DIFFERENT MINDS if there’s one thing Ralph Or not. the fact that there are few AN INFECTIOUS THEORY Adolphs wants you to under- absolutes is part of why the set of dis- Much of that insight comes from Pat- stand about autism, it’s this: “it’s orders—autism, Asperger’s, pervasive terson, who pioneered the study of the wrong to call many of the people developmental disorder not otherwise connections between the brain and the on the autism spectrum impaired,” says specified (PDD-NOS)—that fall under immune system in autism, schizophrenia, the Caltech neuroscientist. “they’re autism’s umbrella are referred to as and depression a decade ago. simply different.” a spectrum. As with the spectrum of the main focus of that connection? these differences are in no way insig- visible light—where red morphs into Some kind of viral infection during preg- nificant—they are, after all, why so much orange, which morphs into yellow— nancy, Patterson explains. Or, rather, the effort and passion is being put into un- it is difficult to draw sharp lines immune response that infection inevitably derstanding autism’s most troublesome between the various diagnoses in engenders. traits—but neither are they as inevitably the autism spectrum. to bolster his argument, Patterson devastating as has often been depicted. And, like the autism spectrum itself, points to a recent study by hjordis O. they are simply differences; intriguing, the spectrum of autism research at Atladottir of Aarhus University, Denmark, fleeting glimpses into minds that work in Caltech also runs a gamut. Adolphs, and colleagues—“an extraordinary look at ways most of us don’t quite understand, for example, studies brain differences over 10,000 autism cases” in the Danish and yet which may ultimately give each between adults on the high-functioning Medical Register, which is a comprehen- and every one of us a little more insight portion of the autism spectrum and the sive database of every Dane’s medical into our own minds, our own selves. general public—the so-called neuro- encounter from cradle to grave—that What makes autism so fascinating, typical population. Neurobiologist John showed a strong epidemiological link Adolphs notes, is what also makes it so Allman’s work on a particular set of neu- between autism in a child and a first- difficult to study, to get a good grasp on: rons is providing insight into a possible trimester viral infection in the mother. the diversity of the population itself. if basis for some of autism’s social quirks. “And we’ve found that if you give a mouse you’ve met one person with autism, the And then there’s neurobiologist Paul the flu during pregnancy, or activate the saying goes, you’ve met one person Patterson, who literally has just finished mother’s immune system directly without with autism. writing the book on the connection a pathogen, the offspring will show a Still, there are characteristic tenden- between the immune system and neuropathology characteristic of autism, cies and traits, gifts and gaps. According autism, and who is collaborating with as well as the three cardinal symptoms to psychiatry’s diagnostic bible, familiarly biologist Sarkis Mazmanian to explore of autism.” known as the DSM-IV, autism involves the connections between gastrointes- in mouse terms, that means exhibit- an “impairment” in social interaction and tinal symptoms and the brain in autism ing repetitive behavior such as excessive communication, as well as “restricted re- spectrum disorders. self-grooming and compulsively and petitive . patterns of behavior, interests, they and half a dozen or so of their furiously burying marbles placed on its and activities.” What this means to the colleagues have come together in a bedding. Freaking out, rather than making rest of us is some combination of these: sort of informal Autism Working Group, friends, when faced with an unfamiliar Lousy eye contact. Social awkwardness. which meets regularly to talk about their mouse. And communicating much less hand flapping. toe walking. Late-talking individual findings and to brainstorm as a young pup with its mother, or as an babies. Kids who can’t seem to get the together. “People don’t think of Caltech adult with other mice. (Mice “talk” to one hang of playing cops and robbers with when they think about autism research,” another at ultrasonic frequencies, requir- friends, yet can talk for an hour about says Patterson. “But we have a lot go- ing a special microphone and recording Egyptian gods, elevators, or elephants. ing on here; a lot of insight to offer.” equipment to make their conversations Adults who speak in flat tones, who audible to human ears.) come off as rigid, uncomfortable, brilliant. 