Nicotine normalises brain activity in schizophrenia patients

January 25, 2017

Washington, Jan 25: A steady stream of nicotine normalises genetically-induced impairments in brain activity associated with schizophrenia, according to a new study that could lead to new non-addictive, nicotine-based treatments for the 51 million people worldwide who suffer from the disease.

BrainThe finding sheds light on what causes the disease and why those who have it tend to smoke heavily.

It could also potentially have applications for treating addiction, Attention Deficit Hyperactivity Disorder, Bipolar disorder and other psychiatric conditions.

"Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit," said Jerry Stitzel, researcher at the Institute for Behavioural Genetics (IBG) in the US.

The study found that when mice with schizophrenic characteristics were given nicotine daily, their sluggish brain activity increased within two days. Within one week it had normalised.

"Basically the nicotine is compensating for a genetically determined impairment. No one has ever shown that before," said Stitzel.

The scientists set out to explore the underlying causes of "hypofrontality"?a reduction of neuronal firing in the prefrontal cortex of the brain.

Hypofrontality is believed to be the root cause of many of the signature cognitive problems experienced by schizophrenics, including trouble paying attention, remembering things, making decisions and understanding verbal explanations.

Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.

Eighty to 90 per cent of people with schizophrenia smoke and most are very heavy smokers, a fact that has long led researchers to suspect they are self-medicating.

The research team first took mice with the CHRNA5 gene variant and used state-of-the-art brain imaging technologies to see if they had hypofrontality.

Then they conducted behavioural tests to see if the mice shared key characteristics of schizophrenics, like being unable to suppress a startle response and being averse to social interaction.

The results validated that the gene variant likely plays a role in schizophrenia by causing hypofrontality, said Stitzel.

Nicotine appeared to reverse this in the mice, normalising brain activity by acting on nicotinic receptors in regions of the brain key to healthy cognitive function.

The study appears in the journal Nature Medicine.

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Agencies
May 2,2020

Clinician-scientists have found that Irish patients admitted to hospital with severe coronavirus (COVID-19) infection are experiencing abnormal blood clotting that contributes to death in some patients.

The research team from the Royal College of Surgeons in Ireland found that abnormal blood clotting occurs in Irish patients with severe COVID-19 infection, causing micro-clots within the lungs.

According to the study, they also found that Irish patients with higher levels of blood clotting activity had a significantly worse prognosis and were more likely to require ICU admission.

"Our novel findings demonstrate that COVID-19 is associated with a unique type of blood clotting disorder that is primarily focussed within the lungs and which undoubtedly contributes to the high levels of mortality being seen in patients with COVID-19," said Professor James O'Donnell from St James's Hospital in Ireland.

In addition to pneumonia affecting the small air sacs within the lungs, the research team has also hundreds of small blood clots throughout the lungs.

This scenario is not seen with other types of lung infection and explains why blood oxygen levels fall dramatically in severe COVID-19 infection, the study, published in the British Journal of Haematology said.

"Understanding how these micro-clots are being formed within the lung is critical so that we can develop more effective treatments for our patients, particularly those in high-risk groups," O'Donnell said.

"Further studies will be required to investigate whether different blood-thinning treatments may have a role in selected high-risk patients in order to reduce the risk of clot formation," Professor O'Donnell added.

According to the study, emerging evidence also shows that the abnormal blood-clotting problem in COVID-19 results in a significantly increased risk of heart attacks and strokes.

As of Friday morning, the cases increased to 20,612 cases in Ireland, with 1,232 deaths so far, according to the Johns Hopkins University.

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June 30,2020

Between 30-40 per cent of deaths from studies in intensive care units from different countries are people with diabetes, said Paul Zimmet, Professor of Diabetes, Monash University, Australia.

