Sex differences in schizophrenia and other psychotic disorders: a 20-year longitudinal study of psychosis and recovery

Abstract

This longitudinal study was designed to provide data on sex differences in the course of illness in schizophrenia and other psychotic disorders. Ninety-seven participants (43 women and 54 men) were assessed during index hospitalization when they were in the acute phase of illness, and then reassessed prospectively at 6 consecutive followups over a 20 year period. Patients were evaluated by a series of standardized measures on many aspects of illness including the presence of psychosis, global outcome, and rate of recovery. When women were compared to men in this sample, the data demonstrated a lower percentage of psychotic activity for women over the course of illness (significant at the 7.5 and 20 year followups), and a significant improvement in psychotic activity over 20 years for women (p<.05), but not for men. Additionally, women showed significantly better global functioning (p<.05) at 3 of the 6 followups (the 2, 7.5, and 10-year followups). Significantly higher percentages (p<.05) of women were in recovery at 2 of the 6 followup years (the 2 and 10-year followups). Cumulatively, 61% of the women with schizophrenia showed a period of recovery at some point during the 20 year period, compared to 41% of the men. The sex difference patterns were similar for patients with schizophrenia and for those with other types of psychotic disorders. Sex differences in this sample were specifically not attributable to differences in age of onset or premorbid developmental achievements.

Dysregulation of kisspeptin and neurogenesis at adolescence link inborn immune deficits to the late onset of abnormal sensorimotor gating in congenital psychological disorders

“…EAE was induced in adult offspring of control or poly-I:C-treated rats by immunization with MBP 68-86 emulsified in CFA, 29 and clinical symptoms of encephalomyelitis were monitored daily. The offspring of poly-I:C-treated rats showed a delayed onset and a shorter duration of EAE symptoms following MBP [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86] vaccination, compared to the controls (Table 1b). These results supported our contention that immune activation during pregnancy is associated with reduced immune response to brain antigens in the offspring.…”

“…As expected, adult offspring of the poly-I:Ctreated rats showed a reduction in PPI compared to the progeny of saline-treated animals (Supplementary Figure 1). To measure alterations in immunity to brain-specific antigens in the poly-I:C-affected offspring, we vaccinated female and male offspring at adulthood with the myelin basic protein (MBP)-derived peptide, MBP 68-86 , a CNS-associated self-antigen known to be the immune-dominant epitope in this strain, 33 and examined lymphocyte proliferation in response to the injected antigen, MBP [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86] , as well as to Con-A, a lymphocyte mitogen, or to Ova (an irrelevant antigen). We found, in lymphocytes of the offspring of the poly-I:C-treated animals, a significant reduction in the proliferative response to MBP (Table 1a).…”

“…Adult rats were immunized at the base of the tail with 75 mg of the peptide MBP [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86] (YGSLPQKSQR-SQDENPV) 27 (synthesized at the Weizmann Institute of Science), emulsified in an equal volume of complete Freund's adjuvant (CFA; DIFCO LABORA-TORIES, Detroit, MI, USA) containing 5 mg ml…”

“…Nevertheless, the present findings might suggest a novel approach for uncovering the mystery of gender differences in psychotic diseases. 82 Finally, we demonstrated the causal relation between reduced Kiss1 expression and the abnormal behavior in SCID mice. Injection of Kp-10, a polypeptide derived from Kiss1, previously shown to activate GPR54 in vivo, 78,79 restored PPI in SCID mice to normal.…”

Association between PNPLA8 gene polymorphism and schizophrenia in male patients

“…Interestingly, a recent study showed that the BanI polymorphism in PLA2G4A (cytosolic PLA2; cPLA2) affects the mean age of schizophrenia onset only in male patients. [5] Evidence suggests that sex differences among patients with schizophrenia have included age of onset, symptom severity, treatment response, course of illness, and outcome, favouring females, [6] which may be associated with the neuroprotective action of female sex hormones in the brain. Therefore, the possible neuroprotective effects of female sex hormones in the presence of the PNPLA8 rs40876 could be checked in the context of schizophrenia.…”