Tag: anxiety

Screening for alcohol use disorder gets a diagnostic accuracy check-up

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In a recent systematic review published in the journal JAMA, researchers evaluated the diagnostic accuracies of screening tools for alcohol usage disorder (AUD) using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.

Alcohol usage is a primary cause of accidents, infections, and cancer, especially among young and elderly individuals. Pregnant women have an increased risk of fetal alcohol syndrome. Screening rates for alcohol use disorder (AUD) are low, warranting the re-evaluation of the accuracy of screening tests to fit with the DSM-5 criteria. New case definitions have an impact on the accuracy of existing screening instruments, with 12% to 61% fewer individuals identified with AUD than those diagnosed using DSM-IV criteria. Understanding non-harmful drink numbers and terminology is necessary for assessing excessive alcohol usage.

In the present systematic review, researchers conducted qualitative (systematic literature review) and quantitative (meta-analysis) research to assess the diagnostic accuracy of AUD screening tools using DSM-5.

Does This Patient Have Alcohol Use Disorder? The Rational Clinical Examination Systematic Review. Image Credit: Syda Productions / Shutterstock

Clinical case scenario and methodology

An 18-year-old lady visits her healthcare physician with anxiety symptoms she believes are the result of personal life stress. Her systolic/diastolic blood pressure is 145/90 mmHg, and her heart rate is 100 beats per minute. She exhibits minor trembling, which she attributes to anxiety over the visit. Her medical history is disease-free, although she admits to drinking alcohol at least once a week, “mostly when out with friends.” The doctor wonders how much more information might be obtained from basic screening instruments to determine her AUD risk.

The researchers searched the Embase and MEDLINE databases for original research evaluating the diagnostic accuracies of AUD screening tools following DSM-5 guidelines published in English between January 1, 2013, and February 24, 2023. They retained studies with screening tools identifying high-risk or excessive alcohol intake among individuals aged 9.0 to 18 years, those aged ≥65 years and expecting women since AUD diagnosis does not include excessive alcohol intake as a screening criterion. The researchers calculated likelihood ratios (LR), specificity, and sensitivity. They also conducted meta-analytical research to derive a cumulative LR.

Two researchers independently reviewed the data using the Rational Clinical Examination evidence levels to assess study quality. They used the Quality Assessment of Diagnostic Accuracy Studies tool to evaluate the risk of bias. They assessed the estimated prevalence of high-risk alcohol usage and AUD in the general public from the United States Substance Abuse and Mental Health Services Administration estimates and calculated the pooled prevalence using random-effects models.

Results and Scenario Resolution

From the 4,303 identified studies, the researchers retained 35, including 79,633 individuals, of whom 11,691 consumed alcohol excessively or were diagnosed with AUD. Among the 35 included studies, the overall prevalence of AUD was 19% in adults, 21% in young people, 25% in women, 33% in men, and 8.1% in pregnant individuals.

Across ages, a ≥8.0 score on the AUD Identification Test (AUDIT) elevated AUD likelihood (LR, 6.50). Positive screening results using the AUDIT tool identified AUD better among women (LR, 6.90) than men (LR, 3.80). A <8.0 AUDIT score reduced the AUD likelihood by comparable magnitudes for both genders (LR, 0.3). The AUDIT-Consumption (AUDIT-C) test has a gender-specific threshold of ≥4.0 for men and ≥3.0 for women but showed lower utility for AUD identification (LRs of 1.8 and 2.0 for males and females, respectively). AUDIT-C seemed beneficial for identifying excessive alcohol intake among individuals aged 9.0 to ≤18 years and those aged >60 years.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) pediatric age-specific alcohol intake cut-offs helped estimate AUD likelihood at the lowermost risk cut-off (LR, 0.2), at moderate-level AUD risk cut-off (LR, 3.40), and the uppermost risk cut-off (LR, 15). Among pregnant women screened within two days postpartum, AUDIT scores of ≥4.0 identified individuals likely to develop AUD (LR, 6.40), whereas scores below 2.0 in the Tolerance, Annoyed, Cut-Down, and Eye-Opener (T-ACE) and the Tolerance, Worried, Eye-Opener, Amnesia, and Cut-Down (TWEAK) screening tools identified AUD to a similar extent (LR, 0.1).

Non-specific clinical signs such as hypertension and symptoms such as anxiety may result from excessive alcohol consumption. According to the NIAAA instrument, the female patient reported drinking once per week over the previous year as a positive screening result with an LR of 15, increasing the likelihood of AUD to between 60% and 72%. With this screening result, physicians should undertake a thorough DSM-5 diagnostic interview. If the DSM-5 diagnostic interview results are positive, she should receive guideline-directed therapies appropriate to the severity of her AUD. If the DSM-5 diagnostic interview does not indicate AUD, the therapist should inquire about her drinking habits and offer advice on the hazards of alcohol consumption and ways to reduce usage.

Based on the systematic review findings, the AUDIT tool can identify AUD among adults and individuals within two days of delivery. The NIAAA tool helps identify pediatric and adolescent AUD cases. AUDIT-C could benefit excessive alcohol intake identification among youngsters and older individuals.

