GxExAge

23 05 2014

Here are fascinating findings regarding the Genes – Enviroment interaction and mental illness onset:

http://www.nimh.nih.gov/news/science-news/2014/genes-impact-suspect-cortex-areas-more-as-youth-mature.shtml





The Earliest the Better

16 01 2013

So many times we heard about the great importance of  early diagnosis and intervention in preventing or reducing the effect of health conditions. Well, that is true, in life, the earliest you identify a problem and address the better.  This time, I want to share with you the recent post of Dr. Insel, NIMH director about this issue in the context of mental health.  Enjoy!

 

The Case for Preemption

By Thomas Insel on January 16, 2013

Let’s start with some good news. Over the past few decades in the United States, we have seen dramatic reductions in mortality due to coronary artery disease (an over 60 percent reduction, with 1.1 millions deaths averted each year), AIDS (a 40 percent reduction, with over 30,000 deaths averted each year), and stroke (a 30 percent reduction, with over 20,000 deaths averted each year). Indeed, last month AIDS was declared a chronic disease, recognizing that a young person who becomes infected with HIV will likely survive for decades and die of other causes. These are extraordinary achievements, largely due to biomedical research. More specifically, research has taught us to detect each of these diseases early and intervene quickly to preempt later stages. The simple concept of “treatment as prevention,” whether to reduce heart attacks and strokes or to prevent the spread and advance of AIDS, has yielded better outcomes than treating the late stages of these disorders.

Unfortunately, when we look at the big picture and consider overall longevity, compared to the rest of the world, our news is not so good. A report out last week from the Institute of Medicine and the National Research Council describes high rates of mortality for Americans under 50, relative to rates of mortality in 18 other developed countries.1 It’s a sobering report. American men ranked last and American women ranked next to last in life expectancy within this age range. The authors cite car accidents, gun violence, and drug overdoses as factors contributing to higher mortality rates in this country. For people with mental disorders, the news from the United States is especially concerning. Suicide rates are trending higher not lower, especially in select demographic groups. Longevity, which has increased in the U.S. general population, remains shortened by years, possibly decades, in people with serious mental illness.

Is there a lesson to be learned from the successes of biomedical research? One observation that is driving the science of neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease is that changes in the brain precede changes in behavior, sometimes by more than a decade. The brain appears wired to preserve behavior even in the face of massive cell death or cortical atrophy. Much of our research effort today in Alzheimer’s disease focuses on identifying these earlier stages and developing interventions that will preempt or forestall dementia. In Parkinson’s disease, where the symptoms only emerge after 80 percent of dopamine cells have been lost, if we could halt the disorder when only 40 percent of cells have died, the symptoms might be prevented.

What about mental disorders or, as we often call them, “behavioral disorders”? We now understand these as brain circuit disorders, but we define them based on changes in behavior. If the symptoms of psychosis are a late stage of schizophrenia, are we missing the most important time to intervene? A recent review looks at the evidence for a prodrome or high-risk syndrome before the psychosis of schizophrenia, analogous to the stages of heart disease before a heart attack.2 Most of the studies of this high-risk state have relied on behavioral symptoms, suggesting that we are already late in the process. Nevertheless, as this review concludes, this approach has already revealed an interlude before psychosis when intervention could prevent psychosis.

Of course, we face two big questions going forward in this research. First, can changes in brain function or some biomarker yield better prediction and longer lead-times for intervening to preempt psychosis? We now have the neuroimaging and cerebrospinal fluid measures in Alzheimer’s disease and the cardiac imaging and lipid measures in heart disease to define risk with more precision. Imagine the cognitive, imaging, and plasma measures that might redefine what we now call the risk state for schizophrenia so that early prediction becomes precise for any given individual.

The second question is how to intervene. The first studies with medications have been disappointing.2 We do not have a “statin” for preempting psychosis. But medication might not be the best way to build prefrontal circuits or strengthen executive function. Imagine a toolkit of interventions with cognitive training, family supports, and social engagement to prevent psychosis in even 20 percent of the 100,000 young people who will have a first episode this year.

The NIMH-supported North American Prodrome Longitudinal Study (NAPLS) has been on this path for the past decade. This dedicated consortium of scientists is not there yet, but already they are working on a combination of neurocognitive testing, neuroimaging, and plasma biomarkers that can redefine how we think about schizophrenia, revealing that psychosis is indeed a late event in a process that starts many years earlier. This year we will avert 1.1 million deaths from heart disease because we have not waited for a heart attack to diagnose and treat coronary artery disease. The 100,000 young Americans who will have a first episode of psychosis this year will join over 2 million with schizophrenia. Nearly 5 percent of people with schizophrenia will die by suicide. Our best hope of reducing mortality from this and other brain disorders will come from realizing that just like other medical disorders, we need to diagnose and intervene before the symptoms become manifest.

effect of early prevention on schizophrenia

References

1 National Research Council and Institute of Medicine. (2013). U.S. Health in International Perspective: Shorter Lives, Poorer Health. Panel on Understanding Cross-National Health Differences Among High-Income Countries, Steven H. Woolf and Laudan Aron, Eds. Committee on Population, Division of Behavioral and Social Sciences and Education, and Board on Population Health and Public Health Practice, Institute of Medicine. Washington, DC: The National Academies Press.

