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The link between our food, gut microbiome and depression
That’s slowly changing. The largest analysis of depression and the gut microbiome to date, published in December, found several types of bacteria notably increased or decreased in people with symptoms of depression.
“This study provides some real-life evidence that you are what you eat,” says study author Andre Uitterlinden, who researches genetics at Erasmus Medical Centre in Rotterdam, Netherlands.
Or to be exact, how you feel is closely related to what you consume.
The gastrointestinal system has been featured in brain research for centuries. In the early 1800s, John Abernethy, a popular London physician, held that “gastric derangement” was the root of all mental disorders.
And gastrointestinal symptoms often are reported in people with psychiatric illness. Weight and appetite changes are common among people with depression, from adolescence to older age. Anxiety has been tied to a heightened risk of nausea, heartburn, diarrhea and constipation. The link between food and mood is there even when we reach for macaroni and cheese to comfort us during a stressful time.
Interest in the gut-brain axis has had a resurgence in the past 20 years. A host of studies has pointed to a connection between the microbiota living in our intestinal tract, and our minds, including our memory, mood and cognitive skills.
Such research has spawned an industry of probiotics, prebiotics and fermented everything. Scientific names like bacteroidetes and lactobacillus, two of the most common bacteria found in healthy humans, have become household terms.
The health trend has gotten a bit ahead of the evidence. Most of the studies linking depression and the gut, for example, have been in animals and studies involving human participants have been small.
Still, the evidence thus far shows a link between the two. In one noteworthy study, entitled “Transferring the Blues,” bacteria-free rats given fecal samples from humans diagnosed with major depression became anxious and disinterested in pleasurable activities. Their metabolism of tryptophan, a chemical connected to depression, changed. But the mechanics behind the microbe-mood pathway — and which bacteria matter — has been harder to uncover.
Bacteria that predict depressive symptoms
This new study moves that needle, largely because of its size. The investigators, led by Najaf Amin, who researches population health at Oxford University, analyzed data from the Rotterdam Study, a decades-long effort to understand the health of the local population.
Amin and her colleagues focused specifically on a phase of this study that included fecal sample collection from more than 1,000 individuals. These participants also provided a self-report on depression using a 20-item assessment.
The researchers parsed the data for associations between the bacteria populations in the fecal samples with scores from the depression assessment. They then conducted the same tests using data from another 1,539 Dutch citizens encompassing a range of ethnicities. (Validating the findings from one large group in a second large group makes them particularly reliable.)
The analysis revealed 16 types of bacteria that the authors called “important predictors” of depressive symptoms to varying degrees. For example, the study, published in Nature Communications, found a depletion of Eubacterium ventriosum among people who were depressed. Interestingly, this same decrease has been spotted in microbiome studies of traumatic brain injury and obesity, both of which are tied to depression, supporting the notion that this species of bacteria has something to do with this mood disorder.
The study authors also took a stab at answering the big question: Do any particular gut flora cause depression? It’s a tricky proposition. Major depression disorder has been linked to more than 80 different genetic mutations and all of these connections are weak.
“There’s no gene that causes depression,” said Jane Foster, professor of psychiatry at UT Southwestern, who studies the gut-brain connection and was not involved with this study.
Technology to clearly establish causation does not exist. So the researchers turned to a crafty statistical calculation known as Mendelian randomization, which can tease out the direction of an influence when the gene-disease connection is strong. That’s not the case with depression, which makes the calculation here interesting but not necessarily useful.
Still, the calculation did point to an abundance of one bacteria — Eggerthella — in people with depression as a possible cause of depressive symptoms. The finding didn’t surprise Amin.
Eggerthella, she notes, “is found to be consistently increased in abundance in the guts of depressed individuals.” The result provides evidence that changes in the gut flora may trigger depressive symptoms. “We cannot exclude our own DNA as a contributing source,” Foster said. “It’s a combination of the DNA you were born with, your experiences in life to date, and your environment.”
Whether the flora cause the depression or vice versa may be beside the point. “Causation isn’t a one-way street,” said Jack Gilbert, who directs the Microbiome and Metagenomics Center at the University of California at San Diego, and was not involved with the new study.
Rather, the gut and brain cycle together. For instance, it appears that comfort eating after a stressful event can change the microbial community in our intestines, which in turn exacerbates depressed feelings.
What is clear, Gilbert said, is that when we are depressed, the gut microbiome is often missing beneficial flora. “If we can add those elements back in,” Gilbert said, “maybe we can re-energize that cycle.”
