Time-Slip Common In Autism

Neuroskeptic notes that a phenomena known as time-slip has been associated with autism spectrum disorders in Japan but not been discussed in the psychiatric literature elsewhere. The comments to his blog post suggest that the association is in fact widespread, despite the fact that it hasn't been discussed formally in the academic literature on autism.

The omission sheds light on a larger issue, which is the failure of mental health researchers to thoroughly characterize mental health conditions once a bare bones set of diagnostic criteria that are sufficient to but mental health conditions into boxes have been established. Once the box is in place, it is easy to let inertia take hold and accept it uncritically, so this concern may extend to a wide variety of formally recognized mental health conditions. The hope would be that identification of non-diagnostic traits associated with particular mental health condition, like time-slip in autism, might help us to better understand what is going on in those conditions.

READ MORE - Time-Slip Common In Autism

Physiological Test Predicts Effectiveness of Talk Therapy For Depression

[A] quick, inexpensive, and easy to administer physiological measure, pupil dilation in response to emotional words, not only reflects activity in brain regions involved in depression and treatment response but can predict which patients are likely to respond to cognitive therapy[.]. . . activity in the brain's cortical emotion regulatory systems is strongly related to pupil size when people are viewing emotion-laden words . . . It is because of this relationship between eye and brain that pupil measurements predict the response to cognitive therapy."

Cognitive therapy is a type of psychotherapy designed to help individuals overcome difficulties by modifying negative or irrational thoughts and behavior, which, in turn, can improve mood and reduce stress. It is usually completed in weekly sessions, with 10-20 sessions being effective for most individuals who benefit.

From here, citing Greg J. Siegle, Stuart R. Steinhauer, Edward S. Friedman, Wesley S. Thompson, Michael E. Thase. "Remission Prognosis for Cognitive Therapy for Recurrent Depression Using the Pupil: Utility and Neural Correlates." Biological Psychiatry, 2011; 69 (8): 726 DOI: 10.1016/j.biopsych.2010.12.041.

The abstact of the paper provides more details:

Although up to 60% of people with major depressive disorder respond to cognitive therapy (CT) in controlled trials, clinicians do not routinely use standardized assessments to inform which patients should receive this treatment. Inexpensive, noninvasive prognostic indicators could aid in matching patients with appropriate treatments. Pupillary response to emotional information is an excellent candidate, reflecting limbic reactivity and executive control. This study examined 1) whether pretreatment assessment of pupillary responses to negative information were associated with remission in CT and 2) their associated brain mechanisms.

We examined whether pretreatment pupillary responses to emotional stimuli were prognostic for remission in an inception cohort of 32 unipolar depressed adults to 16 to 20 sessions of CT. Twenty patients were then assessed on the same task using functional magnetic resonance imaging. Pupillary responses were assessed in 51 never-depressed controls for reference.

Remission was associated with either low initial severity or the combination of higher initial severity and low sustained pupillary responses to negative words (87% correct classification of remitters and nonremitters, 93% sensitivity, 80% specificity; 88% correct classification of high-severity participants, p < .01, 90% sensitivity, 92% specificity). Increased pupillary responses were associated with increased activity in dorsolateral prefrontal regions associated with executive control and emotion regulation. For patients with higher severity, disruptions of executive control mechanisms responsible for initiating emotion regulation, which are indexed by low sustained pupil responses and targeted in therapy, may be key to remitting in this intervention. These mechanisms can be measured using inexpensive noninvasive psychophysiological assessments.

The small study obviously needs to be replicated in a larger sample before being used on a widespread basis, but the 88% rate at which this simple test determines if high severity depressed patients will respond to cognitive therapy, compared to a 60% response rate in the absence of screening, is a major improvement for a technique that requires no investment in drugs or equipment and only minimal additional training for mental health practitioners. This test could spare more than half of severely clinically depressed individuals time and misery trying cognitive therapy that is unlikely to be effective for them, allowing them to use alternative therapies like drug treatments that are likely to be more effective for them immediately, while allowing about half of severely clinically depressed individuals to receive cognitive therapy, knowing that it has a very high probability of being successful, and avoiding the need for them to undergo a psychiatric drug treatment regime that is unnecessary for their recovery. The fact that the benefit is statistically significant at the 99% level in this small study also makes a study calculated to replicate this result look like a promising good investment.

Given that clinical unipolar depression is one of the most common mental health conditions, and is by far the most common one that is not typically congenital, which makes it disproportionately likely to be a condition dealt with by a primary care physician as opposed to a specialist mental health care professional, this kind of advance has particularly great practical relevance. Also, since unipolar depression is so common, the cost savings to the health care system of a diagnostic tool for determining what kind of treatment will be most effective could be an evidence based medicine technique that could make a material dent in the overall cost of mental health care.

Since this is a diagnostic approach, rather than a drug or device, it also doesn't need a long and costly approval process from the Food and Drug Administration. Funding of a simple large scale replication of this study which could be completed in a year or two, would be enough to include this diagnostic technique as part of the standard by the book treatment regime for unipolar depression nationally. Of course, since this isn't an approach would have a biotech company backing it, this kind of study almost necessarily would need to be funded by the public sector, for example, through a National Institute of Mental Health (NIHM) grant.