 2 Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rössler A, Schultze-Lutter F, Keshavan M, Wood S, Ruhrmann S, Seidman LJ, Valmaggia L, Cannon T, Velthorst E, De Hann L, Cornblatt B, Bonoldi I, Birchwood M, McGlashan T, Carpenter W, McGorry P, Klosterkötter J, McGuire P, Yung A. The Psychosis High-Risk State.JAMA Psychiatry. 2013;70(1):107-120. doi:10.1001/jamapsychiatry.2013.269.

 

 





“Understanding of mental illness as a neurodevelopmental disorder is key”

3 10 2012

“[Mental illnesses] are brain disorders and by that I don’t mean you have a tumor or a lesion but that they are disorders of circuits. These are brain circuit problems. It’s is not a question of behavior but of the genetics of the organ, the brain in this case”.

“The brain is incredibly resilient… behavior is the last thing to go,” says Dr. Insel. Trying to treat a mental disorder by addressing behavior is difficult and not the most effective method. By that time, the illness is already in Stage IV of its development and symptoms have begun to show, the brain has already been deeply impacted. The warning signs of an impending illness (stage II) have already passed and the first episodes have already occurred (stage III). As with heart disease, if you wait until the last thing happens—a heart attack in the case of heart disease—outcomes aren’t good.

“….Studies are being made and research is being conducted that allows for more accurate images of the brain that in turn have allowed us to examine the different levels of an illness. Instead of addressing merely the behavioral manifestations of the brain disorder, we can hopefully begin to address the illness in the prodromal, or beginning, stages. Looking at the behavioral symptoms is still important but we need to find out what’s going on at the level of physiology, at the level of cells and genes and molecules, to get a much more comprehensive picture”.

New techniques such as diffusion spectrum imaging have allowed scientists to begin to map the neural fiber pathways of the brain. While these methods are still in their infancy they show promise. They allow us to decode the “bowl of spaghetti”. With the new technologies we can now begin to see into that mass in the middle. We hope that by the end of this year we will be able to tell what the actual connectivity is between two parts of the brain. Ultimately being able to discover what is exactly different between individuals with depression and individuals with schizophrenia, what part of the brain changes with treatment.

“For the first time we can begin to say, ‘So this is what depression looks like… these are the parts of the brain that are involved in PTSD or the parts that are involved in OCD  or schizophrenia.’”

“The understanding of mental illness as a neurodevelopmental disorder is key. Continued research on the early stages of the development of mental illness will result in treatments that can truly begin to address the core of the problem rather than focusing on mitigating the visible expressions of the illness”.

“Research into the circuits of the brain is not the only thing to be done. It’s not just a matter of getting clearer pictures of the brain, identifying the neurons, cells and structures in the brain. Evidence has continued to show one thing, over and over: “If you look at those things that help to build resilience… one of the best is simply by getting families involved.” It’s not just all the brain talk that’s important, it’s the human talk too”.

These very important and exciting things were said by Dr. Thomas Insel, Head of the National Institute of Mental Health (USA). Now I hope to hear the same thing from policy makers in Israel…

To read the full article enter:

http://www.nami.org/Template.cfm?Section=About_Research&template=/ContentManagement/ContentDisplay.cfm&ContentID=142938

And a related article by Insel:

http://www.nimh.nih.gov/about/director/2012/words-matter.shtml?utm_source=govdelivery&utm_medium=email&utm_campaign=govdelivery





The Role of Infections in Mental Illness

28 03 2012

This time I am “hosting” the Director of the National Institute of Mental Health Thomas Insel. I find this line of research very important and promising.

“In a visit to a mental asylum in 1912 you would have seen many patients with “general paresis.” The word “paresis” is Latin for weakness. General paresis was a form of psychosis with delusions, hallucinations, and memory problems often of rapid onset and thought to be due to a general constitutional weakness. At least that was the explanation until 1913, when general paresis was shown to be caused by syphilitic infection of the brain. The first treatments were awarded a Nobel Prize in 1917. The advent of antibiotics 30 years later led to the virtual eradication of neuro-syphilis, as the disorder came to be called, in this country.

The idea that mental or behavioral disorders could be due to infection is, therefore, not new but it remains surprisingly difficult to accept. When I was in training in the 1970’s, peptic ulcer disease was the prototype of a “biopsychosocial” disorder, with stress and a Type A personality considered the causes and psychodynamic therapy recommended as the treatment. Although helicobacter pylori was identified as the cause of peptic ulcer disease by Australians Robin Warren and Barry Marshall in the 1980’s, there was very little awareness (within the mental health community) that the disorder could be cured with antibiotics until Warren and Marshall received the Nobel Prize in 2005.

