From the Editor
My patient could recognize the damage done by alcohol. The lost friendships. The failed marriage. The firing of her job of 15 years. And yet, she was still puzzled. “How did I get into this mess?”
In a new American Journal of Psychiatry paper, Andrea King (of the University of Chicago) and her co-authors explore the draw of alcohol with a major new study that measures the subjective response to alcohol challenges at five and ten year follow ups. “Initial stimulant and rewarding effects of alcohol predicted heavy alcohol use, and the magnitude of these positive subjective effects increased over a 10-year period in those who developed alcohol use disorder compared with those who did not develop the disorder.” We discuss this big paper.
Dr. Philip Seeman had an extraordinary career with major achievements. Some argue that he should have shared the Nobel prize. He died on 9 January 2021 at his home. The Globe obituary is our second selection. Dr. Seeman was a generous mentor of many young scientists, and a husband, father, and grandfather. And his work was impactful: Dr. Seeman’s interest in dopamine helped change the way we practice today.
And in our final selection, we look at a new essay by Dr. Gaurav Sharma, a resident of psychiatry at the University of Toronto. The disaster of Ontario’s long term care homes has made many headlines. For this young doctor, the problems are close to home, affecting his godmother. He writes about her life and her downward turn. “In my training as a psychiatry resident, a basic principle I’ve learned is that every mental health crisis has its triggers. In Lucy’s case, the crisis that led to her hospitalization was prompted by a precarious housing situation.”
Selection 1: “Subjective Responses to Alcohol in the Development and Maintenance of Alcohol Use Disorder”
Andrea King, Ashley Vena, Deborah S. Hasin, et al.
The American Journal of Psychiatry, 5 January 2021 Online First
Heavy drinking is increasing among U.S. adults and remains a major preventable contributor to disability and mortality worldwide. It is also a strong predictor of subsequent alcohol use disorder (AUD), which carries additional serious consequences for health and functioning. Given the global burden of alcohol misuse, identifying factors that increase the susceptibility to the development and maintenance of AUD is a critical public health need.
One way to examine vulnerability to AUD is to characterize acute subjective responses to alcohol at different stages of development of the disorder. Two large studies have found that greater initial stimulation and reward responses to alcohol, as well as lesser intoxicating and sedating responses, predict future drinking problems through young adulthood. These acute responses may change with chronic heavy drinking as a result of neuroadaptations that produce either tolerance or sensitization. Tolerance, or a diminished response to the same dose of a drug after repeated use, is a diagnostic criterion for AUD. Conversely, sensitization, or an increased drug effect with repeated exposure, has also been linked to addiction…
So begins a paper by King et al.
Here’s what they did:
- “Young adult drinkers (N=190) participated in an initial alcohol challenge (0.8 g/kg of alcohol compared with placebo) that was repeated 5 and 10 years later.”
- They were also assessed on drinking behavior and AUD symptoms at numerous intervals across the decade.
- To be included, participants must have consumed at least five drinks on one occasion at one point in their life.
- Exclusion criteria: non-drinker, chronic medical conditions, suicide attempts.
- Statistical analyses were done.
Here’s what they found:
- “Participant retention in the Chicago Social Drinking Project was high, with 99% (184 of 185) of the nondeceased active participants completing follow-up at 10 years…”
- “At the end of the decade, 21% of participants met criteria for past-year AUD.”
- “Overall, the AUD+ group exhibited increasing sensitivity for pleasurable alcohol responses during the decade of participation, while the AUD− group showed low initial levels on these measures with little to no change through the testing phases. Specifically, alcohol produced initially higher stimulation in the AUD+ group relative to the AUD− group during the early portion of the breath alcohol concentration curve, and stimulation level increased in intensity through the reexamination phases.”
- Over time, those with AUD had increased alcohol-induced simulation and wanting.
A few thoughts:
- This is an excellent study.
- The above summary attempts to explain a very complicated study – the authors describe it as “the most extensive repeated human testing study of its kind.”
- Here is a Twitter-worthy summary: for those who went on to develop alcohol problems, alcohol had a strong draw early (in terms of initial stimulant and rewarding effects) and the euphoria processes didn’t wane with time.
- Why some develop an alcohol use disorder is complicated. This study does a nice job of tying to subjective experiences – as opposed to, say, just genetics.
- Limitations? The authors note several, including that “we could not assess how acute alcohol-related skin flush, smoking, and preexisting psychiatric disorders contributed to the rate of binging in this sample because these were exclusion factors for our study.”
- What are the public policy implications? “In terms of prevention of alcohol problems, rather than a sole focus on tolerance, young adults might be informed that marked stimulant-like, pleasurable, and appetitive effects after consuming alcohol are risk factors for the development and maintenance of addiction.” Of course, we could incorporate this into practice, as well. We can talk about amounts and tolerance, yes, but the draw of alcohol could also be mentioned.
The full paper can be found here:
Selection 2: “Researcher Philip Seeman shed new light on biology of schizophrenia”
The Globe and Mail, 27 January 2021
Through hard work and inventiveness, molecular neuropharmacologist Philip Seeman transformed medical science’s understanding of schizophrenia and other brain conditions. He discovered the importance of the dopamine D2 receptor in 1974, showing that the schizophrenia drugs of that era – which were widely used but poorly understood – targeted this brain receptor.