The real value of treatment effectiveness prediction tools as a means to improve the quality of patient care while reducing health care costs, a field which is coming into its own as a subfield of psychiatry and psychology, also suggests another funding possibility. Health insurance companies have historically viewed themselves primarily as financial institutions and as institutions through which patients can collectively bargain for provider health care pricing. But, the health insurance industry might be well advised to develop and fund a non-profit research foundation to develop treatment effectiveness prediction tools that do not have drug companies or medical equipment makers to fund them, as a way to promote health enhancing quality control.

The benefits of this little study aren't just practical in an immediate sense either. This is some of the hardest empirical evidence yet that there are medically relevant subtypes of unipolar depression in existence, with some indication of what the underlying neurological basis of that subtyping might involve. One of the deep issues in psychiatric classification of mental health conditions, for which the DSM-IV is the current industry standard, is that diagnosis of psychiatric conditions is almost entirely based upon non-physiological symptoms. It is entirely possible that some common DSM-IV conditions are really a cluster of separate conditions with similar symptoms but different causes (and hence different courses of treatment that are likely to be effective), and that other common DSM-IV conditions currently viewed are in fact merely distinctive syndromes that arrives when separate co-morbid conditions are present.

For example, this study shows that there are at least two types of unipolar depression, one of which is talk therapy responsive and one of which is not. This very likely indicates that the causes of the two types of unipolar depression are different. If this insight in incorporated into prior research on the causes of unipolar depression, the sometimes muddy and contradictory theories about what causes unipolar depression and how it can best be addressed might be clarified. One leading theory regarding the cause of unipolar depression conceptualizes it as a situation where prolonged stress and anxiety cause the body's normal responses to stress to shut down and try the new strategy of becoming depressed to deal with the situation. This might be a primary causal mechanism in one but not the other of subtypes of unipolar depression. If so, somewhat muddy data linking this cause to depression might become much more definitive with regard to the relevant subtype of depression, while clearing the decks for a search for one or more alternative causal mechanisms for the other subtype of depression.

Another possibility is that the pupil dilation response to emotion laden words may be a congenital element of a person's personality that is present even in the absence of unipolar depression. If this is the case, this trait might be one of many that is routinely tested for in children or young adults along with traits like blood type. Children with the trait might be at higher risk for the cognitive therapy responsive subtype of depression. Similarly, medical records could indicate which children are at risk for non-responsiveness to cognitive therapy as a treatment for unipolar depression. Since the physiological test for this trait is quite objective and easy to administer on a mass basis, it might also be possible to see if this trait corrolates with other mental health conditions, particularly those which are often co-morbid with unipolar depression (a co-mordidity pattern that might be more stark when restricted to a particularly subtype of depression), and to determine if it has a hereditary component. Patterns of co-morbidities associated with a particular subtype of unipolar depression might shed insight into the causal mechanism of a variety of mental health conditions which in turn might shed light on the kind of treatment regimes that are likely to be effective for those co-morbid mental health conditions.

Indeed, it might even be possible to provide these children or young adults, on a prophylactic basis, the kind of cognitive training that people with unipolar depression receive after they are diagnosed to help these individuals deal with situations that could lead to clinical depression before they happen.

There is no obvious reason that the benefits of cognitive behavioral therapy, which boils down to teaching people habits of thinking and mental tools for coping with certain kinds of problematic cognitive habits or tendencies, in general, can't be almost as effective when administered in advance as they are when administered as therapy after the fact. It might be possible to put together a set of empirically validated cognitive behavioral therapy regimes into a comprehensive set of coping skills that could be transmitted on a mass basis in a manner not unlike the model by which we instruct people in first aid, CPR, rescue breathing, the use of abdominal thrusts to respond to choking incidents, the proper way to respond to house fires, tornados and tsunamis, or suicide and bullying prevention programs. People who experience cognitive behavioral therapy responsive conditions anyway may benefit for refresher instruction and may be able to make more sense of what these therapies involve when they actually have the conditions that they are designed to alleviate, but it isn't unreasonable to think that this kind of public health preparedness model could materially reduce the overall incidence and impact of many common mental health conditions, some of which are subclinical or would otherwise never be diagnosed as such.

READ MORE - Physiological Test Predicts Effectiveness of Talk Therapy For Depression

The Sociology of Brain Disorder Treatment

There are two medical specialties that deal with brain disorders and conditions. One is neurology. The other is psychiatry. Where does one draw the line between the two?

Neuroskeptic compares the number of articles on particular conditions in leading academic journals for each specialty (Neurology and the American Journal of Psychiatry), to look empirically at how the line has been drawn within the medical profession.

The division doesn't seem to be very strongly linked to the extent that a condition is biologicallly based. As he notes:

Schizophrenia, which is probably considered "the most neurological" psychiatric disorder, is in fact the least talked about in Neurology.