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April 11, 2024
Gut-friendly psychobiotics could brighten moods and fight depression
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In a recent review published in the journal Nutrients, researchers investigated the psychobiotic treatment of depression by restoring microbial balance and regulating the microbiome-gut-brain (MGB) axis.

Depression is a global health concern that causes pain, lost productivity, higher healthcare expenditures, and a high risk of suicide. Dysbiosis, a disruption in gut microbiome homeostasis, can affect the gut-brain axis (GBA), resulting in microbial alterations. Psychobiotics, which have favorable effects on the gut barrier, immunological responses, cortisol expression, and the hypothalamic-pituitary-adrenal (HPA) axis, might be used as a supportive treatment for depression, particularly in treatment-recalcitrant depression (TRD) cases.

The Power of Psychobiotics in Depression: A Modern Approach through the Microbiota–Gut–Brain Axis: A literature Review. Image Credit: T. L. Furrer / Shutterstock

About the review

In the present review, researchers presented clinical evidence and elucidated the underlying mechanisms of psychobiotic therapies for depression via their effects on gut-brain communication.

Association between the gut-brain axis and depressive disorders

Depression is a complex biological disorder influenced by a variety of molecular mechanisms, such as neurotransmitter reduction, a decrease in brain-derived neurotrophic factor (BDNF), an abnormally stressed HPA axis, an increase in pro-inflammatory gut microbial responses, and vagus nerve interaction between gut microbiota and brain. The GBA and intestinal microbes are inextricably linked, with MGB influencing neurobehavioral outcomes via endocrine, neuronal, and immunological mechanisms. Dysbiosis, or a disruption in the GBA axis, can alter the intestinal microbiome, influencing neuronal function, immunology, and gut inflammation.

Chronic stress impairs intestinal homeostasis and changes gut microbial composition, increasing Faecalibaculum and Clostridium in individuals while decreasing Lactobacillus and Bifidobacterium. Recent animal models have demonstrated a relationship between the gut-brain axis and stress sensitivity and resilience. The intestinal microbiome influences inflammatory responses and brain states and is associated with psychiatric conditions such as major depressive disorder, bipolar disorder, psychosis, schizophrenia, anorexia nervosa, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and attention-deficit hyperactivity disorder (ADHD).

Graphical Abstract

Gut microbial metabolites involved in antidepressant actions

The gut microbiome is a vital metabolite source, facilitating communications between the gut and the central nervous system. These metabolites consist of tryptophan, gamma-aminobutyric acid (GABA), serotonin, histamine, 5-hydroxytryptamine (5-HT), short-chain fatty acids (SCFAs), acetylcholine, and dopamine (DA). Microbial metabolites impact various mechanisms important for mental health, such as immunological and neuroendocrine system development, nutrition metabolism modulation, and xenobiotic transformation. They also help to maintain gut barrier function, strengthen the intestinal mucosa, and keep dangerous infections and poisons out of circulation. SCFAs are necessary for emotional states and cognition, impacting the host’s brain via G-protein-coupled receptors. They supply energy to colonocytes, protect the intestinal barrier, regulate inflammatory responses, and regulate hunger hormones. Increased SCFAs can reduce neuroinflammation and boost BDNF synthesis, boosting brain neuroplasticity.

Impact of probiotic gut microbes on depression

Psychobiotics are probiotic bacteria that boost mental health by improving the intestinal barrier and modifying the immune response in the gut-associated lymphoid tissue (GALT), which plays a role in inflammation development. The gut microbiota is crucial in the pathophysiology of depression since it regulates inflammatory processes. Bifidobacterium breve boosts BDNF levels, lowers interleukin-6 (IL-60) and TNF-alpha (TNF-α) levels, and enhances cognitive function.

Lactic acid bacteria (LAB) reduce neuroinflammation, lower kynurenine levels, and promote tight junction (TJ) expression. Lactobacillus plantarum 299v boosts dopamine levels and helps with selective serotonin reuptake inhibitor (SSRI) therapy, resulting in better cognitive performance and lower kynurenine levels. Akkermansia muciniphila suppresses inflammatory cytokines in microglial cells, which lowers depressive-like behavior. Clostridium butyricum protects against neurological dysfunction, whereas Faecalibacterium prausnitzii lowers corticosterone and C-reactive protein (CRP) levels while boosting IL-10 levels and lowering cognitive impairment in Alzheimer’s disease rats.

Clinical evidence highlighting the psychobiotic features of bacterial strains

Postbiotics such as Bacillus coagulans MTCC 5856 and Bifidobacterium longum 1714 can help with irritable bowel syndrome (IBS) symptoms and depression. Probiotics such as Bifidobacterium longum 1714 and NCC3001 help to decrease stress and enhance memory. When coupled with antidepressants, these probiotics can effectively cure TRD. Probiotics such as Lactobacillus casei Shirota and Lactobacillus gasseri CP2305, at 2.5 × 109 CFU/g, enhance general health and lower mood disorders. Multi-strain probiotic medication also boosts general health, alleviates anxiety symptoms, and reduces inflammation. Lactobacillus gasseri fermented black soybean beverage helps healthy individuals sleep better and feel less stressed. Probiotic milk drinks and fermented soybean seed paste improve cognitive performance in individuals with moderate cognitive impairment and Alzheimer’s disease.

