New Findings Show Dopamine’s Complex Role in Schizophrenia

That is the title of this article I am reviewing today. "'Recent advances in understanding the role of dopamine signaling in schizophrenia are highlighted in a special edition of the journal Biological Psychiatry. Seven reviews show the complexity of the neurotransmitter’s action, and several articles describe how new insights may eventually improve treatment for the disorder. Dopamine alterations are some of the most well-established research findings in schizophrenia, said Anissa Abi-Dargham, M.D., of Stony Brook University, New York, and a deputy editor of Biological Psychiatry.'Unlike any other neurobiological hypothesis of the disease, the dopamine hypothesis has confirmatory evidence from in vivo studies in patients and from pharmacological therapies, she said.'"Now they are going back to what they said in the first place caused mental illness dopamine. I understand that they have to understand it to find better medicine and therapy.
The article goes on to say: "'Despite this, researchers have yet to fully understand when and how dopamine alterations arise in the brain, or their relationship with the diversity of symptoms in the disease. 'This issue highlights the complexity of the findings in patients with the disorder, and raises the possibility that dopamine alterations can lead to a vast array of consequences on the circuitry, on learning and behavior that can explain the vast array of symptom clusters,' Abi-Dargham said.
The body of work collated in the issue ranges from human studies to animal models. New technology in the form of neuroimaging, genetic, and molecular imaging studies have helped clarify the regional differences of dopamine dysfunction throughout the brain. Importantly, the studies have detailed the timing of dopamine alterations in relation to development, symptom onset, and other neurobiological alterations in the disease. Moreover, animal models have allowed researchers to further refine and test the hypothesis, and explore mechanisms behind the dysregulation.'"I know the consequences they have to find out what caused this problem and how to fix it.  What causes dopamine to act up and give a person a mental illness?
The article ends with: "'Clarifying the role of dopamine signaling in schizophrenia also shows promise for improving treatment for the disorder. 'We include here some examples of exciting new targeted therapeutic approaches that are currently under development,' Abi-Dargham said.
Although the dopamine system has long been pegged as the culprit for psychotic symptoms in schizophrenia, a review in this issue using a computational approach provides an explanation for how dopamine dysfunction could lead to the range of symptoms present in the disorder. The therapeutic approaches proposed in the issue aim to find new strategies for targeting dopamine signaling to improve the limitations of current antipyschotic drugs. The new strategies are necessary as the current methods only treat psychotic symptoms and come with a host of major side effects. Researchers say the new focus will be to target new pathways and tap into dopamine’s role in other regions of the brain." I understand that this could cause new drugs to come out without the side effects.  I know that even I that function pretty good my medication I have to take with food.  I also have take it when I know I want to sleep because after two hours it puts me to sleep.  The big thing I still want to know is why I have this disease.  I sure would like to know before I die.  I know I am lucky in that it did not come for me until my late twenties. So I had some life before this illness and need to understand the why now.