Both mental retardation and autism are middle ground between the two specialties, with mental retardation leaning towards neurology, and autism leaning towards psychiatry.

Eyeballing the data, one way to think of the way that the conditions have been allocated is that psychiatrist deal with conditions that influence your personality and social interactions, other than pure cognition, while neurologists deal with other conditions and conditions that impact pure cognition.

This explains the mental retardation v. autism divide, for example. While both have a cognitive function element, explaining the neurological interest in both conditions, what distinguishes an autism diagnosis from a mental retardation diagnosis that is not autism is the diagnostic and treatment focus on how autism affects personality, social interaction and empathy, particularly in the case of autism spectrum disorders like Asperger's, where IQ is often in the normal range.

The gray area for ADHD, likewise, can be explained as a product of the lingering ambiguity over whether to think of the condition as a personality disorder that is a cogential part of who someone is, or as a developmental disorder of something large is part of a larger cognition process.

Psychaitry is concerned with "who you are" while neurology is concerned with "what you are" even though there isn't obviously any fundamental difference between the kind of brain functions that lead to schizophrenia and those that lead to congential epilepsy. The looming question behind Neuroskeptic's post is whether the divide says more about perhaps unfounded biases about mental health that pervade even the supposedly enlightened medical profession, than it does about science.

There are other ways to see the distinction, of course. One is that neurologists deal with issues that are believed to be exclusively "hardware" issues, while a core issue for psychiatrists is to parse "hardware" from "software" issues and address each appropriately. Some conditions may not neatly fit that divide today simply because historical ambiguity led a condition to be assigned to one category or the other, and given that all of the physicians involved have a similar allopathic medical background and training, there is no compelling reason to upset the apple cart of institutional and funding and bureaucratic arrangements based on the distinction at this point, even if it isn't terribly logical.

In the same way, no one is urgently pushing to have responsibility for counterfeiting enforcement removed from the duties of the United States Secret Service even though this doesn't logically have much to do with is primary responsibility to provide bodyguard protection to the President and other senior federal officials and candidates, because the skill set for the two tasks is similar.

Still, the divide has a strong impact on treatment modality. Neurologists use drugs and sometimes surgery, while seeing little place for therapy. Psychiatrists, while also prescribing drug treatments, recognize the value of psychological talk therapies as a complementary treatment modality to a much greater extent.

A footnote to the post in the study is also interesting:

"Gathering" this data took me 15 minutes. 20 years ago, it would have taken... well, you'd have had to read and manually categorize 30,000 abstracts. Even at 2 minutes per abstract (bare minimum) that's, er, 1000 man-hours of work.

READ MORE - The Sociology of Brain Disorder Treatment

Does Prenatal Testosterone Make You Smart?

Prenatal exposure of higher levels of testosterone turns out to be a relatively easy thing to measure because it manifests in a person's second to fourth digit ratio on their hands. Previous studies of digit ratio have suggest that this exposure may increase one's likelihood of being homosexual. A new study suggests that it may increase one's odds of having an IQ over 130, adding to prior work showing connections to primate social behavior, math test scores of seven year olds, and sports performance in women, to name just a few.

Scientists have also discovered a type of cell in the intestines that produces opium-like substances called tuft cells.

Also, in proof that probably dubious seeming experiments can produce good results, Japanese scientists have discovered that soaking superconductor material in Sake dramatically increases the rate at which the superconductors are produced. Further experimentation determined that superconductor materials prefer red wine to whiskey, suggesting that the alcohol itself is probably not the critical factor.

READ MORE - Does Prenatal Testosterone Make You Smart?

Neuroscience of Binge Drinking Better Understood

[M]anipulating two receptors in the brain, GABA receptors and toll-like receptor 4 (TLR4), "caused profound reduction" of binge drinking for two weeks in rodents that had been bred and trained to drink excessively." The study was published online the week of Feb. 28 in the journal the Proceedings of the National Academy of Sciences.

About 30 percent of Americans who drink do so excessively, and about 75,000 people die each year from the effects of excessive drinking. Current treatments for excessive alcohol drinking include prescription drugs Revia and Campral for controlling cravings. To ease withdrawal symptoms, doctors often prescribe medications such as Valium and Librium that carry their own risks of addiction. Valium and Librium reduce the anxiety alcoholics feel when they stop drinking but do not reduce cravings for alcohol.

The new study found that treatments that manipulate both the GABA receptor and toll-like receptor 4 have the potential to reduce anxiety and control cravings, with little to no risk for addiction[.] . . .

GABA receptors are a class of receptors in the brain that react to the neurotransmitter GABA and act as inhibitory receptors, calming down or inhibiting the activity of neurons in the brain. GABA receptors react to alcohol, giving drinkers a calm and euphoric feeling and reinforcing excessive drinking behavior. . . . This is the first scientific study to document GABA receptors' key involvement in binge drinking specifically, though scientists already believed that the receptors had a role in excessive drinking in general. . . .

