Neural Circuit Taxonomy

Neural network circuits

Brain stuff -- interesting to find out what might go on in that grey matter.

"Precision psychiatry: a neural circuit taxonomy for depression and anxiety"

By Dr. Leanne M Williams, PhD

Summary

"Although there have been tremendous advances in the understanding of human dysfunctions in the brain circuitry for self-reflection, emotion, and cognitive control, a brain-based taxonomy for mental disease is still lacking. 

As a result, these advances have not been translated into actionable clinical tools, and the language of brain circuits has not been incorporated into training programs. 

To address this gap, I present this synthesis of published work, with a focus on functional imaging of circuit dysfunctions across the spectrum of mood and anxiety disorders. 

This synthesis provides the foundation for a taxonomy of putative types of dysfunction, which cuts across traditional diagnostic boundaries for depression and anxiety and includes instead distinct types of neural circuit dysfunction that together reflect the heterogeneity of depression and anxiety. 

This taxonomy is suited to specifying symptoms in terms of underlying neural dysfunction at the individual level and is intended as the foundation for building mechanistic research and ultimately guiding clinical practice."

And from Wikipedia:

"Dysfunction in the salience network have been observed in various psychiatric disorders, including anxiety disorders, post-traumatic stress disorder, schizophrenia, frontotemporal dementia, and Alzheimer's disease. 

The AI node of the salience network has been observed to be hyperactive in anxiety disorders, which is thought to reflect predictions of aversive bodily states leading to worrisome thoughts and anxious behaviors. 

In schizophrenia, both structural and functional abnormalities have been observed, thought to reflect excessive salience being ascribed to internally generated stimuli.

In individuals with autism, the relative salience of social stimuli, such as face, eyes, and gaze, may be diminished, leading to poor social skills."

Pattern Seeking: Finding Order in Chaos

From yee Wiki:

Apophenia /æpoʊˈfiːniə/ is the human tendency to perceive meaningful patterns within random data.

The term apparently dates back to 1958, when Klaus Conrad published a monograph titled Die beginnende Schizophrenie. Versuch einer Gestaltanalyse des Wahns ("The onset of schizophrenia: an attempt to form an analysis of delusion"), in which he described in groundbreaking detail the prodromal mood and earliest stages of schizophrenia. He coined the word "Apophänie" to characterize the onset of delusional thinking in psychosis. Conrad's theories on the genesis of schizophrenia have since been partially, yet inconclusively, confirmed in psychiatric literature when tested against empirical findings.

Conrad's neologism was translated into English as "apophenia" (from the Greek apo [away from] + phaenein [to show]) to reflect the fact that a person with schizophrenia initially experiences delusion as revelation.

In 2001 neuroscientist Peter Brugger referenced Conrad's terminology and defined the term as the "unmotivated seeing of connections" accompanied by a "specific experience of an abnormal meaningfulness."

Apophenia has come to imply a universal human tendency to seek patterns in random information, such as gambling.

In the News: ADHD, Autism, Schizophrenia, Other Psychiatric Disorders Genetically Linked In Huge New Study

In response to ischaemia (a reduction in blood flow), the neurotransmitter glutamate is released from neurons and other brain cells (astrocytes; not shown). This induces Ca²⁺ entry (green arrows) into responsive neurons through NMDA-type glutamate receptors and Ca²⁺-permeable AMPA-type glutamate receptors. Ca²⁺ also enters through voltage-gated Ca²⁺ channels and several other types of Ca²⁺-permeable membrane channel, and is released from intracellular stores. The NCX proteins represent a primary cellular defence against Ca²⁺ overload, pumping Na⁺ ions in and Ca²⁺ ions out. But Bano et al.¹ show that in ischaemic conditions NCX is destroyed by the Ca²⁺-activated protease calpain.

by Lauran Neergaard

Washington — The largest genetic study of mental illnesses to date finds five major disorders may not look much alike but they share some gene-based risks. The surprising discovery comes in the quest to unravel what causes psychiatric disorders and how to better diagnose and treat them.

The disorders – autism, attention deficit-hyperactivity disorder or ADHD, bipolar disorder, major depressive disorder and schizophrenia – are considered distinct problems. But findings published online Wednesday suggest they're related in some way.

