Recently, schizophrenia has become a high-profile disease, attributed to well-known victims like John Nash, whose turbulent life has been dramatized by Russell Crowe in "A Beautiful Mind" and historical evidence of depression has led scholars to believe that both Vincent Van Gogh and Abraham Lincoln suffered from the disease [1]. Schizophrenia, a psychologically degenerative illness, is characterized by reduced activity in the left front-temporal brain and by frequent hallucinations, and alters the mind and perceived realities of one out of every one hundred people worldwide [2].

A recent study by the Institute of Psychiatry revealed the relationship between brain abnormalities, schizophrenia, and social inefficacy. Diagnosed schizophrenics often find it difficult to see the world from differing perspectives, as well as to feel empathy for others. The consequences of this social dysfunction are grave: victims often cannot relate to people, make friends, or remain employed. Dr. Tonmoy Sharma, a leading researcher working to develop treatment for this dehumanizing affliction, states that the ability to "recognize emotions is what makes us human" in his December 2002, study published in the American Journal of Psychiatry [3].

The exact cause of schizophrenia is currently unknown, but studies concerning the biochemistry, molecular biology, genetic predisposition, and cerebral blood flow (CBF) of the disease are underway. CBF studies assert that most people, when thinking or speaking, show an increase in the activity of the frontal lobes of their brains that is offset by a decrease in the activity of the temporal lobes, which are responsible for receiving and transmitting auditory information [3]. PET scans of the brains of schizophrenics, in contrast, have revealed no changes in these areas, which has led researchers to believe that the brain of a patient with schizophrenia is constantly bombarded by sensory stimuli. As a result of this sensory overload and imbalances in brain chemistry, schizophrenics often experience hallucinations that they mistake for reality. Many studies have noted significant neurochemical imbalances among patients, and thus neurotransmitterrs that allow communication between brain cells have been scrutinized as possible agents of schizophrenia [3].

Erminio Costa, the scientific director of the Psychiatric Institute at the University of Illinois at Chicago, has identified reelin as a protein essential for the migration and differentiation of Human Neural Stem Cells (HNSCs) during the final stage of neural development, and collaborated with other scientists in the proposition of a "two hit" model of schizophrenia [4]. Initially, Costa speculates, a defect in the reelin gene results in the misplacement of neurons, which establishes a certain "genetic vulnerability" that will, in conjunction with other factors, result in the expression of the psychosis. Costa believes that later on in life (the average onset of schizophrenia occurs between the ages of 16 and 25), during the final part of brain maturation, these genetic defects resurface in full-blown schizophrenia.

HNSCs are significant in that they contribute to the neuroplasticity of the brain, which allows humans to respond and adapt to environmental clues throughout adult life. Costa's experimental results indicate that sixty percent less reelin exists in the post-mortem brains of sixty schizophrenic patients, leading him to believe that reelin plays a substantial role in the differentiations of HNSCs, and thus the functioning of the mature brain [5]. Furthermore, the research of UIC scientists has indicated that reelin may play a key role in the biochemical mechanisms active in memory functions and in the process of learning [3].

In order to test his hypothesis, Costa employed a serum-free HNSC culture system for in vitro differentiation in his experiments so that he could monitor the molecular interactions of the NSCs during migration and differentiation in the brains of three-month-old male mice. Upon transplanting NSCs into reeler mice (Costa's name for mice lacking the reelin protein) and wild-type mice, Costa observed that, while the wild-type mice experienced normal migration and movement of neuron and glial cells, the implanted NSCs in the reeler mice were confused and, consequently, did not differentiate and mature in the brain; in fact, the only cells that did migrate were reelin-positive HNSCs. Consequently, the wild-type mice experienced normal cognitive development due to reelin-facilitated neural cell movement. Further analysis revealed that the transplantation of stem cells into senile rat brains actually improved the rats' cognitive abilities [5].

UIC researchers hypothesized that the endogenous stem cells of reeler mice might have migratory deficiencies upon analyzing their stem cell populations. After analyzing stem cell movement in reeler mice, however, a lack of BrdUrd-positive stem cells in the hippocampus and olfactory bulbs of the brain was noted, which led researchers to speculate that schizophrenia may be caused by a reelin-related deficiency that interferes with stem cell migration [5].

Costa's pioneer research on the reelin protein is significant because, before his research, its function in brain chemistry was a mystery. Currently it is believed that reelin, the neuro-cellular organizer, "allows neurons to pass between subplate neurons; regulates neuronal movement by changing microtubule organization; maintains a balance of BrdUrd-positive cells in the olfactory bulb and hippocampus; and coordinates cell migration in HNSCs imperative in brain development and inter-lobe communication." Therefore, it was concluded that both reelin-assisted migration and the reelin transduction-signaling pathway are essential in NSC migration [5].

While the difficult quest for treatment of schizophrenia continues to daunt researchers, an early diagnosis and treatment of the disease vastly improves prognosis [2]. Similarly, although significant advances have been made to uncover the origin of schizophrenia, no concrete conclusions have been made. Costa's research on reelin, however, has been of paramount importance in psychological research: he has succeeded in expanding the present base of knowledge on schizophrenia, as well as in generating a plausible avenue which may make it possible for victims of schizophrenia to be biochemically treated in the future.

Tara is a first-year student majoring in biochemistry. She aspires to enter the field of medicine.