Science has traditionally considered TLR4 to be an innate immunity receptor involved with neuroinflammation in the brain. Scientists associated TLR4 with microglia, cells that support inflammatory responses in the brain. "What makes this finding particularly important for the field of neuroscience is that we're showing that TLR4 plays a significant role in neurons, specifically, the neurons that are connected to the GABA receptor," . . . . To establish the connection between the GABA receptors, TLR4 and alcohol, the scientists manipulated this pathway in the binge drinking rodents . . . [with] a herpes viral vector . . . to deliver a gene-modifying agent directly to the neurons in the brain, to target TLR4 and GABA receptors. The scientists found that when they artificially stimulated the GABA receptors and TLR4 in order to simulate the good feelings binge drinkers feel when drinking alcohol, the rats lost interest in alcohol for two weeks after the procedure.

Compounds exist that would stimulate the receptors in the same way the scientists did in the study. "It's very likely that, down the road, these compounds could become new therapies for binge drinking . . . These compounds would act like a substitute for alcohol, much like methadone acts as a substitute for heroin. They would help alcoholics stop drinking, giving them relief from their cravings and from the anxiety that they try to alleviate with drinking."

From here.

So, drugs to end a predisposition to binge drink may be on the horizon in our near future, and there is a methodological precedent for determining a cause and developing a treatment for other kinds of substance addictions.

Given the strong connection between alcoholism and other kinds of substance abuse, and a wide range of socially unacceptable behavior and crimes, the next question is whether these treatments promise a world in which those social ills are dramatically less of problem.

Also, if such drugs existed, what would it take to get binge drinkers to take it? Will drug testing for probationers cease to become a matter of seeing that they aren't taking illegal drugs and become a matter of confirming that they are taking drugs that treat their vulnerabilities?

Given the poor track record of science at observing ethical standards with vulnerable or institutionalized populations, there is also good reason to fear abuses along the same lines in the future.

There may also be an upside to the complexity of many polygenetic mental health traits. While it may take just a single disruption of one of thousands of genes that go into a health functioning brain, if dysfunctional processes are equally complex, a single way to disrupt that process may deal with problems that have a wide variety of causes. This seems to be the story of modern psychiatry. We have found drugs that can manipulate a handful of neurochemicals in the brain, but those drugs treat a large number of patients with neurochemical imbalances in the neurochemical systems that most commonly go awry.

Drugs that act on neurochemical receptors and reuptake channels seems to address a great many mental health conditions. This part of the brain seems particularly succeptable to treatment with drugs. There may be other parts of the brain that are equally important, perhaps miswired neurons, for example, but we don't understand how to treat them as well.

READ MORE - Neuroscience of Binge Drinking Better Understood

Possible Prion Disease Drug Identified

Using trial and error methodology that Thomas Edison could relate to, scientists have located a drug that may have the potential to treat prion diseases such as mad cow disease, scrapie and chronic wasting disease in animals, and diseases including Creutzfeldt-Jakob Disease, Fatal Familial Insomnia, and Kuru in humans, that "result from deposits of abnormal prion protein in brain tissue. Prion diseases are invariably fatal and no treatments are yet available." At this point testing is in mouse models and cell cultures.

Treatments exist for most other major classes of disease causing agents, such as bacterial infections, viruses, funguses, venoms, and parasites, but not for prions.

Prions are also worrisome because they are resistant to sterilization methods that destroy most other disease agents: "Prions are generally quite resistant to proteases, heat, radiation, and formalin treatments, although their infectivity can be reduced by such treatments." Strong acids in combination with higher than typically used heats are necessary to render them non-infectious.

READ MORE - Possible Prion Disease Drug Identified

Key Piece of Genetic Autism Puzzle Discovered

Boys shows signs of autism spectrum disorders more often than girls. But, autism is strongly hereditary. What's going on? The most parsimonious assumption is that there are one or more X chromosome linked genes that are protective against problems created by autism causing genes elsewhere in the genome.

The DIA1R gene (which stands for "deleted in autism one related" because it influeces the expression of the autosomal DIA1 gene on chromosome 3 which is "deleted in autism") seems to fit the bill:

[M]utations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. . . . [DIA1 and DIA1R synthesize two very similar] signal peptides for targeting to the secretory pathway [probably for the same system in the brain]. Both genes are ubiquitously expressed, including in fetal and adult brain tissue.

Another similar X linked gene with the same kind of protective role that was previously discovered was DDX53-PTCHD1.

Since girls have two X chromosomes and since one protective gene seems to provide at least some benefit even if that girl also has a deleted DIA1R gene, girls are more likely to have some protection from their deleterious autism related genes. But, a boy with a deleted DIA1R gene in his one X chromsome lacks to XLMR/autism spectrum disorder protective trait and shows more autism spectrum disorder or retardation symptoms. A girl with some, but not all of the protective X linked genes, may sometimes not be symptom free but may still experience a milder autism spectrum disorder (e.g. Asperger's) than a boy who lacks more of these protective genes.