His research led to a better understanding of schizophrenia and how to treat it. Dopamine and its receptors also play a key role in Parkinson’s and Huntington’s, and his discoveries furthered approaches to these other brain diseases as well.
‘Before this, our theories about what causes schizophrenia were primitive and blaming,’ said Paul Garfinkel, staff psychiatrist with the Centre for Addiction and Mental Health (CAMH). ‘They blamed the mother or the family dynamic. His studies showed there’s a biology to this brain illness that’s nobody’s fault.’
So begins the obituary.
Dr. Seeman’s scientific contributions are noted, including his work furthering the dopamine hypothesis, and his particular focus on the second dopamine receptor. His research had clinical relevance: “Dr. Seeman also discovered that anti-psychotics that did not linger for long on the D2 dopamine receptor caused fewer side effects. He cloned four of the five known dopamine receptors, including the D2. His later research revealed that smaller doses of anti-psychotics could effectively treat schizophrenia.”
The article notes his recognitions: “a fellow of the Royal Society of Canada in 1985 and winning the Killam Prize in health sciences in 1996. He was named an officer of the Order of Canada in 2001.” However, a big recognition alluded him, perhaps unfairly: “In 2000, three of his international colleagues studying dopamine won the Nobel Prize in physiology or medicine, but Dr. Seeman was left out.”
Dr. Seeman, who was born in Winnipeg, trained at McGill University, and did his PhD in New York’s Rockefeller University, before doing a fellowship at Cambridge University.
The article also mentions his marriage to Dr. Mary Seeman, who he met in medical school. “On the first day, he sat beside Mary Szwarc, one of the eight women in the class of 100. He asked her to be in his group studying the anatomy of cadavers, but she was not interested, plus she had promised another female student they’d work together. On the sly, Philip persuaded that woman to join his group, thereby ensuring Mary would work with him.”
A few thoughts:
- This is a beautiful obituary.
- Dr. Seeman did many things – among them, he was an accomplished scientist and mentor. He was also a warm and engaging individual. The writer captures this a bit, describing his conversation with one of his son’s after not getting the biggest prize in medicine: “‘Neil, I didn’t get it,’ Philip told his son, laughing, and then the two went outside to play catch.”
- Returning back to the point about clinical relevance. His work helped shift psychiatry away from the mega-dosing of antipsychotics – and the resulting problems, including tardive dyskinesia, so common then.
The full essay can be found here:
Selection 3: “I won’t let you forget about Lucila Iqbal”
8 January 2021
In a long-term care home in Scarborough on Christmas Day 2020, Lucila Iqbal died in isolation and silence. While I wept for our loss at her funeral yesterday, I grappled with how my once independent and feisty godmother’s life could come to such a quiet end. Lucila’s story must be told not only because it intersects with those of many of the lives lost over the past year — but because it reveals as much about the woman as about the society she lived in.
Back in 1988, my parents were looking for a tenant for their Junction home when a skinny South Asian man hurriedly arrived on their porch. He insisted that he had someone for them who would be ‘not cause any trouble’. A few days later, a middle-aged Filipina woman arrived alone, with bags in tow.
Working through the language barriers, Lucila soon befriended my mother and became an indispensable part of the family.
So begins an essay by Dr. Sharma.
He notes her role in the family, and in his childhood. “We would go for walks to the corner store or for donuts at the neighborhood bakery (where Lucy might indulge in one or two as well). Cheerful and chatty, Lucy was known for talking circles around whoever was listening, even though her train of thought was hard to follow.”
The essay describes her life, initially filled with hope and promise – she studied chemistry – but then touched by mental illness. “Lucy’s mental health eventually deteriorated further, and in a few years she could no longer work or live independently. Eventually, she arrived on my family’s porch.”
“Lucy’s most remarkable trait was always her desire to share what little she had. Whether it was the biweekly cheque she picked up from her Public Guardian and Trustee, toys she found at the Salvation Army, or some of the fries from her lunch tray, giving brought Lucy peace. She would smile, gently whisper ‘It just comes back’, and finish stuffing a $20 bill in my pocket despite my continued protests.”
The author and Iqbal
Later years were coloured by illness. “I naively rushed over to visit her, anticipating that she would soon be discharged. Instead, Lucy’s time in hospital extended from weeks to months – she was not welcome back to her new home. I watched her characteristic zeal wear thin. Her discharge was delayed by the search for a long-term care placement. A medical student at the time, I wanted to talk to her healthcare team about her diagnosis and why she needed to go to long-term care, but these questions were respectfully sidestepped. I was not privy to her health information, they were looking into all options, and someone would call me with an update. No update came.”
She is admitted to long-term care. And her health deteriorates. She has a fall; she grows quieter. And then COVID-19 strikes, killing 30% of the residents. She dies on Christmas Day. “There must be others who watch their loved one follow a similar trajectory through long-term care and wonder which setbacks in their health could have been avoidable.”
A few thoughts:
- This is a moving essay.
- In the coming years, we will hear much about what happened in our long-term care homes, and the struggles of the residents. This essay reminds us of others who were deeply affected – the families and friends who couldn’t visit, and who ultimately lost.
- Dr. Sharma writes excellent prose.
The full essay can be found here:
Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.