The review highlights probiotics’ involvement in lowering depressive symptoms and their importance in mental health. The gut microbiota is crucial for digestion, food absorption, and psychiatric concerns such as stress reduction and anxiety. With a shift in the emphasis in modern life from infectious disorders to more common mental illnesses such as depression, good dietary habits and optimal intestinal function are critical for mental well-being, with probiotics playing an important role.
Journal reference:

Dziedzic, A.; Maciak, K.; Bliźniewska-Kowalska, K.; Gałecka, M.; Kobierecka, W.; Saluk, J. The Power of Psychobiotics in Depression: A Modern Approach through the Microbiota–Gut–Brain Axis: A literature Review. Nutrients 2024, 16, 1054. DOI: 10.3390/nu16071054, https://www.mdpi.com/2072-6643/16/7/1054
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April 8, 2024
Exploring prebiotics and probiotics as dual fighters against depression and obesity

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Depression is among the most prevalent and potentially serious mental health disorders, accounting for up to 800,000 suicides a year. The risk factors for depression have, therefore, undergone much exploration.

A recent study published online in Nutrients deals with the interactions between depression and nutrition, coupled with exercise.

Study: The Role of Gut Microbiota, Nutrition, and Physical Activity in Depression and Obesity—Interdependent Mechanisms/Co-Occurrence. Image Credit: Bits And Splits/Shutterstock.com

About depression

Depressive disorders include several categories, including persistent depressive disorder (dysthymia), premenstrual dysphoric disorder, as well as depression induced by addictive drugs or medications or by medical conditions.

All are characterized by sadness and irritability, with bodily and mental changes. The effect is a lowered quality of life and impaired functioning.

Moreover, depression is known to increase the risk for a number of metabolic diseases, such as diabetes, obesity, and ischemic heart disease.

Conversely, dietary patterns are linked to mental health as well as malnutrition. For instance, excessive fat intake leads to chronic inflammation and obesity.

Obesity

Obesity is defined as the accumulation of body fat in excess, as measured by the body mass index (BMI) and the body fat percentage. It is associated with a higher risk of cardiovascular disease (CVD), insulin resistance, cancer, and nerve damage.

Risk factors for obesity are well-known and include gender, age, smoking, apart from the consumption of excessive fat and of processed foods, which are typical of Western diets.

Obesity and depression often affect the same individual, along with anxiety disorders. They have a common mechanism of action, as seen by their bidirectional association.

People who are depressed often indulge in comfort eating, which may increase body weight, especially if the person is also inactive. The risk of obesity in people undergoing emotional stress is almost 40% higher.

Similarly, obese people are almost 20% more likely to become anxious or depressed because of negative self-image as well as adverse social perceptions that they are too lazy or undisciplined to regulate their diet and their weight. The treatment of depression with antidepressants is effective but may cause weight increase.

Unfortunately, both obesity and depression are among the most prevalent disorders globally and have a high death rate, leading to powerful scientific interest in their interrelationships.

Gut microbiota

The gut microbiota is essential to proper energy storage and metabolism, but shows marked variability in obese vs lean individuals. This includes lower diversity and fewer commensal bacteria but more pathogenic microbes in the obese. The resulting aberration in metabolism may contribute to obesity.

The need for a rational diet along with therapies like psychotherapy and medication to treat patients with depression is stressed by some scientists.

In addition, probiotics and prebiotics may be required, along with nutritional supplements, to correct dysbiosis and vitamin deficiencies.

Probiotics and gut microbiota

The researchers sought to understand how gut microbes may be useful in treating both obesity and depression and the role of probiotics and prebiotics in such therapy.

The review suggests that about 57% of the composition of the gut microbiota responds to dietary patterns.

Probiotics strengthen the gut barrier and modulate the immune system. Their use is associated with improving depressive symptoms, perhaps by supplying vitamin D and short-chain fatty acids (SCFAs), which combat inflammation.

Some strains of probiotic bacteria directly affect neural pathways. They inhibit the depression-inducing hypothalamic–pituitary–adrenal axis (HPA axis), and promote the secretion of the anti-stress neurotransmitter GABA, also known as gamma-aminobutyric acid.

Others produce gut neurotransmitters that also affect the brain, affecting the mood for the better.

Some clinical trials in humans suggest a positive effect of probiotics on depressive disorders as well as on obesity and related metabolic conditions like insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).

Further research is essential to validate these results, especially as probiotics work well on gut health and overall disease control only as part of a holistic management strategy, including proper diet, exercise, stress regulation, and adequate sleep.