Since this basic genetic model involving autosomal autism causing traits that frequently arise by novel mutation and X linked protective genes was proposed in 2007, scientists have identified at least the two key X linked protective genes described above and have gained some insight into what at least one of them does. Researchers have also in the last three and a half years, increasingly come to conclude that there is not a single primary autism causing gene, although all of the known autism causing genes do appear to be dominant rather than recessive in effect.

Researchers also know that the gene DIA1, and probably other genes appear to contribute to autism, but that there also appear to be a whole host of other autism causing mutations. About two-thirds of these arise from new mutations in sperm cells that are not present in the parent, while the other third are inherited from a less symtomatic mother or a mildly symptomatic father, or both.

The brain chemistry system that genes like DIA1R and DDX53-PTCHD1 protect is apparently highly prone to malfunction from a large number of other genes, none of which is predominant as a cause of autism, perhaps because the process impacted is intricate and delicate, without these protective genes. But, we actually have only a dim idea of precisely which process or processes in the brain that autism disrupts, and in general. We know what happens when this process, whatever it is, goes wrong, in great detail, but not why a problem with this process causes this effect. This is, of course, unfortunate, since it is hard to treat autism in people who have it already until we have a better idea of what is broken that causes these symptoms. But, the more we can pin down the genes produce autism spectrum disorders, the more we can engage in a narrow and targeted effort to understand how this process in the brain works and what these genes do to disrupt its normal functioning.

READ MORE - Key Piece of Genetic Autism Puzzle Discovered

Fungi Are Gender Benders

One of the most fascinating discoveries that I made as a 9th grader sitting in the high school greenhouse taking biology at Talawanda High School was that there are some kinds of living things that have reproductive cycles far more complicated than that of simply dividing cloning cells, two gender system vertebrates, and multi-stage life cycle creatures like frogs (who early on look like fish called tadpoles) and butterflies (if you mother didn't tell you about the butterfly life cycle, you must have been an exceptionally beautiful and graceful child).

A received an echo of that moment again reading "The Host" by Stephenie Meyer, a little while ago, that has a story within a story sketch about an alien life form with a more complicated than two gender reproductive system.

Among the only reproductive concepts that have rivalled this revelation since then, most of which I have encountered first in science fiction, are the notion that viruses can change genomes, the discovery that some kinds of vertebrates can have virgin births in certain circumstances, the discovery that one can have mixed paternity twins (or even more amazingly mixed DNA individuals), the discovery that we are probably part Neanderthal, and the notion that ancient DNA might be used to create living versions of extinct creatures a la Jurassic Park: Japan has set out to resurrect the Mammoth by 2015.

Then, I came across a post at Replicated Typo today that recalled that moment for me. You see, some of the most complex reproductive systems of any living things are fungi.

Their reproductive mechanisms is rather unexpectedly complex, in that the normal conventions of sex do not apply. Not all fungi reproduce sexually, and many are isogamous, meaning that their gametes look the same and differ only in certain alleles in certain areas called mating-type regions. Some fungi only have two mating types, which would give the illusion of being like animal genders. However, others, like Schizophyllum commune, have over ten thousand (although these interact in an odd way, such that they’re only productive if the mating regions are highly compatible (Uyenoyama 2005)).

Some fungi are homothallic, meaning that self-mating and reproduction is possible. This means that a spore has within it two dissimilar nuclei, ready to mate – the button mushroom apparently does this (yes, the kind you buy in a supermarket.) Heterothallic fungi, on the other hand, merely needs to find another fungi that isn’t the same mating type – which is pretty easy, if there are hundreds of options. Other types of fungi can’t reproduce together, but can vegetatively blend together to share resources, interestingly enough. Think of mind-melding, like Spock. Alternatively, think of mycelia fusing together to share resources.

In short, the system is ridiculously confusing, and not at all like the simple bipolar genders of, say, humans (if we take the canonical view of human gender, meaning only two.) I’m still trying to find adequate research on the origins of this sort of system. Understandably, it’s difficult. Mycologists agree:

“The molecular genetical studies of the past ten years have revealed a genetic fluidity in fungi that could never have been imagined. Transposons and other mobile elements can switch the mating types of fungi and cause chromosonal rearrangements. Deletions of mitochondrial genes can accumulate as either symptomless plasmids or as disruptive elements leading to cellular senescence…[in summary,] many aspects of the genetic fluidity of fungi remain to be resolved, and probably many more remain to be discovered.” (Deacon, 1997: pg. 157)

There is a linguistic angle in the original post on gender agreement in language, but quite frankly, it doesn't interest me. But, amazing complex versions of sex do. What benefit do mushrooms receive from their more elaborate forms of reproduction? Are there downsides to it? How does it work? What are the general patterns of the diversity in reproductive arrangement in fungi?

