Amir Ali Sepehry

Inflammatory Cytokine Alterations in Schizophrenia: A Systematic Quantitative Review

BACKGROUND Cytokines play an important role in infection and inflammation and are crucial mediators of the cross-talk between the brain and the immune system. Schizophrenia would be associated with an imbalance in inflammatory cytokines, leading to a decrease in Th1 and an increase in Th2 cytokine secretion. However, data published so far have been inconsistent. The primary objective of the present meta-analysis was to verify whether the cytokine imbalance hypothesis of schizophrenia is substantiated by evidence. METHODS Cross-sectional studies were included if they assessed in vivo plasma or serum cytokine concentrations and/or in vitro secretion of cytokines by peripheral blood leukocytes from schizophrenia patients and healthy volunteers. RESULTS Data from 62 studies involving a total sample size of 2298 schizophrenia patients and 1858 healthy volunteers remained for analysis. Ten cytokines were assessed, including the prototypic Th1 and Th2 cytokines gamma interferon (IFN-gamma) and interleukin 4 (IL-4) as well as IL-2, soluble IL-2 receptor (sIL-2R), IL-1beta, IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-alpha (TNF-alpha), IL-6, soluble IL-6 receptor (sIL-6R), and IL-10. The results show that an increase occurs in in vivo IL-1RA, sIL-2R, and IL-6 and a decrease occurs in in vitro IL-2 in schizophrenia. No significant effect sizes were obtained for the other cytokines. CONCLUSIONS These findings provide the first evidence of establishment of an inflammatory syndrome in schizophrenia, which refutes the current hypothesis of a Th2 slant. Caveats are presented to data interpretation, including the role of stress and the effect of weight gain that develops in schizophrenia.

Pain and the Risk for Falls in Community-Dwelling Older Adults: Systematic Review and Meta-Analysis

OBJECTIVE To conduct a systematic review and meta-analysis to establish the association between pain and falls in community-dwelling older adults. DATA SOURCES Electronic databases from inception until March 1, 2013, including Cochrane Library, CINAHL, EBSCO, EMBASE, PubMed, and PsycINFO. STUDY SELECTION Two reviewers independently conducted the searches and completed methodological assessment of all included studies. Studies were included that (1) focused on adults older than 60 years; (2) recorded falls over 6 or more months; and (3) identified a group with and without pain. Studies were excluded that included (1) participants with dementia or a neurologic condition (eg, stroke); (2) participants whose pain was caused by a previous fall; or (3) individuals with surgery/fractures in the past 6 months. DATA EXTRACTION One author extracted all data, and this was independently validated by another author. DATA SYNTHESIS A total of 1334 articles were screened, and 21 studies met the eligibility criteria. Over 12 months, 50.5% of older adults with pain reported 1 or more falls compared with 25.7% of controls (P<.001). A global meta-analysis with 14 studies (n=17,926) demonstrated that pain was associated with an increased odds of falling (odds ratio [OR]=1.56; 95% confidence interval [CI], 1.36-1.79; I(2)=53%). A subgroup meta-analysis incorporating studies that monitored falls prospectively established that the odds of falling were significantly higher in those with pain (n=4674; OR=1.71; 95% CI, 1.48-1.98; I(2)=0%). Foot pain was strongly associated with falls (n=691; OR=2.38; 95% CI, 1.62-3.48; I(2)=8%) as was chronic pain (n= 5367; OR=1.80; 95% CI, 1.56-2.09; I(2)=0%). CONCLUSIONS Community-dwelling older adults with pain were more likely to have fallen in the past 12 months and to fall again in the future. Foot and chronic pain were particularly strong risk factors for falls, and clinicians should routinely inquire about these when completing falls risk assessments.

