respectively after tryptophan-enriched cereal ingestion as well as improving anxiety and depression symptoms. Cereals enriched with tryptophan may be useful as a chrononutrition tool for alterations in the sleep/wake cycle due to age.
Reduced brain serotonin function is acknowledged as a vulnerability factor for affective disturbances. Since the production of serotonin is limited by the availability of its plasma dietary amino acid precursor tryptophan (TRP), the beneficial effects of tryptophan-rich alpha-lactalbumin whey protein (ALAC) have recently been studied. The effects of ALAC remain rather modest, and alternative protein sources of tryptophan may be more effective.
We tested whether hydrolyzed protein (HPROT) has greater effects on the plasma TRP/large neutral amino acids (LNAA) ratio and mood than intact ALAC protein in healthy volunteers.
In a double-blind, randomized cross-over study, plasma amino acids and mood were repeatedly measured in 18 healthy subjects before and after intake of ALAC and HPROT as well as after placebo protein, pure tryptophan, and a tryptophan-containing synthetic peptide. Except for the placebo protein, all interventions contained 0.8 g TRP.
Significantly faster and greater increases in plasma TRP/LNAA were found after HPROT than after ALAC. In addition, the effects of HPROT on plasma TRP/LNAA were comparable with the effects of the tryptophan-containing synthetic peptide and even exceeded the effect of pure tryptophan. Sixty minutes after intake, mood was improved only following intake of HPROT and pure tryptophan, whereas longer-lasting mood effects were only found after intake of HPROT.
The use of a tryptophan-rich hydrolyzed protein source may be more adequate to increase brain tryptophan and 5-HT function compared with intact alpha-lactalbumin protein or pure tryptophan.
This paper reviews and interprets a method for determining the nutritional value of D-amino acids, D-peptides, and amino acid derivatives using a growth assay in mice fed a synthetic all-amino acid diet. A large number of experiments were carried out in which a molar equivalent of the test compound replaced a nutritionally essential amino acid such as L-lysine (L-Lys), L-methionine (L-Met), L-phenylalanine (L-Phe), and L-tryptophan (L-Trp) as well as the semi-essential amino acids L-cysteine (L-Cys) and L-tyrosine (L-Tyr). The results show wide-ranging variations in the biological utilization of test substances. The method is generally applicable to the determination of the biological utilization and safety of any amino acid derivative as a potential nutritional source of the corresponding L-amino acid. Because the organism is forced to use the D-amino acid or amino acid derivative as the sole source of the essential or semi-essential amino acid being replaced, and because a free amino acid diet allows better control of composition, the use of all-amino-acid diets for such determinations may be preferable to protein-based diets. Also covered are brief summaries of the widely scattered literature on dietary and pharmacological aspects of 27 individual D-amino acids, D-peptides, and isomeric amino acid derivatives and suggested research needs in each of these areas. The described results provide a valuable record and resource for further progress on the multifaceted aspects of D-amino acids in food and biological samples.
An essential component of the human diet, L-tryptophan is critical in a number of metabolic functions and has been widely used in numerous research and clinical trials. This review provides a brief overview of the role of L-tryptophan in protein synthesis and a number of other metabolic functions. With emphasis on L-tryptophan's role in synthesis of brain serotonin, details are provided on the research uses of L-tryptophan, particularly L-tryptophan depletion, and on clinical trials that have been conducted using L-tryptophan supplementation. The ability to change the rates of serotonin synthesis in the brain by manipulating concentrations of serum tryptophan is the foundation of much research. As the sole precursor of serotonin, experimental research has shown that L-tryptophan's role in brain serotonin synthesis is an important factor involved in mood, behavior, and cognition. Furthermore, clinical trials have provided some initial evidence of L-tryptophan's efficacy for treatment of psychiatric disorders, particularly when used in combination with other therapeutic agents.