"These disorders that we thought of as quite different may not have such sharp boundaries," said Dr. Jordan Smoller of Massachusetts General Hospital, one of the lead researchers for the international study appearing in The Lancet.

That has implications for learning how to diagnose mental illnesses with the same precision that physical illnesses are diagnosed, said Dr. Bruce Cuthbert of the National Institute on Mental Health, which funded the research.

Consider: Just because someone has chest pain doesn't mean it's a heart attack; doctors have a variety of tests to find out. But there's no blood test for schizophrenia or other mental illnesses. Instead, doctors rely on symptoms agreed upon by experts. Learning the genetic underpinnings of mental illnesses is part of one day knowing if someone's symptoms really are schizophrenia and not something a bit different.

"If we really want to diagnose and treat people effectively, we have to get to these more fine-grained understandings of what's actually going wrong biologically," Cuthbert explained.

Added Mass General's Smoller: "We are still in the early stages of understanding what are the causes of mental illnesses, so these are clues."

The Psychiatric Genomics Consortium, a collaboration of researchers in 19 countries, analyzed the genomes of more than 61,000 people, some with one of the five disorders and some without. They found four regions of the genetic code where variation was linked to all five disorders.

Of particular interest are disruptions in two specific genes that regulate the flow of calcium in brain cells, key to how neurons signal each other. That suggests that this change in a basic brain function could be one early pathway that leaves someone vulnerable to developing these disorders, depending on what else goes wrong.

For patients and their families, the research offers no immediate benefit. These disorders are thought to be caused by a complex mix of numerous genes and other risk factors that range from exposures in the womb to the experiences of daily life.

"There may be many paths to each of these illnesses," Smoller cautioned.

But the study offers a lead in the hunt for psychiatric treatments, said NIMH's Cuthbert. Drugs that affect calcium channels in other parts of the body are used for such conditions as high blood pressure, and scientists could explore whether they'd be useful for psychiatric disorders as well.

The findings make sense, as there is some overlap in the symptoms of the different disorders, he said. People with schizophrenia can have some of the same social withdrawal that's so characteristic of autism, for example. Nor is it uncommon for people to be affected by more than one psychiatric disorder.

Online:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60223-8/abstract

Opinion: Elyn R. Saks Successful and Schizophrenic

by Elyn R. Saks, The New York Times, The Opinion Pages, January 25, 2013

Thirty years ago, I was given a diagnosis of schizophrenia. My prognosis was “grave”: I would never live independently, hold a job, find a loving partner, get married. My home would be a board-and-care facility, my days spent watching TV in a day room with other people debilitated by mental illness. I would work at menial jobs when my symptoms were quiet.

Following my last psychiatric hospitalization at the age of 28, I was encouraged by a doctor to work as a cashier making change. If I could handle that, I was told, we would reassess my ability to hold a more demanding position, perhaps even something full-time.

Then I made a decision. I would write the narrative of my life. Today I am a chaired professor at the University of Southern California Gould School of Law. I have an adjunct appointment in the department of psychiatry at the medical school of the University of California, San Diego, and am on the faculty of the New Center for Psychoanalysis. The MacArthur Foundation gave me a "genius grant."

Although I fought my diagnosis for many years, I came to accept that I have schizophrenia and will be in treatment the rest of my life. Indeed, excellent psychoanalytic treatment and medication have been critical to my success. What I refused to accept was my prognosis.

Conventional psychiatric thinking and its diagnostic categories say that people like me don’t exist. Either I don’t have schizophrenia (please tell that to the delusions crowding my mind), or I couldn’t have accomplished what I have (please tell that to U.S.C.’s committee on faculty affairs). But I do, and I have. And I have undertaken research with colleagues at U.S.C. and U.C.L.A. to show that I am not alone. There are others with schizophrenia and such active symptoms as delusions and hallucinations who have significant academic and professional achievements.

Over the last few years, my colleagues, including Stephen Marder, Alison Hamilton and Amy Cohen, and I have gathered 20 research subjects with high-functioning schizophrenia in Los Angeles. They suffered from symptoms like mild delusions or hallucinatory behavior. Their average age was 40. Half were male, half female, and more than half were minorities. All had high school diplomas, and a majority either had or were working toward college or graduate degrees. They were graduate students, managers, technicians and professionals, including a doctor, lawyer, psychologist and chief executive of a nonprofit group.

