Adam Lanza: Will genetics reveal what sleuthing cannot?

Will Adam Lanza’s genes help answer the incomprehensible?

Connecticut’s chief medical examiner, Dr. H. Wayne Carver II, has said that he has asked a geneticist at the University of Connecticut to contribute to the investigation of Lanza, the 20-year-old who last week shot 20 children and six adults at a school in Newtown, Conn., and then turned the gun on himself as police arrived.

Hope of peering into Lanza’s state of mind as he prepared his final act has been dashed by the assailant’s apparent destruction of his computer’s hard drive. The first step of his rampage--killing his mother, Nancy Lanza, who by many accounts was his sole companion--puts details of his path to massacre forever out of reach.

What is left is Lanza’s DNA, which might help piece together a picture of the young man’s underlying mental state. But experts warn that genes alone seldom tell a story. Genes can set the stage for a person’s behavioral predispositions. But a child’s environment--the quality of a mother’s care, the educational opportunities he receives, his childhood traumas, friendships, social setbacks and experimentation with drugs and alcohol--all these can powerfully interact with genes to shrink or increase the risk of a person lashing out.

Here are a few things a genetic sleuth might look for in Lanza’s DNA:

Fragile X: The most common cause of inherited intellectual disability in boys, Fragile X is an abnormal elongation of a portion of DNA on the X chromosome. A faulty repeat of the FMR1 gene results in a shortage of a key protein needed for the brain to grow and function properly. Because it can result in speech and language difficulties and a tendency to avoid eye contact, Fragile X is often misdiagnosed as autism--or the milder former of autism known as Asperger’s syndrome, which Lanza’s family told some friends he had. Fragile X affects roughly 1 in 4,000 babies, and the genetic transcription error can be passed to a child even when a parent does not manifest symptoms. Depending on the extent of the error, a child with Fragile X can range from being nonverbal to having communications skills that are mildly impaired. As I wrote in a May 1, 2011, article on Fragile X treatments under study, “it can seem like a train wreck of conditions — autism, attention deficit, bipolar disorder, anxiety and more — rolled into a single kid.”

Depression: The role of genes in predisposing an individual to depression is an area of intensive research, and scientists have found a number of sites in human DNA that appear implicated. Most influence, in one way or another, the availability or action of the neurochemical serotonin in the brain. But the genes that influence serotonin are widely scattered, and not only do they interact with each other in unpredictable ways. The environmental influences on a child--the “nurture” side of the nature-nurture equation--affect whether and how these genes express themselves.

An April 2012 article, however, took what is known about the genes that predispose for depression and translated that into a potential blood test for early depression. In a study published in the Journal of Translational Psychiatry, researchers looked at the messenger molecules that carry out genetic instructions for producing or inhibiting proteins, hunting specifically for 11 distinct molecules that were found in the blood and brains of rats that were genetically predisposed to depression and then exposed to early-life hardships. When they tried the test on 28 teens, half of whom suffered from major depression, the scientists found significantly higher concentrations of the 11 molecules in the depressed teens’ brains and blood than they did in those of their healthy control group. In the small group, a further assortment of “biomarkers,” the scientists found, appeared to distinguish between anxious or irritable depression and the variant of depression that results in listless, sad behavior.

Aggression and impulsivity: Emerging research has found a genetic variation that operates on the monoamine oxidase A--or MAO-A--gene and may interact powerfully with a child’s early experiences to influence his or her propensity to aggression and impulsivity. Dubbed the “warrior gene,” the MAO-A polymorphism has been linked to heightened aggression and underpowered prefrontal cortex activity in humans. Mice bred to have it showed particularly combative tendencies, especially when they had been subjected to isolation and hardships early in life. In 2009, lawyers cited the “warrior gene” polymorphism in Bradley Waldroup, who fatally shot his wife’s friend and then tried to kill his wife with a machete. The strategy succeeded in sparing Waldroup a first-degree murder conviction that could have resulted in the death penalty.

Though the MAO-A polymorphism has been linked to impulsive aggression, it is present in 34% of those of European descent, so it’s a poor predictor of dangerousness. And childhood trauma or abuse--none of which has been reported so far in the case of Adam Lanza--appears to be an important condition for this genetic variation to express itself.