Zimmet, who is President International Diabetes Federation, added that the actual mechanism as to why COVID-19 may cause diabetes is as yet unknown, however, several possibilities exist. "COVID-19 is a very destructive and cunning virus and causes terrible damage to tissues including the lungs and pancreas," said Zimmet. Below are excerpts from an exclusive chat with IANS.

Why do you say Diabetes is dynamite if a person has been infected with COVID-19?

There have been many deaths in many countries, e.g. Italy, China, the UK and US among people with diabetes after infection with COVID-19 (SARS-Cov-2).

The mortality tends to be mainly in older Type 2 diabetics. Between 30-40 per cent of deaths from studies in intensive care units from different countries are people with diabetes. This outcome and other complications from the virus, particularly pneumonia, are more likely in people with diabetes which is poorly controlled with high blood sugars (poor metabolic control).

Diabetes is often associated with other chronic conditions, including obesity, hypertension and heart disease compounding the risk. These latter conditions all convey higher risk to COVID-19 infections.

ACE-2, which binds to SARS-Cov-2 and allows the virus to enter human cells is also located in organs and tissues involved in glucose metabolism. Is there solid evidence that virus after entering tissues may cause multiple and complex impairment of glucose metabolism?

The actual mechanism as to why COVID-19 may cause diabetes is as yet unknown.

However, several possibilities exist. Firstly, COVID-19 is a very destructive and cunning virus and causes terrible damage to tissues, including the lungs and pancreas.

A new study just published showed that in miniature lab-grown pancreas, and other cells such as liver, made using human stem cells, COVID-19 caused destruction of the pancreas beta cells that produce insulin.

It is possible that the virus causes disruption of the cells by disrupting cellular metabolism. This is possibly the way it brings about new-onset diabetes. ACE-2 exists in high concentration in the lung as this also explains the terrible lung side effects of COVID-19 infections.

Can COVID-19 lead to a new mechanism of diabetes? Probably a new form of diabetes or a new form of disease?

The COVID-19 virus has only been with us for about 5 months and there is a huge amount that we still must learn about its cunning and devastating ways. The purpose of the Global COVIDIAB Diabetes Registry, a joint initiative of Monash University in Australia, and King’s College London is to gain a much better understanding of how common is the appearance of COVID-19 related diabetes, what form does it take be it type 1 or type 2 or a new form, and how common are the complications that we already know e.g. diabetic keto-acidosis, hyperosmolar coma and high insulin requirements are causing high rates of ill health and mortality worldwide. The knowledge gained will aid our understanding for developing strategies to prevent and treat this terrible virus that has caused destruction globally.

Diabetes is one of the most prevalent chronic diseases in India. According to a recent study, sugar levels of diabetic persons increased by 20 per cent during nationwide lockdown in India to contain COVID-19 outbreak. Even after lockdown was lifted, many people are confined within their home. Do you think lack of physical activity will create more problems for diabetics?

My own major research has been on studying populations with high rates of diabetes, including ethnic Indian communities including India, Mauritius, and Fiji so I am very well aware of this. It is now well established that along with diabetes, that associated poor metabolic control of their diabetes places these people at the highest risk for COVID infection and its devastating complications and the associated morbidity and mortality. And these communities have high prevalence of heart disease as well.

Lockdown not only has deleterious effects on metabolic control of the diabetes through reduced opportunities for exercise to be protective serious consequences of SARS-CoV-2 infection, lockdown usually results in disruption of the regular medical care and the regular monitoring of metabolic control. This may also be partly due to the stress and poor compliance, or inability to afford their medications such as insulin. It may also be compounded by inability to access the care during the pandemic. Nevertheless, we now know that poor metabolic control heightens their risk as described above.

You have said diabetes is itself a pandemic just like Covid-19, and the two pandemics could be clashing. How could governments address this problem?

