Apoptotic mechanisms in the pathophysiology of schizophrenia

Plasma nitrite/nitrate concentrations in patients with schizophrenia

“…NO can release cytochrome C from mitochondria (32) and the apoptotic mechanism includes caspase-3 activation following down-regulation of Bcl-2 and up-regulation of Bax protein levels (33). The evidence for progressive clinical deterioration and subtle neurostructural changes following the onset of schizophrenic psychosis has led to the hypothesis that apoptosis may contribute to the pathophysiology of schizophrenia (34). Obvious morphological brain changes in schizophrenics, reduced cortical Bcl-2 protein (35), a 50% higher Bax/Bcl-2 ratio in the temporal cortex of schizophrenics compared with non-psychiatric subjects suggest that cortical cells are vulnerable to apoptosis (36).…”

Interleukin 3 and schizophrenia: the impact of sex and family history

“…61 Imbalance of apoptosis in the early stages of development of the central nervous system has been suggested as a cause of schizophrenia. 14,62 Indeed, a higher Bax/Bcl-2 ratio, an index of apoptotic activation, is observed in schizophrenia patients. 63 In recent years, key components in this pathway, like the tumor necrosis factor, 64 Akt1 65 and Gsk3b, 66 have been implicated in schizophrenia.…”

Increased Lymphocyte Caspase-3 Activity in Patients with Schizophrenia

“…A developmental concept of synaptic apoptosis suggests that the activation of this process may be localized in terminal neurites without neuronal death (14). Synaptic apoptosis represents a potential mechanism of synaptic remodeling and elimination of synapses, in physiological as well as pathological conditions, which may have a direct influence on synaptic plasticity (32).…”

“…Synaptic apoptosis represents a potential mechanism of synaptic remodeling and elimination of synapses, in physiological as well as pathological conditions, which may have a direct influence on synaptic plasticity (32). It is thought that in Alzheimer's disease this form of synaptic loss has a direct effect on early cognitive depletion that ends in neuronal death (14). A few studies showed that synap tosome apoptosis might be activated by various pro-apoptotic stimuli (33).…”

“…Although much less DNA fragmentation in individuals with schizophrenia than in healthy controls was found (12) the results of Coulson (13) based on the studies of apoptotic nuclei, caspase-3 activity, and protein levels of Bcl-2, Bax and p53 P392Ser in dermal fibroblast cell lines suggested significant abnorma lities in the regulation of apoptosis in schizophrenia that did not occur in non-schizophrenic psychiatric disorders, and healthy subjects. The exact role of apoptosis in schizophrenia remains uncertain, but the potential involvement of non-lethal localized apoptosis appears plausible (14).…”