Cerebral Asymmetry / Asperger Brain Differences

Philosophical Transactions of the Royal Society / Biological sciences

The evolution and genetics of cerebral asymmetry

http://rstb.royalsocietypublishing.org/content/364/1519/867/

Michael C Corballis

Circadian Rhythm Disturbances / Bipolar – Asperger Syndrome

Bipolar Disorder is thought to be co-morbid to Asperger Syndrome. I want to introduce material from Circadian Rhythm studies.

Circadian Rhythm

Social cues help set sleep patterns

Social cues help set sleep patterns

© 2002 Psychiatric Times. All rights reserved. Circadian Rhythms Factor in Rapid-Cycling Bipolar Disorder by Ellen Leibenluft, M.D. Psychiatric Times May 1996 Vol. XIII Issue 5

The nervous systems of people with bipolar disorder frequently make specific types of regulatory errors. Many of those errors involve the body’s internal clock, which controls the phenomena known as circadian rhythms. These are the regular rhythmic changes in waking and sleeping, activity levels, and sensations of hunger and thirst.

Phototherapy and melatonin, two interventions that manipulate the circadian system, are being used widely for seasonal affective disorder, jet lag and some forms of insomnia. Scientists continue to make tremendous strides in understanding the regulation of the circadian system in humans and animals. We now know that the body’s clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, and that the SCN regulates the pineal gland’s secretion of the hormone melatonin (Klein and colleagues). In humans as well as animals, light suppresses melatonin secretion; recent evidence shows that even ordinary room light can have this effect. Because light suppresses melatonin secretion, the hormone is typically secreted at night. Furthermore, the SCN can “remember” the day-length to which it has been recently exposed, so the timing of nocturnal melatonin secretion is determined by the “lights on” and “lights off” times of the preceding days. In 1994, scientists cloned genes regulating circadian rhythms in mice, making the circadian system the first complex behavioral system whose genetic underpinnings could begin to be unraveled in mammals (Vitaterna and coworkers).

In mood disorder research, interest in circadian rhythms is not new. For at least 50 years, investigators have questioned whether abnormalities in circadian rhythm regulation might be involved in the pathogenesis of mood disorders, including rapid-cycling bipolar disorder. These questions were motivated by three clinical observations. The first of these was that the sleep duration of patients often changes dramatically as they cycle between mania and depression; bipolar depression is typically associated with hypersomnia, while mania is characterized by extreme and sometimes total insomnia.

The second observation was that approximately 60 percent of depressed patients experience remission after a night of total or partial sleep deprivation (SD). In bipolar patients, sleep deprivation (SD) may actually cause a switch into hypomania or mania. However, this “upward” switch usually lasts only until the patient undergoes recovery sleep, leading to the formulation that SD, or extended wakefulness, is antidepressant, (or manicogenic), while sleep is depressogenic, (Wehr). The antidepressant effects of SD are conceptually important because they show that changes in sleep duration are more than just symptoms of the illness, and also play a pathogenic role.

Using a longitudinal analysis of mood and sleep in a sample of patients with rapid-cycling bipolar disorder, we recently demonstrated that decreased sleep duration precedes, rather than simply follows, a switch into hypomania or mania (Leibenluft and coworkers, in press). Furthermore, in this sample, decreased sleep duration was more consistently associated with a shift to an earlier wake-up time than it was with a shift to a later bedtime. Pharmacologically, it is easier to manipulate the time a patient goes to sleep than to change the time he or she wakes up; perhaps for this reason, clinicians have generally attended less to wake-up time than to sleep-onset time. However, these data indicate that interventions designed to shift patients’ wake-up time may deserve further study.

The third observation implicating abnormal circadian rhythms in the pathogenesis of mood disorders concerns diurnal variation. In its classic, typical form, diurnal variation is defined as a gradual improvement in the patient’s depressed mood as the day wears on. Like sleep deprivation, typical diurnal variation demonstrates that extended wakefulness is associated with an antidepressant response. We recently extended the concept of diurnal variation to bipolar patients with data demonstrating that rapid-cycling patients are more likely to switch “up” (i.e., from depression or euthymia into hypomania) during the day, and to switch “down” (from hypomania or euthymia into depression) overnight, while they sleep (Susana Feldman-Naim, M.D., and coworkers, unpublished data). Thus, once again, extended wakefulness is associated with an antidepressant response, while sleep appears to be depressogenic.