Changing your diet to improve your mood
This is where diet enters the picture. An individual who does not consume enough fiber, for example, may experience a decrease in butyrate-producing bacteria, Amin said, leading to stress and inflammation and, potentially, symptoms of depression.
It may feel like a letdown that the message from all this work is to eat plenty of fruits and vegetables and not so much excess sugar. But the sheer amount of research confirming the power of a healthy gut has become undeniable for even the most hard-bitten skeptic, Gilbert included.
“When the evidence points to the fact that eating healthy, doing a little bit of exercise and taking mindfulness breaks can have benefits, we should probably listen to that data,” he says.
Research is slowly illuminating exactly how bacteria talk to the brain. For example, many of them produce short-chain fatty acids such as butyrate and acetate, which influence brain activity. Others generate a chemical called GABA, deficits of which are linked to depression.
This progress means that diet may not be the only way to improve our gut colonies. The use of probiotics to prevent and treat depression could become more of an exact science, leading eventually to effective alternatives to antidepressants, which, Gilbert points out, still carry a stigma in many communities.
And profiling the bacteria could help identify people at risk for depression, notes Foster. Her lab is searching for signs among gut flora indicating what drug is most likely to benefit someone suffering from depression.
All this research has convinced Uitterlinden that adopting a gut-improving diet comes with just one significant side effect. “You’ll get happier,” he said.
Do you have a question about healthy eating? Email EatingLab@washpost.com and we may answer your question in a future column.
A “Missing Link” – Researchers Shed Light on the Origin of Complex Life Forms
Cryo-electron tomography provided insight into the cellular structure of a newly cultured Asgard archaeon illustrated here. Remarkable are the extensive actin cytoskeleton filaments (orange) in the cell bodies and cell protrusions, as well as the unique cell envelope (blue). Credit: © Margot Riggi, The Animation Lab, University of Utah
Researchers at the University of Vienna and ETH Zurich cultivate “missing link” microorganism.
What led to the emergence of complex organisms on Earth? It’s a significant unanswered question in biology. Researchers from Christa Schleper’s team at the University of Vienna and Martin Pilhofer’s team at ETH Zurich have taken a step towards resolving it. The scientists succeeded in cultivating a special archaeon and characterizing it more precisely using microscopic methods.
This member of the Asgard archaea exhibits unique cellular characteristics and may represent an evolutionary “missing link” to more complex life forms such as animals and plants. The study was recently published in the journal Nature.
All life forms on earth are divided into three major domains: eukaryotes, bacteria and archaea. Eukaryotes include the groups of animals, plants and fungi. Their cells are usually much larger and, at first glance, more complex than the cells of bacteria and archaea. The genetic material of eukaryotes, for example, is packaged in a cell nucleus and the cells also have a large number of other compartments. Cell shape and transport within the eukaryotic cell are also based on an extensive cytoskeleton. But how did the evolutionary leap to such complex eukaryotic cells come about?
One of the currently most popular evolutionary theories assumes that eukaryotes (including animals, plants and fungi) arose from the fusion of an Asgard archaeon with a bacterium. Credit: © Florian Wollweber, ETH Zürich
Most current models assume that archaea and bacteria played a central role in the evolution of eukaryotes. A eukaryotic primordial cell is believed to have evolved from a close symbiosis between archaea and bacteria about two billion years ago. In 2015, genomic studies of deep-sea environmental samples discovered the group of the so-called Asgard archaea, which in the tree of life represent the closest relatives of eukaryotes. The first images of Asgard cells were published in 2020 from enrichment cultures by a Japanese group.
Asgard archaea cultivated from marine sediments
Christa Schleper’s working group at the University of Vienna has now succeeded for the first time in cultivating a representative of this group in higher concentrations. It comes from marine sediments on the coast of Piran, Slovenia, but is also an inhabitant of Vienna, for example in the bank sediments of the Danube. Because of its growth to high cell densities, this representative can be studied particularly well. “It was very tricky and laborious to obtain this extremely sensitive organism in a stable culture in the laboratory,” reports Thiago Rodrigues-Oliveira, postdoc in the Archaea working group at the University of Vienna and one of the first authors of the study.
