Biological Studies in Schizophrenia

Abstract

The question of whether schizophrenia is associated with structural or functional abnormalities of the nervous system, or both, has become the principal focus of biological studies of schizophrenia. Computed tomography studies have revealed ventricular enlargement and cortical atrophy in a subgroup of schizophrenic patients. While present from the early stages of the illness, they appear to be most severe in patients with negative symptoms and poor outcome. Quantitative neuropathological studies have tentatively demonstrated decreased volume of specific brain areas, neuronal loss, and other changes in the limbic system, basal ganglia, and frontal cortex. Dopamine (DA) remains the neurotransmitter most likely to be involved in schizophrenia, although there is also evidence for disturbances of serotonin and norepinephrine. Post-mortem and positron emission tomographic studies suggest an increased number of D2 DA receptors in some schizophrenics. Neuroendocrine studies reinforce the role of DA in schizophrenics. Viral infections and autoimmune disturbances may be responsible for some types of schizophrenia, but there is no firm experimental evidence to support either hypothesis. The possibility that mixtures of structural abnormalities and functional changes involving DA occur in the same patients rather than independently as part of two syndromes (Type I, II) seems attractive. Future studies should identify subtypes of schizophrenia based on biological criteria and contribute to identification of specific genetic abnormalities which increase vulnerability to manifest the schizophrenic phenotype.

Metabolomic mapping of atypical antipsychotic effects in schizophrenia

“…1 Theories of the pathophysiology underlying schizophrenia have centered on neurotransmitters and their receptors and therapeutic drug development has largely targeted dopamine, serotonin and glutamate systems. [2][3][4] While such therapies are proven effective in short-term trials, the vast majority of individuals discontinue treatment over time for lack of effectiveness or development of side effects and not all patients respond similarly to these medications. [5][6][7][8] Over the past two decades, evidence has accrued that phospholipids, which play a critical role in the structure and function of membranes, seem to be impaired in schizophrenia.…”

Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients

“…The role of serotonin (5-HT) in the pathophysiology of some subtypes of schizophrenia has recently achieved renewed interest (for review, see Meltzer, 1987Meltzer, , 1989Bleich et al, 1988). This is due, in part, to recent findings of serotonergic abnormalities in schizophrenia, to a greater appreciation of the role of 5-HT in the action of atypical antipsychotic drugs such as clozapine, and to increased understanding of 5-HT psysiology.…”

Schizophrénies et réactivité à la douleur

“…Cette hypothèse est à l'origine du développement d'un axe de recherche important dans les années 1980, mais les résultats furent décevants et contradictoires [60]. Une étude a porté sur 3 patients schizophrènes chez qui la naloxone, antagoniste des récepteurs aux opioïdes, a été donnée pour bloquer l'activité des endorphines alors qu'une stimulation électrique était appliquée [61].…”