Schizophrenia pathogenesis

Weinberger, DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch. Gen. Psychiat. 44 660-669. 

Diathesis stress model A multifactorial model of pathogenesis suggesting that schizophrenia is due to the complex interaction between a number of internal and external factors. 

However, the dopamine hypothesis does not account for some important observations. If an abnormality of dopamine physiology were solely responsible for the pathogenesis of schizophrenia, antipsychotic drugs would do a much better job in treating patients. As it is, they are only partially effective for most and ineffective for some patients. Moreover, there is evidence that diminished glutamatergic activity also plays a role in... 

Genetic factors are important in the pathogenesis of schizophrenia (Karayiorgou and Gogos, 1997), and the notion that such factors may be more salient in very early onset-cases fueled two classic family studies of childhood-onset cases (Kallmann and Roth, 1956 Kelvin et al., 1971). 

Environmental factors, such as prenatal maternal infections and perinatal complications, have been implicated in the pathogenesis of schizophrenia. Also, the correlation of only 0.6 for age of onset in monozygotic twins concordant for schizophrenia suggests that non-genetic factors play a role in determining the age of onset (Kendler et ah, 1987). A greater frequency or severity of these factors could conceivably result in an earlier onset of schizophrenia. 

The role of other factors in the pathogenesis of schizophrenia, such as prenatal nutritional deprivation or prenatal maternal infections, have, to our knowledge, not been investigated in patients with childhood-onset schizophrenia. Given the rarity of this condition, such studies are unlikely. 

The psychosis that least resembles dreaming is that of schizophrenia, because, like mania, it has the paranoia and accusatory auditory hallucinations (which dreaming lacks), and the emotional tone is often flat (about as far away from dream elation as we can get). Anxiety is about the only shared property, and that is not very specific. Perhaps it should come as no surprise that the typical schizophrenic psychosis is so different from that of dreaming. After all, it is the neuromodulator dopamine that has been most strongly implicated in the pathogenesis of schizophrenia, and that is the only neuromodulator that has not been implicated in dreaming. We will discuss this interesting difference in more detail when we consider how antipsychotic medication may work. 

Because of the prevalence of schizophrenia, this chapter concentrates on the treatment of this psychotic disorder. Also, the pathogenesis and subsequent treatment of other forms of psychosis are similar to... 

Circunstantial evidence directly implicating dopamine in the pathogenesis of duodenal ulcer in man is the unusual incidence of peptic ulcer disease in dopamine-deficient disorders. From purely descriptive clinical and epidemiologic studies we know that patients with Parkinson s disease, before the introduction of dopamine therapy, had an excess of ulcer disease (72). One report even comments on the curiosity that after initiation of L-DOPA administration the ulcer symptoms have virtually disappeared (72 ). On the other hand, less clearly, schizophrenia which is associated with dopamine excess and/or receptor hyperactivity is accompanied by virtual lack, or decreased prevalence, of peptic ulcer (73-76). Schizophrenia associated with ulcer disease has been viewed as a reportable curiosity in medical literature (75). At present, possibly because of the widespread therapeutic application of neuroleptics, the lack of peptic ulcer disease in schizophrenics is less striking than in the past. On the other hand, we recently observed in our autopsy series perforated duodenal ulcers in two schizophrenic patients who had been on large doses of haloperidol therapy (Szabo, unpublished observation). Thus, even in man, dopamine may indeed be implicated in the pathogenesis of duodenal ulcer disease. 

Tsai SJ. 2005. Central N-acetyl aspartylglutamate deficit A possible pathogenesis of schizophrenia. Med Sci Monit 11 HY39-HY45. 

Environmental factors such as exposure to viral infections (Leweke et al., 2004) autoimmune, toxic or traumatic insults and stress during gestation, birth or childhood (Marcelis et al., 1998 Cannon et al., 2000 Rosso et al., 2000) have been implied in the pathogenesis of schizophrenia. Lately, models based on epigenic factors and interaction between a susceptible genotype and the environmental factors have been proposed for this complex disease (Petronis, 2004). 

Early Studies of Phospholipid Changes in Schizophrenia and the Membrane Phospholipid Hypothesis for the Pathogenesis of Schizophrenia... 

Karoutzou G, Emrich HM, Dietrich DE. 2008. The myelin-pathogenesis puzzle in schizophrenia A literature review. Mol Psychiatry 13 245-260. 

Polymorphisms of the alpha la adrenoceptor gene were found to play no major role in the pathogenesis of schizophrenia or in clozapine-induced urinary incontinence (194). 

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