Modulating central serotonergic function by acute tryptophan depletion (ATD) has provided the fundamental insights into which cognitive functions are influenced by serotonin. It may be expected that serotonergic stimulation by tryptophan (Trp) loading could evoke beneficial behavioural changes that mirror those of ATD. The current review examines the evidence for such effects, notably those on cognition, mood and sleep. Reports vary considerably across different cognitive domains, study designs, and populations. It is hypothesised that the effects of Trp loading on performance may be dependent on the initial state of the serotonergic system of the subject. Memory improvements following Trp loading have generally been shown in clinical and sub-clinical populations where initial serotonergic disturbances are known. Similarly, Trp loading appears to be most effective for improving mood in vulnerable subjects, and improves sleep in adults with some sleep disturbances. Research has consistently shown Trp loading impairs psychomotor and reaction time performance, however, this is likely to be attributed to its mild sedative effects.
Recent research has suggested that anxiety may be associated with processing biases that favor the encoding of emotionally threatening information. However, the available data can be accommodated by alternative explanations, including response bias accounts. The current study introduces a novel paradigm that circumvents such interpretative problems by requiring subjects to make a neutral response (button press) to a neutral stimulus (visual dot probe). The position of this dot probe was manipulted on a VDU (visual display unit) screen relative to visually displayed words, which could either be threat related or neutral in content. Probe detection latency data were then used to determine the impact of threat-related stimuli on the distribution of visual attention. Clinically anxious (but not clinically depressed) subjects consistently shifted attention toward threat words, resulting in reduced detection latencies for probes appearing in the vicinity of such stimuli. Normal control subjects, on the other hand, tended to shift attention away from such material. The results were interpreted as supporting the existence of anxiety-related encoding bias, and it is suggested that this cognitive mechanism may contribute to the maintenance of such mood disorders.
An information-processing paradigm was used to examine attentional biases in clinically depressed participants, participants with generalized anxiety disorder (GAD), and nonpsychiatric control participants for faces expressing sadness, anger, and happiness. Faces were presented for 1000 ms, at which point depressed participants had directed their attention selectively to depression-relevant (i.e., sad) faces. This attentional bias was specific to the emotion of sadness; the depressed participants did not exhibit attentional biases to the angry or happy faces. This bias was also specific to depression; at 1000 ms, participants with GAD were not attending selectively to sad, happy, or anxiety-relevant (i.e., angry) faces. Implications of these findings for both the cognitive and the interpersonal functioning of depressed individuals are discussed and directions for future research are advanced.
This study aimed to assess cognitive and affective theory of mind (ToM) in patients with eating disorders and to explore its relationship with the clinical and psychopathological profile.
Theory of mind was assessed in 65 women, consisting of 22 with anorexia nervosa (AN), 19 with bulimia nervosa (BN), and 24 healthy controls (HC), using the Reading the Mind in the Eyes Test and the Faux Pas Test. These tasks evaluate affective and cognitive ToM, respectively. We also examined the correlations between performance on ToM tasks and the clinical psychopathological profile, which was extensively evaluated through self-report instruments and clinical interviews.
Patients with AN had poorer performance than BN patients and HCs had in the affective ToM task, particularly in recognizing negative emotions and emotions in male eyes. Moreover, this deficit showed no correlation with the psychopathological profile. Performance in the BN group was equivalent to that of HCs in both tasks.
In this study, patients with AN showed an impairment in affective ToM, independent of their clinical status. Consistent with other studies, our findings demonstrate a specific difficulty in social cognition in patients with AN. This may be a trait marker in this population and should be considered in treatment. Furthermore, patients with AN and BN have different difficulty profiles in this domain of social cognition. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.
A sophisticated ability both to generate displays of emotion and to respond to expressive behaviors of other individuals has emerged as a specialization in the course of primate evolution. Studies of the social behavior of nonhuman primates, especially those most related to ourselves, indicate that monkeys and apes are able to interpret social signals so as to assess the motivations of others. Studies of brain activity in monkeys looking at pictures of faces, facial expressions, and body movements, reveal regions of apparent specialized responsiveness to visual social stimuli. The existence of a discrete neural system in humans for cognition which generates a psychological model of others is suggested by patterns of deficit seen in certain neurologic syndromes. Empathy has several components and appears to lie on an evolutionary continuum.
