A far-reaching study by Navy researchers has found that exposure to munitions blast waves from combat and training may be causing brain injuries the aggregation of which is resulting serious and often deadly ailments such as depression, PTSD and suicide.
[N]early two-thirds of those experiencing chronic homelessness in metro Denver suffer from some kind of brain injury[.]
Most people who try drugs don’t get addicted, even to opioids or methamphetamine, which suggests that factors other than simply being exposed to a drug can contribute to addiction. The majority of people who do get hooked have other psychiatric disorders, traumatic childhoods or both — only 7 percent report no history of mental illness. Nearly 75 percent of women with heroin addiction were sexually abused as children — and most people with any type of addiction have suffered at least one and often many forms of childhood trauma.
Chandra Sripada, professor of psychiatry and philosophy at the University of Michigan, argues that distorted thinking is more important in addictive behavior than overwhelming desire, leading to what he calls “unreliable” control over use. . . . During addiction . . . despairing thoughts about oneself and the future — not just thoughts about how good the drug is — predominate. At the same time, thoughts about negative consequences of use are minimized, as are those about alternative ways of coping. Drugs are overvalued as a way to mitigate distress; everything else is undervalued. The result is an unstable balance, which, more often than not, tips toward getting high.This theory is helpful for explaining who is most likely to get addicted and what is most likely to generate recovery. Risk factors like poverty, a traumatic childhood and mental illness generate excess stress while tending to produce negative thoughts about oneself. In my case, I was depressed and isolated because of what I later learned was undiagnosed autism spectrum disorder — and hated myself for my inability to connect. The result was a mental climate conducive to relying on drugs, even when they no longer provided relief.Factors linked to recovery — like social support and employment — can offset distorted thoughts and inflated valuation of drug use. Essentially, people make better choices when they recognize and have access to better options. If you are locked in a room with an escape route unknown to you hidden under the carpet, you are just as trapped as if that exit didn’t exist. My recovery began when I saw that there was a bearable way out.This is why punitive approaches so often backfire: Causing more pain to people who view drugs as their only way to cope drives desire to use even more. Punishment doesn’t teach new skills that can allow better decisions.
From the New York Times.
Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets.
We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume.
Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups.
These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.
Controls were randomly selected from the full control cohort to roughly match a 1:4 ratio in cases and controls. . . . we excluded individuals with a moderate to severe mental retardation (ICD10: F71-F79) from both the case and control cohort.
Autism spectrum disorder cases were further categoried into four subtypes: childhood autism (cha, ICD10 F84.0); atypical autism (ata, ICD10 F84.1); Asperger’s syndrome (asp, ICD10 F84.5); and pervasive disorders, unspecified and others (pdm, ICD10 F84.8+9).
It appears that ADHD cases were not subtyped, which is something of a shame. There is good reasons to think that the genetic basis of ADHD predominantly inattentive type (i.e. without hyperactivity), has a different genetic basis than ADHD combined type (and ADHD predominately hyperactive which probably overlaps heavily with the combined type). This level of information ought to have been available although empirically efforts to further subtype ADHD probably wouldn't have been available in the data. See, e.g, prior posts at this blog from September 8, 2012, April 3, 2012, and October 18, 2017 (Genetics of ADHD hyperactivity/impulsivity and inattention dimensions are quite different),
A Key Figure From The Paper
A serious limitation of this study is that the design relies on the common psychiatric nosology that in particular for ASD and ADHD has been problematic, surely in the past when only one of both diagnosis was allowed. Given the high comorbidity between ADHD and ASD, and among other psychiatric disorders in general, plus the fact that recent research shows that ‘genes do not respect diagnostic classifications’ (see CDG publications) I would rather see a focus on the shared genetic findings for ADHD and ASD, in aiming to find general genetic/biological vulnerabilities for trans diagnostic neurodevelopmental problems, instead of relying on a classification system that has surely proven its value in clinical practice but does not seem to guide biological underpinnings of those disorders.
and
Concerning the used sample, I would appreciate getting some more details on the assessment of comorbid ASD and ADHD in the respective cohort. While some of the individuals might have been diagnosed under DSM-IV, which did not allow a comorbid diagnosis of ADHD, I wonder if and how this was accounted for in the datasets. In light of the cited Meta-study 25-32% of ASD individuals do fulfill the criteria for ADHD. In this study, the comorbid cohort accounts for 10% of the sample (assuming they were from both the ASD and the ADHD cohorts).