Co-first author Rafael Ponce sampling marine sediment at the Seca Canal in Piran, Slovenia. Credit: © Thiago Rodrigues-Oliveira, Univ. Wien
Asgard archaea have a complex cell shape with an extensive cytoskeleton
The remarkable success of the Viennese group to cultivate a highly enriched Asgard representative finally allowed for a more detailed examination of the cells by microscopy. The ETH researchers in Martin Pilhofer’s group used a modern cryo-electron microscope to take pictures of shock-frozen cells. “This method enables a three-dimensional insight into the internal cellular structures,” explains Pilhofer.
Scanning electron micrograph of a Lokiarchaeum ossiferum cell showing the long and complex cell protrusions. Credit: © Thiago Rodrigues-Oliveira, Univ. Wien
“The cells consist of round cell bodies with thin, sometimes very long cell extensions. These tentacle-like structures sometimes even seem to connect different cell bodies with each other,” says Florian Wollweber, who spent months tracking down the cells under the microscope. The cells also contain an extensive network of actin filaments thought to be unique to eukaryotic cells. This suggests that extensive cytoskeletal structures arose in archaea before the appearance of the first eukaryotes and fuels evolutionary theories around this important and spectacular event in the history of life.
Future insights through the new model organism
“Our new organism, called Lokiarchaeum ossiferum, has great potential to provide further groundbreaking insights into the early evolution of eukaryotes,” comments microbiologist Christa Schleper. “It has taken six long years to obtain a stable and highly enriched culture, but now we can use this experience to perform many biochemical studies and to cultivate other Asgard archaea as well.” In addition, the scientists can now use the new imaging methods developed at ETH to investigate, for example, the close interactions between Asgard archaea and their bacterial partners. Basic cell biological processes such as cell division can also be studied in the future in order to shed light on the evolutionary origin of these mechanisms in eukaryotes.
Reference: “Actin cytoskeleton and complex cell architecture in an Asgard archaeon” by Thiago Rodrigues-Oliveira, Florian Wollweber, Rafael I. Ponce-Toledo, Jingwei Xu, Simon K.-M. R. Rittmann, Andreas Klingl, Martin Pilhofer and Christa Schleper, 21 December 2022, Nature.
DOI: 10.1038/s41586-022-05550-y
Spain: 1 dead in church machete attacks, terror link probed
BARCELONA, Spain (AP) — A machete-wielding man killed a sexton and injured a priest at two Catholic churches in the city of Algeciras on Wednesday before being arrested, Spain’s interior ministry said. Authorities are investigating the attacks as a possible act of terrorism.
The suspect is in the custody of Spain’s National Police. The ministry did not identify him.
Algeciras is near the southern tip of Spain, resting across from a bay from Gibraltar. It is home to an important port with ferry connections to northern Africa.
The attack started around 7 p.m., when an armed man went into the church of Maria Auxiliadora y San Isidro and assaulted a priest, who was seriously injured, the ministry said.
The assailant then went to a second church, Nuestra Señora de La Palma, a five-minute walk away, where he attacked the sexton. The sexton, whose job it is to take care of the church, fled outside to a public square, where the attacker dealt him mortal wounds, the ministry said.
The Algeciras town hall said the sexton was named Diego Valencia and identified the wounded priest as Antonio Rodríguez. The town hall said he was hospitalized and in stable condition.
Local media reported that at least three other people were injured.
Spain’s National Court said a judge has opened an investigation into a possible act of terrorism.
Police are investigating the incident, the interior ministry said, to determine the “nature of the attack.” It offered no detail on the attacker’s motive.
Spanish Prime Minister Pedro Sánchez joined the outpouring of support.
“I want to express my sincerest condolences for the families of the sexton slain in the terrible attack in Algeciras,” Sánchez wrote on Twitter. “I wish the injured a swift recovery.”
The secretary general of Spain’s Episcopal Conference, Francisco García, wrote on Twitter that “I have received the news of the incident in Algeciras with great pain.” The conference is an organization of Spain’s Catholic bishops, based in Rome.
“These are sad moments of suffering, we are united by the pain of families of the victims and for the Diocese of Cádiz,” García added.
The town hall declared a day of mourning when flags will fly at half-staff.
“We are all stunned by these acts, which have filled us with pain,” Mayor José Landaluce said. “Algeciras has always been a city where concord and tolerance reign, despite incidents like this that create an image that does not correspond to reality.”
A Link Between Schizophrenia and Vascular Alterations in the Brain
Summary: A new study uncovers a link between astrocytes derived from patients with schizophrenia and the formation of narrower blood vessels in the brain. Findings suggest the astrocytes from those with schizophrenia promote less vascularization.
