Empathy and evil

Simon Baron-Cohen, professor of psychology at Cambridge Univ and author of the extreme male theory of autism (described in chap. 3 of my book), has written a new book, “The Science of Evil”. He is interested in understanding human cruelty, and wishes to replace the term “evil” with “the absence of empathy”. This is useful as “evil” is most often used in a religious context while empathy can be measured and quantified, and brain circuits mediating empathy can even be examined with functional brain imaging (fMRI). “Empathy” also lacks a definitive link with cruelty. For instance, subjects with autism spectrum disorder can display a lack of empathy by failing to read the social signals that people emit. This relates to the “theory of mind”, which is defined as the ability to attribute a mental state to oneself or to others, and autistic subjects can have deficits in this area. But this would certainly not be portrayed as cruelty or evil.

There are a few fascinating studies indicating that mice and rats can also display empathy. This could be useful in further characterizing rodent models of autistic features (chap. 6). In one test, a mouse becomes more sensitive to heat if it is watching another mouse in pain (Langford et al., 2006). In different test, a mouse watches (behind a transparent barrier) another mouse being socially defeated (an aggressor bullied him  into a corner). The witness mouse subsequently displays signs of stress and even depression: his corticosteroid levels go up dramatically, his social interactions with other mice decrease, and he is more anxious (see chap. 6 for these and other assays of depression). These data were presented by Carlos Bolamos-Guzman at a meeting last year, but I have not seen a publication on this yet. Another, rather mysterious example comes from a new study of “bystander stress” in pregnant rats (Mychasiuk et al., 2011). In this experiment, a pregnant rat is not stressed herself, but she is housed with another female who is exposed to daily stress (removed from the cage and placed on an elevated table under bright lights for 30 min). In a control experiment, a pregnant rat is housed with another female who is removed from their cage but not stressed. The interesting result is that the offspring of the pregnant rat whose cage mate was stressed display some subtle changes in neuron structure 3 weeks after birth. Note that the pregnant rat does not actually see her cage mate being put in a stressful situation. The mechanism of this effect is completely unknown, but it suggests a form of empathy that alters fetal brain development.

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9 Responses to Empathy and evil

  1. blackheart says:

    Hi Paul

    Redirected here from pD (passionlessDrone) both fascinating areas of science which seem to my most pleasant surprise ‘angst’ free.

    I left pD a couple of studies I found interesting (speculative) I can see some (perhaps) some cross over with ‘stress’ and mouse behaviour. I have a background in Abnormal Psych not the sciences per se.

    Aberrant NF-KappaB Expression in Autism Spectrum Condition: A Mechanism for Neuroinflammation 2011

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098713/

    Expression Profiling of Autism Candidate Genes during Human Brain Development Implicates Central Immune Signaling Pathways

    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0024691

    (Might have to google that one to get full paper which has been published on plosone.

    Cheers

    • phpatterson says:

      Thx for those refs Blackheart. Those are indeed right up my alley. The NFKb connection with autism is potentially important because this protein is at the hub of the network that receives, computes, and outputs responses to inflammatory signals impinging on cells. Thus, changes in NFkB levels or activity can profoundly influence how a cell responds to cytokines, for instance. The second paper, on profiling autism candidate genes is somewhat speculative, but places many immune/inflammation genes at the heart of the autism gene network. This is consistent with the paper by Dan Geschwind and colleagues at UCLA that I consider to be the gold standard of gene network analysis in autism brains (http://www.ncbi.nlm.nih.gov/pubmed/21614001). In that paper, Dan found that the specially expressed genes in autism fell into two groups, one having to do with synapses and neuronal function, and the second having to do with glia and immune function. This place immune function once more at the heart of autism gene network activity.

  2. blackheart says:

    Thanks for the reply ..

    I’ve had an amateur look at some aspects of NFkB in autism and some of the other aspects that seem to correspond to the some ‘types’ of ASD. Allergies , Eczema , asthma , sleep disturbances , anxiety, and inflammatory bowel disease. (I can send you some of the paper links if you like)

    Am I correct (and I don’t mind being wrong) that this is supplementing evidence of two phenotypes of autism (that has been yet to be published I believe but) presented at a South Pacific Autism conference by David Amaral at University of California Davis MIND Institute.

    http://www.theaustralian.com.au/news/health-science/us-researchers-discovery-promises-answers-on-autism/story-e6frg8y6-1226131763200

    “One group of children – all boys – had enlarged brains and most had regressed into autism after 18 months of age; another group appeared to have immune systems that were not functioning properly.”

    ——————–

    I’m not clear I have read this part properly

    “Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism.

    In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process.”

    Is this suggesting two distinct pathways (aetiology) – one being genetically based and the other due environment ?

    • phpatterson says:

      Blackheart: I asked David Amaral about that Australian newspaper article and he says that they got it wrong. The point he was making was that larger brains correlate with the regressive form of ASD. This finding will appear in PNAS tomorrow.
      RE the Geschwind point about two distinct modules of genes altered in autism: they found that a group of changes in gene expression cluster around neuronal function and include many known candidate genes for ASD. The other module (glial or immune) does not include the candidate genes and so may involve environmental rather than genetic influences.