The responses gave rise to a table regarding the shared risk genes:
Researchers show it is possible to improve specific human brain functions related to self-control and mental flexibility by merging artificial intelligence with targeted electrical brain stimulation. . . .
[T]hey identified a brain region -- the internal capsule -- that improved patients' mental function when stimulated with small amounts of electrical energy. That part of the brain is responsible for cognitive control -- the process of shifting from one thought pattern or behavior to another, which is impaired in most mental illnesses.An example might include a person with depression who just can't get out of a "stuck" negative thought. Because it is so central to mental illness, finding a way to improve it could be a powerful new way to treat those illnesses.The team developed algorithms, so that after stimulation, they could track patients' cognitive control abilities, both from their actions and directly from their brain activity. The controller method provided boosts of stimulation whenever the patients were doing worse on a laboratory test of cognitive control.This system can read brain activity, "decode" from that when a patient is having difficulty, and apply a small burst of electrical stimulation to the brain to boost them past that difficulty. The analogy I often use is an electric bike. When someone's pedaling but having difficulty, the bike senses it and augments it. We've made the equivalent of that for human mental function.The study is the first to show that:
* A specific human mental function linked to mental illness can be reliably enhanced using precisely targeted electrical stimulation;
* There are specific sub-parts of the internal capsule brain structure that are particularly effective for cognitive enhancement; and
* A closed-loop algorithm used as a controller was twice as effective than stimulating at random times.Some of the patients had significant anxiety in addition to their epilepsy. When given the cognitive-enhancing stimulation, they reported that their anxiety got better, because they were more able to shift their thoughts away from their distress and focus on what they wanted. Widge says that this suggests this method could be used to treat patients with severe and medication-resistant anxiety, depression or other disorders.
. . .
The research team is now preparing for clinical trials. Because the target for improving cognitive control is already approved by the Food and Drug Administration for deep brain stimulation, . . . this research can be done with existing tools and devices -- once a trial is formally approved -- and the translation of this care to current medical practice could be rapid.
"We found that 4 major psychiatric disorders -- major depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder -- show a surprisingly high level of similarity in their brain structural abnormalities," said Dr. Opel. The shared brain areas showing structural aberrations were mainly in cortical areas associated with cognitive processing, memory and self-awareness.
On the flipside, Dr. Opel added, "we were able to identify regional abnormalities with high specificity for certain disorders." Interestingly, these distinct structural differences sometimes appeared in the same area for two disorders, but in opposite directions from the norm.
In contrast, attention-deficit/hyperactivity disorder and autism spectrum disorder did not share brain structural signatures with any other disorders. That may be because those disorders are considered developmental diseases with a distinct etiology from the other psychiatric conditions, which have more in common.
The researchers do not yet understand the mechanisms behind the shared structural elements, but a growing body of evidence shows that these psychiatric disorders also share common genetic as well as environmental influences, which might underlie the current findings.From Science Daily. The paper and its abstract are as follows:
Background
Neuroimaging studies have consistently reported similar brain structural abnormalities across different psychiatric disorders. Yet, the extent and regional distribution of shared morphometric abnormalities between disorders remains unknown.
