A Paranoid’s Guide to HistoryINRECO doc #2Section 818.08pgPsychology Division
Schizophrenia and its Neurological Connections
Schizophrenia is a multi-symptom, neural-psychological
disease with an elusive pathology. There have been
increasing discussions as to the accuracy and functionality
of the term schizophrenia applied to such a wide range
symptoms (Andreasen, 1999; Walters). One reason for this
is that the behaviors that characterize schizophrenia can
be significantly divergent, as evidenced by the categories
and types listed in the DSM-IV. On one hand, wildly
inappropriate aggressive behavior coupled with other
positive symptoms can garner the classification, as can
catatonic behavior coupled with negative symptoms (Braff,
1999; Andreasen, 1999). Faced with this dilemma,
psychologists have a daunting scientific task: to locate
the neurological origins for schizophrenia. It is possible
that the increased sophistication of the tools available
for examining brain functions will produce more nuanced
diagnoses, classifications and treatments.
The history of schizophrenia and mental illness in
general, sheds some light on the debates surrounding
schizophrenia. The mentally ill have always been with us.
Evidence of the symptoms goes as far back as Pharaonic
Egypt. The ancient Greeks referred to similar conditions
as “divine madness,” granting a supernatural origin. The
significant issue in this case is what constitutes a
disease. Unlike people with heart or kidney dysfunction,
schizophrenia is not physically life threatening. This is
not to discount the untold suffering of the 1% of the
population afflicted with this condition.(Walters) To make
matters worse, in industrialized countries a large
percentage of the homeless are schizophrenic, thus pushing
the condition even further out toward the fringes of
The term schizophrenia was originally coined in 1911
by a Swiss psychologist Eugen Bleuler and was meant to
describe the mental disconnection of the patient from
reality. Since Bleuer’s categorization psychologists have
sought to uncover the relationship between schizophrenia
and the brain. (Walters) While there is little doubt as to
the origin of schizophrenia somewhere in the brain, it is
unsettled as to what prepares the brain for the onset of
the disease. Various causes have been suggested: genetics,
in- and ex-utero viral infections, stress, abnormal
development and environmental conditions. Regardless of
the initial causal factors, schizophrenics share a common
dysfunction in the cognitive and emotional brain functions.
Several different chemicals have been indicated in the
condition: dopamine, glutamate, serotonin, acetylcholine,
GABA and norepinephrine. These connections have been
discovered over the years through the administration of
drugs with known effects. In the case of dopamine, the use
of Thorazine lead to the belief that schizophrenia might be
located in the pre-frontal cortex (PFC). Scientists came
to this conclusion because of the effect on patients and
the high concentration of dopamine receptors in that part
of the brain. Additionally, the symptomatic
disorganization of thought in schizophrenics is credited to
a deficit in working memory, a primary function of the
Newer models of schizophrenic pathopsychology posit
forms of systemic neural circuit failure. Two
possibilities seem to offer meaningful theoretical
advances. Both approach the problem of schizophrenia by
characterizing the problem as an emergent system. One
hypothesis, which has been developing since the late 1970s,
focuses on the corollary discharge, feed forward systems of
thought (CD-FF) (Feinberg, 1998). The other approach
centers on the cortico-cerbellar-thalamic-cortical circuit
(CCTCC) as the genesis of schizophrenia (Andreasen, 1999).
These systems have the advantage of searching not for a
single anatomical factor in schizophrenia, but rather
examining the multiple processing systems of the brain.
This approach fits with the latest studies that show deeply
interconnected, broad regions of the brain are active
during psychotic or hallucinatory episodes(Silbersweig,
1995). This is significant because it reveals that
schizophrenic delusions are real in as much as there is
corollary brain activity. Both visual and auditory
hallucinations were associated with activity in visual and
auditory association cortices (Silbersweig, 1995).
The schizophrenic experience is so all-encompassing
that, when fully active, it hijacks consciousness. It is
perhaps this multi-dimensional aspect of the disease that
lead researchers to the CD-FF and CCTCC models. Empirical
evidence of brain activity helps understand how the neuro
circuitry of schizophrenics gives rise to its symptoms.
