Posts Tagged ‘corpus callosum’

Schizophrenia Brain

Larry H. Bernstein, MD, FCAP, Curator


Neuroimaging studies using fMRI and PET to examine functional differences in brain activity in patients with schizophrenia have shown that differences seem to most commonly occur in the frontal lobes, hippocampus, and temporal lobes. These differences are heavily linked to the neurocognitive deficits which often occur with schizophrenia, particularly in areas of memory, attention, problem solving, executive function and social cognition.

Earlier studies from the researchers reported evidence suggesting that schizophrenia is not a single disease but a group of eight genetically distinct disorders, each with its own set of symptoms. Results found that distinct sets of genes were strongly associated with particular clinical symptoms.

The current study investigates the brain’s anatomy and shows that there are distinct subgroups of patients with a schizophrenia diagnosis that correlates with symptoms.  This also explains the difficulty in past studies to identify a single set of biomarkers for a single type of schizophrenia.

The current study evaluated scans taken with magnetic resonance imaging (MRI) and a technique called diffusion tensor imaging in 36 healthy volunteers and 47 people with schizophrenia. Results show that the scans of patients with schizophrenia had various abnormalities in portions of the corpus callosum, a bundle of fibers that connects the left and right hemispheres of the brain and is considered critical to neural communication. Characteristics across the corpus callosum revealed in the brain scans matched specific symptoms of schizophrenia. Patients with specific features in one part of the corpus callosum typically displayed bizarre and disorganized behaviour. In other patients, irregularities in a different part of that structure were associated with disorganized thinking and speech and symptoms such as a lack of emotion; other brain abnormalities in the corpus callosum were associated with delusions or hallucinations.  The lab conclude that their findings provide further evidence that schizophrenia is a heterogeneous group of disorders rather than a single disorder.

The team surmise that they didn’t start with people who had certain symptoms and then look to see whether they had corresponding abnormalities in the brain. They note that they just looked at the data, and the patterns began to emerge. They go ony to add that this kind of granular information, combined with data about the genetics of schizophrenia, one day will help physicians treat the disorder in a more precise way.

Many genes responsible for the creation of synaptic proteins have previously shown to be strongly linked to schizophrenia and other brain disorders, however, until now the reasons have not been understood.  Now, researchers from Cardiff University have identified a critical function of what they believe to be schizophrenia’s ‘Rosetta Stone’ gene that could hold the key to decoding the function of all genes involved in the disease.  The team state that the breakthrough has revealed a vulnerable period in the early stages of the brain’s development that they hope can be targeted for future efforts in reversing schizophrenia.  The study is published in the journal Science.

The gene identified in the current study is known as ‘disrupted in schizophrenia-1’ (DISC-1). Earlier studies have shown that when mutated, the gene is a high risk factor for mental illness including schizophrenia, major clinical depression and bipolar disorder.  The aim of the current study was to determine whether DISC-1’s interactions with other proteins early on in the brain’s development had a bearing on the brain’s ability to adapt its structure and function, also known as ‘plasticity’, later on in adulthood.

In order for healthy development of the brain’s synapses to take place, the DISC-1 gene first needs to bind with two other molecules known as ‘Lis’ and ‘Nudel’.  The experiments in mice revealed that by preventing DISC-1 from binding with these molecules prevents cortical neurons in the brain’s largest region from being able to form synapses.  The ability to form coherent thoughts and to properly perceive the world is damaged as a consequence of this.

Preventing DISC-1 from binding with ‘Lis’ and ‘Nudel’ molecules when the brain was fully formed had no effect on its plasticity. However, the researchers were able to pinpoint a seven-day window early on in the brain’s development, one week after birth, where failure to bind had an irreversible effect on the brain’s plasticity later on in life.

The researchers hypothesize that DISC-1 is schizophrenia’s Rosetta Stone gene and could hold the master key to help unlock the understanding of the role played by all risk genes involved in the disease.  They go on to add that they have identified a critical period during brain development that will assist in testing whether other schizophrenia risk genes affecting different regions of the brain create their malfunction during their own critical period.


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