Source: FAPESP
A study conducted in Brazil and reported in an article published in Molecular Psychiatry suggests that schizophrenia may be associated with alterations in the vascularization of certain brain regions.
Researchers at the State University of Campinas (UNICAMP), D’Or Research and Education Institute (IDOR) and the Federal University of Rio de Janeiro (UFRJ) found a link between astrocytes (central nervous system cells) from patients with schizophrenia and formation of narrow blood vessels.
Schizophrenia is a severe multifactorial mental health disorder affecting around 1% of the world population. Common symptoms include loss of contact with reality (psychosis), hallucinations (hearing voices, for example), delusions or delirium, disorganized motor behavior, loss of motivation and cognitive impairment.
In the study, the researchers focused on the role of astrocytes in development of the disease. These glial cells are housekeepers of the central nervous system and important to its defense. They are the central elements of the neurovascular units that integrate neural circuitry with local blood flow and provide neurons with metabolic support.
The study points to novel therapeutic targets and advances scientists’ understanding of the molecular mechanisms behind schizophrenia.
“We show that astrocytes may be involved with an alteration in the thickness of blood vessels in the brain, which in turn may be associated with a reduction in the metabolic flux in certain brain regions, a key factor in schizophrenia.
“Our findings highlight the role of astrocytes as a central element in the disease and suggest they could therefore be a target for novel therapies,” Daniel Martins-de-Souza, penultimate author of the article and a professor at UNICAMP’s Institute of Biology, told Agência FAPESP.
The study was supported by FAPESP via a Thematic Project and a postdoctoral scholarship awarded to Juliana Minardi Nascimento, first author of the artilce, alongside Pablo Trindade, a researcher affiliated with UFRJ and IDOR.
Abnormal vascularization
The researchers compared astrocytes derived from schizophrenic patients’ skin cells with others from people without the disease. This part of the study was conducted at the laboratory of Stevens Rehen, a researcher at IDOR and a professor at UFRJ’s Institute of Biology.
To this end, they reprogrammed epithelial cells from patients with schizophrenia and the control group to become induced pluripotent stem cells (iPSCs). They then induced differentiation of the iPSCs into neural stem cells, which can give rise to both neurons and astrocytes.
“Previous research suggested that both molecular and functional abnormalities of astrocytes could be involved in the pathogenesis of schizophrenia. In our study, we proved this involvement using iPSCs. Without this technique, it would be impossible to study astrocytes the way we did,” Martins-de-Souza said.
The researchers conducted two series of tests with astrocytes derived from patients and healthy controls. The first was a proteomic analysis in which all proteins present in each sample were identified in order to detect differences between the two sets of astrocytes. This part was conducted at UNICAMP’s Laboratory of Neuroproteomics.
“In our analysis of the cells’ proteomes, we observed immune alterations associated with astrocytes. In the case of the cells from patients with schizophrenia, we also found differences in the levels of pro-inflammatory cytokines and several other proteins that indicated angiogenic action in brain vascularization,” Nascimento said.
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels. It is a normal part of growth and healing but can play a role in disease.
After the proteomic analysis, the researchers performed functional trials to show that the inflammatory response in the astrocytes from patients with schizophrenia was altered and that the cells secreted substances that affected vascularization. These tests were part of the postdoctoral research of Pablo Trindade.
The model of the vascular system they used is known as the chicken chorioallantoic membrane (CAM) assay. Derived from chickens’ eggs, the CAM has a dense network of blood vessels and is widely used to study angiogenesis.
The assay was conducted by researchers at the University of Chile in Santiago, Chile. “Put simply, we placed conditioned astrocyte media containing all the substances secreted by these cells in the vascular region of fertilized eggs.
As the vascular cells multiplied, it was possible to see how vessel formation proceeded since egg vascularization could be induced or inhibited by the substances secreted,” Trindade said.
In addition to their effects on vascularization, the astrocytes derived from patients with schizophrenia displayed chronic inflammation.
“Astrocytes are known to regulate the immune response in the central nervous system, so it’s possible that they promote more immature or less efficient vascularization. Our patient-derived astrocytes secreted more interleukin-8 (IL-8) than the controls. IL-8 is pro-inflammatory and suspected to be the main agent of the vascular dysfunction associated with schizophrenia,” he said.
