Jason Schiffman

Effects of alcohol, expectancies, and partner type on condom use in college males: Event‐level analyses

Sexually active heterosexual college males (N = 93) provided data on over 1,500 sexual encounters. Alcohol consumption, expectancies about alcohols impact on condom use, and partner type each contributed to use of a condom. Partner type covaried with alcohol consumption and condom use. The men consumed significantly more alcohol with new partners, followed by casual partners, and then by regular partners. In contrast, they were more likely to use condoms with new partners than with casual or regular partners. Drinking alcohol decreased condom use, but only with casual partners. Expectancies about alcohols disinhibiting sexual effects decreased condom use as well. These data suggest that alcohol consumption does decrease condom use, particularly with casual partners and when drinkers believe alcohol alters sexual disinhibition. Improving knowledge about HIV and other STD transmission in casual partners and challenging expectancies about alcohol as a sexual disinhibitor could help decrease the spread of HIV and other STDs.

Symptoms of schizotypy precede cannabis use.

The current investigation uses a large non-clinical sample of undergraduate college students (N=189) to investigate schizotypal traits among cannabis and non-cannabis users, as well as the temporal order of the onset of these traits and cannabis use. Findings suggest that regular cannabis users are significantly more prone to cognitive and perceptual distortions as well as disorganization, but not interpersonal deficits, than non-regular users and those who have never used. Additionally, the onset of schizotypal symptoms generally precedes the onset of cannabis use. The findings do not support a causal link between cannabis use and schizotypal traits.

Early developmental milestones and risk of schizophrenia: A 45-year follow-up of the Copenhagen Perinatal Cohort

The aim of the present study was to investigate the relationship between age of neuromotor milestone attainment and risk of adult schizophrenia. 5765 mothers of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the childs first year of life. Cohort members were followed until they were 46-48 years old through record linkage with the Danish Psychiatric Central Research Register. The age at which milestones were met in the 92 individuals who later developed schizophrenia was compared with milestone attainment in the 691 individuals who developed other psychiatric disorders and in the 4982 cohort controls who were never admitted to a psychiatric department. Group comparisons were adjusted for gender, mothers age, fathers age, parental social status, breadwinners education, single mother status and parity. Individuals who developed schizophrenia reached all developmental milestones later than controls and differed significantly from the controls with respect to the mean age of reaching the 12 milestones. Five developmental milestones in particular (smiling, lifting head, sitting, crawling, and walking) differed significantly. Individuals who later developed psychiatric disorders other than schizophrenia reached most developmental milestones earlier than those who developed schizophrenia, but later than the controls. The two psychiatric groups only differed significantly with respect to age of walking without support. The findings corroborate and methodologically extend previous research from prospective longitudinal cohort studies suggesting developmental delays observable as early as within the first year of life. These early developmental delays may not only characterize schizophrenia, but may be associated with a range of psychiatric disorders.

Psychosis risk screening in youth: A validation study of three self-report measures of attenuated psychosis symptoms

Brief self-report questionnaires that assess attenuated psychosis symptoms have the potential to quickly and effectively screen many people who may benefit from clinical monitoring or early intervention. The current study sought to examine and compare the criterion validities of attenuated symptoms screening tools with diagnoses obtained from the clinician-administered Structured Interview for Psychosis Risk Syndromes (SIPS). Three screening questionnaires (Prime Screen, Prodromal Questionnaire-Brief, and Youth Psychosis At-Risk Questionnaire-Brief) were administered just prior to the SIPS interview in a sample of adolescents and young adults seeking mental health services. Using thresholds recommended by instrument authors as well as empirically derived optimal thresholds, the sensitivity, specificity, positive predictive value, and overall accuracy of each self-report measure with regard to SIPS diagnosis were obtained. Screeners correlated highly with the SIPS and demonstrated equivalent overall efficiency in capturing psychosis risk status. All three screeners appear to be useful and valid assessment tools for attenuated symptoms, with each instrument demonstrating relative benefits. The validation of attenuated symptoms screening tools is an important step toward enabling early, wide-reaching identification of individuals on a course toward psychotic illness.