These are “The Times of COVID-19”. Most nations of the world were totally unprepared for a pandemic of this magnitude. They underestimated its potential impact and the destructive nature of the viral infection. This should prompt all countries to upgrade their guidelines to take into account the lessons learnt on infection control including training of staff specialising in infectious diseases and improved public education and taking their communities into their confidence about the terrible nature of COVID-19. The risks of COVID-19 infection need a much higher priority in the general community, particularly for people with chronic conditions such as diabetes, obesity, and cardiac conditions.

Governments are faced with chronic diseases (NCDs) like diabetes and communicable diseases (CDs) like viral and enteric diseases and TB. In general WHO gives the highest priority to communicable diseases and much less attention and funding to chronic diseases like diabetes (I was an adviser to WHO for many years (about 30) on diabetes and obesity and it was very frustrating to deal with this situation).

This attitude to diabetes, for example, has a flow down effect so that diabetes funding in countries by governments, rich and poor, suffered and was insufficient.

So now we have a COVID-19 pandemic and who are those at highest risk, yes people with diabetes and other NCDs, it is very important that now the two, Diabetes and COVID-19 are clashing face-to-face. This is a major issue that WHO and national governments have to face with equal priority’

Stressed people suffering from diabetes run a greater risk of poor blood glucose levels, what do you suggest to these people?

As mentioned in the answer above, stress is an important factor in upsetting the blood sugar (metabolic) control of diabetes. Additive to this is poor compliance with medications and diet. These and potential associated comorbidities due to other chronic conditions are part of the dynamic dynamite mixture.

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News Network
June 20,2020

Washington, Jun 20: Pregnant and postpartum women are usually at a high risk of depression and anxiety - one in seven women struggle with symptoms in the perinatal period and the coronavirus pandemic is exacerbating those struggles according to a recent study.

The study was published in Frontiers in Global Women's Health, which found that the likelihood of maternal depression and anxiety has substantially increased during the health crisis.

"The social and physical isolation measures that are critically needed to reduce the spread of the virus are taking a toll on the physical and mental health of many of us," said Dr. Margie Davenport of the University of Alberta, Canada, who co-authored the study.

For new moms, those stresses come with side effects.

"We know that experiencing depression and anxiety during pregnancy and the postpartum period can have detrimental effects on the mental and physical health of both mother and baby that can persist for years," said Davenport.

Such effects can include premature delivery, reduced mother-infant bonding, and developmental delays in infants.

The study surveyed 900 women - 520 of whom were pregnant and 380 of whom had given birth in the past year - and asked about their depression and anxiety symptoms before and during the pandemic.

Before the pandemic began, 29 percent of those women experienced moderate to high anxiety symptoms, and 15 percent experienced depressive symptoms. During the pandemic, those numbers increased - 72 percent experienced anxiety and 41percent experienced depression.

Because lockdown measures have affected daily routines and access to gyms, researchers also asked women whether their exercise habits had changed. Of the women surveyed, 64 percent reduced their physical activity since the pandemic began, while 15 percent increased and 21 percent experienced no change.

Exercise is a known way to ease depression symptoms, so limited physical activity may result in an uptick in depressive symptoms. Indeed, the study found that women who engaged in at least 150 minutes of moderate physical activity a week had significantly lower symptoms of depression and anxiety.

The findings are somewhat limited given the fact that researchers could not survey women before the pandemic began (since they could not know a pandemic would occur). The women surveyed could only offer their pre-pandemic symptoms in hindsight.

Also, while the researchers asked women about their symptoms using validated measures, only mental health care professionals can validly diagnose an individual with depression or anxiety.

The study was specifically interested in the impact of COVID-19 on new moms, but Davenport says maternal mental health is a critical issue no matter the time.

"Even when we are not in a global pandemic, many pregnant and postpartum women frequently feel isolated whether due to being hospitalized, not having family or friends around or other reasons," she said.

"It is critical to increase awareness of the impact of social (and physical) isolation on the mental health of pregnant and postpartum women," Davenport added.

Increased awareness makes diagnosis and treatment - the ultimate goal - more likely.

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