Methods
Here, we conducted a cross-disorder analysis of brain structural abnormalities in 6 psychiatric disorders based on effect size estimates for cortical thickness and subcortical volume differences between healthy control subjects and psychiatric patients from 11 mega- and meta-analyses from the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta Analysis) consortium. Correlational and exploratory factor analyses were used to quantify the relative overlap in brain structural effect sizes between disorders and to identify brain regions with disorder-specific abnormalities.
Results
Brain structural abnormalities in major depressive disorder, bipolar disorder, schizophrenia, and obsessive-compulsive disorder were highly correlated ( r = .443 to r = .782), and one shared latent underlying factor explained between 42.3% and 88.7% of the brain structural variance of each disorder. The observed shared morphometric signature of these disorders showed little similarity with brain structural patterns related to physiological aging. In contrast, patterns of brain structural abnormalities independent of all other disorders were observed in both attention-deficit/hyperactivity disorder and autism spectrum disorder. Brain regions showing high proportions of independent variance were identified for each disorder to locate disorder-specific morphometric abnormalities.
Conclusions
Taken together, these results offer novel insights into transdiagnostic as well as disorder-specific brain structural abnormalities across 6 major psychiatric disorders. Limitations comprise the uncertain contribution of risk factors, comorbidities, and medication effects to the observed pattern of results that should be clarified by future research.
The study, published in the journal JAMA Psychiatry on Wednesday, found that infections requiring hospitalizations were associated with an about 84% increased risk of being diagnosed with any mental disorder and an about 42% increased risk of using psychotropic drugs to treat a mental disorder. Less severe infections treated with anti-infective medications, like antibiotics, were associated with increased risks of 40% and 22%, respectively, the study found. . . .
The researchers found associations between any treated infection and the increased risk of later being prescribed medication for various childhood and adolescent mental disorders, with the risks differing for specific disorders.
Risks were increased for schizophrenia spectrum disorders, obsessive-compulsive disorder, personality and behavior disorders, mental retardation, autism spectrum disorders, attention-deficit hyperactivity disorder, oppositional defiant disorder/conduct disorder and tic disorders[.]
By disrupting adenosine signaling in the auditory thalamus, we have extended the window for auditory learning for the longest period yet reported, well into adulthood and far beyond the usual critical period in mice," said corresponding author Stanislav Zakharenko, M.D., Ph.D., a member of the St. Jude Department of Developmental Neurobiology. "These results offer a promising strategy to extend the same window in humans to acquire language or musical ability by restoring plasticity in critical regions of the brain, possibly by developing drugs that selectively block adenosine activity."The paper is:
The link is strongest in the second trimester, when a single fever is associated with a 40 percent increase in autism risk. Three or more fevers after the first trimester triples the risk of having a child with autism, according to the study, which appeared 13 June in Molecular Psychiatry.
The findings support the idea that a pregnant woman’s immune response, which often includes fever, can disrupt brain development in the fetus, says lead researcher Mady Hornig, associate professor epidemiology at the Columbia University.
The study is inconclusive on whether drugs that lower fever mitigate the risk, but the results hint that they might, says Sarkis Mazmanian, professor of biology at theCalifornia Institute of Technology. . . .15,701 of the mothers reported on a health questionnaire that they’d had one or more fevers while pregnant. The team followed all of the participants’ children until they reached age 9, on average, and found that 583 received an autism diagnosis.The timing of the fever matters for autism risk, the researchers found. Compared with the 40 percent increase in the second trimester, having a fever in the first trimester carries a 34 percent increase in the risk of autism, but that result is not statistically significant. Having a fever in the third semester has no effect on autism risk.The researchers also found a dose-response relationship for fever: The increase in risk ranges from 30 percent throughout pregnancy for one or two episodes of fever, to more than threefold for three or more episodes in the second trimester and beyond.Still, the vast majority of women who have a fever during pregnancy do not have a child with autism and the absolute increase in risk is small. Even among mothers who had three or more fevers, only 5 out of 308 children (about 1.6 percent) have autism, compared with 376 of 65,502 children (about 0.6 percent) whose mothers reported no fevers. . . .