Specific theories have been advanced as to how circadian rhythm dysfunction might lead to rapid-cycling bipolar disorder. In 1968, Halberg suggested that some, but not all, circadian rhythms in such patients were not synchronized with the 24-hour day-night cycle (Halberg). According to Halberg’s hypothesis, the interaction between the unsynchronized, “free-running” rhythms and the normally synchronized (entrained) rhythms causes switches back and forth between mania and depression.

Kripke and colleagues then presented data demonstrating what appeared to be a free-running temperature rhythm in five of seven rapid-cycling patients. In these patients, the period (time taken to complete one cycle) was abnormally short, in essence showing that patients with rapid mood cycles had rapid physiological cycles. However, subsequent investigators have not generally found either free-running or unusually fast circadian rhythms in patients with rapid-cycling bipolar disorder.

In the 1970s and ’80s Wehr and collaborators, working at the National Institute of Mental Health, continued to study biological rhythms in this patient population. Using both cross-sectional and longitudinal designs, they showed that the phase (timing) of patients’ sleep, temperature and motor activity rhythms varied systematically as they cycled between hypomania or mania and depression. Specifically, the timing of these rhythms appeared to be earlier in manic than in depressed patients, and earlier in depressed patients than in controls (Wehr and colleagues 1980). We now have preliminary data indicating a similar pattern in the time of onset of nocturnal melatonin secretion. These new data show that, in rapid-cycling bipolar patients, the time of nocturnal melatonin onset may be approximately 90 minutes earlier when they are hypomanic, compared to when they are depressed (Leibenluft and colleagues 1993). It is as if rapid-cycling patients might have an endogenous form of jet lag, internally traveling back and forth over one or two time zones as they cycle between hypomania and depression. Indeed, several studies show that bipolar patients are at risk to develop an affective episode when they travel across time zones (Young).

What might cause these shifts in the phase (time) of onset of nocturnal melatonin secretion? It is possible that phase shifts.i.phase shifts; in nocturnal melatonin secretion precede the patients’ mood switches and play a pathogenic role in mood cycling. However, it is also possible that the phase shifts are epiphenomena caused by the patient’s symptoms. Specifically, the phase shifts may be secondary to the changes in the sleep-wake cycle.i.sleep-wake cycle; that occur with mood cycling. The phase of circadian rhythms is determined by zeitgebers (“time-givers”).

While light is the most potent zeitgeber, physical activity, eating and social routines can probably also affect the timing of circadian rhythms. The timing of all these zeitgebers is often different when a patient is hypomanic, compared to when he or she is depressed, and shifts in the timing of zeitgebers would cause phase shifts in circadian rhythms.

However, a third possibility also exists. We suggest that phase shifts in melatonin secretion and other circadian rhythms are not the primary cause of mood cycling, but they are also not irrelevant epiphenomena. We hypothesize that phase shifts in melatonin secretion are secondary to the patient’s symptoms or to more fundamental causes of bipolar illness, but they nonetheless have pathogenic significance and contribute to the development of a full-blown affective episode.

This formulation is analogous to that of Wehr and coworkers (1987) in describing the contribution of sleep deprivation to the development of manic episodes. These authors suggested that insomnia, which is itself a symptom of mania, contributes to the development of a manic episode because it causes sleep deprivation. In other words, insomnia is both a symptom and a cause of mania. If one treats the insomnia early and aggressively, one can truncate an episode, or prevent mild or moderate symptoms from snowballing into a severe and destructive episode. Similarly, it is possible that the shifts in circadian rhythms, while not the initial cause of a mood switch, contribute to the severity and duration of an episode, and thus play a role in determining the course of illness.

We are currently testing this hypothesis by determining whether interventions designed to prevent phase shifts in nocturnal melatonin secretion have therapeutic effects in rapid-cycling bipolar patients. One such experimental treatment involves the use of phototherapy. Data indicate that midday bright light may increase the amplitude of nocturnal melatonin secretion. Since increasing the amplitude of a rhythm makes it more resistant to phase shifts, midday light might be expected to stabilize the time of nocturnal melatonin secretion. In other words, midday phototherapy administered to these patients might prevent the shifts in timing of nocturnal melatonin secretion that we believe have pathogenic significance. After encouraging results with a small number of patients, we are now conducting a formal, controlled trial of this intervention. Interestingly, morning bright light, which shifts patients’ circadian rhythms, may have caused several of our rapid-cycling bipolar patients to cycle more dramatically.