According to the authors, the findings reinforce the role of neurodevelopment in schizophrenia and clearly show that astrocytes are important as mediators.
See also
“The symptoms of the disease usually manifest in young adulthood, but as our study shows, these patients’ glial cells are different from the start, affecting fetal neurodevelopment. Differentiation and brain formation are both altered. It may be the case, therefore, that systematically altered vascularization leads to early brain circuit malformation, and this in turn leads to schizophrenia later on,” Nascimento said.
Another point made in the article is how important astrocytes are to neurological disorders.
“The role of glial cells, including astrocytes, not only in schizophrenia but also in neurological disorders generally has been discovered relatively recently. The predominant view used to be that researchers should focus on neurons. Our vision and understanding of the disease are expanding,” Martins-de-Souza said.
About this schizophrenia and neuroscience research news
Author: Heloisa Reinert
Source: FAPESP
Contact: Heloisa Reinert – FAPESP
Image: The image is in the public domain
Original Research: Closed access.
“Induced pluripotent stem cell-derived astrocytes from patients with schizophrenia exhibit an inflammatory phenotype that affects vascularization” by Daniel Martins-de-Souza et al. Molecular Psychiatry
Abstract
Induced pluripotent stem cell-derived astrocytes from patients with schizophrenia exhibit an inflammatory phenotype that affects vascularization
Molecular and functional abnormalities of astrocytes have been implicated in the etiology and pathogenesis of schizophrenia (SCZ).
In this study, we examined the proteome, inflammatory responses, and secretome effects on vascularization of human induced pluripotent stem cell (hiPSC)-derived astrocytes from patients with SCZ.
Proteomic analysis revealed alterations in proteins related to immune function and vascularization. Reduced expression of the nuclear factor kappa B (NF-κB) p65 subunit was observed in these astrocytes, with no incremental secretion of cytokines after tumor necrosis factor alpha (TNF-α) stimulation.
Among inflammatory cytokines, secretion of interleukin (IL)-8 was particularly elevated in SCZ-patient-derived-astrocyte-conditioned medium (ASCZCM). In a chicken chorioallantoic membrane (CAM) assay, ASCZCM reduced the diameter of newly grown vessels. This effect could be mimicked with exogenous addition of IL-8.
Taken together, our results suggest that SCZ astrocytes are immunologically dysfunctional and may consequently affect vascularization through secreted factors.
The Link Between Mental Health and ADHD Is Strong, so Why Aren’t We Paying Attention?
Summary: An ADHD diagnosis is more predictive of poor mental health outcomes than other neurodevelopmental disorders such as autism.
Source: University of Bath
Adults with high levels of attention-deficit hyperactivity disorder (ADHD) symptoms are more likely to experience anxiety and depression than adults with high levels of autistic traits, according to new research led by psychologists at the University of Bath in the UK.
This study is the first to show that ADHD is more predictive of poor mental health outcomes in adults than other neurodevelopmental conditions, like autism.
Until now, there has been a dearth of information on the effects of ADHD on poor mental health, with far more research focusing on the impact of autism on depression, anxiety and quality of life. As a result, people with ADHD have often struggled to access the clinical care they need to cope with their symptoms.
The authors of the study hope their findings will trigger new research into ADHD and ultimately improve the mental health outcomes for people with the condition. ADHD is a neurodevelopmental condition characterised by inattention and/or hyperactivity and impulsivity. The condition is estimated to affect between 3% and 9% of the population.
Blue Monday
Speaking on Blue Monday (January 16) – the third Monday of January, described by some as the gloomiest day of the year – lead researcher, Luca Hargitai, said: “Scientists have long known that autism is linked to anxiety and depression, but ADHD has been somewhat neglected.
“Researchers have also struggled to statistically separate the importance of ADHD and autism for mental health outcomes because of how frequently they occur together.”
Ms Hargitai, a PhD Researcher at Bath, added: “Our aim was to precisely measure how strongly ADHD personality traits were linked to poor mental health while statistically accounting for autistic traits.”
The new research – a collaborative effort between the Universities of Bath, Bristol and Cardiff, and King’s College London – is published this week in the prestigious journal Scientific Reports. It comes in the same month that two British TV personalities – Johnny Vegas and Sue Perkins – have opened up about their recent diagnoses of ADHD.
“The condition affects many people – both children and adults – and the fact that more people are willing to talk about it is to be welcomed,” said Ms Hargitai.
“The hope is that with greater awareness will come more research in this area and better resources to support individuals in better managing their mental health.”
