1. BRAIN’S MOLECULAR VELCRO
Let’s look at some cool proteins called cadherins.
These proteins form a veritable molecular Velcro that keeps
the neurons adhering to each other. Indeed without
cadherins there would be no contact between brain cells and
no synapses.
Cadherins provide the glue that holds the neurons together

2. The cadherins have to work hand in hand with the proteins
of the neuronal cytoskeleton, especially actin and the
microtubules in order to ensure proper cell to cell contact.
CADHERINS WORK TOGETHER WITH THE PROTEINS OF THE
CYTOSKELETON TO ENSURE CELL SHAPE AND CELLULAR
ADHESION
A defect of the cytoskeleton or cadherins could cause the
neurons to collapse like a popped balloon. This would lead
to the inability of the cadherins to keep the cells in contact
with each other. Indeed the molecular Velcro would fail and
the synapses would break as well.

3. Reelin is another cool extracellular protein that effectively
laminates the outer surfaces of the neurons. It controls the
function of cadherins. And not only that, but also helps the
neurons migrate during early development.
Why do we care about all this?
The reasons we might care are the following:
1. Many discovered genes that are associated with
schizophrenia, bipolar disorder or autism spectrum
disorders code for the proteins of the cytoskeleton,
reelin or cadherins (DISC 1, Neureglin 1, DTNBP1,
RGS4, (Tsuyoshi Hattory “Psychosis and Adhesion
Molecules”).

4. FOUR SCHIZOPHRENIA RISK GENES
2. Defects of cytoskeleton proteins are involved in other
disorders manifested by psychosis such as Alzheimer’s
or Huntington’s disease, in addition to schizophrenia,
bipolar disorder and autism spectrum disorder.
CYTOSKELETAL PROTEINS

5. 3. Reelin gene was found to be defective in schizophrenia
as well as the cytoskeletal proteins. (Cátia M Teixeira
Neuropsychopharmacology (2011) 36, 2395–2405;
doi:10.1038/npp.2011.153; published online 3 August 2011.).
Reelin also has a function in neuronal migration and
maturation.
4. Research data demonstrate that there is no active cell
death (apoptosis) in schizophrenia, as no caspase 3 can
be detected. In spite of this, other markers of
neurodegeneration are present such as increased
BAX/Bcl-2 ratio.

6. CASPASE 3 ACTIVATION IS ABSENT IN SCHIZOPHRENIA
In other words all that we learned about schizophrenia from
the human genom project was that genes associated with it
code for cytoskeletal proteins, neuronal migration, neuronal
adhesion and cell lamination. Indeed only the COMPT gene
is associated with dopamine.
Is it possible that schizophrenia is all about neuronal
orthopedics?
Is it possible that psychosis is just a common manifestation
of various neuronal architectural defects? Just like fever is
the common manifestation of various inflammatory
processes.
ADONIS SFERA, MD