I'm already familiar to some extent with fungi weirdness. In some ways they are more like animals (e.g. they don't generally produce their own food through photosynthesis). In other ways they are more like plants (e.g. they are generally sessile). Some fungi produces remarkable neurological responses. Fungi colonies have also proven to be far more elaborate multi-species ecosystems than most people had realized with lots of undiscovered complexity. But, complex reproductive mechanisms adds a whole new dimension to the brew. And, in an age where we may be nearing the "end of science" in physics and inorganic chemistry, seriously unexplored territory in biology is the place to learn new things whose utility was not previously recognized. Also, because researching fungi involves far less expensive laboratory equipment and conditions and staffing requirements than many other areas of science, while having an unusually large share of unanswered questions, it presents that possibility of pretty small scale scientific pioneers out of anywhere discovering cool new things.

More deeply, and more to the point of the linguistics post cited, how does being forced to look at issues of gender in a far more generalized and complex way than we are now aware that human neurodiversity involves in sometimes rare permutations (male, female; gay, bi, straight; butch-femme; cis and trans gender; dimensions of gender; archaic human-modern human hybrids, etc.) enlighten our thinking about the combinations and interactions encountered by humans.

The details of how fungi do it in interesting systems will have to wait for future posts. But, I wanted to note some access points to start looking into again before the thought left me.

READ MORE - Fungi Are Gender Benders

Quick Science Hits

* The brain structure called the amygdala is closely associated with the instinctual fear. But, that isn't all it does. A large amygdala is associated with "a rich and varied social life among humans" and closely related primates. It has been linked to the social deficits in autism and regulates emotions in social situations in coordination with other parts of the brain. It may play a key part in interpreting facial expressions and monitoring personal space. Atypical amygdala function has been associated with: borderline personality disorder, psychopathy, more severe social phobia, bipolar disorder, autism and schizophrenia. The role of the amygdala in interpreting facial expressions, particularly fearful ones, and in fear generally, appears to be implicated in many of the mental conditions, and the left amygdala seems to be implicated more often than the right amygdala.

* "[A] single DNA change that blocks a gene known as HTR2B was predictive of highly impulsive behavior. HTR2B encodes one type of serotonin receptor in the brain. . . . "we found that the genetic variant alone was insufficient to cause people to act in such ways . . . Carriers of the HTR2B variant who had committed impulsive crimes were male, and all had become violent only while drunk from alcohol, which itself leads to behavioral disinhibition." From here via here.

* Eating fried fish is linked to strokes.

* Out of Africa migrations may have been via a wet Sahara rather than the Nile River Valley or Red Sea:

Analysis of the zoogeography of the Sahara shows that more animals crossed via this route than used the Nile corridor. Furthermore, many of these species are aquatic. This dispersal was possible because during the Holocene humid period the region contained a series of linked lakes, rivers, and inland deltas comprising a large interlinked waterway, channeling water and animals into and across the Sahara, thus facilitating these dispersals. This system was last active in the early Holocene when many species appear to have occupied the entire Sahara. However, species that require deep water did not reach northern regions because of weak hydrological connections. Human dispersals were influenced by this distribution; Nilo-Saharan speakers hunting aquatic fauna with barbed bone points occupied the southern Sahara, while people hunting Savannah fauna with the bow and arrow spread southward. The dating of lacustrine sediments show that the “green Sahara” also existed during the last interglacial (∼125 ka) and provided green corridors that could have formed dispersal routes at a likely time for the migration of modern humans out of Africa.

READ MORE - Quick Science Hits

How Reversible Is Progress?

Sometimes in history, mankind fails. Empires fall. Hard won knowledge is lost. Niceties of civilization disappear. Languages die. Prejudices tamed resurface. Barbarism defeats civilization. Centers of progress stagnate and ossify. Wars, pointless or not, kill millions when wiser statesmen could have secured better outcomes.

We are a fortunate people. We live in a time of technological virtuosity, global communication, remarkable tolerance, greater scientific knowledge than any generation to come before us, awareness of many of the threats to our way of life that loom ahead, economic prosperity viewed in the long term, and a point in time when many countries are liberal democracies, many countries that were once brutal tyrannies like the Soviet Union and early Communist China have changed course, and where truly abysmal countries, like North Korea, are small and isolated and perhaps even on the brink of collapse.

We are, in other words, at a point when we have a great deal to lose.

The risks are not abstract. Our era of toleration has brought out into the open the identities of people who would have been persecuted or killed in all prior eras.

Widespread gay marriage and the end of "Don't Ask, Don't Tell" which has already been matched in much of the Western world, means that hosts of gays and lesbians who would have lived secret lives in the past are now out and public. This openness has brought with it acceptance, toleration, and access to legal recognition with all of its blessings. But, openness comes with the price of constant vigilance. Once out of the closet, a population that will always be in the minority must rely forever after on the good will of a liberal democratic society to protect it.

Gays aren't the only ones taking a risk. Many people have come out publicly as atheists, and if religion becomes established, as there has often been democratic pressure of governments to do, they risk persecution as heretics and apostates and blasphemers.

Pagans are in much the same shoes. The Denver Post on Christmas Day informed us that 45 people in Haiti had been murdered based on accusations of witchcraft connected with its recent cholera outbreak.

Anti-Islamic sentiment has swept much of Europe, and lurks ready to turn ugly in America.

