Schizophrenia SyndromeADONIS SFERA, MD

Two or more of the following symptoms: Delusions Hallucinations Disorganized speech (e.g frequent derailment or

incoherence Grossly disorganized or catatonic behavior Negative symptoms (alogia, avolition, affective flattening).

Social/occupational dysfunctionDuration: at least 6months

Schizophrenia

Episodic With Interepisode Residual Symptoms

Episodic with no Interepisode Residual Symptoms

Single episode in Partial Remission Single Episode in Full Remission Other Unspecified Pattern

Classification of longitudinal course

Paranoid Type Disorganized Type Catatonic Type Undifferentiated Type Residual Type

Subtypes

Genes and the Environment

Etiology: Multifactorial

Classic Autosomal Dominant A single abnormal gene expresses an abnormal product,

with the consequence of causing an inherited disease in a classic autosomal dominant manner.

Mental illness is not autosomal dominant

According to this theory, single abnormal gene can also cause a mental illness.

An abnormal gene would produce an abnormal gene product, which in turn would lead to neuronal malfunction that directly causes a mental illness.

No such gene has been identified, and there is no longer any expectation that such a discovery might be made.

Classic Theory of Inherited Disease

Is Schizophrenia Due to Mutant Genes?

This theory postulates that, rather than genes causing mental illness, genes instead cause individual symptoms, behaviors, personalities or temperaments.

According to this theory an abnormal gene encoding for a symptom, behavior or trait would cause neuronal malfunction leading to that symptom, behavior or trait.

No genes for behaviors or personality have been identified and there is no longer an expectation that such a discovery might be made.

Symptom Endophenotype Model

Mental illness cannot be explained by the endophenotye model

Genes do not encode for mental illnesses, behaviors or personalities. Genes encode for proteins.

Genes may produce genetically altered proteins that code for subtle molecular abnormalities, which in turn may be linked to the development of psychiatric symptoms.

Genes may code for an abnormality in the: neuro-developmental process synthesis or activity of enzymes Transporter proteins receptors components of signal transduction synaptic plasticity machinery and other neuronal components.

Each subtle molecular abnormality may convey risk for the development of mental illness rather than directly causing a mental illness.

Subtle Molecular Abnormalities Theory

Mental illness may be explained by genes causing subtle molecular abnormalities

There is no gene for schizophrenia, bipolar disorder, depression or anxiety and there will never be one.

Genes do not code for psychiatric illnesses or for symptoms of psychiatric illnesses.

Genes operate at a very basic cellular level. They code for molecules and cells such as neuronal cytoskeleton, neuronal migration proteins, myelin, cellular adhesion molecules, and dendritic cone growth.

Genes do not respect the boundaries of psychiatric disorders. For instance most risk genes for schizophrenia are present also in bipolar disorder, schizoaffective disorder, Alzheimer’s disease and anxiety.

Genes Do not Cause Psychiatric Illness

Some genes increase the risk of Schizophrenia

More than a dozen genes have been identified that increase the risk for schizophrenia.

Neuronal Connectivity Is regulated by four genes: BDNF,

Dysbindin, DISC 1 and neuregulin.

These genes affect neurogenesis, neuronal migration, myelination and development of the dendritic tree.

Not convinced yet that genetics are important?

Epigenetics

Once nurture seemed clearly distinct from nature. Now it appears that our diets and lifestyles can change the expression of our genes. How? By influencing a network of chemical switches within our cells collectively known as the epigenom.

This new understanding may lead us to potent new medical therapies.

Epigenetic cancer therapy, for one, already seems to be yielding promising results.

Epigenetic treatment of mental illness is just around the corner.

 

Nature vs. Nurture

What is an Epigenom?

An Epigenome consists of a record of the chemical changes to the DNA and histone  proteins of an organism.These changes can be passed down to offspring.

For the most part, every cell in our body contains exactly the same genes, but inside the individual cells some genes are activated while others are silenced.

When genes are active they are capable of being translated into proteins. When genes are silent, they are inaccessible for translation into proteins.

Active and Silenced Genes

Epigenomics is the science of activating or silencing genes at the level of transcription or translation.

A Silenced Gene is not Transcribed, Translated, or Expressed

Genes can be activated or silenced :

-By modifying the histone proteins (H3 or H4)

-By modifying the DNA (methylation at CpG promoters)

-By small interfering RNAs

Silencing or Activating Genes

Epigenome and the Limbic Music

Systems Neuroscience

Studies the biological substrate underlying cognition.

A branch of physiology and neuroscience brain networks:

1. think(cognition)2. emotion (meaning)3. motivation (goals)

Cognitive Neuroscience

Cognition Working memory (dorsolateral prefrontal cortex) Attention (prefrontal cortex, parietal cortex) Executive function (medial prefrontal cortex)

Emotion Medial prefrontal cortex Subgenual ant. cingulate cortex Amygdala

Motivation Ventral tegmental area Nucleus accumbens Prefrontal cortex

The Mind and Psychiatry

Computation: Information Processing -

Brain is the hardware, mind is the softwareAdvances in microscopy, stem cells and imaging: 150 billion neurons Each neuron up to 900 synapses Number of connections - trillions Connections organized in hubs and networks

Large Brain Networks

Large Scale Brain Networks in Cognition, emerging methods and principles;Steven Bresler, Vinod Menon;

Trends in cognitive science, Vol 14,June 2010, pages277-290;

http://dx.doi.org/10.1016/j.tics2010 .04.004

The salience network initiates dynamic switching between the central-executive and default-mode networks, and mediates between attention to endogenous and exogenous events.

The default network

2. Dorsomedial prefrontal cortex (dmPFC

3. Anterior middle cingulate cortex (ACC):

4. Posteromedial cortices (PMC):

5. Inferior parietal lobule (IPL):

6. Hippocampus

1. Ventromedial prefrontal cortex (vmPFC):