Dopamine: Psychotic fire-starter? The Paykel Lecture 2014

That is the title of this article I am writing about. "The eye-catching title of the 2014 Paykel Lecture certainly lived up to its promise of a fascinating talk. Delivered by Dr Oliver Howes of the Institute of Psychiatry, Psychology and Neuroscience (IoPPN – King’s College London), the title made reference to an early paper on the dopamine hypothesis of schizophrenia, where dopamine was referred to as “the wind of the psychotic fire.” An eloquent review of the dopamine hypothesis followed, from the perspective of studies employing positron emission tomography (PET) and magnetic resonance imaging (MRI).
Dopamine is an important neurotransmitter, playing a crucial role in brain processes such as how we predict events and experience rewards. Its over-abundance in the brain has long been posited as a theory for the symptoms of psychosis seen in people with schizophrenia. Brain imaging techniques such as PET, which uses a radioactively labelled tracer, can help us obtain information about all aspects of the dopamine system. We can specifically study dopamine receptors, dopamine synthesis, its transportation or its release from neurons, and these methods have allowed scientists to pinpoint abnormalities in schizophrenia.  Using this technology, Dr. Howes and colleagues studied people with schizophrenia who had received very little treatment, and found that the abnormality of dopamine appears to be at the level of synthesis and release from brain cells, rather than at the receptor as was initially believed." Wow they found out where it is released from. They can find out how it works.
  The article goes on to say: "But this, Dr. Howes went on to explain, does not tell us whether schizophrenia is caused by an abnormality in dopamine regulation, or whether increased dopamine is a result of having schizophrenia. Therefore, his group decided to conduct research studies with a group of people who were at high risk of developing schizophrenia but do not yet show symptoms adequate for a diagnosis. These people are said to be in the prodromal, or sub-clinical, phase of schizophrenia. Whilst many go on to develop further symptoms, some remain stable at the sub-clinical phase and are able to function perfectly well. A prominent historical example of such a person, Dr. Howes explains, was Joan of Arc. Despite hearing voices (which she attributed to angels), she was able to lead the French army to victory over the British.Thus, using the same PET imaging techniques, Dr Howes and his team found elevated dopamine synthesis in the striatum of people with sub-clinical symptoms, which appeared to be around halfway between controls and people diagnosed with schizophrenia. Further investigation found that this increase in dopamine was in fact specific to those who would go on to develop a full clinical syndrome of schizophrenia, while those with long term sub-clinical symptoms did not demonstrate any increase in dopamine synthesis.
But what is it, Dr. Howes pondered, that the biology of schizophrenia needs to explain? The answer he came up with: Neurodevelopmental and sociodevelopmental risk factors (e.g drugs or stress), and symptoms.  Stay away from drugs and you probably will not get schizophrenia.  Stress is a hard one to stay away from.  That is what brought on my mental illness.  Anger, stress that all brought it on not knowing what was going to happen to me.
The article ends:"Based on research ongoing in his group, Dr. Howes (alongside Professor Sir Robin Murray) proposed a model to explain how these risk factors and symptoms might fit into the dopamine hypothesis. They proposed that a combination of genes and hazards to the brain disrupt the development of the dopamine system, and cause it become very sensitive. Social stress then acts on this sensitised system, increasing dopamine release, leading to irregular cognitive processing of events. This in turn leads to a paranoid interpretation of events and eventually psychosis, which in itself is a stressful experience, causing a vicious cycle of stress and increased dopamine release.
While this model both supports and is supported by much of the research into the dopamine hypothesis, there are many questions outstanding, and the hypothesis is far from being finally accepted or refuted. Dr Howes identified that further work needs to be done to understand why approximately one third of people with schizophrenia are resistant to treatment with antipsychotic drugs, which act on the dopamine system. The causes of the ‘negative symptoms’ of schizophrenia (e.g. affective flattening, or a reduced display of emotion) and the relationship with substance misuse (such as cannabis, which was not found to increase dopamine in the striatum when cannabis smokers experienced psychotic like symptoms as a result of their drug use).
Dr. Oliver Howes is a group head and reader in imaging of neurochemical processing in psychosis at Kings College London and at the MRC CSC psychiatric imaging group, Hammersmith Hospital, Imperial College. Dr. Howes has been the recipient of many prestigious awards, including most recently the Schizophrenia International Research Society Rising Star Award 2013." If it can help those people who are resistant to antipsychotics that would be a big help. If it is the dopamine that is causing schizophrenia then why are they resistant to drugs that help the dopamine?  I believe we are far away from discovering what actually causes schizophrenia.