Bacterial strains linked to improved neural pathways, sometimes called psychobiotics, include multiple Lactobacillus strains like Lactobacillus casei Shirota, Lactobacillus fermentum NS8 and NS9, and Lactobacillus rhamnosus JB-1, as well as Bifidobacterium strains like Bifidobacterium longum Rosell-175, Bifidobacterium longum 1714, and Bifidobacterium longum NCC3001.

Diet and mental health

The brain receives a good share of absorbed nutrients and utilizes them to keep itself healthy. For instance, regeneration, neuroplasticity, and an adequate antioxidant reserve depend on the proper supply of nutrients to the brain.

Supplementation with fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), magnesium, folate, and vitamins E and D have been suggested to be beneficial in countering or mitigating severe depression and reducing neuroinflammation.

Specific diets like the Mediterranean diet (MD), the DASH (Dietary Approaches to Stop Hypertension), or vegetarian diets have frequently been assessed for their relationship with physical and mental health.

The authors of the current study found reduced depression and obesity risk with both the DASH and the MD, but contradictory data with vegetarian and vegan diets. However, high-quality vegetarian diets were protective against depression, underlining the pivotal role of diet quality in the type of diet chosen.

Physical activity and obesity/mood disorders

There is ample evidence that weight management is aided by increasing the overall energy expenditure and improving the mood, with reduced anxiety and depression. Aerobic exercise has been recommended for its ability to build fitness and help reduce weight.

Physical exercise is linked with lengthening telomeres, a metabolic health biomarker. It is also associated with better brain health, sleep quality, and reduced depressive symptoms.

Physical exercise is also linked to better gut microbiota composition, stronger commensals, and more anti-inflammatory bacteria.

Early-life exercise may promote the development of bacteria that can help the host adapt to changing conditions and promote healthy brain development.

The broader impact of obesity and depression

Depression is associated with increased mortality and morbidity, absenteeism, severe decreases in the quality of life, and reduced productivity.

Obesity, which is currently estimated to have a prevalence of 30% in the USA, also has profound impacts on personal and social health. It reduces female fertility, promotes loss of cognitive ability, reduces the lifespan, and may increase employment difficulty.

Conclusions

Obesity and depression have common origins and act to exacerbate each other. This interrelationship significantly impacts the quality of life. One possible explanation for their connections may be via gut dysbiosis.

This has stimulated much study on the potential use of probiotics and prebiotics in depression and anxiety, as well as in obesity.

“Encouraging findings from existing research underscore the need for robust clinical trials to evaluate the therapeutic potential of microbiota modulation.”

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April 4, 2024
Metabolic markers tied to increased risk of depression and anxiety, study finds

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In a recent study published in the JAMA Network Open, a group of researchers determined if carbohydrate, lipid, and apolipoprotein (Apo) biomarkers are linked to the future development of depression, anxiety, and stress-related disorders in a large Swedish cohort.

Study: Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders. Image Credit: hikrcn / Shutterstock

Background

About one-third of people experience depression, anxiety, and stress-related disorders in their lifetime, with growing evidence suggesting a link between these psychiatric conditions and metabolic dysregulation, such as lipid and glucose abnormalities that trigger inflammation. This inflammation may increase the risk of psychiatric disorders by affecting brain health. However, existing research on metabolic biomarkers and their association with psychiatric disorders has been inconsistent, often limited by methodological issues like short follow-up periods and reliance on self-reported depression measures, mainly in older adults. Furthermore, there is a notable gap in research on the connection between these biomarkers and anxiety or stress-related disorders, particularly the long-term effects of Apo’s. Further research is crucial to clarify these associations and explore potential preventative and therapeutic strategies.

About the study

The Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort, spanning from 1985 to 1996 and predominantly in the Stockholm region, includes 812,073 participants (49% men, 51% women) who underwent routine health screenings or were referred for laboratory testing due to health conditions. For this study, 211,200 participants over 16, free from mental disorders at baseline and with at least one biomarker measurement, were selected. Mental disorder histories were confirmed using the Swedish Patient Register, employing various International Classification of Diseases (ICD) revisions for accuracy.

The study included a broad spectrum of stress-related conditions, with both primary and secondary diagnoses considered. Biomarkers of interest include glucose, cholesterol types, triglycerides, apolipoproteins, and their ratios, analyzed by consistent laboratory methods. Covariates like sex, age, fasting status, socioeconomic status, and birth country were also recorded, offering a detailed background for each participant.

Statistical analysis involved Cox proportional hazards regression models to explore the relationship between initial biomarker levels and the risk of psychiatric disorders, adjusting for relevant covariates and employing both categorical and continuous variable analyses. Sensitivity analyses further refined these findings by focusing on employed individuals, outpatient referrals and excluding those with missing socioeconomic data. A case-control study embedded within the larger cohort provided a longitudinal perspective, examining biomarker trends up to 30 years before diagnosis, with controls matched to cases by sex, age, and enrollment year.