Thus, even if circadian abnormalities are neither the sole nor the primary cause of bipolar illness, it is possible that circadian interventions can have therapeutic utility. Compared to psychotropic medications, circadian interventions are relatively flexible therapeutic modalities; they have a rapid onset and offset of action, and their clinical effects may be altered by changing the time that they are administered. This flexibility may be particularly useful in rapid-cycling bipolar patients, whose frequent mood cycles may require rapid alterations in their therapeutic regimen. Further research will indicate what, if any, role circadian dysfunction plays in the pathogenesis of rapid-cycling bipolar disorder, and whether circadian interventions can be helpful to these often treatment-resistant patients.

Ellen Leibenluft, M.D., is chief, Unit on Rapid-Cycling Bipolar Disorder, Clinical Psychobiology Branch, National Institute of Mental Health.

What “The World” Sounds like to (Many) Asperger People

The woman who made this audio track is correct! I could not bear to listen longer than a few seconds. If you can listen to this COMFORTABLY, you will likely not be able to understand what an Asperger person goes through daily, when trapped in social typical environments.

One particular point: It’s nearly impossible to pay attention to and to understand what a person is saying when “background noise” is not in the background! It’s competing with the person speaking; the impulse is to get away from the discordant “sounds” – the effect is like being tortured. Truly!

 

Misdiagnosis of Gifted Children as Asperger and Mentally Ill

  When intensity and sensitivity are combined with idealism, as so often happens with bright children and adults, good things can happen because they can keenly see how things might be. But this can also lead to frustration, disillusionment, and unhappiness. Sometimes this prompts perfectionism; other times it results in existential depression. Through our relationships, we must provide understanding and nurturance so that they do not feel alone and helpless in a world that seems so paradoxical, arbitrary, and even absurd. We can help nurture their idealism, and indeed we must if the world is to become a better place.

Brow Ridge unrelated to cognitive development

Comparing Frontal Cranial Profiles in Archaic and Modern Homo by Morphometric Analysis

FRED BOOKSTEIN et al

There is an 8-page pdf for this paper, but once again I can’t get the URL to connect.

Brain_directions__planes_-_smallINTRO: Archaic and modern human frontal bones are known to be quite distinct externally, by both conventional visual and metric evaluation. Internally this area of the skull has been considerably less well-studied. Here we present results from a comparison of interior, as well as exterior, frontal bone profiles from CT scans of five mid-Pleistocene and Neanderthal crania and 16 modern humans. Analysis was by a new morphometric method, Procrustes analysis of semi-landmarks, that permits the statistical comparison of curves between landmarks. As expected, we found substantial external differences between archaic and modern samples, differences that are mainly confined to the region around the brow ridge. However, in the inner median-sagittal profile, the shape remained remarkably stable over all 21 specimens. This implies that no significant alteration in this region has taken place over a period of a half-million years or more of evolution, even as considerable external change occurred within the hominid clade spanning several species. This confirms that the forms of the inner and outer aspects of the human frontal bone are determined by entirely independent factors, and further indicates unexpected stability in anterior brain morphology over the period during which modern human cognitive capacities emerged.

(New Anat): 257:217–224, 1999. 1999 Wiley-Liss, Inc.

External changes (such as the brow ridge) ARE NOT LINKED morphologically to the frontal brain, which has been stable for 500,000 years of  cognitive development.

Basic CMYK

 

Neurotypical Perception Defects / Inferred Images, Social Filters

Humans rely more on ‘inferred’ visual objects than ‘real’ ones

May 16, 2017
Summary:
Humans treat ‘inferred’ visual objects generated by the brain as more reliable than external images from the real world, according to new research.
“In such situations with the blind spot, the brain ‘fills in’ the missing information from its surroundings, resulting in no apparent difference in what we see,” says senior author Professor Peter König, from the University of Osnabrück’s Institute of Cognitive Science. “While this fill-in is normally accurate enough, it is mostly unreliable because no actual information from the real world ever reaches the brain. We wanted to find out if we typically handle this filled-in information differently to real, direct sensory information, or whether we treat it as equal.”

