From the Editor

This is a moving essay about family and loss – and the long shadow of mental illness.

It’s lengthy, but worth the time.

DG

Schizophrenia and Genetics

“Runs in the Family:

New findings about schizophrenia rekindle old questions about genes and identity”

Siddhartha Mukherjee, The New Yorker, 28 March 2016

http://www.newyorker.com/magazine/2016/03/28/the-genetics-of-schizophrenia

In the winter of 2012, I travelled from New Delhi, where I grew up, to Calcutta to visit my cousin Moni. My father accompanied me as a guide and companion, but he was a sullen and brooding presence, lost in a private anguish. He is the youngest of five brothers, and Moni is his firstborn nephew—the eldest brother’s son. Since 2004, Moni, now fifty-two, has been confined to an institution for the mentally ill (a ‘lunatic home,’ as my father calls it), with a diagnosis of schizophrenia. He is kept awash in antipsychotics and sedatives, and an attendant watches, bathes, and feeds him through the day.

My father has never accepted Moni’s diagnosis. Over the years, he has waged a lonely campaign against the psychiatrists charged with his nephew’s care, hoping to convince them that their diagnosis was a colossal error, or that Moni’s broken psyche would somehow mend itself. He has visited the institution in Calcutta twice—once without warning, hoping to see a transformed Moni, living a secretly normal life behind the barred gates. But there was more than just avuncular love at stake for him in these visits. Moni is not the only member of the family with mental illness. Two of my father’s four brothers suffered from various unravellings of the mind. Madness has been among the Mukherjees for generations, and at least part of my father’s reluctance to accept Moni’s diagnosis lies in a grim suspicion that something of the illness may be buried, like toxic waste, in himself.

Rajesh, my father’s third-born brother, had once been the most promising of the Mukherjee boys—the nimblest, the most charismatic, the most admired. But in the summer of 1946, at the age of twenty-two, he began to behave oddly, as if a wire had been tripped in his brain. The most obvious change in his personality was a volatility: good news triggered uncontained outbursts of joy; bad news plunged him into inconsolable desolation. By that winter, the sine curve of Rajesh’s psyche had tightened in its frequency and gained in its amplitude. My father recalls an altered brother: fearful at times, reckless at others, descending and ascending steep slopes of mood, irritable one morning and overjoyed the next. When Rajesh received news of a successful performance on his college exams, he vanished, elated, on a two-night excursion, supposedly ‘exercising’ at a wrestling camp. He was feverish and hallucinating when he returned, and died of pneumonia soon afterward. Only years later, in medical school, did I realize that Rajesh was likely in the throes of an acute manic phase. His mental breakdown was the result of a near-textbook case of bipolar disorder.

Dr. Siddhartha Mukherjee

So opens an essay written by Siddhartha Mukherjee from The New Yorker. Dr. Mukherjee, a Columbia University-affiliated oncologist, is the Pulitzer Prize-winning author of The Emperor of All Maladies. Here he writes beautifully – and personally.

There are really two essays within this long essay.

In the first, Dr. Mukherjee provides a history of the search for a genetic understanding of schizophrenia. He notes that Eugen Bleuler, a Swiss-German psychiatrist who coins the term schizophrenia, had seen a genetic connection:

“‘If one is looking for ‘the heredity,’ one can nearly always find it,’ he wrote. ‘We will not be able to do anything about it even later on, unless the single factor of heredity can be broken down into many hereditary factors along specific lines.’”

Here’s what Dr. Mukherjee notes:

· “In the nineteen-sixties, Dr. Bleuler’s hunch was confirmed by twin studies. Psychiatrists determined that if an identical twin was schizophrenic the other twin had a forty-to-fifty-per-cent chance of developing the disease—fiftyfold higher than the risk in the general population.”

· Large-scale population studies have confirmed the strong role of genetics.

· In 2006, an international consortium of psychiatric geneticists launched a genomic survey of schizophrenia, showing a strong connection with chromosome 6; the MHC region – heavily tied to the immune system – loomed “like a lone skyscraper towering over the skyline of a newly built metropolis.”

But there is another essay here – of the author’s journey in finding about his family and the troubled lives of his uncles. To that end, Mukherjee goes to India to visit his father’s childhood home, and the psychiatric institution with Moni has lived his life.

Further Reading

The Nature article can be found here:

http://www.nature.com/nature/journal/v511/n7510/full/nature13595.html

And here’s the Manhattan plot referred to by Dr. Lieberman showing a strong connection with chromosome 6.

Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.