It would take a greater calamity to set back human knowledge, science and technology, but would it really take an event so unthinkable. As glorious as a digitized world may seem, the collapse of the Internet remains far more possible than the sack of every decent university and public library on earth. But, if the libraries no long have independent copies of the knowledge upon which we rely, if the technologies we use to access our data cease to be supported for any myriad reasons before the data the technologies make us privy to is converted to new media, how much could we lose?

It is hard to believe that we could ever see a setback as dire as the one that followed the collapse of the Roman Empire. The college textbooks lurking in the basements of hundreds of thousands of middle class families could reconstruct science, if not to the standards of 2010, at least to the start of the art from the 1980s. It might take a long time to rebuild particle accelerators necessary to prove the existence of quarks, and weak force carrier bosons and neutrinos and their properties from first principles and to return to the point where we could answer the remaining open questions of physics. But,a backpack full of graduate school textbooks (or even a binder full of relevant wikipedia printouts) would make the task far less arduous than it was the first time. Not many people know how to run an iron foundry, but again, if just once decent university library of thousands in the United States were to survive, we could learn to do so much more efficiently.

We could easily lose many of the primary documents that back up the story of history. But, there are enough histories out there that it is hard to believe that the broad outlines and even references to many of the key primary sources from which they can be reconstructed, will ever again be lost.

I'd sleep a little better if someone were consciously working out a way to insure that this knowledge survived longer -- printing out a massive library on bronze plates in a dozen different languages maybe -- but even a truly global apocalyptic event would have to be extremely thorough to set back the state of knowledge too far.

It might take a few decades to reconstruct the infrastructure necessary to manufacture decent computers, or mass produce precision stainless steel appliances, or to generate advanced medicines with high levels of purity at reasonable costs. But, there are quite a few copies of the key information available in the kind of technical detail found in patent applications, for example, out there.

More intangibly, how deeply can the modern worldview be suppressed? There have certainly been episodes of history that makes one worry. Who in late tsarist Russia on the verge of Western style liberal democracy could have foreseen Stalinist massacres? Who in the collapsing Chinese empire could have foreseen the Cultural Revolution? The example of Korea is particularly troubling because it was so recent. Dean Koh of the Harvard Law School recounts cities of people with eyes as listless of those of Orwell's 1984 in the hear and now in North Korea, which has been divided from the South for less than sixty years. The return of Albanian society to a medieval state from a similarly brief period of isolation likewise leaves one with qualms.

Yet, Cambodia, while hardly a model of national success, seems to have returned to some semblence of normalcy even after Pol Pot's massacre of the entire bourgouise class in his society. Albania is being reintegrated into Europe. The death of Soviet style communism was traumatic for a generation, but its successor regime seems to be emerging and tentatively is not a total nightmare.

If progress really is inevitable in the long run, despite dire and painful setbacks, then perhaps economic development in places that have not yet experienced its benefits, may also be more or less inevitable. Surely, results achieved from scratch in one place can be secured elsewhere, where they need only be copied, somewhat more easily than they came about in the first place. Or, can they?

Could it be that centuries of ruthless capital punishment that prevailed across Europe was necessary to build a more tame society? Could it be that modern nation states are not really stable unless they arise gradually and naturally from smaller principalities together with all the attendent wars and nationalist strife, unless they arise from a uniform orderly process of colonization? Could it be that liberal democracy has functioned well enough for the last couple of centuries (and far less in much of the world) because it has been sustained by economic growth that has actually only been a coincidental fellow traveler with it?

Historically, mankind has managed to make progress, even as one empire or another has collapsed, by passing the torch of knowledge and tolerance and innovation from one place to another. But, in an increasingly global society, we are increasingly placing all of our eggs in one basket. The collapse of China, or a subcontinental nuclear war between Pakistan and India, or the stagnation of American society, or economic collapse in the European Union due to mismanaged public finance, is no longer the kind of event that the rest of the world can ignore. A major collapse in one part of the world drags the rest of the world down with it to some extent.

In World Wars I and II, Switzerland managed to stay neutral and above the fray. In the next global calamity, there may be no Switzerlands.

The political-economies of the world evolve in very path dependent ways. When something works better than what came before it, it sweeps the "known world" at the time. The invention of farming obliterated the cultures that proceeded it for as far around of empires could spread, even though the extent to which the actual people who followed the old cultures is disputed. Rome expanded as far as the terrain would permit. Every country in the world has a basically modern military, even if its economy carries on with centuries old means of production. All but a handful of legal systems in the world are derived from those of Revolutionary France, the Kaiser's Germany, 17th century England, or 19th century Spain, and the European Civil Law systems had more similarities than differences due to their common Roman origins. There are a few not particularly promising outliers that are more home grown - China, Iran and Saudi Arabia, for example, some of which have a few followers, as do various dictatorships. But, what none of the four or five main political systems that predominate in our big blue marble are up to the next challenge our world needs to overcome.

