Tag Archives: neurobiology

Deconstructing Schizophrenia

Genetic and biomedical researchers have made yet another tremendous breakthrough from analyzing the human genome. This time a group of scientists, from Harvard Medical School, Boston Children’s Hospital and the Broad Institute, have identified key genetic markers and biological pathways that underlie schizophrenia.

In the US alone the psychiatric disorder affects around 2 million people. Symptoms of schizophrenia usually include hallucinations, delusional thinking and paranoia. While there are a number of drugs used to treat its symptoms, and psychotherapy to address milder forms, nothing as yet has been able to address its underlying cause(s). Hence the excitement.

From NYT:

Scientists reported on Wednesday that they had taken a significant step toward understanding the cause of schizophrenia, in a landmark study that provides the first rigorously tested insight into the biology behind any common psychiatric disorder.

More than two million Americans have a diagnosis of schizophrenia, which is characterized by delusional thinking and hallucinations. The drugs available to treat it blunt some of its symptoms but do not touch the underlying cause.

The finding, published in the journal Nature, will not lead to new treatments soon, experts said, nor to widely available testing for individual risk. But the results provide researchers with their first biological handle on an ancient disorder whose cause has confounded modern science for generations. The finding also helps explain some other mysteries, including why the disorder often begins in adolescence or young adulthood.

“They did a phenomenal job,” said David B. Goldstein, a professor of genetics at Columbia University who has been critical of previous large-scale projects focused on the genetics of psychiatric disorders. “This paper gives us a foothold, something we can work on, and that’s what we’ve been looking for now, for a long, long time.”

The researchers pieced together the steps by which genes can increase a person’s risk of developing schizophrenia. That risk, they found, is tied to a natural process called synaptic pruning, in which the brain sheds weak or redundant connections between neurons as it matures. During adolescence and early adulthood, this activity takes place primarily in the section of the brain where thinking and planning skills are centered, known as the prefrontal cortex. People who carry genes that accelerate or intensify that pruning are at higher risk of developing schizophrenia than those who do not, the new study suggests.

Some researchers had suspected that the pruning must somehow go awry in people with schizophrenia, because previous studies showed that their prefrontal areas tended to have a diminished number of neural connections, compared with those of unaffected people. The new paper not only strongly supports that this is the case, but also describes how the pruning probably goes wrong and why, and identifies the genes responsible: People with schizophrenia have a gene variant that apparently facilitates aggressive “tagging” of connections for pruning, in effect accelerating the process.

The research team began by focusing on a location on the human genome, the MHC, which was most strongly associated with schizophrenia in previous genetic studies. On a bar graph — called a Manhattan plot because it looks like a cluster of skyscrapers — the MHC looms highest.

Using advanced statistical methods, the team found that the MHC locus contained four common variants of a gene called C4, and that those variants produced two kinds of proteins, C4-A and C4-B.

The team analyzed the genomes of more than 64,000 people and found that people with schizophrenia were more likely to have the overactive forms of C4-A than control subjects. “C4-A seemed to be the gene driving risk for schizophrenia,” Dr. McCarroll said, “but we had to be sure.”

Read the entire article here.

Heavenly Light or Neuronal Hallucination

Many who have survived near-death experiences recount approaching a distant light as if closing in on the exit from a dark tunnel. Is it a heavenly light beckoning us towards the eternal afterlife in paradise? Perhaps, there is a simpler, scientific explanation.

From the Washington Post:

It’s called a near-death experience, but the emphasis is on “near.” The heart stops, you feel yourself float up and out of your body. You glide toward the entrance of a tunnel, and a searing bright light envelops your field of vision.

It could be the afterlife, as many people who have come close to dying have asserted. But a new study says it might well be a show created by the brain, which is still very much alive. When the heart stops, neurons in the brain appeared to communicate at an even higher level than normal, perhaps setting off the last picture show, packed with special effects.

“A lot of people believed that what they saw was heaven,” said lead researcher and neurologist Jimo Borjigin. “Science hadn’t given them a convincing alternative.”

Scientists from the University of Michigan recorded electroencephalogram (EEG) signals in nine anesthetized rats after inducing cardiac arrest. Within the first 30 seconds after the heart had stopped, all the mammals displayed a surge of highly synchronized brain activity that had features associated with consciousness and visual activation. The burst of electrical patterns even exceeded levels seen during a normal, awake state.

In other words, they may have been having the rodent version of a near-death experience.