Hornig’s team examined whether medications that lower body temperature would reduce the risk. More than 5,600 women took acetaminophen for fever during their second trimester. The team found an association between acetaminophen use and a decrease in autism risk, but it was not statistically significant. Only 161 women took ibuprofen during the second trimester, and none of them have a child with autism. (About half of pregnant women use acetaminophen at least once, but doctors generally advise against ibuprofen use during pregnancy.) . . .
A 2013 study led by Hertz-Picciotto found that drugs that lower fever mitigate the increase in autism risk associated with fever.
Important differences might not show up in brain scans. For example, we can’t see schizophrenia in a brain scan, yet schizophrenia is important. Hearing voices that aren’t there, even when they give useful tips [“They’re all against you! They all must die!”] has social significance.From G. Cochran
Genetic susceptibility to Intellectual disability (ID), autism spectrum disorder (ASD) and schizophrenia (SCZ) often arises from mutations in the same genes, suggesting that they share common mechanisms. We studied genes with de novo mutations in the three disorders and genes implicated by SCZ genome-wide association study (GWAS). Using biological annotations and brain gene expression, we show that mutation class explains enrichment patterns more than specific disorder. Genes with loss of function mutations and genes with missense mutations were enriched with different pathways, shared with genes intolerant to mutations. Specific gene expression patterns were found for each disorder. ID genes were preferentially expressed in fetal cortex, ASD genes also in fetal cerebellum and striatum, and genes associated with SCZ were most significantly enriched in adolescent cortex. Our study suggests that convergence across neuropsychiatric disorders stems from vulnerable pathways to genetic variations, but spatiotemporal activity of genes contributes to specific phenotypes.
There is a popular belief in neuroscience that we are primarily data limited, and that producing large, multimodal, and complex datasets will, with the help of advanced data analysis algorithms, lead to fundamental insights into the way the brain processes information.
These datasets do not yet exist, and if they did we would have no way of evaluating whether or not the algorithmically-generated insights were sufficient or even correct. To address this, here we take a classical microprocessor as a model organism, and use our ability to perform arbitrary experiments on it to see if popular data analysis methods from neuroscience can elucidate the way it processes information. Microprocessors are among those artificial information processing systems that are both complex and that we understand at all levels, from the overall logical flow, via logical gates, to the dynamics of transistors.
Eric Jons and Konrad Kording, "Could a neuroscientist understand a microprocessor?" (Pre-Print November 14, 2016). doi: http://dx.doi.org/10.1101/055624We show that the approaches reveal interesting structure in the data but do not meaningfully describe the hierarchy of information processing in the microprocessor. This suggests current analytic approaches in neuroscience may fall short of producing meaningful understanding of neural systems, regardless of the amount of data. Additionally, we argue for scientists using complex non-linear dynamical systems with known ground truth, such as the microprocessor as a validation platform for time-series and structure discovery methods.
The search for biomarkers has been one of the leading endeavours in biological psychiatry; nevertheless, in spite of hundreds of publications, hardly any marker has proved useful in clinical practice. To study how biomarker research has progressed over the years, we performed a systematic review of the literature to evaluate (a) the most studied peripheral molecular markers in major psychiatric disorders, (b) the main experimental design features of studies in which they are proposed as biomarkers and (c) whether their patterns of variation are similar across disorders.
An automated search revealed that, out of the six molecules most commonly present as keywords in articles studying plasmatic markers of schizophrenia, major depressive disorder or bipolar disorder, five (BDNF, TNF-alpha, IL-6, C-reactive protein and cortisol) were the same across the three diagnoses. An analysis of the literature on these molecules showed that, whilst 66% of original articles compared their levels between patients and controls, only 35% were longitudinal studies, and only 10% presented an evaluation of diagnostic efficacy, a pattern that has not changed significantly over two decades.
