Brain circuit needed to incorporate new information may be linked to schizophrenia

Good news!

"... MIT neuroscientists have now identified a gene mutation that appears to give rise to this type of difficulty. In a study of mice, the researchers found that the mutated gene impairs the function of a brain circuit that is responsible for updating beliefs based on new input.

This mutation, in a gene called grin2a, was originally identified in a large-scale screen of patients with schizophrenia. The new study suggests that drugs targeting this brain circuit could help with some of the cognitive impairments seen in people with schizophrenia. ...

More recently, researchers ... used a different strategy, known as whole-exome sequencing, to reveal gene mutations linked to schizophrenia. This technique sequences only the protein-coding regions of the genome, so it can reveal mutations that are located in known genes.

Using this approach on about 25,000 sequences from people with schizophrenia and 100,000 sequences from control subjects, the researchers identified 10 genes in which mutations significantly increase the risk of developing schizophrenia. ..."

From the abstract:

"Belief updating is thought to be impaired in schizophrenia, leading to delusions. The neural substrates underlying belief updating are unknown, in part due to a lack of appropriate animal models and behavior readouts.

We generated mice bearing a schizophrenia-associated point mutation in Grin2a (Grin2aY700X+/−) and developed a computationally trackable foraging task to assess belief-driven decision strategies in mice. Grin2aY700X+/− mice performed less optimally than their wild-type (WT) littermates, due to unstable cognitive states related to noisy representation of dynamic task values. We identified the mediodorsal (MD) thalamus as being hypofunctional in Grin2aY700X+/− mice and showed that MD neurons encode dynamic task values and cognitive states in WT mice. Optogenetic inhibition of MD neurons in WT mice phenocopied Grin2aY700X+/− mice and enhancing MD activity rescued task deficits in Grin2aY700X+/− mice. Together, our study identifies the MD thalamus as a key node for schizophrenia-relevant cognitive dysfunction and a potential target for future therapeutics."

Brain circuit needed to incorporate new information may be linked to schizophrenia | MIT News | Massachusetts Institute of Technology "Impairments of this circuit may help to explain why some people with schizophrenia lose touch with reality."

Reduced mediodorsal thalamus activity underlies aberrant belief dynamics in a genetic mouse model of schizophrenia (no public access)

A common biomarker of schizophrenia and bipolar disorder revealed

Good news!

"... Researchers ... reviewed and analyzed the findings of previous studies to further test this hypothesis and validate the existence of a psychosis spectrum of disorders. Their paper, published in Nature Mental Health, outlines common brain features in patients with schizophrenia and BD, particularly differences in the integrity of white matter. ...

Most notably, they observed shared white matter alterations in a region called the corpus callosum. This is a brain structure that connects the brain's left and right hemispheres.

"This alteration was observed across the entire psychosis spectrum, rather than being limited to a single diagnosis," said Saccaro. "Importantly, these findings remained significant (and in some cases became clearer) after accounting for age and sex, suggesting they are unlikely to be explained simply by illness duration or aging. This supports the idea that disruptions in brain connectivity may represent a core biological feature of psychosis." ..."

From the abstract:

"Psychotic and mood disorders, including schizophrenia and bipolar disorder, are increasingly viewed as part of a psychosis spectrum disorder (PSD) continuum, sharing genetic and neurobiological features.

This systematic review and meta-analysis examines fractional anisotropy and mean diffusivity using diffusion tensor imaging in PSD. Across 96 studies (N = 4,424 PSD, N = 5,004 controls for fractional anisotropy; N = 1,607 PSD, N = 1,709 controls for mean diffusivity), fractional anisotropy reductions were consistently observed in the corpus callosum, whereas mean diffusivity increases were found in cortico-spinal projections.

Controlling for age and gender strengthened these findings, suggesting that they contribute to PSD pathophysiology rather than reflecting disease progression. Subgroup analyses revealed overlapping but distinct patterns in schizophrenia and bipolar disorder. These findings support a transdiagnostic model of psychosis, with corpus callosum abnormalities as a potential biomarker. Future longitudinal studies are needed to clarify causality and clinical implications."

A common biomarker of schizophrenia and bipolar disorder revealed

A systematic review and meta-analysis of transdiagnostic impairments in white matter integrity across the psychosis continuum (no public access)

Reduced FA, psychosis spectrum, TBSS studies only, corrected for age and gender.

One surprising psychosis treatment that works: learning to live with the voices.

Good news!

"Noah Hudnut’s family had already spent $150,000 on his psychiatric care when police hauled him to the emergency room in handcuffs. On top of the family’s expenses, Hudnut’s insurance company was billed at least $1,000 a day for his hospitalizations. Yet, his psychosis persisted. 

