Schizophrenia and Major Depression

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RESPONSE:

Schizophrenia

a. Etiology

There is no known single cause of schizophrenia. Research suggests there is interplay of genetic, behavioral, and other factors. It is known to run in families, the chances of getting schizophrenia increases if one family member also has the disorder. However, scientists do not yet fully understand all of the factors necessary to produce schizophrenia, but all the tools of modern biomedical research are being used to search for genes, critical moments in brain development, and other factors that may lead to the illness. (http://www.mental-health-today.com/sphra/schiz.htm)

b. Pathophysiology (cells and molecules)

There is chemical imbalance, viral and immune theories of schizophrenia.

If schizophrenia is a autoimmune disease, it involves antibodies circulating and present in plasma and/or CSF that cross brain Proteins, but is also a consequence of complex interaction between predisposing genes and environmental factors that are played out according to a dynamic network of immune-regulatory cells and molecules (Pearce, 2002, http://books.google.ca/books?id=_fmolX9OALkC&pg=PA90&lpg=PA90&dq=schizophrenia+pathophysiology+(cells+and+molecules)&source=bl&ots=YJoKxBw5z2&sig=8bo7L_gXmYjD5in04JrjU1hPiRo&hl=en&ei=u7SwSbC0FJK2sAOYs8Ry&sa=X&oi=book_result&resnum=4&ct=result#PPP9,M1).

On the other hand, if schizophrenia is caused by a virus, other studies focus on cytokines and inflammatory mediators. Most studies have found an increase in interleukin2 soluble receptor (IL-2sR) in schizophrenia, which is an indicator that T-cells are activated. Also, in schizophrenia, the relative and absolute numbers of lymphocytes, NK cells, B cells, T cells, and CD4/CD8 T-cells subpopulations have been variously reported as increased, decreased or unchanged. However other studies are more convincing and suggest schizophrenia is caused by a dysregulation of CD4 helper cells (Pearce, 2002, http://books.google.ca/books?id=_fmolX9OALkC&pg=PA90&lpg=PA90&dq=schizophrenia+pathophysiology+(cells+and+molecules)&source=bl&ots=YJoKxBw5z2&sig=8bo7L_gXmYjD5in04JrjU1hPiRo&hl=en&ei=u7SwSbC0FJK2sAOYs8Ry&sa=X&oi=book_result&resnum=4&ct=result#PPP9,M1).

Schizophrenia is characterized by increased nonspecific innate immunity, decreased type 1 T helper cell (Th1)-specific cellular immunity, and a Th1?{Th2 imbalance with a shift to the Th2 system.6 The innate immune activation in schizophrenia has been based on the findings of increased monocyte numbers, increased activity of macrophage, increased proinflammatory cytokine levels such as IL-1, IL-6, IL-18 and tumor necrosis factor(TNF)- . Schizophrenia is also characterized by a decrease in IL-2 production and interferon(IFN)- , traditionally classified as Th1 cytokines, and an increase in IL-416 and IL-10, traditionally classified as Th2 cytokines. On the other hand, there have been reports of an increased Th1 system in schizophrenia, specifically an increased IL-2 level in plasma19 and in cerebrospinal fluid20,21 and increased production of IL-2 and IFN- .22 Interestingly, in one study, they found that decreased IL-2 production may be associated with an increased IL-2 serum level in schizophrenic patients, supporting the T cell exhaustion theory that lower IL-2 production may be induced by a consequence of overproduction of in vivo IL-2. (http://www.nature.com/mp/journal/v7/n10/full/4001084a.html)

Research also suggests that there is an increased expression of Wnt-1 in schizophrenic brains in the hippocampus. For example, one study investigated the expression of Wnt-1 in the hippocampal region, which is believed to be closely involved in the pathophysiology of schizophrenia, of postmortem brains from 10 schizophrenic and 10 control individuals. Using immunohistochemical analysis, they found that with polyclonal antibodies recognizing Wnt-1 revealed immunoreactivity primarily in the pyramidal cell layer, particularly in CA3 and CA4 regions. They observed a significant elevation in the number of Wnt-1-immunoreactive neurons in the great majority of schizophrenic brains relative to that in controls. The expression of Wnt-1 may be related to cell adhesion, synaptic rearrangement, and plasticity. Therefore, the increase in Wnt-1 immunoreactivity in schizophrenic hippocampi suggests an altered plasticity of this structure in a large proportion of schizophrenic brains. These findings suggest an abnormality of the wingless/Wnt pathway present in the schizophrenic brain and may support the ¼~eurodevelopmental hypothesis' of schizophrenia (http://linkinghub.elsevier.com/retrieve/pii/S0920996498001790).

However, like for Major depression, there is still no consensus (agreement) as to which, if any, of these theories is correct, or whether the diseases are caused by a combination of factors. Because Schizophrenia and Major depression? causes are unknown, the diseases are defined by a set of symptoms.

c. Clinical Manifestations

Schizophrenia is characterized by profound disruption in cognition and emotion, affecting the most fundamental human attributes: language, thought, perception, affect, and sense of self. The array of symptoms, while wide ranging, frequently includes psychotic manifestations, such as hearing internal voices or experiencing other sensations not connected to an obvious source (hallucinations) and assigning unusual significance or meaning to normal events or holding fixed false personal beliefs (delusions). No single symptom is definitive for diagnosis; rather, the diagnosis encompasses a pattern of signs and symptoms, in conjunction with impaired occupational or social functioning (Source: DSM-IV - Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR).

Symptoms are typically divided into positive and negative symptoms because of their impact on diagnosis and treatment. Positive symptoms are those that appear to reflect an excess or distortion of normal functions. People diagnosed with schizophrenia usually experience a combination of positive (i.e. hallucinations, delusions, racing thoughts), negative (i.e. apathy, lack of emotion, poor or nonexistant social functioning), and cognitive (disorganized thoughts, difficulty concentrating and/or following instructions, difficulty completing tasks, memory problems). (http://www.schizophrenia.com/diag.php)

The diagnosis of schizophrenia, according to DSM-IV, requires at least ...