Interestingly, these molecules varied similarly across the three disorders, suggesting them to be nonspecific systemic consequences of psychiatric illness rather than diagnostic markers. On the basis of this, we discuss how research fragmentation between diagnoses and publication practices rewarding positive findings may be directing the biomarker literature to nonspecific targets, and what steps could be taken to increase clinical translation in the field.
These findings may suggest new treatments targeting GABA receptors for "normalizing" synaptic pruning in diseases such as autism and schizophrenia, where synaptic pruning is abnormal. Research has suggested that children with autism may have an over-abundance of synapses in some parts of the brain. Other research suggests that prefrontal brain areas in persons with schizophrenia have fewer neural connections than the brains of those who do not have the condition.From here.
Intermittent explosive disorder (IED) is defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, as recurrent, impulsive, problematic outbursts of verbal or physical aggression that are disproportionate to the situations that trigger them. IED is thought to affect as many as 16 million Americans, more than bipolar disorder and schizophrenia combined. . . .From here. The source for the quoted article is Emil F. Coccaro, et al., "Toxoplasma gondii Infection." The Journal of Clinical Psychiatry (2016).
Coccaro and his colleagues examined possible connections [of IED] to toxoplasmosis, an extremely common parasitic infection. Transmitted through the feces of infected cats, undercooked meat or contaminated water, toxoplasmosis is typically latent and harmless for healthy adults. However, it is known to reside in brain tissue, and has been linked to several psychiatric diseases, including schizophrenia, bipolar disorder and suicidal behavior.
The research team recruited 358 adult subjects from the U.S., who were evaluated for IED, personality disorder, depression and other psychiatric disorders. Study participants were also scored on traits including anger, aggression and impulsivity. Participants fell into one of three groups. Roughly one third had IED. One third were healthy controls with no psychiatric history. The remaining third were individuals diagnosed with some psychiatric disorder, but not IED. This last group served as a control to distinguish IED from possible confounding psychiatric factors.
The research team found that IED-diagnosed group was more than twice as likely to test positive for toxoplasmosis exposure (22 percent) as measured by a blood test, compared to the healthy control group (9 percent). Around 16 percent of the psychiatric control group tested positive for toxoplasmosis, but had similar aggression and impulsivity scores to the healthy control group. IED-diagnosed subjects scored much higher on both measures than either control group.
Across all study subjects, toxoplasmosis-positive individuals scored significantly higher on scores of anger and aggression. The team noted a link between toxoplasmosis and increased impulsivity, but when adjusted for aggression scores, this link became non-significant.
Gary Pardo Jr., whose parents live across the street from Dalton in Kalamazoo Township, described him as a family man who seemed fixated on cars and often worked on them.
"He would go a month without mowing his lawn but was very meticulous with his cars," Pardo said, explaining that Dalton, at times, owned a Chevrolet Camaro and two Hummer SUVs.
Progressive Insurance confirmed that he once worked for the company before leaving in 2011. Dalton was an insurance adjuster who did auto-body estimates and once taught an auto-body repair class at an area community college, said James Block, who has lived next door to him for 17 years.
"He loved to do things outside with his kids" like taking them for rides on his lawn tractor, Block said.His family is distancing themselves from him and his horrible acts in a statement released by attorneys whom they hired. Law enforcement and neighbors had initially feared for their lives, but Dalton's family was not harmed, although they may have left the family home for their own safety once they were altered by the sheriff.
Matt Mellen told CNN he rode in Dalton's car just before the shootings started. "We got about a mile from my house, and he received a telephone call," Mellen told CNN. . . . Dalton told the caller he had a passenger in the car and would call the person back, according to Mellen.
"Once he hung up with that phone call is when he started driving erratically," Mellen said, recounting side-swiping a car, running a stop sign and red lights.
"I was pleading with him to stop the vehicle so he could let me out. He was surprisingly calm the whole time."