Study results

In the substantial cohort of 211,200 participants, consisting of 58% males and 42% females, with the vast majority born in Sweden (89.4%), the study observed notable trends over a mean (SD) follow-up period of 21 years. The participants had an average age of 42.1 years at their first blood sampling, with diagnoses of depression, anxiety, or stress-related disorders emerging at a mean age of 60.5 years. The incidence rates for these disorders varied, with depression, anxiety, and stress-related disorders recorded at rates of 21.5, 16.6, and 10.5 per 10,000 person-years, respectively. Notably, a segment of the cohort was diagnosed with multiple disorders, yet only 0.4% received diagnoses across all three categories.

The analysis revealed a correlation between metabolic biomarker levels and psychiatric health risks. Elevated glucose and triglyceride (TG) levels significantly increased the risk of psychiatric disorders, whereas higher levels of high-density lipoprotein cholesterol (HDL-C) offered a protective effect. The delineation of risk did not change markedly between low and normal glucose levels, suggesting a particular risk threshold. This pattern persisted across gender lines and when evaluating each psychiatric condition individually, reinforcing the robustness of these findings.

Further analysis, specifically among employed individuals, yielded consistent results with the primary analysis, underscoring the relationship between metabolic health and psychiatric conditions regardless of employment status. When examining the impact of outpatient care referrals on biomarker measurements, the associations remained similar for glucose and TGs, though the protective role of HDL-C lessened. Additionally, higher levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), ApoB, and the ApoB/ApoA-I ratio were inversely associated with the risk of psychiatric disorders, indicating a complex interplay between various lipid biomarkers and mental health.

Socioeconomic status also emerged as a significant factor, with lower incidence rates of psychiatric disorders observed among those with higher socioeconomic standing. This trend held true even after adjusting for potential confounders, including missing socioeconomic data, further emphasizing the socioeconomic gradient in psychiatric disorder risk.

Longitudinal analysis, tracking biomarker levels up to 30 years prior to diagnosis, illustrated that patients eventually diagnosed with anxiety, depression, or stress-related disorders exhibited consistently higher levels of TGs, glucose, and TC two decades before diagnosis. Additionally, higher levels of ApoA-I and ApoB were noted in the decade leading up to diagnosis, indicating a prolonged period of metabolic dysregulation preceding psychiatric diagnoses.

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April 4, 2024
Banning smartphones is tempting but it won’t solve anxiety in children

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Rolf Vennenbernd/dpa/Alamy

PANIC is spreading – in the press and the playground – about the impact of social media and smartphones on children.

There are many questions around what modern technologies are doing to young minds. Some claim that when we first gave children smartphones, it was the largest uncontrolled experiment humanity ever performed on its own children. That young brains are being rewired, and that social media is responsible for an alarming rise in childhood anxiety.

There has indeed been an increase in anxiety in young people, as we report in our special issue, starting with “The new evidence that explains what anxiety really is”…

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April 3, 2024
Wastewater study sheds light on tracking cannabis use challenges

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In a recent study published in the journal Water Research, researchers discussed the progress in wastewater-based surveillance (WBS) of cannabis use.

Cannabis is the most used drug globally, and its frequent use is associated with anxiety, depressive disorders, brain development interference, and social/legal consequences. Moreover, cannabis consumption can strain healthcare systems and legal frameworks. Notwithstanding these concerns, cannabis is being increasingly legalized for recreational and medicinal purposes.

Making waves: Wastewater-based surveillance of cannabis use. Image Credit: SpiritArt / Shutterstock

Preliminary signs/results of this legalization indicate increased daily intake and tax revenues and decreased arrest rates. This has also enabled the implementation of harm-reduction strategies. Thus, continuous monitoring of cannabis use is crucial to gain insights into spatiotemporal trends and assess the impact of new enforcement measures, legal status, and harm reduction initiatives. WBS and wastewater-based epidemiology (WBE) have become popular for public health monitoring.

WBE monitors changes and spatial differences in drug use, complementing established indicators. Thus, it is a vital source of information on community-level drug consumption. Nevertheless, there have been uncertainties with WBE-derived estimates of cannabis use than other drugs. The present study discussed the progress in WBS of cannabis use and existing challenges.

Analytical barriers

The analytical techniques in WBS involve determining diverse biomarkers, where 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THC-COOH), the primary urinary metabolite of the principal psychoactive compound in cannabis, tetrahydrocannabinol (THC), is just one of the analytes to be measured. A single analysis of multiple analytes is time-saving, economical, and more efficient, albeit a compromise of experimental conditions is required. Furthermore, analyzing THC-COOH requires pH adjustment.

At acidic pH, the hydrophobic molecular form of THC-COOH favors adsorption to sampling/processing material surfaces or particulate matter. Thus, a best-practice analytical protocol was proposed to avoid acidification. Nevertheless, the lipophilic features of cannabinoids impede analytical determination. As such, more specific techniques have been introduced to detect THC and its metabolites in influent wastewater solids.

Challenges due to in-sewer and sample dynamics

Quantification of THC and metabolites in suspended solids and aqueous phase of influent wastewater showed their partitioning in the two phases of the influent. Further, it is speculated that fecal matter from non-users and users may impact the total load in the aqueous phase. These insights have opened additional inquiries, unveiling knowledge gaps warranting further analyses on the impact of influent composition, sampling uncertainty related to the collection of solids, and partitioning dynamics during in-sewer transport.