We may be looking at a similar reluctance to accept an infectious cause of pediatric sudden onset obsessive compulsive disorder (OCD) – in a debate that has been ongoing for almost two decades. In the early l990s, pediatrician Dr. Susan Swedo identified a subgroup of children whose OCD symptom onset didn’t fit the typical pattern. Instead of emerging gradually over weeks or months, they experienced ferocious bouts of compulsive behaviors and other symptoms “overnight and out of the blue.” As a pediatrician, Swedo’s familiarity with the ways of infectious agents and autoimmune mechanisms, together with her careful observations in the child psychiatry clinic of the NIMH Intramural Research Program, sparked the surprising hypothesis that a strep infection could trigger OCD symptoms via an autoimmune process.

This proved more complicated than syphilis or helicobacter. Part of the problem has been that strep is very common in childhood, making it methodologically difficult to prove a causal connection between the microbe and the OCD symptoms. The onset has not always been linked precisely with a strep infection and the critical increase in antibodies to strep has not been evident consistently. Nevertheless, immune-based treatments have proven successful, leading to the growing acceptance of the concept of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS).

Fortunately, the field is moving toward consensus on some of the larger issues, such as a broader concept of “acute and dramatic” onset of the same profile of psychiatric symptoms identified in PANDAS – but of unknown cause. There is also consensus on the need to establish a centralized registry to facilitate data analysis, so that causes and appropriate treatments can eventually be pinpointed.

This rapprochement recently took form in criteria for a broadened syndrome of acute onset OCD, published last month by Swedo, James Leckman at Yale and Joel Rose at Johns Hopkins. Their proposed Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) builds on and subsumes PANDAS. It embraces youth who experience acute onset of OCD or anorexia symptoms, mixed with a varying profile of other neuropsychiatric symptoms – cause unspecified.

Meanwhile, to strengthen evidence in support of immune-based treatment for the subset of youth whose illness is strep-related, Swedo, Leckman, and Madeleine Cunningham of the University of Oklahoma, and colleagues, are collaborating on a multi-site, double blind, placebo-controlled trialExternal Link: Please review our disclaimer. It is testing intravenous immunoglobulin (IVIG) for OCD symptoms in PANDAS. IVIG, an infusion of normal antibodies, restores normal immune function by neutralizing errant antibodies. A similar pilot study testing IVIG and another immune-based treatment more than a decade ago found that all treated children with PANDAS improved, with more than half completely cured or experiencing only subclinical symptoms after one year.

Despite doubt in some quarters, hints of possible involvement of infectious agents and/or autoimmune processes in other serious brain disorders, such as autism, have spurred interest in PANDAS as a model for a type of illness process that may be more informative than widely assumed.

MRI scans of a PANDAS patient, showing reduced inflammation in the caudate nucleus(area circled just to the left of black area in center of brain), part of the basal ganglia, following IVIG treatment. Evidence suggests that this brain structure is targeted by errant anti-brain antibodies, triggered by a strep infection, in PANDAS”.

Reference:

Swedo, SE, Leckman JF, Rose, NR. From Research Subgroup to Clinical Syndrome: Modifying the PANDAS criteria to describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Feb 2012, Pediatrics & Therapeutics.





“People with serious mental illness are 10 times more likely to be the victim of a violent crime than the perpetrator”

28 02 2012

One of the most common beliefs about people with mental illness is that they are violent and  dangerous. Here is an article that was published today which reinforces what we already know: “Although research suggests that there are factors that may increase risks of violence – such as co-occurring substance use, or not being engaged in treatment – people living with mental illness are 10 times more likely to be victims of violence than perpetrators.” Would this fact reduce mental illness stigma? probably not…





Neuropsychoanalysis

21 02 2012

Following the previous post, here is an approach to understand the mind-body link. This approach, among others (that will be mentioned in future posts) may also provide an alternative to the term “mental illness”.

Panksepp & Solmsm, the founders of the Neuropsychoanalysis (NPA) approach, argue that NPA seeks to understand the human mind, especially as it relates to first-person experience while recognizing the essential role of neuroscience in such quests. However, unlike most branches of neuroscience, it positions mind and brain on an equal footing. It recognizes that the mammalian brain is not only an information processing device for behavior, but also the fount of the dynamics that is called mind, from joyous and sad feelings to banal cognitions and idiosyncratic flights of fancy. That is to say, it is impossible to explain complex behaviors without reference to neural networks that mediate subjective mental events: that is, the causal effects of thoughts and feelings.

Neuropsychoanalysis emerged during the 1990s as a response to the need to reconcile psychoanalytic and neuroscientific perspectives on the mind, with the goal of yielding a better understanding of the basic emotional foundations of psychiatric disorders, in the hope of promoting better nosology and therapeutics.

For more information click HERE and HERE