Mellen said he was able to jump out of the car and call 911.According to Mellen: "He said Dalton introduced himself as "Me-Me" and had a dog in the backseat."
The first victim of the Uber gunman threw herself in front of children when the gunman opened fire and gave police crucial information to track him down.
Tiana Carruthers was outside her Kalamazoo, Michigan, apartment with several youngsters on a playground at around 5:00pm on Saturday when the suspect, who's been named as Jason Dalton, pulled up in his Chevrolet.
Sensing trouble, the mother put herself between the attacker and the children, and was shot multiple times as a result, but survived and was able to give the police vital evidence that helped them catch the suspected killer.
Joi Coleman, 12, and sister Megan were two of the children she saved. Joi was holding Carruthers' hand when Dalton started firing.
Her actions meant the pair were able to get inside one of the houses and call 911.
Travis Gettys and Devin Fletter, who live next door to Coleman's, told WWMT they saw Dalton earlier in the day talking to children in the neighborhood just an hour before the shooting [ed. i.e. at about 4:45 p.m., shortly after the "wild ride" and phone call with Mellen].
One person said he asked where 'Mazy' was, leading some to believe he was looking for someone specific.
When police arrived at her family's home after the shooting, they found 10 shell casings on the floor around Carruthers.
According to MLive, Carruthers was able to give deputies a description of the man who shot her at the scene.Another report noted suggests that Dalton was not known to Carruthers personally:
At the scene, Carruthers was able to give deputies a description of the man who shot her, describing him as an older, heavy-set white male with brown and graying hair.
Sparrow testified that Carruthers told deputies her attacker left in a silver sport-utility vehicle. Other witnesses told deputies the vehicle was either a Chevrolet Equinox or Traverse.
Sparrow said that deputies later learned that the vehicle, after leaving Meadows Townhomes was involved in a crash after it sideswiped another vehicle at the intersection of Gull Road and East G Avenue.
When she was shown a police lineup after the shooting, Sparrow said Carruthers identified Dalton as the man who shot her.So, Dalton was still in a rage when he left the complex, presumably because he hadn't found "Mazy" and had just shot someone multiple times for some reason related to his search for her, perhaps in a case of mistaken identity. What happened next?
There was a four hour time period between the first shooting at Meadows Townhomes and the second shooting at Seelye Kia, we are told police are trying to find out what he was doing during that time period, and revealed he made phone calls to several people.Presumably, all of those people will be interviewed as witnesses in the case.
"He was here to kill, like to shoot somebody.”
That’s how Travis Gettys described the man suspected of shooting and wounding a woman at Richland Township townhomes complex . . .
At the Meadows Townhomes, tire tracks from the car taking off were still visible Sunday and spray paint marked where 10 bullet casings were found. Seven bullet holes could be seen in siding at the front of a near-by apartment.
Neighbors told 24 Hour News 8 that kids were out playing just before 6 p.m. Saturday when the shooter circled around the block before he opened fire. . . . .
Neighbors say the woman recently moved in to the Meadows and was outside with her kids when the shooter, believed to be 45-year-old Jason Dolton, asked if she was a woman with a different name. People who spoke to 24 Hour News 8 said they think it was a ploy to get her to come close to his car.
“She was talking about her kids, talking about, ‘He asked if I was so-and-so,'” said George’s mother, Tammy.
Witnesses say the victim’s three children were outside with her. Thankfully, they ran away and avoided being shot.
James George and his friends, who were playing video games, also avoided injury when four of the bullets came flying through the wall of his home.Authorities claim that the first shooting was random, despite the fragmentary evidence that seems to point to a contrary conclusion, such as the fact that Dalton came to the complex twice an hour apart and asked for a named individual before shooting, and that he seemed to have a purpose to kill from the outset.
Block said Dalton was home ‘between the shootings’ Saturday because his niece saw Dalton pull out of his driveway about 7 p.m. The first shooting occurred about an hour earlier.