Correlations schizophrenia

Displacement studies with a wide range of neuroleptics showed good correlation with their clinical potency in schizophrenia. 

Polulin J., Daoust A M., Forest G., Stip E., Godbout R. (2003). Sleep architecture and its clinical correlates in first episode and neuroleptic-naive patients with schizophrenia. Schizophr. Res. 62, 147-53. 

Another crucial problem for any neurochemical model is cause and effect. Neuroleptics have a high affinity for dopamine receptors, particularly the D2-subtype. There is also a highly significant positive correlation (r > +0.9) between this receptor binding and their clinical potency (Seeman, 1980). But, this does not necessarily implicate elevated dopamine levels as the cause of schizophrenia. Moreover, blockade of dopamine receptors happens very rapidly, whereas clinical benefits are only seen after chronic treatment. Rose (1973) has criticised the reductionist statement that an abnormal biochemistry causes schizophrenia because it relates cause and effect at different organisational levels (namely, the molecular and behavioural). But, while it can be legitimate to discuss cause and effect at the same level that chlorpromazine blocks dopamine receptors (one molecule altering the response of another), it is not valid to infer that increased dopamine activity causes schizophrenia. Put another way ... 

Traditionally, most affective disorders have been treated with compounds that resemble the neurotransmitters that are deficient or in excess in specific brain regions. The aberrant levels of neurotransmitters (or their receptors), such as norepinephrine, dopamine, acetylcholine, and serotonin, have correlated with behavioral symptoms of schizophrenia, depression, anxiety, sleep disorders, motor dysfunctions, attention difficulties, and cognitive disorders. Most drugs discovered for these disorders resulted from screening compounds directly in rodent behavioral models that mimic the behavior of the disease. In these cases, the molecular target" or mechanism of action was assumed to be the deficiency or excess of a neurotransmitter. 

Iwamoto, K., Bundo, M., Yamada, K., et al. (2005) DNA methylation status of SOXIO correlates with its downregulation and oligodendrocyte dysfunction in schizophrenia. J. Neurosci. 25, 5376-5381. 

This is but one classihcation of symptoms and signs in schizophrenia, representing a natural progression from the positive-negative dichotomy with its proposed pathogenic correlates (Crow, 1985). Other approaches include that of... 

One of the few studies directly identifying an abnormality in dopamine neurotransmitter in schizophrenia demonstrated a lateralised, left hemisphere, elevation in the amygdala (Reynolds, 1983), which added to the evidence for the view of schizophrenia as a left temporal lobe disorder. This elevation is not, however, interpreted as a primary pathology it seems likely that it reflects a dysfunction or dehcit in the neuronal systems controlling dopaminergic activity, and a correlation with diminished levels of a marker for GABA support this interpretation (Reynolds et ah, 1990). 

There are some indications that GABAergic axonal innervation is diminished in the cortex in schizophrenia. A deficit of GAD-immunoreactive puncta was reported in frontal cortex (Woo et al., 1998) and hippocampus (Todtenkopf Benes, 1998), while the cortical plexus of (GABAergic) parvalbumin-immunoreactive fibres is also diminished (Reynolds et al., 2001). The latter two studies reported a positive correlation of these measures of innervation with total antipsychotic drug exposure, indicative of protective or stimulatory effects of chronic drug treatment. 

Neurochemical imaging and MRS techniques have obvious, although longterm studies of neurochemistry in vivo have yet to be applied to schizophrenia. One correlate of the neurodegenerative process proposed in the NMDA receptor hypofunction hypothesis is demonstrated in the relationship between anterior cingulate NAA deficits and disease duration (Ende et al., 2000). A... 

Table 1. Some neurotransmitter and synaptic abnormalities in schizophrenia, their possible underlying pathologies and hypothetical symptom correlates...

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. 

Patients with adult-onset schizophrenia have been shown to have subtle but demonstrable impairments in premorbid language as well as in motor and social development (Davies et ah, 1998), and a poor outcome in schizophrenia is correlated with more pronounced early developmental abnormalities. Several independent studies have found that very early-onset schizophrenia is associated with similar but more pronounced abnormalities (Watkins et ah, 1988 Alaghband-Rad et ah, 1995 Holhs, 1995). 

Schulz, E., Fleischhaker, C., and Remschmidt, H. (1996) Correlated changes in symptoms and neurotransmitter indices during maintenance treatment with clozapine or conventional neuroleptics in adolescence and young adulthood schizophrenia. / Child Adolesc Psychopharmacol 6 119-131. 

Medical illness or medication side effects may directly affect cognition virtually all classes of medication have been implicated. In adult patients, glucocorticoids can impair memory at relatively low doses (Keenan et ah, 1995 Newcomer et ah, 1999), as there are postulated effects on hippocampal neurons. Newcomer et ah, (1999) have reviewed the literature on illnesses in adults in which memory inversely correlates with cortisol levels, such as in Cushing s disease, Alzheimer s dementia, schizophrenia, and depression. There is no similar literature on the pediatric population. The risk of memory impairment puts chronic steroid treatment, such as that seen in certain pediatric rheumatologic disorders and severe asthmatics, for example, into a different perspective, however. Documentation of memory both before and during chronic steroid treatment might help determine detrimental effects in the pediatric population. 

I. F. Small et al. 1986), and in our experience the same may hold true for some young patients with schizophrenia. However, confounding variables such as age and gender have not been addressed in these studies. In patients with major depressive disorder, we found no relation between seizure threshold and unipolar versus bipolar or psychotic versus nonpsychotic subtypes. Similarly, Coffey et al. (1995a) found no correlation between initial seizure threshold and severity of depressive illness or the unipolar-bipolar distinction. Finally, we found that history of ECT did not predict seizure threshold (Krueger et al. 1993). 

Jeste DV, Eastham JH, Lohr JB, et al Treatment of disordered behavior and psychosis, in Clinical Geriatric Psychopharmacology, 3rd Edition. Edited by Salzman C. Baltimore, MD, Williams Wilkins, 1998, pp 107-149 Jimerson DC, Post RM, Carman JS, et al CSF calcium clinical correlates in affective illness and schizophrenia. Biol Psychiatry 14 37-51, 1979 Joffe RT, Levitt AJ Major depression and subchnical (Grade 2 hypothyroidism. 

---