Visual thinkers are all too aware of this reality deficit in the “typical” perception of reality; I can’t say that the mechanism described here is the “cause” of discrepancies between “typical” perception and the greatly enhanced perception of visually-oriented brains, but it does point out that the typical human brain has evolved “short cuts” that result in varying accuracy in the  perception of the environment. This deficit, combined with de facto “magical-social” thinking has dire consequences for survival.

Links:

Article in Science Daily: https://sciencedaily.com/releases/2017/05/170516080752.htm

Original Paper with figures, charts: 10.7554/eLife.21761

Posts on inattentional blindness: https://aspergerhuman.wordpress.com/2015/12/04/visual-thinking-inattentional-blindness/

https://aspergerhuman.wordpress.com/2015/12/04/inattentional-blindness-why-the-u-s-gets-sucker-punched-by-terrorists/

Immune System Introgressions / Neandertal, Denisovan HLA alleles


Neanderthal, State Museum, Halle, Germany

Denisovan admix today: Low – Black / High – Red

 

The Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans

Laurent Abi-Rached,1 (see original paper for list of authors)

Abstract

Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic HLA class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.

Example: Includes similar graphics for Neanderthal and Denisovan HLA alleles

Fig. 3 Effect of adaptive introgression of Neandertal HLA class I alleles on modern human populations. (A) All six Neandertal HLA-A, -B and -C alleles are identical to modern HLA class I alleles…

 

Inflammatory Diseases, Deadly Modern Environments / ASD, Depression

quick summation from Torrey Institute for Molecular Studies: 

Inflammatory Disorders (click here for website)

Inflammation is the body’s protective response to injury and infection; it is a complex process involving many cell types, as well as different components of blood.

The inflammatory process works quickly to destroy and eliminate foreign and damaged cells, and to isolate the infected or injured tissues from the rest of the body. Inflammatory disorders arise when inflammation becomes uncontrolled, and causes destruction of healthy tissue. There are dozens of inflammatory disorders. Many occur when the immune system mistakenly triggers inflammation in the absence of infection, such as inflammation of the joints in rheumatoid arthritis. Others result from a response to tissue injury or trauma but affect the entire body.

There are many ways by which normal cells and tissues can be damaged during inflammation. One important mechanism is by assembly of a complex of proteins that forms holes on the surface of a cell, where it causes damage and can potentially kill the cell. This complex is called a Membrane Attack Complex or MAC. Torrey Pines Institute researchers are working to understand how MAC contributes to a number of inflammation-associated disorders, including the complications of diabetes and rheumatoid arthritis. Understanding how MAC assembles will provide insights into the design of drugs to prevent inflammatory damage to cells.

Inflammation is also an important secondary component of many diseases. An example of this is atherosclerosis, or hardening of the arteries, where inflammation can cause more damage to arteries in a failed attempt to heal the artery wall. There is also an important link between obesity and inflammation, because substances that promote inflammation are released from fat cells, as well as from other cells embedded in fat tissue. The Institute’s scientists are leading the way in understanding these new and exciting areas of inflammation research.

The first article below presents the hypothesis that psychological stress and depression may be associated with “inflammatory” diseases.

The second presents the evolutionary “Inflammatory Bias” that has lead to rampant inflammatory disease in modern humans.

___________________________________________________________________________________________

Article 1: Brain Behav Immun. Author manuscript; available in PMC 2014 Jul 1.

 Published in final edited form as: Brain Behav Immun. 2013 Jul; 31: 1–8. Published online 2013 Apr 30. doi:  10.1016/j.bbi.2013.04.009

Malaise, Melancholia and Madness: The Evolutionary Legacy of an Inflammatory Bias

Technical paper, so I’m looking for a credible translation into common language!

Excerpt that may possibly be significant to ASD, Asperger’s and other “social” disorders.  

 5a. Immune Pathways and the Inflammasome

In a paper in this issue, Iwata et al. propose the provocative hypothesis that the recently characterized inflammasome may serve as a critical link between psychological stress and depression, as well as other illnesses related to inflammation (Iwata et al. 2012).