Pharmacokinetic barriers

Interestingly, WBS can estimate drug consumption via a back-calculation using influent mass loads, pharmacokinetic excretion factors, and molar mass ratio of parent/metabolite. Distinct excretion correction factors (36.4 and 182) derived from urinary levels of THC-COOH have been proposed for cannabis. While these correction factors accounted for uncertainty, they do not consider (other) metabolites excreted in feces. As such, more investigations are required to corroborate and increase knowledge of urinary and fecal excretion (of THC-COOH).

Administration routes

Different administration routes of cannabis yield distinct excretion rates, affecting back-calculations. Although smoked cannabis is the most common route, the use of vaping and edible cannabis has been increasing. In 2020, more than one-fifth of 12^th-grade students tried vaping cannabis, which is twice the estimate from five years ago.

Such changes can vary by country and time and could be related to cannabis legalization. This can also lead to changes in the type of cannabis used; for instance, cannabidiol has increasingly become popular. Therefore, there is a need for techniques that can distinguish between analytes when other cannabis types become prevalent.

Current state of WBS of cannabis

WBS is an instrumental tool that can report high-resolution trends and changes. However, currently, careful interpretation of WBS data is necessary to evaluate cannabis consumption. Some researchers have described how best to utilize these data. Caution should be exercised for spatial comparisons of excreted quantities of THC and metabolites in the influent.

Influent wastewater and sewer catchments exhibit variations across locations; consequently, spatial trends may be susceptible to greater uncertainty. Further, cannabis use trends derived from WBS have an inherent temporal value when catchment demographics remain unchanged. The relative scale of drug use is often essential to identify problem areas and make policy decisions.

Concluding remarks

Taken together, the study highlighted the current barriers to accurate cannabis consumption estimates. The authors propose that future research should better understand administration and clearance routes, integrate fecal data into correction factors, and develop a consensus for a common approach to report estimates from WBS data. They also suggest caution while drawing conclusions from WBS data until these challenges are addressed.

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April 3, 2024
The new evidence that explains what anxiety really is

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WHEN I was asked to write this article, my heart started beating faster, my hands started shaking and my thoughts went into overdrive coming up with what felt like hundreds of objectively sensible reasons why I couldn’t do it. I could tell you that as chief subeditor at New Scientist I don’t often get a chance to write. But the truth is I rarely write because I am very anxious about it. What if the people I contact don’t respond? What if I write something stupid? What if I am stupid? What if, what if, what if.

Clearly, I chose to write this article, partly because I am stubborn and hate that these anxious feelings hold me back from doing things I might enjoy, and partly because I find that doing the things that make me anxious helps me overcome that feeling (see “Five scientific ways to help reduce feelings of anxiety”). But my main motivation was to answer questions that have been bothering me for years: what exactly is anxiety and what is happening in my body and brain to cause this feeling?

Answering that first question is difficult, in part because there is no one way to feel anxious. “I’d say there’s as many types of anxiety as there are people in the world,” says Oliver Robinson, head of the Anxiety Lab at University College London.

We do know everyone experiences anxiety – it helps prime us to be ready in possibly risky situations. Consider walking home alone in the dark, where that feeling…

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April 2, 2024
Green environments linked to lower depression and anxiety risk, study finds

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In a prospective cohort study published in the journal Nature Mental Health, researchers in China investigated the potential association between exposure to residential greenness and the incidence of anxiety and depression and explored the underlying pathways. They found prolonged residence in green environments was linked to a lower risk of depression and anxiety, potentially via air pollution.

Study: Long-term exposure to residential greenness and decreased risk of depression and anxiety. Image Credit: p-jitti / Shutterstock

Background

Mental disorders, including depression and anxiety, are among the most debilitating conditions, with their impact on global health burden rising steadily. These disorders affect millions worldwide and are influenced by genetic, behavioral, and environmental factors. Recognizing modifiable factors associated with mental health issues could offer valuable targets for interventions and inform potential treatment strategies.

A growing body of evidence now recognizes residential greenness as a significant environmental factor in reducing stress and improving health, particularly mental well-being. While some longitudinal studies suggest a negative association between green spaces and depression, inconsistent findings highlight the need for larger, well-designed prospective cohort studies to better understand this relationship. Although long-term exposure to greenness is hypothesized to provide cumulative mental health benefits through various pathways, there is a dearth of population-based evidence, and the predominant mechanism remains uncertain. In the present cohort study, researchers explored the link between long-term exposure to residential greenness, depression, and anxiety while examining the potential pathways and factors.

About the study

Data from 409,556 participants were obtained from the United Kingdom (UK) Biobank, a large prospective cohort. The median age of participants was 58 years, and 52.4% were female. About 90.8% of the participants were white, and 86.2% resided in urban areas. Participants provided detailed information through questionnaires, physical measurements, and biological samples. The analysis focused on associations between residential greenness and incident depression and anxiety, excluding those with pre-existing mental health issues. Subsets of participants were analyzed to explore the potential pathways. The mean follow-up duration was 11.9 years.

