Background. The base rate of transition from subthreshold psychotic experiences (the exposure) to clinical psychotic disorder (the outcome) in unselected, representative and non-help-seeking population-based samples is unknown. Method.A systematic review and meta-analysis was conducted of representative, longitudinal population-based cohorts with baseline assessment of subthreshold psychotic experiences and follow-up assessment of psychotic and non-psychotic clinical outcomes.Results. Six cohorts were identified with a 3-24-year follow-up of baseline subthreshold self-reported psychotic experiences. The yearly risk of conversion to a clinical psychotic outcome in exposed individuals (0.56 %) was 3.5 times higher than for individuals without psychotic experiences (0.16 %) and there was meta-analytic evidence of dose-response with severity/persistence of psychotic experiences. Individual studies also suggest a role for motivational impairment and social dysfunction. The evidence for conversion to non-psychotic outcome was weaker, although findings were similar in direction.Conclusions. Subthreshold self-reported psychotic experiences in epidemiological non-help-seeking samples index psychometric risk for psychotic disorder, with strong modifier effects of severity/persistence. These data can serve as the population reference for selected and variable samples of help-seeking individuals at ultra-high risk, for whom much higher transition rates have been indicated.

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Iron deficiency has been shown to effect the dopaminergic system. Iron deficient rats have low dopamine D2 receptor levels and modified dopamine-mediated behaviors, including reversal of circadian cycles of these behaviors. Abnormal iron deposits have been found in the brains of schizophrenics in CT and post mortum studies. We examined serum iron levels at 0800, 1700 and 2400 hours in 26 medication free schizophrenic patients in acute psychotic relapse and compared them to iron levels in a normal control group. The results show significant decreases in the iron levels at 1700 and 2400, and a non significant drop in the 0800 levels. A feedback mechanism involving iron and dopamine is proposed.

Genomic copy number variants (CNVs) have been strongly implicated in the etiology of schizophrenia (SCZ). However, apart from a small number of risk variants, elucidation of the CNV contribution to risk has been difficult due to the rarity of risk alleles, all occurring in less than 1% of cases. We sought to address this obstacle through a collaborative effort in which we applied a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. We observed a global enrichment of CNV burden in cases (OR=1.11, ), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7e -6 ). CNV burden is also enriched for genes associated with synaptic function (OR = 1.68, ) and neurobehavioral phenotypes in mouse (OR = 1.18, ). We identified genome-wide significant support for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. We find support at a suggestive level for nine additional candidate susceptibility and protective loci, which consist predominantly of CNVs mediated by non-allelic homologous recombination (NAHR).