However, an alternative model suggests that at Ieast some of the crucial developmental events occur in adolescence. Recent neuropathological studies report a decrease in the volume of the cortex, an increase in neuronal density, and also loss of synaptic markers, findings compatible with synaptic loss.122-124 Keshavan and colleagues125 have used magnetic resonance spectroscopy (MRS) to show that schizophrenics show Inhibitors,research,lifescience,medical a phosphomonoesterase pattern suggestive of failure of new synapse production and excessive synaptic reduction. They suggest that the ventricular enlargement and cortical volume decrement may arise in part from an excess of the normal cortical pruning that occurs in normal adolescence.126 This has been
christened the “late” Inhibitors,research,lifescience,medical (as opposed to “early”) neurodevelopmental
model.127 This model could perhaps explain the seemingly contradictory findings concerning whether brain deviance in schizophrenia occurs prior to illness onset, or is progressive.128,129 The initial evidence suggested the former, but in recent years there have been suggestions that some cerebral ventricular enlargement and volumetric reductions in the temporal lobes in schizophrenia, may have a progressive Inhibitors,research,lifescience,medical course,130,131 which is possibly limited in time.132 Lieberman et al133 examined 107 first-onset cases, of which 51 were followed over 1 to 6 years. They confirmed the presence of ventricular enlargement and hippocampal volume reductions at the time of the first episode. In addition, they reported
a progressive increase in ventricular volume in those patients with poor outcome only, but found no further reductions in cortical or hippocampal volumes on follow-up. Another longitudinal study focusing Inhibitors,research,lifescience,medical on childhood-onset schizophrenia, reported that brain abnormalities were progressing during adolescence, but became stable in early adulthood.134 Further work from the same group using high-resolution MRI scans showed that, compared with 12 matched controls, 12 adolescent early-onset patients had accelerated gray matter loss over a 5-year follow-up period. The authors interpret the dynamics of their anatomical findings in the light of family and twin imaging studies. Inhibitors,research,lifescience,medical They conclude that early neurodevelopmental deviances and later gray-matter loss are probably Pifithrin-�� cell line related and influenced by common genes, many while they also support the notion that nongenetic triggers contribute to the onset and initial progression of the illness.135 Possibly, first-onset patients presenting in childhood or adolescence may show the brain structural consequences of synaptic pruning, but those samples that, comprise adult patients may show little change. This is an interesting view, but the supporting evidence so far is sparse. Allin and Murray136 point out that many questions remain on the progression of brain morphology deviances in schizophrenia. Finding answers will require larger samples, controlling for the interactions of clinical outcome and medication, and longer follow-up periods.