Cognitive discernible factors between schizophrenia and schizoaffective disorder

BACKGROUND Schizophrenia (SZ) and schizoaffective disorders (SA) are associated with cognitive deficits. Generally, a schizoaffective diagnosis is associated with better prognosis on the level of social integration. It is also well established that cognition is an important factor for good social outcome in schizophrenia. We hypothesized that, although patients suffering from SA share symptoms with SZ, they can be differentiated on the basis of neurocognitive function and that SA perform better in several domains. METHOD Performances of two groups SA (N = 13) and SZ (N = 44) were compared on several visual-motor tasks using CANTAB [Motor Screening (MOT), Reaction Time (RTI), Paired Associates Learning Task (PAL), and Stockings of Cambridge items (SOC)]. The two groups were matched for symptom severity. ANOVA with repeated measures was employed to determine whether any difference in cognitive scores during a 2-year period was significantly related to the diagnostic status. RESULTS A significant and durable difference was observed between SZ and SA on motor screening and explicit memory tests where SA performed better. CONCLUSION Neurocognitive tests may be relevant for distinguishing schizoaffective from schizophrenia, chiefly via tests tapping into visuo-spatial and visuo-motor coordination abilities (e.g., paired associated learning and motor screening).

The impact of atypical antipsychotic medications on long-term memory dysfunction in schizophrenia spectrum disorder: a quantitative review

This meta-analytic review examines the ef.cacy of antipsychotic medications in ameliorating schizophrenia-related long-term memory (LTM) impairments. Twenty-three studies were reviewed that compared schizophrenia spectrum patients treated (a) with atypical versus typical antipsychotic medications, or (b) with various atypical treatments. In 17 atypical versus typical trials aggregating 939 participants, superior overall (verbal and nonverbal) LTM was detected in patients assigned to atypical trials. However, this difference was small (effect size estimate (ES) 0.17; 95% Con.dence Interval (CI) 0.04 to 0.31) and speci.c to certain atypical treatments. Relative to typical antipsychotic trials, LTM superiority was marginally signi.cant for risperidone trials (ES 0.20; 95% CI 0.03 to 0.44) and signi.cant for olanzapine trials (ES 0.29; 95% CI 0.08 to 0.49). In contrast, clozapine trials did not produce a LTM advantage over typical trials (ES 0.06; 95% CI 0.35 to 0.23). Due to the lack of available studies, the effect of quetiapine was indeterminate. Direct comparison between atypical trials revealed a similar effect pattern. A marginally signi.cant superiority in overall LTM was detected for risperidone and olanzapine compared to clozapine (ES 0.28; 95% CI 0.04 to 0.59), which reached signi.cance for verbal LTM (ES 0.36; 95% CI 0.04 to 0.67). Finally, the bene.cial impact of antipsychotic medications emerged as a function of differences in the anticholinergic properties of the treatment arms being compared.

The Association Between Obstructive Sleep Apnea and Alzheimer’s Disease: A Meta-Analysis Perspective

Alzheimer’s disease (AD) and obstructive sleep apnea (OSA) are highly prevalent, chronic conditions with intriguing, yet poorly understood epidemiological overlap. To date, the amount of OSA syndrome present in patients with AD across literature remains unknown. To address this question, we collected all available published clinical data and analyzed them through a quantitative meta-analytical approach. The results of our quantitative meta-analysis suggest that the aggregate odds ratio for OSA in AD vs. healthy control was 5.05 and homogeneous. This reflects that patients with AD have a five times higher chance of presenting with OSA than cognitively non-impaired individuals of similar age. Moreover, these data suggest that around half of patients with AD have experienced OSA at some point after their initial diagnosis. The additive impact of progressive changes in sleep quality and structure, changes in cerebral blood flow and the cellular redox status in OSA patients may all be contributing factors to cognitive decline and may further aggravate AD progression. It is hoped that the high OSA rate in AD patients, as suggested by the findings of our meta-analysis, might provide a sufficient clinical incentive to alert clinicians the importance of screening patients for OSA in AD, and stimulate further research in this area.