Discovery of novel drug target may lead to better treatment for schizophrenia

That is the title of this article I writing about.  "A novel drug target that could lead to the development of better antipsychotic medications has been discovered by researchers.  Current treatment for patients with schizophrenia involves taking medications that block or interfere with the action of the neurotransmitter dopamine.  However, because this D2-blocking action my cause unwanted side-effects, such as slow gait, stiffness and tremor, the team looked for new ways to interfere with the action of D2 receptors, without causing these side-effects.  Scientists at the Centre for Addiction and Mental Health (CAMH) have identified a novel drug target that could lead to the development of better antipsychotic medications. Dr. Fang Liu, senior scientist in CAMH's Campbell Family Mental Health Research Institute and professor in the Department of Psychiatry, University of Toronto, and her team published their results online in the Journal Neuron.  Current treatment for patients with schizophrenia involves taking medications that block or interfere with the action of the neurotransmitter dopamine, which acts on dopamine D2 receptors in the brain. However, because this D2-blocking action may cause unwanted side-effects, such as slow gait, stiffness and tremor, Dr. Liu and her team looked for new ways to interfere with the action of D2 receptors, without causing these side-effects."  Nobody wants to have side-effects.  It could be the reason that a lot of people with mental illness do not like taking the medication.  I know when my arm was shaking with stelazine I did not want to take who wants to look like a freak just to be well.
The article goes on to say: " Dr. Liu and colleagues showed that the D2 receptor could combine with a protein called the Disrupted-In-Schizophrenia (DISC1) protein. Then, they showed that levels of this combined protein were higher in post-mortem brain tissues of deceased patients with schizophrenia, suggesting it was associated with the illness. Delving even further, the researchers identified the regions where the two proteins bound together. With this information, they were able to generate a peptide to disrupt the binding of the two proteins, speculating that it may reduce symptoms. In animal models of schizophrenia, they were able to demonstrate that this disruption led to antipsychotic effects, comparable to commonly used antipsychotic medications, but without their side-effects."  That would be great news if this new medication really works in people.  No side effects will really be big news.
The article ends: "'The most exciting aspect of our finding is not the antipsychotic effect of this peptide, which all current antipsychotics have, but rather the possibility of a lack of the side-effects in humans compared to current medications,' says Dr. Liu. 'We hope that it will lead to a better treatment for schizophrenia patients who experience side-effects from current medications.'These side-effects discourage some patients from taking their medications, which impacts recovery. Schizophrenia is a chronic, often severe and disabling mental illness that affects one percent of the general population. 'Our future steps are to determine how this discovery can be translated into a novel treatment for patients as soon as possible,' says Dr. Liu. 'We are optimistic that our findings will lead to new and better options for treatment for schizophrenia.'"  For all those people who do not like to take their medication because of the side effects help might be on the way.  They do not say how long though until they find out if it works on people.  News this good has been slow in coming we really need more research done.  To help people who suffer from this disease. I do not have side-effects anymore.  I am glad as I had them in the past and it was hard to take the medication.  It got rid of the positive effects but not the negative.

Spotlighting Dopamine to Probe Alcohol Addiction

That is the title of this article I am writing about. “A new technology called optogenetics is helping researchers gain a better understanding of the neurochemical basis of addiction.  Optogenetics allows researchers to control the activity of specific populations of brain cells, or neurons using light.  Amazingly, we have pond scum to thank for the new technique; the method was devised to understand how the tiny green algae that give pond scum its distinctive color detect and use light to grow.  The technology allowed Evgeny A. Budygin, Ph.D., an assistant professor of neurobiology and anatomy at Wake Forest Baptist Medical Center, to address critical questions regarding the roles of dopamine in alcohol drinking-related behaviors.  Well it is nice to see that technology can be used in different ways.  To be able to use it in alcohol addiction to find and help people who may have a problem drinking.