Greenness around residential areas was evaluated using NDVI (short for Normalized Difference Vegetation Index), a measure based on land surface reflection of infrared wavelengths within buffer regions of sizes 300 m, 500 m, 1,000 m, and 1,500 m. Data were obtained from moderate-resolution imaging spectroradiometer remote sensing. Preprocessing was performed to remove cloudy and snow-covered areas, and water body impacts were addressed. Anxiety or depression diagnoses at baseline and follow-up were confirmed using hospital admissions, death registry, primary care records, and self-reports verified by healthcare professionals. Cases were identified using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes.

Various potential confounders and mediators were considered in the analysis, including sociodemographic factors (age, gender, ethnicity, income, education, residence location), lifestyle factors (body mass index (BMI), smoking status, drinking status), and environmental factors (air pollutants, noise, water percentage, urban morphometric measures). Statistical analyses involved time-varying Cox proportional hazard models, hazard ratios (HR), restricted cubic splines, mediation analysis, subgroup analysis, and sensitivity analysis.

Results and discussion

In the study period, about 4.1% and 3.5% of the total participants were diagnosed with anxiety (HR = HR = 0.86) and depression (HR = 0.84), respectively. Residential greenness exposure consistently showed a protective effect on depression and anxiety, with significant reductions in risk observed across different buffer sizes. Mediation analyses indicated that air pollution, mainly particulate matter of diameter 2.5 microns (PM_2.5), NO₂, NO_x, SO₂, and O₃, significantly mediated the associations between NDVI and both depression and anxiety. Further, IMD (short for index of multiple deprivation) was found to mediate the association between NDVI and depression. Additionally, factors such as distance to coast, factory, and healthcare places, as well as lifestyle factors like sleep duration and social engagement, showed small but significant mediation effects. The protective effects of green surroundings were found to be more pronounced against depression and anxiety in older adults and males.

Sensitivity analyses confirmed the robustness of the main findings. The large sample size, long follow-up duration, detailed adjustment for potential confounders, and exploration of potential mediators strengthen the findings. However, the study is limited by the lack of details on green space quality, the potential influence of extraneous factors on greenness exposure, healthy volunteer bias, and potential bias introduced by using diagnosis rather than symptom onset. Further research is warranted to confirm these findings.

Conclusion

In conclusion, this is the first prospective cohort study to provide comprehensive insights into the association between exposure to greenness and mental health. The findings reveal that long-term exposure to residential greenness is linked to lower risks of depression and anxiety. Higher levels of green surroundings showed more substantial positive effects on mental health, with reduced air pollution identified as a significant mediator. These findings call for strategic urban planning interventions by local governments to promote mental well-being by enhancing green spaces.

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April 1, 2024
Promising new compound reduces alcohol dependence in animal studies

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Scripps Research scientists have found that LY2444296-;a compound that selectively blocks the kappa opioid receptor (KOP)-;may reduce drinking in cases of alcohol dependence in animal studies. The findings, which were published March 9, 2024, in Scientific Reports, could eventually inform new treatment options for people who experience alcohol use disorder (AUD).

Compounds designed to selectively block the KOP are very promising because this receptor is involved in a lot of mental illnesses, such as anxiety and depression. The KOP system is also important in alcohol use disorder, so the idea is if it’s targeted and blocked, you can stop alcohol abuse.”

Rémi Martin-Fardon, PhD, Associate Professor, Department of Molecular Medicine

The KOP system controls brain circuits that affect a range of neurological processes, including addiction, emotion, pain and reward seeking. Both acute and chronic exposure to alcohol negatively affects this system, according to the study’s first author, Francisco Flores-Ramirez, PhD, a postdoctoral fellow at Scripps Research.

For their study, Martin-Fardon and Flores-Ramirez sought to find out whether orally administering LY2444296 could decrease alcohol consumption in rats that formed alcohol dependency. The aim was to mitigate withdrawal symptoms, which would hypothetically lead to reduced alcohol intake. Once rats received LY2444296 at doses as low as 3 mg per kg following 8 hours of abstinence-;when acute withdrawal symptoms typically start-; withdrawal signs and alcohol consumption tapered down significantly. The researchers also determined that LY2444296 may be innocuous, as it had neither a positive nor negative effect on rats without alcohol dependency.

Martin-Fardon and his team didn’t expect LY2444296 to reduce withdrawal signs after only 8 hours of alcohol abstinence because earlier studies showed that other compounds capable of binding to the KOP had no effect on alcohol withdrawal. The scientists don’t yet know why LY2444296 was effective in the present study, and they plan to investigate further.

“People drink to get rid of the sensations of withdrawal,” Martin-Fardon says. He added that withdrawal is associated with physical pain, and that oftentimes, “the only thing that can fix the problem is to have a drink.” But if LY2444296 is taken before withdrawal symptoms begin, “you can decrease the symptoms, so you feel better and drink less.”