Meta-analysis of depressive symptoms in dual-diagnosis schizophrenia

Substance abuse is highly prevalent in schizophrenia and associated with numerous negative consequences. While studies have regularly reported more severe depressive symptoms in addicted schizophrenia patients relative to non-abusing patients, some studies have not corroborated this finding. The current meta-analysis was performed to quantify the relative severity of depressive symptoms in dual-diagnosis schizophrenia. A search of the literature using computerized engines was undertaken. Studies were retained in the analysis if (i) they assessed depressive symptoms using validated scales specific to depression (e.g. Hamilton Depression Rating Scale); and (ii) groups of schizophrenia patients were divided according to substance use disorders (alcohol, amphetamines, cannabis, cocaine, hallucinogens, heroin and/or phencyclidine). According to the inclusion criteria, 20 studies were available for mathematical analysis. A small, positive and significant effect size estimate (n =3283; 1680 dual diagnosis; 1603 single diagnosis; adjusted Hedgess g =0.292; p =0.003) was obtained, within a random-effect model, suggesting that some dual-diagnosis patients experience more severe depressive symptoms than single-diagnosis patients. This significant difference was found only for studies using the Hamilton Depression Rating Scale but not for other depression scales. The results of the present meta-analysis suggest that addicted schizophrenia patients experience more severe depressive symptoms compared to non-abusing patients, but that the difference is smaller than commonly assumed. The meta-analysis also shows that the significance of results is related to the scale used to measure depressive symptoms. These results have methodological implications for future studies of depressive symptoms in dual-diagnosis patients, and potential implications for the prevention and treatment of depressive symptoms in schizophrenia.

A meta-analysis of prevalence estimates and moderators of low bone mass in people with schizophrenia

To assess the prevalence and moderators of low bone mass, osteopenia and osteoporosis in schizophrenia patients.

A quantitative systematic review of domain-specific cognitive impairment in lacunar stroke

Objective: To quantitatively characterize domain-specific cognition in individuals with symptomatic lacunar stroke in a systematic review. Methods: Systematic searches of MEDLINE and EMBASE were conducted. Inclusion criteria were all articles published prior to December 2011 evaluating domain-specific cognitive status in individuals with a symptomatic lacunar infarct. Data extraction identified cognitive domains with reported impairment and effect size calculations and heterogeneity analyses were completed to assess the magnitude of this impairment for all studies with control group data. Results: Results of the search yielded 12 cross-sectional and 5 longitudinal studies that met inclusion criteria. Effect size calculations revealed small to medium effect sizes (ES) estimations for impairment after stroke in the domains of executive function (ES −0.44, 95% confidence interval [CI] −0.83, −0.50), memory (ES −0.55, 95% CI −0.96, −0.13), language (ES −0.63, 95% CI −0.92, −0.33), attention (ES −0.37, 95% CI −0.67, −0.07), and visuospatial abilities (ES −0.61, 95% CI −1.03, 0.19), and large effect sizes for global cognition (ES −0.90, 95% CI −1.48, −0.31) and information processing speed (ES −0.93, 95% CI −1.63, −0.23). Heterogeneity analyses revealed that a subset of these domains were heterogeneous and identified moderating factors accounting for this heterogeneity. Conclusions: Results of this systematic review are consistent with previous characterizations of cognitive impairment associated with lacunar strokes. However, impaired cognition in this stroke subtype appears less selective than previously thought, involving all major cognitive domains.

Do antipsychotics prevent postoperative delirium? A systematic review and meta-analysis

To summarize the effect of antipsychotics for preventing postoperative delirium.

Structural and functional neural adaptations in obstructive sleep apnea: an activation likelihood estimation meta-analysis

Highlights • The right basolateral amygdala, the hippocampus and the right insular cortex are important nodes in obstructive sleep apnea (OSA).• Functional characterization of these regions suggested associated dysfunction of emotional, sensory, and limbic processes in OSA.• Connectivity analysis demonstrated that these regions are part of a joint network comprising the anterior insula, posterior-medial frontal cortex and thalamus.