Perspective-taking has become a main focus of studies on moral judgments. Recent fMRI studies have demonstrated that individual differences in brain activation predict moral decision making. In particular, pharmacological studies highlighted the crucial role for the neuropeptide oxytocin in social behavior and emotional perception. In the present study N=154 participants were genotyped for a functional polymorphism (rs2268498) in the promoter region of the OXTR gene. We found a significant difference between carriers and non-carriers of the C-allele in exculpating agents for accidental harms (F((1,152))=11.49, p=.001, η(2)=.07) indicating that carriers of the C-allele rated accidentally committed harm as significantly more blameworthy than non-carriers. This is the first study providing evidence for a genetic contribution to moral judgments.
It is generally agreed that at least some aspects of abnormal eating behaviour is indeed due in part to disordered cognition. The accumulated literature illustrates cognitive impairment in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Yet beyond being inconsistent, these independent studies also do not reveal the magnitude of impairment within and across studies and fail to give due consideration to the magnitude of impairment so as to understand the severity and breadth of impairment and/or differences in cognitive profiles between patients with AN and BN. Hence, the present review on the subject sought to articulate the magnitude of cognitive impairment in patients with AN and BN by quantitatively synthesizing the existing literature using meta-analytic methodology. The results demonstrate modest evidence of cognitive impairment specific to AN and BN that is related to body mass index in AN in terms of its severity, and is differentially impaired between disorders. Together, these results suggest that disturbed cognition is figural in the presentation of eating disorders and may serve to play an integral role in its cause and maintenance. Implications of these findings with respects to future research are discussed.
The role of the indoleamines in the affective disorders is reviewed. There is increasing evidence of abnormal indoleamine metabolism in depression and mania. In depression the urinary excretion of tryptamine and the cerebrospinal fluid concentration of 5-hydroxy-indoleacetic acid is considerably reduced. Brain levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid are lower in the brains of suicides than in those of subjects who died by other means. In mania, C.S.F. levels of 5-HIAA were also found be to low. In neither mania nor depression did the lumbar C.S.F. 5-HIAA levels change after clinical recovery. These changes in indoleamine metabolism may play a role in the aetiology of depression, since tryptophan, the amino acid precursor of the indoleamines, administered with or without a monoamine-oxidase inhibitor has a therapeutic action in depressed patients.
A rating-scale instrument derived from the Piaget (1932) story pair method and the Breznitz and Kugelmass (1967) intentionality questionnaire was devised to clarify the relationship between children's judgments of naughtiness of a story character and the story's description of the character's intent and the consequences of his behavior. Each of 7 stories was varied in 4 ways corresponding to the combinations of 2 intent levels and 2 consequence levels. Children as young as 6 yielded reliable ratings. An intent judgment quotient (IJQ) indicated the relative emphasis which each S placed on intent and consequences when judging. Decreases in naughtiness ratings of story variations involving good intent seemed to be a factor involved in the age-related increase in intent-based judgment which Piaget and others had noted previously.
In 1997 in this Journal we published the "Reading the Mind in the Eyes" Test, as a measure of adult "mentalising". Whilst that test succeeded in discriminating a group of adults with Asperger syndrome (AS) or high-functioning autism (HFA) from controls, it suffered from several psychometric problems. In this paper these limitations are rectified by revising the test. The Revised Eyes Test was administered to a group of adults with AS or HFA (N = 15) and again discriminated these from a large number of normal controls (N = 239) drawn from different samples. In both the clinical and control groups the Eyes Test was inversely correlated with the Autism Spectrum Quotient (the AQ), a measure of autistic traits in adults of normal intelligence. The Revised Eyes Test has improved power to detect subtle individual differences in social sensitivity.
During the past several decades, reduction in fat intake has been the main focus of national dietary recommendations to decrease risk of coronary heart disease (CHD). Several lines of evidence. however, have indicated that types of fat have a more important role in determining risk of CHD than total amount of fat in the diet. Metabolic studies have long established that the type of fat, but not total amount of fat, predicts serum cholesterol levels. In addition, results from epidemiologic studies and controlled clinical trials have indicated that replacing saturated fat with unsaturated fat is more effective in lowering risk of CHD than simply reducing total fat consumption. Moreover, prospective cohort studies and secondary prevention trials have provided strong evidence that an increasing intake of n-3 fatty acids from fish or plant sources substantially lowers risk of cardiovascular mortality. In this article, we review evidence from epidemiologic studies and dietary intervention trials addressing the relationship between dietary fat intake and risk of CHD, with a particular emphasis on different major types of fat, n-3 fatty acids and the optimal balance between n-3 and n-6 fatty acids. We also discuss the implications of the available evidence in the context of current dietary recommendations.
