Neuroimaging study begins to map alterations in human brain connections for severe schizophrenia.


People with a severe form of schizophrenia have major differences in their brain networks compared to others with schizophrenia, bipolar disorder and healthy individuals, a new study from the Centre for Addiction and Mental Health (CAMH) shows.  The team state that finding ways to help this particular group of people with schizophrenia is a priority as recovery is unlikely, even up to 20 years after the initial diagnosis. Social isolation, lack of work and relationships, and chronic disability are very common.

Schizophrenia, which affects one in 100 people, is generally known for symptoms of delusions and hallucinations, which can be treated with antipsychotic medications. However, lack of motivation and social withdrawal are also characteristic symptoms of the illness. These are known as negative symptoms.  Approximately one in five people with schizophrenia experience these negative symptoms in a pronounced way, state the researchers. At this point, there is no treatment for negative symptoms, yet they have the greatest impact on a person’s daily functioning once the psychosis is managed.

The team explain that the value of having a biological, brain-based indicator is that it may help identify this group of patients when they initially present for treatment of psychosis. Otherwise it can take years to determine social disability through clinical observation.

The current study involved magnetic resonance brain imaging (MRI) with 128 people with schizophrenia and 130 healthy individuals at two sites, and with 39 patients with bipolar disorder and 43 healthy individuals at a third site. Patients with bipolar disorder also experience psychotic symptoms but not negative symptoms, so these patients served as an additional comparison group. The three sites were at CAMH, the Zucker Hillside Hospital and the Central Institute of Mental Health in Mannheim.

The researchers used a unique approach called network analysis to study the overall network density, or level of connectivity, in the brain.  The team found alterations in a number of relationships between brain regions among those with more severe schizophrenia compared with the other groups, including those with less severe schizophrenia.  The data providing strong evidence that schizophrenia is not just one brain disorder.

The study also confirms previous research from the team showing changes in the white matter tissues connecting those same regions in the brain, among those with more severe schizophrenia.

The team state that these impaired networks are important to the brain processes related to negative symptoms and social function that patients experience. Based on these findings the investigators will conduct a multi-centre study of a large number of people with schizophrenia to establish the full range of impairment in brain circuitry that predicts social impairment.

Through this current research, specific brain circuits can be targeted to develop new therapeutic approaches for negative symptoms and social impairment. Such studies are now underway at CAMH using virtual reality technology and brain stimulation.

Source:  Centre for Addiction and Mental Health (CAMH)

 

Simulation of the mammal thalamocortical system with 2 million neurons (Izhikevich phenomenological neuron model, multiple compartments) with 282 million synapses using SpikeFun demo simulator (v0.67).  Simulation models AMPA, NMDA and GABA receptor kinetics, myelinated and non-myelinated axons, axonal bifurcations as well as short and long term synaptic plasticity (STDP) using model of Markram et. al.  Neurons are created using data gathered by analysis of cortical neurons located in the primary visual cortex of a cat (Binzegger et al., 2004). Axonal projections through white-matter are guided using Diffusion Spectrum Imaging (DSI) imaging of healthy human adults. Pyramidal axons bifurcate into multiple projections depending on the cell sub-type and project ipsilaterally or contralaterally to distant cortical zones / thalamus.  Credit:  Ivan Dimkovic 2013.  http://www.dimkovic.com.

Simulation of the mammal thalamocortical system with 2 million neurons (Izhikevich phenomenological neuron model, multiple compartments) with 282 million synapses using SpikeFun demo simulator (v0.67). Simulation models AMPA, NMDA and GABA receptor kinetics, myelinated and non-myelinated axons, axonal bifurcations as well as short and long term synaptic plasticity (STDP) using model of Markram et. al. Neurons are created using data gathered by analysis of cortical neurons located in the primary visual cortex of a cat (Binzegger et al., 2004). Axonal projections through white-matter are guided using Diffusion Spectrum Imaging (DSI) imaging of healthy human adults. Pyramidal axons bifurcate into multiple projections depending on the cell sub-type and project ipsilaterally or contralaterally to distant cortical zones / thalamus. Credit: Ivan Dimkovic 2013. http://www.dimkovic.com.

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