Recent findings suggest that substance abuse may precipitate schizophrenia or that early onset of psychotic symptoms could be a risk factor for substance abuse. The study was published in the Br. J. Psychiatry by a team from Imperial College Faculty of Medicine (London, UK) and found an earlier onset of psychosis in patients who reported a lifetime history of comorbid substance abuse.
This study aimed to examine the association between substance abuse and age at onset of substance abuse and age at onset in a UK, inner-city sample of people with recent-onset schizophrenia. It comprised 152 individuals who were recruited to the West London First-Episode Schizophrenia Study and collected information on age at onset of psychosis and self-reported data on drug and alcohol use. The mental state, cognition (IQ, memory and executive function) and social function of patients were also assessed. A total of 60% of participants were smokers, 27% reported a history of alcohol problems, 35% reported current substance abuse problems (not including alcohol) and 68% reported lifetime substance abuse (using cannabis and psychostimulants most commonly).
The researchers found that both cannabis use and gender had independent effects on the age of onset of psychosis (after adjusting for alcohol misuse and other drug use). Women were, on average, 4.2 years older at age of onset of psychosis than men, whereas, when compared with no use, cannabis use was significantly associated with a younger onset (on average 5 years). Both groups had similar levels of social function and there was no difference between those with and without comorbid substance use with respect to IQ or cognition.
“These results confirm the high prevalence of lifetime substance abuse in first-episode patients with schizophrenia”, say Barnes and coworkers. “From a clinical perspective, given that such substance use tends to predict a poorer initial outcome, our findings reinforce the need to routinely assess and consider appropriate treatment intervention for substance abuse in people with schizophrenia when they first present to psychiatric services”.
In finding a strong association between self-reported cannabis use and earlier onset of psychosis, this study provides further evidence that schizophrenia may be precipitated by cannabis use and/or that the early onset of symptoms is a risk factor for cannabis use.
Stenting: an added option for recalcitrant cerebral arterial occlusions
Researchers from the University of Buffalo (NY, USA) have reported early results demonstrating an encouraging success rate for stent-assisted recanalization in acute stroke patients with recalcitrant occlusions.
Intra-arterial therapy is an alternative for patients who are not candidates for intravenous tissue plasminogen activator; however, both intra-arterial pharmacological and mechanical thrombolysis can fail and, for patients in such a position, there are few options available currently. This study, published in Neurosurgery, shows that stent-assisted recanalization in acute stroke patients after failed thrombolysis may improve recanalization rates.
The researchers performed a retrospective analysis of 19 patients, who were treated at two institutions between July 2001 and March 2005 and who had intracranial stenting of a vessel resistant to standard thrombolytic techniques. A total of six women and 13 men with a median baseline NIH Stroke Scale (NIHSS) score of 16 (range: 15–22) were studied, involving demographic, clinical and radiographical presentation and outcomes. Eight lesions were located at the internal carotid artery terminus, seven in the M1/M2 segment and four in the basilar artery.
The overall recanalization rate (thrombolysis in cerebral infarction grade 2 or 3) was 79%. The researchers stress that this compares favorably with the reported rates of 66% for intra-arterial pharmacological thrombolysis and up to 64% for mechanical clot retrieval. All four patients with persistent occlusions died; however, where recanalization was achieved, patients were more likely to have a favorable outcome (nine of these patients achieved a modified Rankin Scale score of 3 or less).
There were two deaths despite recanalization: one following a progression of their stroke and the other because of delayed complications of a tracheostomy. Of the surviving patients, one postoperative asymptomatic intracerebral hemorrhage occurred that did not affect the patient’s outcome, and the median NIHSS score at discharge had improved to an average of 5 overall.
“Our preliminary data suggest that stenting may be indicated for intracranial vessels resistant to current recanalization options”, the team concludes.
The study indicates that stent-assisted recanalization may be an option for recalcitrant cerebral arterial occlusions following the initial data that a high recanalization rate and low intracranial hemorrhage rate are associated with stent-assisted recanalization following acute stroke resulting from intracranial thrombotic occlusion.
The researchers conclude: “Further investigation is needed to define the population who will derive the greatest benefit from this intervention”.
Neuroprotective effect of microglial IL-1ra
A study published in the April issue of Glia has confirmed the hypothesis that endogenous interleukin (IL)-1 receptor antagonist (IL-1ra) has neuroprotective effects in vivo and in vitro and also looked to identify its mechanism of action.