Cognitive impairment is a common feature of depressive illness. While accumulating evidence suggests that brain serotonin (5-HT) pathways play an important role in the neurobiology of depression, the extent to which altered 5-HT function is responsible for the associated changes in cognition and emotion remains unclear.
The present study examined the effects of acute dietary depletion of tryptophan (TRP) on cognitive and affective processing in healthy volunteers and explored the putative role of 5-HT in the neuropsychology of depression.
We administered computerised cognitive tests to healthy control participants following ingestion of TRP-free and nutritionally balanced amino acid drinks in a double-blind, placebo-controlled, crossover design.
The TRP-free amino acid mixture significantly lowered plasma total and free TRP concentrations relative to baseline values and produced selective deficits similar to those observed previously in cases of clinical depression. In particular, TRP depletion increased response times for happy but not sad targets in an affective go/no-go task and slowed responding in a visual discrimination and reversal learning task. These deficits were not due to a global sedative effect, as planning ability was unimpaired.
The present data indicate that serotonergic factors may be more involved in the disrupted inhibitory and emotional processing characteristic of depression than in other aspects of executive function, such as planning ability. These findings support the recent proposal that serotonergic manipulation may have greater effects on tasks mediated by frontal circuitry that includes the orbitofrontal cortex than by dorsolateral prefrontal cortex circuitry.
SB-399885 (N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide) has high affinity for human recombinant and native 5-HT(6) receptors, with pK(i) values 9.11+/-0.03 and 9.02+/-0.05, respectively and is a potent competitive antagonist (pA(2) 7.85+/-0.04). It displays over 200-fold selectivity for the 5-HT(6) receptor over all other receptors, ion channels and enzymes tested to date. SB-399885 inhibited ex vivo [(125)I]SB-258585 (4-Iodo-N-[4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-benzenesulfonamide) binding with an ED(50) of 2.0+/-0.24 mg/kg p.o. in rats. It had a minimum effective dose of 1 mg/kg p.o. in a rat maximal electroshock seizure threshold test and a long duration of action, overall demonstrating an excellent pharmacokinetic-pharmacodynamic correlation. Repeated administration of this agent (10 mg/kg p.o., b.i.d. for 7 days) significantly reversed a scopolamine-induced deficit (0.5 mg/kg i.p.) in a rat novel object recognition paradigm. Moreover, in aged rats (22 months old) SB-399885 (10 mg/kg p.o., b.i.d. for 7 days) fully reversed the age-dependent deficit in water maze spatial learning compared to vehicle-treated age-matched controls and significantly improved recall of the task measured by increases in the searching of the target quadrant on post-training days 1, 3 and 7. In vivo microdialysis in the rat medial prefrontal cortex demonstrated that acute SB-399885 (10 mg/kg p.o.) significantly increased extracellular acetylcholine levels. These data demonstrate that SB-399885 is a potent, selective, brain penetrant, orally active 5-HT(6) receptor antagonist with cognitive enhancing properties that are likely to be mediated by enhancements of cholinergic function. These studies provide further support for the potential therapeutic utility of 5-HT(6) receptor antagonists in disorders characterised by cognitive deficits such as Alzheimer's disease and schizophrenia.