Childhood Motor Coordination and Adult Schizophrenia Spectrum Disorders

OBJECTIVE The authors examined whether motor coordination difficulties assessed in childhood predict later adult schizophrenia spectrum outcomes. METHOD A standardized childhood neurological examination was administered to a sample of 265 Danish children in 1972, when participants were 10-13 years old. Adult diagnostic information was available for 244 members of the sample. Participants fell into three groups: children whose mothers or fathers had a psychiatric hospital diagnosis of schizophrenia (N=94); children who had at least one parent with a psychiatric record of hospitalization for a nonpsychotic disorder (N=84); and children with no parental records of psychiatric hospitalization (N=66). Psychiatric outcomes of the offspring were assessed through psychiatric interviews in 1992 when participants were 31-33 years of age, as well as through a scan of national psychiatric registers completed in May 2007. RESULTS Children who later developed a schizophrenia spectrum disorder (N=32) displayed significantly higher scores on a scale of coordination deficits compared with those who did not develop a mental illness in this category (N=133). CONCLUSIONS Results from this study provide further support for the neurodevelopmental hypothesis of schizophrenia and underscore the potential role of cerebellar and/or basal ganglia abnormalities in the etiology and pathophysiology of schizophrenia.

Perspective-taking deficits in people with schizophrenia spectrum disorders : a prospective investigation

BACKGROUND This study examined data from a Danish prospective longitudinal project in attempt to address the state/trait controversy regarding theory of mind deficits in schizophrenia. Deficits in perspective-taking--a component of theory of mind--were investigated prospectively among children who developed schizophrenia spectrum disorders as adults in comparison to children who did not develop schizophrenia spectrum disorders. METHOD A total of 265 high risk and control subjects were studied in 1972. At the time of initial assessment, the Role-Taking Task (RTT) was administered. Two hundred and forty-two of these children were evaluated in 1992 during follow-up examinations. Sixteen developed schizophrenia, 10 developed a schizophrenia spectrum disorder, 70 had outcomes of other psychopathology, and 146 did not develop a mental illness. RESULTS Children who later developed schizophrenia or a schizophrenia spectrum disorder had lower RTT scores, controlling for verbal IQ and age, compared to those who did not develop any mental illness. Although in the expected direction, RTT scores for those with schizophrenia spectrum disorders were not significantly different from those who developed a non-psychotic disorder. CONCLUSIONS Deficits in perspective-taking among children who later developed schizophrenia spectrum disorders suggest that a facet of theory of mind is impaired prior to development of schizophrenia. Our findings lend support to the hypothesis that theory of mind deficits in schizophrenia are trait markers of the disorder.

Perception of parent–child relationships in high-risk families, and adult schizophrenia outcome of offspring

The current investigation examines perceived family relationships prior to the onset of psychopathology in a sample at high-risk for schizophrenia. Previous research suggests that environmental factors, such as family relationships, may contribute to later schizophrenia in high-risk individuals. This investigation extends work by Burman et al. [Burman B, Mednick SA, Machon RA, Parnas J, Schulsinger F. Children at high risk for schizophrenia: parent and offspring perceptions of family relationships. Journal of Abnormal Psychology 1987;96(4):364-6] by examining high-risk subjects from a longitudinal data set who had not yet decompensated to schizophrenia at the time of the Burman study. Findings suggest that having positive relationships with both the mother and father may be protective against schizophrenia among HR children.

Green Tea Polyphenols Potentiate the Action of Nerve Growth Factor To Induce Neuritogenesis: Possible Role of Reactive Oxygen Species

Exogenously administered nerve growth factor (NGF) repairs injured axons, but it does not cross the blood–brain barrier. Thus, agents that could potentiate the neuritogenic ability of endogenous NGF would be of great utility in treating neurological injuries. Using the PC12 cell model, we show here that unfractionated green tea polyphenols (GTPP) at low concentrations (0.1 μg/ml) potentiate the ability of low concentrations of NGF (2 ng/ml) to induce neuritogenesis at a level comparable to that induced by optimally high concentrations of NGF (50 ng/ml) alone. In our experiments, GTPP by itself did not induce neuritogenesis or increase immunofluorescent staining for β‐tubulin III; however, it increased expression of mRNA and proteins for the neuronal markers neurofilament‐L and GAP‐43. Among the polyphenols present in GTPP, epigallocatechin‐3‐gallate (EGCG) alone appreciably potentiated NGF‐induced neurite outgrowth. Although other polyphenols present in GTPP, particularly epigallocatechin and epicatechin, lack this activity, they synergistically promoted this action of EGCG. GTPP also induced an activation of extracellular signal‐regulated kinases (ERKs). PD98059, an inhibitor of the ERK pathway, blocked the expression of GAP‐43. K252a, an inhibitor of TrkA‐associated tyrosine kinase, partially blocked the expression of these genes and ERK activation. Antioxidants, catalase (cell‐permeable form), and N‐acetylcysteine (both L and D‐forms) inhibited these events and abolished the GTPP potentiation of NGF‐induced neuritogenesis. Taken together, these results show for the first time that GTPP potentiates NGF‐induced neuritogenesis, likely through the involvement of sublethal levels of reactive oxygen species, and suggest that unfractionated GTPP is more effective in this respect than its fractionated polyphenols.