Still, the question remains which specific parts of the brain are best targeted to mitigate withdrawal symptoms. Next on their agenda, Martin-Fardon and Flores-Ramirez hope to determine whether LY24444296 can block the effects of stress and other cues that can trigger alcohol relapse.

“We’re also interested in what brain regions are changing as a function of alcohol dependence,” Flores-Ramirez says. “Maybe we could target them to see if the compound could reverse both drinking and relapse behavior.”

Source:

Scripps Research Institute

Journal reference:

Flores-Ramirez, F. J., et al. (2024). LY2444296, a κ-opioid receptor antagonist, selectively reduces alcohol drinking in male and female Wistar rats with a history of alcohol dependence. Scientific Reports. doi.org/10.1038/s41598-024-56500-9.

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March 29, 2024
Having a ruff day? Study says spending time with dogs can help

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In a recent study published in PLoS ONE, researchers examined how interacting with dogs affects the emotions and psychophysiology of humans using an electroencephalogram (EEG).

Their results indicate that people are significantly less stressed when they interact with dogs, with specific activities showing associations with heightened emotional stability, relaxation, creativity, concentration, and attention.

Study: Psychophysiological and emotional effects of human–Dog interactions by activity type: An electroencephalogram study. Image Credit: 4 PM production/Shutterstock.com

Background

Since the domestication of dogs more than 30,000 years ago, they have been humans’ constant companions, providing invaluable assistance for herding livestock, guarding people and property, hunting, and working in many other domains.

The emotional and physiological benefits of interacting with animals, particularly dogs, are now well-known, as they reduce levels of cortisol and, thus, behavioral distress, anxiety, and stress reactivity and improve mental and cardiovascular health.

This has led to the use of animal-assisted interventions (AAI) and animal-assisted activities (AAA) for various domains such as social work, education, and health.

However, the effects of these interventions have usually been assessed using before-after or experiment-control comparisons, and evidence on the underlying mechanisms, such as changes in brain activity, is lacking.

About the study

In this study, researchers investigated people’s psychophysiological responses while interacting with dogs through various activities.

Participants were recruited from an animal grooming academy and pet salons in South Korea, excluding those with cynophobia or dog allergies and a medical history of conditions like unstable angina, high blood pressure, heart surgery, heart attack, or psychopathological disease.

Individuals receiving medication for these conditions or pregnant or lactating were also excluded. During the study, participants avoided stimulants and did not drink caffeinated beverages or smoke.

The dog they interacted with was a four-year-old female poodle who had been trained in aggression, sociability, manners, and basic obedience. She was healthy and vaccinated, and a professional handler was available to ensure her safety.

Participants engaged in eight activities in a single session: meeting, walking, hugging, photography, grooming, massage, feeding, and play. These activities were chosen to prioritize direct interactions and take place over an hour.

Their responses were measured using EEGs for three minutes during each activity, while their emotional responses were assessed using self-reported mood questionnaires such as the Stress Numeric Rating Scale (Stress NRS), the Profile of Mood State (POMS), and the Semantic Differential Method (SDM). Demographic information like weight, height, sex, and age were also collected.

The collected data were analyzed using descriptive statistics, one-way analysis of variance (ANOVA), statistical testing, and Duncan’s post-hoc analysis.

Findings

The study included 30 individuals, of whom 15 were male and 15 were female, and they were 27.9 years old on average.

Results from the EEG analysis showed that playing with the dog significantly increased activity in both frontal lobes and the left prefrontal lobe.

Walking also boosted activity in both prefrontal lobes. Playing correlated with heightened activation in both frontal lobes, while walking specifically activated the right prefrontal lobe.

Massage and grooming activities are elevated in the prefrontal and left frontal lobes. Massage also activated the right frontal lobe. However, no significant differences were found across activities in the parietal and occipital lobes.

Playing with the dog showed consistent activation in multiple brain regions, including those associated with focused attention, meditative states, and cognitive and sensory processing areas.

The subjective reports of emotional states were analyzed across six categories, namely depression-dejection, fatigue, tension-anxiety, confusion, vigor, and anger-hostility.

Individuals reported lower levels of depression, fatigue, and stress during AAAs than they did while resting. They also experienced more vigor when they engaged in feeding, relaxed when they engaged in massaging the dog, and comfortable when they walked her.

Participants experienced more positive mood states when they hugged, massaged, or fed her.

Conclusions

The findings from this study, which included both pet owners and those without pets, support the use of AAI for stress management and emotional relaxation, with different activities eliciting different brainwave reactions.

Responses in the prefrontal lobe are significant as this region plays important roles in regulating memory, language, emotional, behavioral, and cognitive functioning while the parietal lobe is essential for perceiving stimuli, motor function control, spatial orientation comprehension, and sensory information integration.

In addition to the limited sample size, another possible limitation of this study is that participants in AAI are more likely to be those who are not afraid of animals and enjoy being with them.

People without a pre-existing fondness for animals are likely to respond very differently to AAA, and this difference could lead to a selection bias in the findings.

Further studies are needed to validate these findings and shed more light on the mechanisms that make interacting with dogs and other animals so beneficial for humans.

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March 29, 2024