“On a fundamental level, this study makes us think about the neurobiology of the dying brain,” said senior author and anesthesiologist George A. Mashour. It was published Monday online by the Proceedings of the National Academy of Sciences.

Near-death experiences have been reported by many who have faced death, worldwide and across cultures. About 20 percent of cardiac arrest survivors report visions or perceptions during clinical death, with features such as a bright light, life playback or an out-of-body feeling.

“There’s hundreds of thousands of people reporting these experiences,” Borjigin said. “If that experience comes from the brain, there has to be a fingerprint of that.”

An unanswered question from a previous experiment set her down the path of exploring the phenomenon. In 2007, Borjigin had been monitoring neurotransmitter secretion in rats when, in the middle of the night, two of her animals unexpectedly died. Upon reviewing the overnight data, she saw several unknown peaks near the time of death.

This got her thinking: What kinds of changes does the brain go through at the moment of death?

Then last year, Borjigin turned to Mashour, a colleague with expertise in EEG and consciousness, for help conducting the first experiment to systematically investigate the brain after cardiac arrest. EEG uses electrodes to measure voltage fluctuations in the brain caused by many neurons firing at once. A normal, awake brain should show spikes depending on what types of processing are going on; in a completely dead brain, it flat-lines.

When the heart suddenly stops, blood flow to the brain stops and causes death in a human within minutes. A likely assumption would be that, without a fresh supply of oxygen, any sort of brain activity would go flat. But after the rats went into cardiac arrest, Mashour and his colleagues observed the opposite happening.

Read the entire article here.

Image courtesy of Discovery.

What Makes Us Human

Psychologist Jerome Kagan leaves no stone unturned in his quest to determine what makes us distinctly human. His latest book, The Human Spark: The science of human development, comes up with some fresh conclusions.

From the New Scientist:

What is it that makes humans special, that sets our species apart from all others? It must be something connected with intelligence – but what exactly? People have asked these questions for as long as we can remember. Yet the more we understand the minds of other animals, the more elusive the answers to these questions have become.

The latest person to take up the challenge is Jerome Kagan, a former professor at Harvard University. And not content with pinning down the “human spark” in the title of his new book, he then tries to explain what makes each of us unique.

As a pioneer in the science of developmental psychology, Kagan has an interesting angle. A life spent investigating how a fertilised egg develops into an adult human being provides him with a rich understanding of the mind and how it differs from that of our closest animal cousins.

Human and chimpanzee infants behave in remarkably similar ways for the first four to six months, Kagan notes. It is only during the second year of life that we begin to diverge profoundly. As the toddler’s frontal lobes expand and the connections between the brain sites increase, the human starts to develop the talents that set our species apart. These include “the ability to speak a symbolic language, infer the thoughts and feelings of others, understand the meaning of a prohibited action, and become conscious of their own feelings, intentions and actions”.

Becoming human, as Kagan describes it, is a complex dance of neurobiological changes and psychological advances. All newborns possess the potential to develop the universal human properties “inherent in their genomes”. What makes each of us individual is the unique backdrop of genetics, epigenetics, and the environment against which this development plays out.

Kagan’s research highlighted the role of temperament, which he notes is underpinned by at least 1500 genes, affording huge individual variation. This variation, in turn, influences the way we respond to environmental factors including family, social class, culture and historical era.

But what of that human spark? Kagan seems to locate it in a quartet of qualities: language, consciousness, inference and, especially, morality. This is where things start to get weird. He would like you to believe that morality is uniquely human, which, of course, bolsters his argument. Unfortunately, it also means he has to deny that a rudimentary morality has evolved in other social animals whose survival also depends on cooperation.

Instead, Kagan argues that morality is a distinctive property of our species, just as “fish do not have lungs”. No mention of evolution. So why are we moral, then? “The unique biology of the human brain motivates children and adults to act in ways that will allow them to arrive at the judgement that they are a good person.” That’s it?

Warming to his theme, Kagan argues that in today’s world, where traditional moral standards have been eroded and replaced by a belief in the value of wealth and celebrity, it is increasingly difficult to see oneself as a good person. He thinks this mismatch between our moral imperative and Western culture helps explain the “modern epidemic” of mental illness. Unwittingly, we have created an environment in which the human spark is fading.

Some of Kagan’s ideas are even more outlandish, surely none more so than the assertion that a declining interest in natural sciences may be a consequence of mothers becoming less sexually mysterious than they once were. More worryingly, he doesn’t seem to believe that humans are subject to the same forces of evolution as other animals.

Read the entire article here.