      • blackheart says:

        Thanks … http://www.pnas.org/content/early/2011/11/14/1107560108.abstract
        Yes it was interesting that the regression related to brain size (rather than an immune system) …

        I had these studies on my desk so to speak…because I was trying to understand the two phenotypes described. Can you have a look and give me some thoughts ?

        NF-kB: a crucial transcription factor for glial and neuronal cell function
        http://www.cell.com/trends/neurosciences/abstract/S0166-2236%2896%2901035-1

        Nuclear Factor κB-Dependent Neurite Remodeling Is Mediated by Notch Pathway
        http://www.jneurosci.org/content/31/32/11697.short

        These data suggest the relevance of future studies on the role of Notch/NF-κB cross talk in regulating cortex structural plasticity in physiological and pathological conditions.

        Role of nitric oxide produced by iNOS through NF-κB pathway in migration of cerebellar granule neurons induced by Lipopolysaccharide

        http://www.sciencedirect.com/science/article/pii/S0898656810003049

        The role of NF-κB was showed by using the inhibitor JSH-23, which decreased NO•– production and neuronal migration in LPS activated cultures. These results suggest that neuronal migration during development is susceptible to be modified by pro-inflammatory stimulus such as LPS through intracellular pathways associated with their receptors.

        Density of cerebellar basket and stellate cells in autism: Evidence for a late developmental loss of Purkinje cells

        http://onlinelibrary.wiley.com/doi/10.1002/jnr.22056/full

        • phpatterson says:

          Blackheart: The NF-kB pathway is a central hub in regulating the cell’s response to extracellular influences such as cytokines and growth factors, among others. Thus, it plays a key role in both normal function and in the response to insults such as inflammation. Since ASD involves an inflammation-like condition, we expect that NF-kB will be important in this disorder. Regarding the 2009 paper on Purkinje cells, my group is particularly interested in this neuropathology that is often reported in ASD because we found a Purkinje cell deficit in our maternal infection model of ASD features (Shi et al., Brain Behav Immun, 2009).

  3. blackheart says:

    This new research hot off the press so to speak …

    Something you will probably be most interested in …

    http://www.ncbi.nlm.nih.gov/pubmed/22175527

    “The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy.

    Methods. AF samples of 331 ASD cases and 698 controls were analyzed for inflammatory cytokines using Luminex xMAP technology utilizing a historic birth cohort. Clinical data were retrieved from nationwide registers, and case-control differences in AF cytokine levels were assessed using chi-square tests, logistic and tobit regression models.

    Results.

    1. Overall, individuals with ASD had significantly elevated AF levels of TNF-α and TNF-β compared to controls.

    2. Analyzing individuals diagnosed only with ICD-10 codes yielded significantly elevated levels of IL-4, IL-10, TNF-α and TNF-β in ASD patients.

    3. Restricting analysis to infantile autism cases showed significantly elevated levels of IL-4, TNF-α and TNF-β compared to controls with no psychiatric comorbidities.

    4. Elevated levels of IL-6 and IL-5 were found in individuals with other childhood psychiatric disorders (OCPD) when compared to controls with no psychiatric comorbidities.

    Conclusions.

    AF samples of individuals with ASD or OCPD showed differential cytokine profiles compared to frequency-matched controls. Further studies to examine the specificity of the reported cytokine profiles in ASD and OCPD are required.”

    ————————

    Any thoughts ?

    The implications in regards to other childhood psychiatric disorders seems quite profound.

    Does this fit into an infection or maternal antibody model ?

    • phpatterson says:

      Blackheart, AKA piratescum, beat me to this as I was going to do a post on it. This new paper from the very active Danish group is the second in an apparent series analyzing amniotic fluid for signs of abnormal immune activity in pregnancies that eventually gave rise to ASD offspring. They earlier reported the elevated levels of the chemokine MCP1 is associated with ASD pregnancies, and now they find elevated cytokines are also associated with an ASD outcome. The association of both classically defined pro- (TNF) and anti- (IL-4 and 10) inflammatory cytokines with ASD is particularly interesting. IL-10 was also identified in ASD brains by Pardo and colleagues. Is this an example of how the classical definitions of pro and anti are not always meaningful, and that the immune state in ASD is novel and not classically inflammatory? Or does it suggest that initial pro-inflammatory events are being followed, as they usually are, by an anti-inflammatory cycle? Interestingly, we are finding something similar in our mouse model of maternal infection, so maybe further work of this type will help clarify the situation.

      Blackheart also asks if these amniotic fluid results fit better with a maternal infection or with a maternal antibody response? That is, there is evidence in animal models that the cytokines induced by maternal infection are sufficient to alter fetal brain development and lead to behavioral abnormalities in the offspring that resemble those found in both autism and schizophrenia. On the other hand, injecting pregnant mice and monkeys with antibodies taken from the blood of women who have given birth to ASD offspring can cause the animal offspring to exhibit behaviors consistent with ASD. It is thought that molecules in the amniotic fluid some primarily from the fetus, so the presence of cytokines would seem to point to a disturbed immune state in the fetus, which could be evoked by infection-induced maternal and/or placental cytokines diffusing into the fetus. Or, perhaps if maternal antibodies attacked the fetus, a cytokine response may be induced there. Further animal work should be able to shed light on this question as well.

  4. Blackheart says:

    Thanks Paul..

    Happy to read a full post on this topic from you.

    Merry Christmas from all Pirates and fellow scum of the Seven Seas.

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