Overly active, as though driven by a motor
The study used a large, nationally representative sample of adults from the UK population. All participants completed gold standard questionnaires – one on autistic traits, the other on ADHD traits – responding to statements such as “I frequently get strongly absorbed in one thing” and “How often do you feel overly active and compelled to do things, like you were driven by a motor?”
The researchers found that ADHD traits were highly predictive of the severity of anxiety and depression symptoms: the higher the levels of ADHD traits, the more likely a person is to experience severe mental health symptoms.
Through innovative analytical techniques, the study authors further confirmed that having more of an ADHD personality was more strongly linked to anxiety and depression than autistic traits.
These results were replicated in computerised simulations with a 100% ‘reproducibility rate’. This showed, with great confidence, that ADHD traits are almost certainly linked to more severe anxiety and depression symptoms in adults than autistic traits.
Shifting the focus of research and clinical practice
Ms Hargitai said: “Our findings suggest that research and clinical practice must shift some of the focus from autism to ADHD. This may help to identify those most at risk of anxiety and depression so that preventative measures – such as supporting children and adults with the management of their ADHD symptoms – can be put in place earlier to have a greater impact on improving people’s wellbeing.”
According to Dr Punit Shah, senior author and associate professor of Psychology at Bath, another important aspect of the new study is that it advances scientific understanding of neurodevelopmental conditions.
“By addressing the shortcomings of previous research, our work provides fresh information about the complex links between neurodiversity and mental health in adults – an area that is often overlooked.
“Further research is now needed to delve deeper into understanding exactly why ADHD is linked to poor mental health, particularly in terms of the mental processes that might drive people with ADHD traits to engage in anxious and depressive thinking.
“At the moment, funding for ADHD research – particularly psychological research – is lacking. This is especially pronounced when you compare it to the relatively high level of funds directed at autism.
“As the evidence becomes clear that ADHD isn’t just a childhood condition but persists throughout life, we must adjust our research agendas to better understand ADHD in adulthood.”
Commenting on the new findings, Dr Tony Floyd, CEO of ADHD Foundation, The Neurodiversity Foundation, said: “This research demonstrates clear evidence of the increased risks of mental health comorbidities associated with adult ADHD. This is a step towards recognising the broader impact of unmanaged and untreated ADHD. We hope this research will lead to more research being commissioned in this area. We also hope it will result in changes to the design and delivery of health services.
See also
“The cost implications to the NHS of leaving ADHD untreated, and the need to better train health practitioners in both primary and secondary care, are now more apparent. And of course there are other costs too that need to be considered – to the health of UK citizens with ADHD and to their family life, employability and economic wellbeing. These costs are often hidden but they are considerable.
“This research from Bath University will add to the growing national debate and the business case for a national review of health services for ADHD across a person’s lifespan.”
About this ADHD and mental health research news
Author: Chris Melvin
Source: University of Bath
Contact: Chris Melvin – University of Bath
Image: The image is in the public domain
Original Research: Open access.
“Attention-deficit hyperactivity disorder traits are a more important predictor of internalising problems than autistic traits” by Punit Shah et al. Scientific Reports
Abstract
Attention-deficit hyperactivity disorder traits are a more important predictor of internalising problems than autistic traits
Autism Spectrum Disorder (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) are both linked to internalising problems like anxiety and depression. ASD and ADHD also often co-occur, making their individual statistical contributions to internalising disorders difficult to investigate.
To address this issue, we explored the unique associations of self-reported ASD traits and ADHD traits with internalising problems using a large general population sample of adults from the United Kingdom (N = 504, 49% male).
Classical regression analyses indicated that both ASD traits and ADHD traits were uniquely associated with internalising problems. Dominance and Bayesian analyses confirmed that ADHD traits were a stronger, more important predictor of internalising problems.
However, brief depression and anxiety measures may not provide a comprehensive index of internalising problems.
Additionally, we focused on recruiting a sample that was representative of the UK population according to age and sex, but not ethnicity, a variable that may be linked to internalising disorders.
Nevertheless, our findings indicate that while ASD and ADHD uniquely predict internalising problems, ADHD traits are a more important statistical predictor than ASD traits.
We discuss potential mechanisms underlying this pattern of results and the implications for research and clinical practice concerning neurodevelopmental conditions.