14 ENGINEERING & SCIENCE WINTER 2012 DIFFERENT MINBy Lori Oliwenstein DS Caltech researchers are gaining insight into what autism is, what autism gives, and where autism lives. WINTER 2012 ENGINEERING & SCIENCE 15 this is an impor- dysfunction there—then the breakdown tant clue connecting product gets into the bloodstream. And the mother’s im- research has indeed found that this mune reaction to the happens more often in kids with autism fetus’s brain develop- than in typical kids.” ment. it’s known that there’s similarly strong evidence, he the interleukins are says, implicating our normally helpful inflammation-boosters, and cooperative intestinal bacteria—as and inflammation is it turns out, the various types of bacteria all well and good found in the digestive systems of typical when you need to and autism spectrum kids tend to differ. wake up the immune But while the bowel-bacterium-brain system and get it to connection is clear, it’s still not known pour white cells into just how widespread it is. “Estimates an infected area. But of the percentage of people with autism it has its unintended who are affected by these gastro- side effects as well; intestinal differences vary from 20 to Patterson observed the same neuro- the inflammatory response often takes 70 percent,” Patterson says. “Clearly, pathology and behavior in mice who had a scattershot approach, meaning that the science is lagging; there’s still a lot never had an infection, but were instead healthy tissues can also get caught up of work to be done.” given synthetic molecules that mimic in the onslaught. Which is why the science-and- the presence of a virus. in other words, For instance, grad student Elaine advocacy group Autism Speaks recently Patterson found that simply mounting hsiao is finding that iL-6 and other brought Patterson and Mazmanian to- an immune response may be enough cytokines not only work directly on the gether with immunologist Paul Ashwood to steer a fetus down a path that could fetal brain, but can also alter the func- at UC Davis and pediatrician Alessio eventually lead to an autism-like condi- tion of the placenta, which would have Fasano from the University of Maryland tion after birth. indirect effects on fetal development. to explore the gut-brain-immune con- that “may” is key. there is definitely Why does an immune response nections in mice and in kids with autism a connection between infections during sometimes result in a developmental spectrum disorders. pregnancy—especially the early months disability—and sometimes not? Pat- “You have Sarkis’s and Alessio’s of pregnancy—and increased risk of terson thinks it could be the timing of expertise in the human gastrointestinal autism (and, as Patterson has also the infection, or the genetic makeup of system, you have Paul’s expertise in shown, schizophrenia) in the offspring, the mother, or her fetus that modulates children with autism, and then you have he says, but that is not the same as the outcome. our mouse model,” says Patterson. “that saying it’s a direct, 100 percent, if-you- the questions Patterson is asking makes for a pretty exciting consortium. it get-sick-while-you’re-pregnant-your- about inflammation and the brain might should allow us to look at autism in new baby-will-have-autism correlation. apply to other parts of the body as and unprecedented ways.” how does it all work? Patterson thinks well. So he and biologist Sarkis cytokines—proteins produced by the Mazmanian are looking at the gastro- LOOKING AND CONNECTING body in response to an infection—play intestinal problems somewhat com- Ralph Adolphs, too, is looking at autism a role. in fact, grad student Steve Smith monly found in kids with autism, and in new ways—and looking at looking in (PhD ’08) found that giving pregnant how those might be related to the autism as well. mice one cytokine in particular, called development of autism. Adolphs, who runs the Autism and interleukin-6 (iL-6), leads to offspring “the evidence that there are gastro- Asperger Syndrome Research Program who exhibit autistic and schizophrenic intestinal issues in children with autism at Caltech, spends most of his time features. “it was really unexpected that is pretty good,” Patterson notes. “You working with high-functioning adults a single injection of a single cytokine test it by feeding a child a molecule with autism. “We’re exploring the social would exert such a powerful effect,” that gets broken down in the gut; differences people with autism have,” Patterson notes. if the gut is leaky—if there is some says Adolphs. “We’re looking at every- 16 ENGINEERING & SCIENCE WINTER 2012 thing from eye-tracking, to reasoning, to about what you notice around you, and not only to your emotional awareness complex theory-of-mind stuff, which is how you respond to it, rather than a lack and empathy, but also to your internal about understanding what others feel of caring.