Monitor on Psychology - February 2012 - (Page 38)

heart disease to depression and Alzheimer’s disease. “I see inflammation as one of the chief evils in mammalian biology,” Pace says. Of course, the immune system serves a critical function — and not just for fighting disease. “The immune system is really important for how the brain develops normally,” says Staci Bilbo, PhD, an assistant professor of psychology and neuroscience at Duke University. Cells called microglia are the resident immune cells in the brain. They’re the central nervous system’s first-line defense against infections and other invaders. And, Bilbo says, “they do a lot of important things for building a brain.” For starters, microglia are involved in synaptic pruning and programmed cell death. They also express cytokines, the signaling molecules that serve as messengers between cells and are a key component of the body’s inflammatory response. Cytokines are important for the development of basic brain structures from blood vessels to axons. They are also involved in regulating cognition and mood, Bilbo says. She explored the brain’s immune cells by infecting infant rats with the bacterium E. coli four days after birth, a developmental period comparable to the third trimester of pregnancy in humans. The young rats recovered fully from the infection, and as adults they performed as well as control rats on tests of memory and cognition. But their early infections had left their mark. The rats’ microglia had been “primed,” Bilbo says; in essence, the cells had been put on high alert for future infections. When the rats experienced a second infection — what she calls a “second hit” — around the time they were learning a new task, they showed profound memory impairments for that task. The primed rats, she discovered, were dramatically over-expressing cytokines in response to the second hit (Journal of Neuroscience, 2011). “Their immune system is changed long-term as a result of the neonatal infection,” she says. “And because the immune system impacts brain function, they are altered behaviorally.” That same pattern appears in many neurodegenerative diseases in humans, she says. “A peripheral infection will suddenly make mental functions decline sharply, and you can measure concentrations of cytokines in the cerebrospinal fluid that were previously undetectable.” inflammation running wild Other animal studies have further filled in some details. Paul Patterson, PhD, a neurobiologist at the California Institute of Technology and author of the book “Infectious Behavior: Brain-Immune Connections in Autism, Schizophrenia, and Depression” (2011), explores the origins of mental illness in mice. He’s infected pregnant mice with influenza virus and also stimulated their immune systems in the absence of a pathogen. “When you activate the mother’s immune system, you turn on a variety of cytokines to fight the infection,” he says. Patterson found that the offspring of the infected mothers exhibited a whole list of abnormal behaviors. Among them 38 were the three “cardinal behavioral symptoms of autism,” he says: impaired communication, reduced social interaction and repetitive, stereotyped behaviors (Trends in Molecular Medicine, 2011). What’s more, the mice showed heightened anxiety and were more sensitive to hallucinogenic drugs — a sensitivity also seen in humans with schizophrenia. These changes can be traced to the presence of a cytokine called interleukin-6 (IL-6). When produced in excess by a pregnant mouse, the molecule activates subsets of neurons in the fetus’s brain. IL-6 also activates cells in the placenta, altering endocrine function and changing growth hormones. “That’s bound to have an effect on [fetal] development,” he says. Cytokines including IL-6 can also interfere with the synthesis of serotonin in the brain, Pace adds. An excess of cytokines leads to a cascade of molecular events that interrupts the synthesis pathway, preventing serotonin from being produced. And serotonin, of course, is a necessary ingredient for healthy mood. This finding may be particularly relevant for depressed patients taking selective serotonin reuptake inhibitors (SSRIs). A study by Charles Nemeroff, MD, PhD, of the University of Miami, and colleagues suggests that depressed people who experienced an adverse event in early life may be less likely to respond to SSRIs than depressed patients who did not endure an early-life stressor (Proceedings of the National Academy of Sciences, 2003). That makes sense if an overactive immune response is working against serotonin in the brain, Pace says. “If inflammation really is driving that problem, then something like Zoloft isn’t going to be as effective while inflammation is running wild.” For that reason, Pace says, “it’s important to get a sense of whether or not somebody has had an early-life traumatic experience.” Such a patient may be more likely to respond to psychotherapy than to antidepressants alone, for instance. Pace and other researchers are now exploring alternative therapies for reducing inflammation and treating depression. He has found evidence that compassion meditation decreases the stress hormone cortisol as well as inflammation, at least in healthy subjects (Psychoneuroendocrinology, 2009). Testing the technique in depressed patients is the next step. Scientists are also investigating the use of anti-inflammatory drugs to treat depression, either alone or in conjunction with traditional antidepressants. Others have begun to test antiinflammatories for treating autism and schizophrenia. The research is still in early stages, but initial results are promising, Patterson says. He predicts that it won’t be long before anti-inflammatory medications are prescribed to treat mood and behavioral disorders. “Watch out for those studies coming along,” he says. “If you modify the immune status, you should be able to modify behavior.” n Kirsten Weir is a writer in Minneapolis. M o n i t o r o n p s y c h o l o g y • F e b ru a ry 2 0 1 2

Table of Contents for the Digital Edition of Monitor on Psychology - February 2012

Monitor on Psychology - February 2012
Letters
President’s column
Contents
From the CEO
APA files two briefs in support of same-sex couples
New registry seeks to understand addiction recovery through ‘crowdsourcing’
APA launches a database of tests and measures
Watch for new member benefit: “APA Access”
Apply now for APA’s Advanced Training Institutes
PsycTHERAPY, APA’s new database, brings therapy demos to life
In Brief
APA scientists help guide tobacco regulation
A-mazing research
‘A machine for jumping to conclusions’
Judicial Notebook
Random Sample
Righting the imbalance
The beginnings of mental illness
Science Directions
Improving disorder classification, worldwide
Protesting proposed changes to the DSM
Interventions for at-risk students
Harnessing the wisdom of the ages
Anti-bullying efforts ramp up
Hostile hallways
R U friends 4 real?
Support for teachers
Speaking of Education
Record keeping for practitioners
Going green
At the intersection of law and psychology
Division Spotlight
Grants help solve society’s problems
Personalities

Monitor on Psychology - February 2012