George Santos: New details link New York congressman to Andrew Intrater, cousin of sanctioned Russian oligarch
Andrew Intrater and his wife each gave the maximum $5,800 to Santos’ main campaign committee and tens of thousands more since 2020 to committees linked to him, according to filings with the Federal Election Commission. Intrater’s cousin is Russian billionaire Viktor Vekselberg, who has been sanctioned by the U.S. government for his role in the Russian energy industry.
The relationship between Santos and Intrater goes beyond campaign contributions, according to a statement made privately by Santos in 2020 and a court filing the following year in a lawsuit brought by the Securities and Exchange Commission against a Florida-based investment firm, Harbor City Capital, where Santos worked for more than a year.
Taken together, the evidence suggests Santos may have had a business relationship with Intrater as Santos was first entering politics in 2020. It also shows, according to the SEC filing, that Intrater put hundreds of thousands of dollars into Santos’ onetime employer, Harbor City, which was accused by regulators of running a Ponzi scheme. Neither Santos nor Intrater responded to requests for comment. Attorneys who have represented Intrater also did not respond.
The congressman, whose election from Long Island last year helped the GOP secure its narrow House majority, has apologized for what he called “résumé embellishment” while rebuffing calls for his resignation. He is under scrutiny by prosecutors in New York and Rio de Janeiro.
Ties between Santos, 34, and Intrater, 60, reflect the ways Santos found personal and political support on his path to public office.
While Intrater is a U.S. citizen, his company, the investment firm Columbus Nova, has historically had extensive ties to the business interests of his Russian cousin. As recently as 2018, when Vekselberg was sanctioned by the Treasury Department, his conglomerate was Columbus Nova’s largest client, the company confirmed to The Post that year.
Intrater’s interactions in 2016 and 2017 with Michael Cohen, who at the time was working as a lawyer for Donald Trump, were probed during special counsel Robert S. Mueller III’s investigation of Russian interference in the 2016 election and possible links between Trump and the Kremlin.
Intrater’s company paid the lawyer and self-described Trump fixer to identify deals for his business, and court records show they exchanged hundreds of texts and phone calls. Neither Intrater nor Vekselberg was accused of wrongdoing in Mueller’s investigation.
In 2020, when Santos was tasked by Harbor City with locating investors in New York, he claimed in a Harbor City meeting held over Zoom that Intrater’s investment firm, Columbus Nova, was a “client” of his, according to footage obtained by The Washington Post.
He made the comment during a discussion of the difficulties of residential real estate investing, in particular for investors who put money into the 1,400-foot tall tower at 432 Park Avenue in Manhattan, which for a time was the tallest residential building in the world. Intrater did not respond to a question about whether he or Columbus Nova was involved in the project.
“You might know who they are,” Santos added in the company meeting, referring to Columbus Nova. “They’ve made the news on several occasions. They were heavily involved with the Russia probe. Unjustified.”
“But they’re a real estate company,” Santos added. “They’re legitimate.”
Santos did not respond to a text message seeking comment. Intrater did not respond to an emailed question about whether his firm was Santos’s client as claimed or about the deposit with Harbor City.
The congressman has falsified substantial aspects of his work experience. And, in the Harbor City Zoom meetings reviewed by The Post, he recounted dealings with other prominent investors or moneyed organizations that those entities denied took place.
But Harbor City was able to land a $625,000 deposit from a company registered in Mississippi that identifies Intrater as its lone officer, according to an exhibit included in the SEC’s complaint against Harbor City. The alleged deposit, which is undated, is included in a chart that lists several entities that the SEC says made payments to Harbor City.
The Mississippi company, FEA Innovations, is registered to Intrater, according to secretary of state records. Registration documents include no other officers or directors and identify Intrater’s address as the same one used by Columbus Nova on Madison Avenue in Manhattan. Columbus Nova is now known as Sparrow Capital.
In the SEC action, initiated in April 2021, regulators accused Harbor City and its founder of running a “classic Ponzi scheme” — promising investors reliable profit and instead bilking them out of millions.
The SEC complaint did not name Santos, who has denied knowledge of the alleged wrongdoing, although he had been told by a prospective investor that the firm was using a fraudulent bank document, as The Post previously reported.
Harbor City’s founder, J.P. Maroney, has denied the SEC allegations, which were brought in federal court in Florida. The company itself has not responded in court. Maroney did not respond to a text message about the alleged deposit from Intrater’s firm. The exhibit that identifies the alleged deposit from Intrater’s company does not elaborate on its purpose or suggest that Intrater had knowledge of purported wrongdoing at Harbor City.