I'm basically an optimist. I think that humanity will come up with a way to maintain modernity without oil and natural gas. I think that humanity will come up with a way to cope with global warming, although I have no confidence that we will have the will to keep it from running its course. I don't think that a global nuclear war will cause our species to go extinct. I am inclined to think that our ability to detect and deal with diseases have reached a point where we can address any new disease before it does irrepairable damage to the species. I don't think that the bulk of our knowledge scientific and otherwise will be lost.

I worry more that we may reach a point where we have a global government, initially a good one, that stagnates and stifles us. Perhaps we need one to prevent global environmental threats and nuclear war from doing us in. But, we aren't anywhere close to that point now. We may be in a single global system, but it is not a united one.

But, I am not a believer in the notion that we are at "the end of history." I fully expect to see rapid change for centuries to come. The social sciences have a moving target to chase, culture constantly evolves, and the scientific and technical advances we are experiencing now will take decades or even a century to run their course.

Yes, there surely must come a time when our constant barrage of new scientific discoveries is the physical sciences slows down and eventually reaches a trickle.

We are close to that point in physics and earth sciences and inorganic chemistry and mathematics. We are coming to that point in civil engineering, chemical engineering, materials science, mechanical engineering, electrical engineering and a great many other practical fields. Computers haven't been perfected to their theoretical limits, but their capabilities are continuing to grow so fast that we will surely come very close, very soon.

There is little in mathematics today that the leaning mathematicians of 1910 could not grasp with a year or so of additional study that would make heavy use of what they already knew. General Relativity has received a lot of experimental confirmation since the theory was published by Einstein in 1915, and several different mathematically equivalent expressions, but it remains state of the art physics 95 years later. Many blanks have been filled into the Periodic Table of the Elements since Dmitri Ivanovich Mendeleev published it in more or less its current form in 1869, and we understand in much more detail why the periodic table has the properties that it does, but it remains the point of departure for modern chemistry (and he also is the man responsible for the fact that liquor is sold primarily at 80 proof strength, a cultural impact still felt today).

The standard model of particle physics, which reached something close to its current form in 1981, and has been refined in a few minor respects since then, isn't quite so musty and will probably be refined further before it reaches its final form, but its resiliance in the face of three decades of intense efforts to find deviations and refinements suggest that whatever beyond the standard model physics are still out there to be discovered may have rather modest practical impact. The Higgs boson which the Large Hadron Collider will either discover or disprove in the next couple of years, was predicted in 1964.

We haven't discovered every species of life on Earth, but for many taxonomy categories, we are very close to having done so, and the tool of genetics has imparted considerable heft to those classifications. Most of the new discoveries have been of new species of existing taxonomic categories; we may well have discovered ever kingdom, phylum, class and order of living thing in existence already, and almost every species of vertebrates, certainly the pace of new discoveries of higher level taxons and new species of large animals and plants is slowing. There are probably undiscovered beetle species out there, and some new deep sea organisms or microbiological organism that have yet to be discovered, but our sense of the extent and shape of the biosphere and its evolutionary origins is already quite refined.

Biotechnology is still hurling forward. It will take time to truly master the genome and the epigenome, to really have a firm grasp of how the brain works, and to master the manipulation of it all. But, we are getting much closer.

The blue print in the form of the complete genome is available on computers already for a host of organisms including many people, even if we don't yet know how to read it fluently. We've identified the functions many key working parts. We know a great deal about the overall structure. We've identified a large share of the genome that is common to every human being alive today, and can even trace which parts changed from our common ancestor with chimpanzees and from our Neanderthal predecessors.

We have working models of the structure of the human brain functionally and involving its major subsystems, of the role of the major components of our brain chemistry, of the connection between the brain and the rest of our body, of the way that neurons bind themselves into networks, of the process by which memory works, of the extent to which knowledge is hardwired or learned, of the connections between our senses and our experience of them. We have some sense of how gender and age influences the brain. We have some sense of the variety of mental conditions that can arise, their usual course, and their causes. We may understand the brain far less well than we understand bacterial infections, the heart, or the liver, but for the most part, it seems as if our work is cut out for us. We don't know everything, but we have a pretty good sense of what we don't know and have to discover.

One time pipe dreams, like cures for many kinds of cancers, cures for nervous system disorders, cures for autoimmune diseases, workable treatments for many kinds of mental illnesses, treatments for hereditary blindness and more, while not yet attained, seem attainable. Science has brought us an understanding of many diseases that is exquisitely detailed. Even when we can't cure a disease yet, we often know with excruciating specificity how it works. The implications of those developments for our society may be profound.

Even if we don't learn all that science can offer us, we may reach a point where what we don't know is largely esoteric and is only of intellectual curiousity, with little practical impact, sooner. While history may not be at an end, I wouldn't be surprised if the pace of progress in the physical sciences and engineering in 2110 is much slower than it is now. By 2210, it will probably have reached a crawl indeed, simply because we will already know so much at that point. Perhaps at that point a certain amount of political stagnantion will be acceptable, because the world will stop changing so fast and our leaders can be enlightened by a large corpus of established scientific knowledge.

READ MORE - How Reversible Is Progress?