The inflammasome is a protein complex that can detect diverse danger signals including not only pathogen-associated molecules but also molecules associated with cellular damage such as adenosine triphosphate (ATP). Upon activation, the inflammasome can generate an inflammatory response notably through the production of IL-1-beta by activation of a caspase that cleaves the precursor peptide pro-IL-1-beta. Given the capacity of the inflammasome to react to danger signals generated by stimuli other than pathogens, the authors suggest that the inflammasome may be uniquely poised to serve as the molecular mechanism that transduces psychological responses to stress into an inflammatory response in the absence of pathogen challenge.

Thus, the inflammasome may represent an evolutionary adaptation that extends the immune and behavioral response to pathogens and the microbial world to include challenges emanating from predators, people and the social world. Although of significant value in detecting and responding to tissue damage and destruction, by virtue of the inflammasome,

the inflammatory bias may have been given an entrée into the modern world where people, not pathogens or predators represent the primary challenges.

____________________________________________________________________________________________

Article 2:

The role of inflammation in depression: from evolutionary imperative to modern treatment target

Andrew G. Miller and Charles L. Raison

Nature Reviews Immunology Volume:16,Pages:22–34Year published:(2016)DOI:doi:10.1038/nri.2015.5 (click to access article)

Fig. 1 Evolutionary legacy of an inflammatory bias. Early evolutionary pressures derived from human interactions with pathogens, predators and human conspecifics (such as rivals) resulted in an inflammatory bias that included an integrated suite of immunological and behavioural responses that conserved energy for fighting infection and healing wounds, while maintaining vigilance against attack.This inflammatory bias is believed to have been held in check during much of human evolution by exposure to minimally pathogenic, tolerogenic organisms in traditional (that is, rural) environments that engendered immunological responses characterized by the induction of regulatory T (TReg) cells, regulatory B (BReg) cells and immunoregulatory M2 macrophages as well as the production of the anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGFβ). In modern times, sanitized urban environments of more developed societies are rife with psychological challenges but generally lacking in the types of infectious challenges that were primary sources of morbidity and mortality across most of human evolution. In the absence of traditional immunological checks and balances, the psychological challenges of the modern world instigate ancestral immunological and behavioural repertoires that represent a decided liability, such as high rates of various inflammation-related disorders including depression.

In proper perspective, modern social environments ARE DEADLY to life; not only to ASD Asperger people, but to ALL HUMANS and to every species that we are driving to extinction – Mass extinction is the likely outcome.

 

Neanderthal- H. Sapiens Ancestral Gene EXCHANGE

Neanderthal inheritance helped humans adapt to life outside of Africa

Phys.org / November 10, 2016

Read more at: https://phys.org/news/2016-11-neanderthal-inheritance-humans-life-africa.html#jCp

Excerpt: All told, the new study identifies 126 different places in the genome where genes inherited from those archaic humans remain at unusually high frequency in the genomes of modern humans around the world. We owe our long-lost hominid relatives for various traits, and especially those related to our immune systems and skin, the evidence shows.

“Our work shows that hybridization was not just some curious side note to human history, but had important consequences and contributed to our ancestors’ ability to adapt to different environments as they dispersed throughout the world,” says Joshua Akey of University of Washington School of Medicine in Seattle.

While the vast majority of surviving Neanderthal and Denisovan sequences are found at relatively low frequencies (typically less than 5%), the new analyses turned up 126 places in our genomes where these archaic sequences exist at much higher frequencies, reaching up to about 65%. Seven of those regions were found in parts of the genome known to play a role in characteristics of our skin. Another 31 are involved in immunity.

“The ability to increase to such high population frequencies was most likely facilitated because these sequences were advantageous,” Akey explains. “In addition, many of the high-frequency sequences span genes involved in the immune system, which is a frequent target of adaptive evolution.”

Generally speaking, the genes humans got from Neanderthals or Denisovans are important for our interactions with the environment. The evidence suggests that hybridization with archaic humans as our ancient ancestors made their way out of Africa “was an efficient way for modern humans to quickly adapt to the new environments they were encountering.”

Reconstruction by Fabrio Fogliazza /

Neanderthals mated with modern humans much earlier than previously thought

February 17, 2016 https://phys.org/news/2016-02-neanderthals-modern-humans-earlier-previously.html#jCp