Administration of the IL-1ra reduces neuronal injury, in contrast to IL-1, which is a pro-inflammatory cytokine that contributes to neuronal inflammation and cell death induced by ischemia, excitotoxicity or trauma. This study by Pinteaux and colleagues used IL-1ra knock-out mice to demonstrate clearly the effect of the IL-1ra. These mice exhibited a dramatic increase in neuronal injury induced by transient cerebral ischemia compared with wild-type animals (3.6-fold increase in infarct size). Cultured cortical neurons from wild-type and IL-1ra knock-out animals demonstrated identical basal cell death and neuronal cell death was increased to an identical extent in wild-type and knock-out animals by NMDA or AMPA (20 µM).
By contrast, glial-neuronal co-cultures from IL-1ra knockout mice exhibited significantly higher basal and NMDA- or AMPA-induced cell death compared with wild-type mice. The researchers also showed that treatment with conditioned medium from NMDA- or AMPA-treated primary neurons stimulated pure microglial cultures but not pure astrocyte cultures to release IL-1ra.
These findings clearly demonstrate that the endogenous IL-1ra produced by microglia is neuroprotective in cerebral ischemia or excitotoxicity. This will no doubt have implications for future therapeutic options in humans.
Controversial link between bipolar illness and polycystic ovary syndrome
There is an intrinsic link between polycystic ovary syndrome (PCOS) and bipolar disorder, which is independent of valproate exposure or treatment. This finding has been published recently in the J. Affect. Disord. following a pilot study.
“Unresolved controversy persists regarding a potential association between valproate use and the development of PCOS”, say researchers.
Kimberly Klipstein (Mount Sinai Medical Center, New York, USA) and Joseph Goldberg (Silver Hill Hospital, CT, USA) screened for the presence of bipolar illness in 78 women with PCOS using the Mood Disorders Questionnaire (MDQ). The pilot study highlights features of bipolar disorder being substantially more prevalent among premenopausal women with PCOS than would be expected for women in the general population.
A total of 21 (26.9%) women either had a clinical history of bipolar disorder or screened positive for bipolar illness on the MDQ. Further analysis of these women together with the 54 women who did not screen positive for bipolar disorder did not reveal any differences between the two groups with regard to current age, race, body mass index or bipolar family history.
“The data are suggestive of a relationship between PCOS and bipolarity, independent of valproate use that warrants further clarification”, say the researchers.
Lifetime valproate exposure among participants was rare and none of the 78 participants were taking valproate during the study and only two women had taken valproate prior to their PCOS diagnosis.
“The present findings support the view that PCOS may inherently arise in a substantial minority of women with possible bipolar disorder, potentially via a shared hypothalamic–pituitary–gonadal axis defect”, says the team.
Possible role for the 620W allele of PTPN22 in multiple sclerosis & Crohn’s disease
A recent study, published in Eur. J. Hum. Genet., has investigated the possible role for the 620W allele of PTPN22 in multiple sclerosis (MS) and Crohn’s disease.
The 620W allele of PTPN22 has previously been associated with susceptibility to various chronic inflammatory diseases, such as systemic lupus erythematosus, Type 1 diabetes mellitus, rheumatoid arthritis and autoimmune thyroiditis. Researchers from Brigham and Women’s Hospital, Harvard Medical School and the Massachusetts Institute of Technology (MA, USA) have now explored its potential role in two further inflammatory diseases (i.e., MS and Crohn’s disease).
The researchers observed reduced transmission of the PTPN22 620W allele in their cohort of 496 MS trios from the UK. However, their Crohn’s disease sample of 169 trios plus 249 Crohn’s disease cases with 207 matched controls from Quebec, Canada, showed no evidence of an association between the PTPN22 620W allele and susceptibility to Crohn’s disease was found.
The researchers then carried out a pooled analyses combining their data with published data, assessing 1496 MS cases and 1019 Crohn’s disease cases, however, no evidence of an association of the PTPN22 620W allele with either disease was demonstrated.
The odds ratios of known-risk alleles for inflammatory diseases are modest, therefore a role for the PTPN22 620W allele in susceptibility to MS or Crohn’s disease cannot be excluded following this study. It is, however, likely that such a putative role would probably be more modest than that reported so far in systemic lupus erythematosus, Type 1 diabetes mellitus, rheumatoid arthritis and autoimmune thyroiditis.