After Harbor City’s assets were frozen, and with assistance from a fellow former Harbor City employee, Santos in 2021 formed a company, the Devolder Organization, that paid him at least $3.5 million over the next two years, according to Florida business records and financial disclosure forms he filed as a candidate. Santos loaned his campaign more than $700,000 but did not report any income from Harbor City despite having been paid by the company as recently as April 2021.
Details of Santos’s tenure at Harbor City were confirmed by a court-appointed lawyer overseeing liquidation of the company’s assets.
Columbus Nova became a subject of interest for the Mueller investigation as prosecutors probed the ties forged by Intrater and his company with Cohen, a confidant of Trump’s at the time.
Intrater donated $250,000 to Trump’s inaugural committee, according to campaign finance records, and attended the 2017 inaugural, along with Vekselberg. The Washington Post has reported that the two men encountered Cohen at the inauguration. Not long after, Columbus Nova began paying Cohen as part of a contract to recruit new investors for the company, The Post reported. Court records show the payments totaled $583,000.
Court records also show that Cohen and Intrater exchanged more than 1,000 calls and text messages between November 2016 and November 2017. Intrater donated $35,000 to attend a 2017 fundraiser for Trump’s reelection, attending at Cohen’s invitation, The Post has reported.
Federal officials questioned both Intrater and Vekselberg during the probe, interviewing the latter after his private airplane made a stop in the United States in 2018, people familiar with the investigation said.
Cohen ultimately pleaded guilty to campaign finance violations, tax and bank fraud and lying to Congress — matters unrelated to his interactions with Columbus Nova. Intrater told the New York Times in 2019 that his omission from Mueller’s final report “confirms what I knew all along — that I’ve done nothing wrong.”
Cohen later turned on Trump, criticizing him in a 2019 congressional hearing and cooperating with investigations into his former boss’ business practices.
Vekselberg and his company, Renova, were sanctioned by the Treasury Department in April 2018, cited for benefiting from Russian President Vladimir Putin’s “malign activity around the globe.” In April 2022, following Russia’s invasion of Ukraine, Vekselberg’s $90 million yacht was seized by Spanish authorities at the request of the United States.
Columbus Nova has long been described as closely associated with the Renova Group, a Russian conglomerate run by Vekselberg. As recently as 2017, a website for Renova Group listed Columbus Nova as one of its companies, and Columbus Nova confirmed to The Post in 2018 that Vekselberg’s conglomerate was at that time its largest client. However, the firm said at the time that it was owned by Americans and had never been controlled by Renova Group or Vekselberg.
Devlin Barrett, Emma Brown and Jonathan O’Connell contributed to this report.
Zelda: A Link To The Past Artwork “Brought To Life” In Absolutely Stunning Animation
If you’ve ever wondered what classic game art might look like if it was brought to life, well here’s a great example. American animator Parker Simmons has transformed parts of The Legend of Zelda: A Link to the Past SNES manual and other materials into living, breathing animations.
The results are absolutely stunning – with artwork of the Super Nintendo action-adventure from 1991 bursting to life. It’s got many Zelda fans on social media requesting an official cartoon in this style, rather than the one we actually got.
Simmons reveals the ‘Link vs Stalfos’ battle was animated in Adobe Animate, had about 110 symbols, 70 frames, and the music was taken from the “Sound and Drama” Zelda CD from the ’90s. Perhaps most surprisingly, the SFX is ripped from Dragon Quest VIII, but it fits! Note: It seems this original art was retrieved from The Legend of Zelda: Art & Artifacts Dark Horse book released 2016/17.
Apart from the beautifully animated ‘Link vs Stalfos’ battle, Simmons showed Link exploring a dungeon and talking to a Sage:
Parker Simmons is best known as the creator of the Cartoon Network animated series, Mao Mao: Heroes of Pure Heart. He’s also worked on OK K.O.! as a writer and in various other roles including voice work.
If you want to see some of The Legend of Zelda: A Link to the Past artwork in its original state, there’s actually an original PDF manual you can access on Nintendo’s official website. And just remember, you can also play the SNES classic A Link to the Past via the Switch Online service. You’ll require a subscription, of course.
As for whether or not we’ll ever see something like this, who knows? With Mario now making his way to the big screen this April, perhaps there is a chance for Link to put the television cartoon series from the late ’90s behind him and write a new chapter in his screen history.