Autism

Autism is a childhood developmental condition that has had a suspected increase in incidence in recent years. It causes a major mental developmental arrest at an early age. Some children begin to develop speech and then regress, a factor that has led to unfortunate theories of causation, such as the hysteria about childhood immunization. Now, a cluster of cases among Somali immigrants in Minnesota might offer some new leads to the cause.

Autism and schizophrenia share some similarities in that both conditions result in problems with social interaction and functional behavior. The autistic child fails to develop speech and other social behavior such as emotional attachment to others. Schizophrenia has similar effects on interpersonal behavior. The autistic child often seems to live in a world cut off from others, responding to inner stimulation but unable to relate to parents or other children. Similarly, the schizophrenic is unable to interpret visual cues and social interaction is difficult. The schizophrenic typically has auditory hallucinations, hearing voices. The autistic child may have similar inner stimuli but is unable to express what is happening because of speech failure.

There are theories about schizophrenia as a consequence of brain development, especially the phenomenon of cerebral dominance which gives us speech and handedness. Now, new theories implicate hormone changes that might be common to both conditions. Animal studies have suggested this association.

Understanding the neurobiological substrates regulating normal social behaviours may provide valuable insights in human behaviour, including developmental disorders such as autism that are characterized by pervasive deficits in social behaviour. Here, we review the literature which suggests that the neuropeptides oxytocin and vasopressin play critical roles in modulating social behaviours, with a focus on their role in the regulation of social bonding in monogamous rodents. Oxytocin and vasopressin contribute to a wide variety of social behaviours, including social recognition, communication, parental care, territorial aggression and social bonding. The effects of these two neuropeptides are species-specific and depend on species-specific receptor distributions in the brain. Comparative studies in voles with divergent social structures have revealed some of the neural and genetic mechanisms of social-bonding behaviour. Prairie voles are socially monogamous; males and females form long-term pair bonds, establish a nest site and rear their offspring together. In contrast, montane and meadow voles do not form a bond with a mate and only the females take
part in rearing the young. Species differences in the density of receptors for oxytocin and vasopressin in ventral forebrain reward circuitry differentially reinforce social-bonding behaviour in the two species.

This is from Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2006 Dec 29;361(1476):2187-98., “Oxytocin, vasopressin and pair bonding: implications for autism.”, by Hammock EA, Young LJ.

This may seem a rather far fetched association with human autism but there is more.

CNS neuroscience & therapeutics. 2008 Fall;14(3):165-70., “Oxytocin levels in social anxiety disorder.”, by Hoge EA, Pollack MH, Kaufman RE, Zak PJ, Simon NM.

Department of Economics, Claremont University, Claremont, CA, USA.
ehoge@partners.org

Oxytocin is a neuropeptide recently associated with social behavior in animals and humans, but the study of its function in populations with social deficits such as autism, schizophrenia, and social anxiety disorder has only recently begun. We measured plasma oxytocin in 24 patients with Generalized Social Anxiety Disorder (GSAD) and 22 healthy controls using an enzyme-linked immunosorbent assay. There were no significant differences in oxytocin level (pg/mL) between patients (M=163.0, SD=109.4) and controls (M=145.0, SD=52.9, z=0.21, P=0.8). Within the GSAD sample, however, higher social anxiety symptom severity adjusted for age and gender was associated with higher oxytocin level (R2=0.21, beta=0.014, SE=0.006, t=2.18, P=0.04). In addition, dissatisfaction with social relationships was associated with higher oxytocin levels (R2=0.18, beta=-0.20, SE=0.10, t=-2.01, P=0.05). Our data provide preliminary support for a link between social anxiety severity and plasma oxytocin. These findings may suggest a possible role for oxytocin as a facilitator of social behavior, an effect which may not be fully utilized in individuals with severe social anxiety.

This is very preliminary but the existence of the Somali cluster of autism cases might allow further work in this association. Oxytocin has been known as the hormone that begins labor and brings the mother’s milk “down” but it is increasingly seen as having other roles in human behavior. It is not unusual to see the hormones, originally thought to have a single function, assume new roles as physiology is investigated. It would be very interesting if these hormones turn out to play a major role in mental illness. Freud is finally gone from the treatment of major mental illness.

“This is one of the first looks into the biological basis for human attachment and bonding,” said Rebecca Turner, PhD, UCSF adjunct assistant professor of psychiatry and lead author of the study. “Our study indicates that oxytocin may be mediating emotional experiences in close relationships.”

The study builds upon previous knowledge of the important role oxytocin plays in the reproductive life of mammals. The hormone facilitates nest building and pup retrieval in rats, acceptance of offspring in sheep, and the formation of adult pair-bonds in prairie voles. In humans, oxytocin stimulates milk ejection during lactation, uterine contraction during birth, and is released during sexual orgasm in both men and women.

Vasopressin is also involved, especially in males. Vasopressin is a hormone secreted by the pituitary gland and associated with water retention by the kidney. It now appears that it has other functions, as well.

Progress in brain research. 2008;170:337-50.

Neuropeptides and social behaviour: effects of oxytocin and vasopressin in
humans.

Heinrichs M, Domes G.