Is the basis of criminality an act that causes harm, or an act undertaken with the belief that one will cause harm? The present study takes a cognitive neuroscience approach to investigating how information about an agent's beliefs and an action's consequences contribute to moral judgment. We build on prior developmental evidence showing that these factors contribute differentially to the young child's moral judgments coupled with neurobiological evidence suggesting a role for the right temporoparietal junction (RTPJ) in belief attribution. Participants read vignettes in a 2 × 2 design: protagonists produced either a negative or neutral outcome based on the belief that they were causing the negative outcome (“negative” belief) or the neutral outcome (“neutral” belief). The RTPJ showed significant activation above baseline for all four conditions but was modulated by an interaction between belief and outcome. Specifically, the RTPJ response was highest for cases of attempted harm, where protagonists were condemned for actions that they believed would cause harm to others, even though the harm did not occur. The results not only suggest a general role for belief attribution during moral judgment, but also add detail to our understanding of the interaction between these processes at both the neural and behavioral levels.
• functional MRI
• medial prefrontal cortex
• morality
• right temporoparietal junction
• theory of mind
5-HT6 receptor antagonists improve cognitive processes in rodents. However, their site(s) of action remains unexplored and their influence upon social memory has been little investigated.
We examined the influence of 5-HT6 receptor ligands upon social memory in rats by use of systemic or local administration into the frontal cortex (FCX), striatum, or nucleus basalis magnocellularis (NBM).
The social recognition test is based upon the ability of an adult rat to recognize a younger conspecific during the second of two 5-min sessions. In a procedure without an inter-session interval, the actions of drugs alone and the ability to reverse "amnesia" induced by the muscarinic antagonist, scopolamine (1.25 mg/kg, s.c.), were examined. The potential promnesic effect of drugs was also investigated in another procedure where a spontaneous deficit of recognition was induced by a 120-min inter-session interval.
The 5-HT6 receptor agonist, WAY-181187 (10.0 mg/kg, i.p.), significantly impaired social recognition. This effect was abolished by the 5-HT6 receptor antagonists, SB-271046 (20.0 mg/kg, i.p.) and SB-258585 (10.0 mg/kg, i.p.). These agents also abolished scopolamine-induced amnesia (10.0 and 2.5 mg/kg, i.p., respectively) and reversed the delay-induced deficit (10.0-20.0 and 2.5-10.0 mg/kg, i.p., respectively). WAY-181187 into the FCX significantly impaired social recognition (0.16-0.63 microg/side). Conversely, SB-271046 into the FCX (2.5-5.0 microg/side), but neither into the striatum nor the NBM, significantly reversed spontaneous deficit.
These results indicate that 5-HT6 receptors modulate social recognition by actions in the FCX and underpin their pertinence as targets for the treatment of psychiatric disorders in which cognitive function is compromised.
Alzheimer's disease (AD) is a devastating neurological condition characterized by a progressive decline in cognitive performance accompanied by behavioral and psychological syndromes, such as depression and psychosis. The neurochemical correlates of these clinical manifestations now appear to involve dysfunctions of multiple neurotransmitter pathways. Because of the extensive serotonergic denervation that has been observed in the AD brain and the important role played by serotonin (5-HT) in both cognition and behavioral control, this neurotransmitter system has become a focus of concerted research efforts to identify new treatments for AD. 5-HT exerts its diverse physiological and pharmacological effects through actions on multiple receptor subtypes. One of the newest members of this family is the 5-HT6 receptor, a subtype localized almost exclusively in the CNS, predominating in brain regions associated with cognition and behavior. With the subsequent development of selective 5-HT6 receptor antagonists, preclinical studies in rodents and primates have elucidated the function of this receptor subtype in more detail. It is increasingly clear that blockade of 5-HT6 receptors leads to an improvement of cognitive performance in a wide variety of learning and memory paradigms and also results in anxiolytic and antidepressant-like activity. These actions are largely underpinned by enhancements of cholinergic, glutamatergic, noradrenergic, and dopaminergic neurotransmission, together with learning-associated neuronal remodeling. A preliminary report that the cognitive enhancing properties of a 5-HT6 receptor antagonist (namely, SB-742457) extends into AD sufferers further highlights the therapeutic promise of this mechanistic approach.
The “Reading the Mind in the Eyes” test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism
- Baron-Cohen
Assignment of moral responsibility and punishment
- Shultz
Shultz TR, Wright K, Schleifer M. Assignment of Moral Responsibility and
Punishment. Child Dev 1986. https://doi.org/10.2307/1130649.