At the same time, most were unmarried and childless, which is consistent with their diagnoses. (My colleagues and I intend to do another study on people with schizophrenia who are high-functioning in terms of their relationships. Marrying in my mid-40s — the best thing that ever happened to me — was against all odds, following almost 18 years of not dating.)

More than three-quarters had been hospitalized between two and five times because of their illness, while three had never been admitted.

How had these people with schizophrenia managed to succeed in their studies and at such high-level jobs? We learned that, in addition to medication and therapy, all the participants had developed techniques to keep their schizophrenia at bay. For some, these techniques were cognitive. An educator with a master’s degree said he had learned to face his hallucinations and ask, “What’s the evidence for that? Or is it just a perception problem?” Another participant said, “I hear derogatory voices all the time. ... You just gotta blow them off.”

Part of vigilance about symptoms was “identifying triggers” to “prevent a fuller blown experience of symptoms,” said a participant who works as a coordinator at a nonprofit group.

For instance, if being with people in close quarters for too long can set off symptoms, build in some alone time when you travel with friends.

Other techniques that our participants cited included controlling sensory inputs. For some, this meant keeping their living space simple (bare walls, no TV, only quiet music), while for others, it meant distracting music. “I’ll listen to loud music if I don’t want to hear things,” said a participant who is a certified nurse’s assistant. Still others mentioned exercise, a healthy diet, avoiding alcohol and getting enough sleep. A belief in God and prayer also played a role for some.

One of the most frequently mentioned techniques that helped our research participants manage their symptoms was work. “Work has been an important part of who I am,” said an educator in our group. “When you become useful to an organization and feel respected in that organization, there’s a certain value in belonging there.” This person works on the weekends too because of “the distraction factor.” In other words, by engaging in work, the crazy stuff often recedes to the sidelines.

Personally, I reach out to my doctors, friends and family whenever I start slipping, and I get great support from them. I eat comfort food (for me, cereal) and listen to quiet music. I minimize all stimulation. Usually these techniques, combined with more medication and therapy, will make the symptoms pass. But the work piece — using my mind — is my best defense. It keeps me focused, it keeps the demons at bay. My mind, I have come to say, is both my worst enemy and my best friend.

THAT is why it is so distressing when doctors tell their patients not to expect or pursue fulfilling careers. Far too often, the conventional psychiatric approach to mental illness is to see clusters of symptoms that characterize people. Accordingly, many psychiatrists hold the view that treating symptoms with medication is treating mental illness. But this fails to take into account individuals’ strengths and capabilities, leading mental health professionals to underestimate what their patients can hope to achieve in the world.

It’s not just schizophrenia: earlier this month, The Journal of Child Psychology and Psychiatry posted a study showing that a small group of people who were given diagnoses of autism, a developmental disorder, later stopped exhibiting symptoms. They seemed to have recovered — though after years of behavioral therapy and treatment. A recent New York Times Magazine article described a new company that hires high-functioning adults with autism, taking advantage of their unusual memory skills and attention to detail.

I don’t want to sound like a Pollyanna about schizophrenia; mental illness imposes real limitations, and it’s important not to romanticize it. We can’t all be Nobel laureates like John Nash of the movie “A Beautiful Mind.” But the seeds of creative thinking may sometimes be found in mental illness, and people underestimate the power of the human brain to adapt and to create.

An approach that looks for individual strengths, in addition to considering symptoms, could help dispel the pessimism surrounding mental illness. Finding “the wellness within the illness,” as one person with schizophrenia said, should be a therapeutic goal. Doctors should urge their patients to develop relationships and engage in meaningful work. They should encourage patients to find their own repertory of techniques to manage their symptoms and aim for a quality of life as they define it. And they should provide patients with the resources — therapy, medication and support — to make these things happen.

“Every person has a unique gift or unique self to bring to the world,” said one of our study’s participants. She expressed the reality that those of us who have schizophrenia and other mental illnesses want what everyone wants: in the words of Sigmund Freud, to work and to love.

Elyn R. Saks is a law professor at the University of Southern California and the author of the memoir “The Center Cannot Hold: My Journey Through Madness.”

Related article:

http://www.nytimes.com/2011/10/23/health/23livesside.html