Department of Psychology, Clinical Psychology and Psychobiology, University of
Zurich, Zurich, Switzerland.

The fundamental ability to form attachment is indispensable for human social relationships. Impairments in social behaviour are associated with decreased quality of life and psychopathological states. In non-human mammals, the neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are key mediators of complex social behaviours, including attachment, social recognition and
aggression. In particular, OXT reduces behavioural and neuroendocrine responses to social stress and seems both to enable animals to overcome their natural avoidance of proximity and to inhibit defensive behaviour, thereby facilitating approach behaviour.

Doesn’t this sound like autism ?

AVP has primarily been implicated in male-typical social behaviours, including aggression and pair-bond formation, and mediates anxiogenic effects. Initial studies in humans suggest behavioural, neural, and endocrine effects of both neuropeptides, similar to those found in animal studies.

Schizophrenia is more common in males and is hereditary. Anxiety is a major factor. There may also be a hereditary association in autism. This is enormously exciting research and might even be the first sign of a cure for these disorders of brain function.

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6 Responses to “Autism”

  1. allan says:

    Just coincidentally, I am a few chapters into a textbook on psychopharmacology written by an adjunct professor of psychiatry at UCSD. I’ll probably come across much of what your post reveals. One thing I’d add here is that he comments on the hereditary aspects with a brief overview of the neurodegenerative hypothesis of schizophrenia. Simply stated, the theory posits…

    “…that progressive loss of neuronal function – whether through loss of dendrites, destruction of synapses, or neuronal death – may underlie symptoms and progression of schizophrenia. Causes of neurodegeneration can range from predetermined genetic programming of neuronal or synaptic destruction; to fetal insults such as anoxia, infection, toxins, or maternal starvation, to glutamate-mediated excitotoxicity that initially can cause positive symptoms, and, as neurons die, lead to residual negative symptoms.”

    Positive symptoms, eg., delusions, hallucinations, disorganized speech and behavior.

    Negative symptoms, eg., loss of affect, emotional withdrawal, poor rapport, lack of pleasure, apathy and passivity.

    The neurodegenerative hypothesis generally maps out stages of onset and increasing degeneration over a lifetime. At this time, there are various antipsychotics that have substantial effect after onset at 15 up to 40, but appear to level off after that stage. And he pointed out early in the book how schizophrenia behaviors, and likely causes, are shared with many other disorders, including autism.

  2. I know that theory but what if, instead of a vague concept of neuronal death, what we are seeing is the loss of oxytocin or vasopressin receptors on neurons ? Maybe it is a sort of Parkinsons with another neurotransmitter ? We still don’t know why the “atypical” anti-psychotic drugs work. They have been assumed to be DOPA receptor agonists or antagonists. Maybe it’s oxytocin. It’s an exciting field and the one I would be going into if I were 24 again.

  3. allan says:

    I walked away from psych long ago, and at the time the field of psychophysiology was still gathering adherents. If I’d stayed, that’s where I would have focused. But it’s clear that the molecular level is the place to be going forward. I am also starting a book on DNA that is working me through history. I’m up to the 1960′s starting from the 1800′s. It’s like little lights being turned back on bringing back long lost worlds of interest, but with the advantage of perspective which I didn’t have as a young man.

  4. I was very interested in immunology as a student and spent some time thinking about a career in transplantation but I decided that I had to choose between basic science, which at the time was physical chemistry since we knew nothing about cell membranes, and clinical practice. I choose the latter but the science is so much better now that real progress can be made. In 1970, the basics were still unknown.

  5. [...] Michael Kennedy put an intriguing blog post on AutismHere’s a quick excerptaggression. In particular, OXT reduces behavioural and neuroendocrine responses to social stress and seems both to enable animals to overcome their natural avoidance of proximity and to inhibit defensive behaviour, thereby facilitating … [...]

  6. DRJ says:

    I was first introduced to this theory in a 1990′s telephone conversation with Prof. Jaak Panksepp (Panksepp J [1992] – Oxytocin effects on emotional processes: separation distress, social bonding, and relationships to psychiatric disorders. In: Pedersen C, Caldwell J, Jirikowski G, Insel T (eds). Oxytocin in Maternal Sexual and Social Processes. Vol 652. New York Academy of Sciences, New York, 243–252) who wrote on the possibility of a connection between oxytocin/pitocin and autism. Among other similarities, Panksepp noted the tendency of pitocin-fed birds to flap their wings in a manner similar to the way autistics stim their hands and fingers.

    Autism researcher Eric Hollander has also written on this connection: http://www.psychiatrictimes.com/autism/article/10168/57071 and http://web.mit.edu/autism/Oxytocin%20Autism%20-%20Hollander.pdf

    My experience suggests we need to know more about the role of hormones in immunology and brain development or, as one of our son’s doctors refers to it, the field of neuroimmunology. Our son has been treated the hormone secretin, and he showed improvement in the crucial brain and behavioral areas. The secretin manufacturer’s research surprisingly indicates that the mechanism secretin uses to take effect occurs in the brain instead of in the gut as was originally thought.

    In general, however, I couldn’t agree more: It’s an exciting time to have an interest in immunology and related fields.