Schizophrenics have under-functioning mechanisms in a wide
range of mental activity: perception, social behavior,
language use, motor skills, emotional and cognitive
inference in addition to psychosis (Andreasen, 1999).
Andreasen points out that there is likely a connection
between the motor coordination “feed back loop” created by
the thalamus the cerebral cortex and the cerebellum
creating CCTCC and cognition. This system provides for a
constant flow of neural activity that synchronizes physical
actions. The process is compared to the memory function in
computers by the use of the term “on-line.” This is an apt
analogy; for a computer to work smoothly it must be able to
process huge amounts of divergent and multifaceted
information in the form of electric digital circuitry and a
binary communications system, much like the human brain.
The CCTCC model uses the fact that a disruption of the
motor function feed back loop leads to physical “dysmetria”
and applies the same principal to the cognitive deficits of
schizophrenia (Andreasen, 1999). Schizophrenic cognitive
dysmetria could arise from a similar disruption in the
“sequencing component of mental activity” (Andreasen,
1999). Earlier, Andreasen made the case that the thalamus
was significant to the schizophrenia’s neuropathology. The
CCTCC includes the thalamus plus the cerebellum and the
prefrontal cortex as part of a multiprocessing system
responsible for monitoring and coordinating sensory input,
perception, cognition, and action (Andreasen, 1999; Braff,
The CD-FF characterization of schizophrenia hits on
some of the same brain regions and processes as the CCTCC.
It also links motor functions to the processes of higher
cognition. According to Feinberg, “the pathophysiology of
schizophrenia lies in the integrative circuits of basal
ganglia, thalamus and frontal cortex.” (Feinberg, 1998)
Additionally the CD-FF makes connections between the types
of hallucinations of schizophrenics and their “cross-
cultural” nature. These types of psychic events also call
into question the most basic human concepts of self and
consciousness: How are thoughts generated and what is the
relationship between the brain and thinking? Regardless of
the sophistication of the tools of observation, the
Schizophrenics seem to be afflicted by a misfiring or
dysymmetry in the processing and coordination of physical,
sensory and mental perception. Since these processes
themselves do not occur as atomized functions in “healthy”
brains, why then should their dysfunction not also be
multilateral. The disruptions called for in the CCTCC and
CD-FF approaches could also account for many of the more
striking features of schizophrenia such as auditory
hallucinations. The inability to recognize their own
thoughts and actions leads schizophrenics to attribute them
to external sources.(Mathalon, 2002) It is this basic
disconnection from self and reality that lead to the use of
the word schizophrenic in the first place.
The psychological study of schizophrenia and psychotic
disorders in general have made momentous strides in the
past century. There have also been significant missteps
along the way. The asylums and treatment of the nineteenth
century were barbaric and inhumane. But how might our
continued use of Electro-shock therapy and powerful
chemical restraints, not to mention the plight of the
undiagnosed or under-treated mentally ill, look to our
counterparts in the future. Unless our scientific inquires
and experimentation maintain a humanistic and empathetic
outlook, and society devotes the resources necessary to
treating the most helpless, our own negligence and
Andreasen, Nancy C. MD A Unitary Model of Schizophrenia,Archives of General Psychiatry, 1999, Vol. 56 No 9
Braff David L. MD, Commentary, Connecting the “Dots” ofBrain Dysfunction in Schizophrenia: What Does the PictureLook Like?, Archives of General Psychiatry, 1999 Vol. 56No 9
Feinberg, Irwin, Schizophrenia – a disorder of thecorollary discharge systems that integrate the motorsystems of thought with the sensory system ofconsciousness, The British Journal of Psychiatry, 1999,Vol. 174 No. 3
Mathalon, Daniel, Response Monitoring Dysfunction inSchizophrenia: An Event Related Brain Potential Studies,Journal of Abnormal Psychology, 2002, Vol. III No.1-22
Silbersweig, D.A., Letter. A Functional Neuroanatomy ofHallucinations in Schizophrenia,1995, Nature Vol. 378 No. 9
Walters, Rhodri, Schizophrenia: A cyclical andheterogeneous dysfunction of cognitive and sensoryprocessing? www.cellscience.com/shdss2.html
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