How will the use this technology? “With this technique, we’ve basically taken control of specific populations of dopamine cells, using light to make them respond almost like flipping a light switch, said Budygin.  These data provide us with concrete direction about what kind of patterns of dopamine cell activation might be most effective to target alcohol drinking, The latest study for Budygin and his team has been published in the journal Frontiers in Behavioral Neuroscience. Co-author Jeffrey L. Weiner, Ph.D., professor of physiology and pharmacology at Wake Forest Baptist, said one of the biggest challenges in neuroscience had been to control the activity of brain cells in the same way that brain controls them. With optogenetics, neuroscientists can turn specific neurons on or off at will, providing that those neurons actually govern specific behaviors.”  What dopamine cells get turned on or off when you are drinking is a good way to find out how to stop.  How that will battle drinking is impressive.  I know for some people quitting drinking is a very hard thing to do.  I finally quit when I wanted to.  I did learn some good things through groups and A.A. but what really made be quit is the crime I did to go to the state hospital it was finally the bottom for me.
The article goes on to say: “We have known for many years what areas of the brain are involved in the development of addiction and which neurotransmitters are essential for this process, Weiner said.  We need to know the casual relationship between neurochemical changes in the brain and addictive behaviors, and optogenetics is making that possible now.  Using a rodent model, the researchers used cutting-edge molecular techniques to express the light-responsive channel rhodopsin protein in a specific population of dopamine cells in the brain-reward system.  They then implanted tiny optical fibers into this brain region and were able to control the activity of these dopamine cells by flashing a blue laser on them.  You can place and electrode in the brain and apply an electrical current to mimic the way brain cells get excited, but when you do that you’re activating all the cells in a part of the brain-reward system.  Using this technique, we discovered distinct patterns of dopamine cell activation that seemed to be able to disrupt the alcohol-drinking behavior of the rats.  A different way to combat alcoholism would be great it does cause a lot of problems if you are an alcoholic like I was.  It causes crime and behaviors you wish you had never done.
The ending of the article states: “Weiner said there is translational value from the study because ‘it gives us better insight into how we might want to use something like deep-brain stimulation to treat alcoholism.’  Doctors are starting to use deep-brain stimulation to treat everything from anxiety to depression and while it works, there is little scientific understanding behind it, he said.  Budygin agreed. Now we are taking the first steps in this direction, he said.  It was impossible before the optogenetics era.”  That is great to not have to take a pill to make you stop drinking now there are new ways to help.  When you are drunk you do stupid things if this will help people I am all for it.

Dopamine Regulates Motivation

I found this article to be very interesting. “The widespread belief that dopamine regulates pleasure could go down in history with the latest research results on the role of this neurotransmitter.  Researchers have proved that it regulates motivation, causing individuals to initiate and persevere to obtain something either positive or negative.”  I thought it gave pleasure that is why addicts used drugs.  Now this article is saying it can give the motivation to use drugs or anything positive or negative.
It says that: “The neuroscience journal NEURON publishes an article by researchers at the Universitat Jaume I of Castellon that reviews the prevailing theory on dopamine and poses a major paradigm shift with applications in diseases related to lack of motivation and mental fatigue and depression, Parkinson’s, multiple sclerosis, fibromyalgia, etc. and diseases where there is excessive motivation and persistence as in the case of addictions.”  They shifted their whole way of thinking in terms of dopamine.  They are looking at a lot of diseases that will be viewed differently.
If it does not give pleasure how does it work?  “It was believed that dopamine regulated pleasure and reward and that we release it when we obtain something that satisfies us, but in fact the latest scientific evidence show that this transmitter acts to act. In other words, dopamine is released in order to achieve something good or to avoid something evil, ‘explains Merce Correa.”  You act to achieve something good. They have been studying this for the last two years.
The article says: “The level of dopamine depends on individuals, so some people are more persistent than others to achieve a goal. ‘Dopamine leads to maintain the level of activity to achieve what is intended.  This principle is positive, however, it will always depend on the stimuli that are sought: whether the goal is to be a good student or to abuse drugs’ says Correa.  High levels of dopamine could also explain the behavior of the so-called sensation seekers as they are motivated to act.” It is positive although the behavior could be bad.  You would abuse drugs or alcohol or does that fit in it? You do get addicted to alcohol just like drugs.
How can this knowledge now be used? “To know the neurobiological parameters that make people be motivated by something is important to many areas such as work, education or health. Dopamine is now seen as a core neurotransmitter to address symptoms such as depression. ‘Depressed people do not feel like doing anything and that’s because of low dopamine levels,’ explains Correa. Lack of energy and motivation is also related to other syndromes with mental fatigue such as Parkinson’s, multiple sclerosis or fibromyalgia, among others.  In the opposite case, dopamine may be involved in addictive behavior problems, leading to an attitude that dopamine of compulsive perseverance.  In this sense, Correa indicates that dopamine antagonists which have been applied so far in addiction problems probably have not worked because of inadequate treatments based on a misinformation of the function of dopamine.”  This new knowledge changes how scientists look at a lot of things. It could help a lot although we will have to wait and see.