Following his release, his family enrolled him at California OnTrack. The classroom-style treatment teaches patients to carry on their lives despite imagined voices, hallucinations and false memories. His 14 months of treatment cost a fraction of what the family and insurers had paid for his care over the previous six years. So far, it has been successful."

The Wall Street Journal What's news

One Surprising Psychosis Treatment That Works: Learning to Live With the Voices

California OnTrack programs

Diagnosing Psychological Disorders In Children

Disclaimer

I have no expertise whatsoever in this area. However, I am not entirely without personal experience. Psychological disorders and their medical treatment is a subject of interest to me. Further, I am only trying to briefly summarize certain thoughts that came to me when reading various articles related to this complex subject. I have intentionally not sourced this article very well for sake of brevity and time.

An Increasing Trend

It appears there has been an increasing trend in recent decades to diagnose children with different forms of psychological disorders (e.g. ADHD, Autism, psychosis etc.). One can almost get the impression of an ongoing, unprecedented epidemy or is it a phenomenon.

I have included Autism here as well, because the unusual outward behavior and the significant expansion of its definition to autism spectrum disorder. Latter development is usually a sign that doctors are clueless when they attach terms like “spectrum”. In my opinion, there is a significant chance for misdiagnosis. Yes, the US government describes Autism on their PubMed website as “… a physical condition linked to abnormal biology and chemistry in the brain. The exact causes of these abnormalities remain unknown, but this is a very active area of research. There are probably a combination of factors that lead to autism. Genetic factors seem to be important.”. Well is this not true of other psychological disorders as well?

Possible Explanations

Doctors have over time become better in diagnosing such disorders, which have been in the past very difficult or impossible to diagnose or children went simply untreated. Latter assertion is quite true for psychology/psychiatry in general and not only in the past. Ambiguous disorders like psychological disorders are great business for doctors. To use a hyperbole, doctors since time immemorial like to expand and deepen their diagnostic tools almost to the point to declare everyone in need of medical treatment who enter their offices. Illnesses are infinite.

In recent times, more focus and money was assigned to this subject. Huge media attention has spread, parents are primed to be alert. Stigma, taboos are reduced, acceptance is improved. E.g. in the US, special needs education has proliferated receiving lots of money and special teachers. The more special needs children the better for school funding and teacher salaries.

There is the distinct possibility that a self-feeding vicious or virtuous cycle was entered in connection with this subject. And it will take perhaps decades before reasonable judgment returns.

Genius And Madness

I believe, most people have heard about the close link between genius and madness. Two recent movies “A Brilliant Beautiful Mind” (about John Nash) or “The Aviator” (about Howard Hughes) captured this topic quite well.

I highly recommend to watch both movies, in particular the first one, because it shows you how this brilliant mathematician and his wife suffered from the medications he was given and how he himself defeated the demons. The way he defeated the demons is, I believe, sometimes also prescribed by doctors even for children to learn how to cope with demons etc. in a playful way.

Children that are perceived as not “normal” may have special talents and gifts unlike other children. Early, aggressive treatment may only achieve forced conformity to “normal” and kill these special talents or gifts that would otherwise develop to the benefit of the child and the world. As they say if you can dream it you can achieve it. Vivid imagination or unusual behavior may after all be completely harmless and beneficial for the child’s development.

I am far from implying here that any child with a diagnosed or perceived psychological disorder is going to be the next genius. This would be a colossal misunderstanding.

Suggestions Or Food For Thought

Parents are naturally very concerned if they observe anything perceived to be not normal about their children. Naturally, parents seek help from a doctor. Given the great ambiguity of this subject, more than one doctor should be consulted and doctors of different specializations or of different approaches.

Keep in mind, psychology and psychiatry still remain very inexact fields of medicine. It’s more charlatanry than medicine.

It is very understandable that parents seek a rational explanation and the best medical treatment for their children, but be alert to the pitfalls. Yes, parents are very concerned about the possibly negative prospects of their child like antie social life/behavior, unsteady professional career, alcoholism, drug abuse, failed relationships, crime etc. that are commonly associated with psychological disorders. However, an overreaction to the diagnosis may have the same or similar outcome.

Depending on the severity or circumstances, I would not easily have my child being treated especially not over an extended period of time with certain psycho pharmaceutical medications, e.g. mood stabilizers, anti convulsants. Sometimes just close observation, change of daily routines, or other behavioral approaches etc. are perhaps better.

Some research seems to indicate that abnormal, psychotic like behavior in childhood disappears even without any treatment as they reach adulthood or later in life.

What are the long-term implications for our children if so many kids are classified as having a disorder and are in need of treatment? I do not mean to be in denial, but I want to caution.