Locally Generated Methylseleninic Acid Induces Specific Inactivation of Protein Kinase C Isoenzymes : RELEVANCE TO SELENIUM-INDUCED APOPTOSIS IN PROSTATE CANCER CELLS

In this study, we show that methylselenol, a selenometabolite implicated in cancer prevention, did not directly inactivate protein kinase C (PKC). Nonetheless, its oxidation product, methylseleninic acid (MSA), inactivated PKC at low micromolar concentrations through a redox modification of vicinal cysteine sulfhydryls in the catalytic domain of PKC. This modification of PKC that occurred in both isolated form and in intact cells was reversed by a reductase system involving thioredoxin reductase, a selenoprotein. PKC isoenzymes exhibited variable sensitivity to MSA with Ca2+-dependent PKC isoenzymes (α, β, and γ) being the most susceptible, followed by isoenzymes δ and ϵ. Other enzymes tested were inactivated only with severalfold higher concentrations of MSA than those required for PKC inactivation. This specificity for PKC was further enhanced when MSA was generated within close proximity to PKC through a reaction of methylselenol with PKC-bound lipid peroxides in the membrane. The MSA-methylselenol redox cycle resulted in the catalytic oxidation of sulfhydryls even with nanomolar concentrations of selenium. MSA inhibited cell growth and induced apoptosis in DU145 prostate cancer cells at a concentration that was higher than that needed to inhibit purified PKCα but in a range comparable with that required for the inhibition of PKCϵ. This MSA-induced growth inhibition and apoptosis decreased with a conditional overexpression of PKCϵ and increased with its knock-out by small interfering RNA. Conceivably, when MSA is generated within the vicinity of PKC, it specifically inactivates PKC isoenzymes, particularly the promitogenic and prosurvival ϵ isoenzyme, and this inactivation causes growth inhibition and apoptosis.

Green tea polyphenols precondition against cell death induced by oxygen-glucose deprivation via stimulation of laminin receptor, generation of reactive oxygen species, and activation of protein kinase Cϵ

Background: Preconditioning protects neuronal cells from cerebral ischemia. Results: Green tea polyphenols (GTPP) induce activation of laminin receptor and subsequent oxidative activation and membrane/mitochondrial translocation of protein kinase Cϵ (PKCϵ). Conclusion: GTPP-induced PKCϵ activation may precondition against cell death induced by oxygen-glucose deprivation/reoxygenation. Significance: Preconditioning mechanisms may be beneficial for the effective use of green tea in preventing ischemic stroke. As the development of synthetic drugs for the prevention of stroke has proven challenging, utilization of natural products capable of preconditioning neuronal cells against ischemia-induced cell death would be a highly useful complementary approach. In this study using an oxygen-glucose deprivation and reoxygenation (OGD/R) model in PC12 cells, we show that 2-day pretreatment with green tea polyphenols (GTPP) and their active ingredient, epigallocatechin-3-gallate (EGCG), protects cells from subsequent OGD/R-induced cell death. A synergistic interaction was observed between GTPP constituents, with unfractionated GTPP more potently preconditioning cells than EGCG. GTPP-induced preconditioning required the 67-kDa laminin receptor (67LR), to which EGCG binds with high affinity. 67LR also mediated the generation of reactive oxygen species (ROS) via activation of NADPH oxidase. An exogenous ROS-generating system bypassed 67LR to induce preconditioning, suggesting that sublethal levels of ROS are indeed an important mediator in GTPP-induced preconditioning. This role for ROS was further supported by the fact that antioxidants blocked GTPP-induced preconditioning. Additionally, ROS induced an activation and translocation of protein kinase C (PKC), particularly PKCϵ from the cytosol to the membrane/mitochondria, which was also blocked by antioxidants. The crucial role of PKC in GTPP-induced preconditioning was supported by use of its specific inhibitors. Preconditioning was increased by conditional overexpression of PKCϵ and decreased by its knock-out with siRNA. Collectively, these results suggest that GTPP stimulates 67LR and thereby induces NADPH oxidase-dependent generation of ROS, which in turn induces activation of PKC, particularly prosurvival isoenzyme PKCϵ, resulting in preconditioning against cell death induced by OGD/R.