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Mark Weiser

Publications and source records attributed to Mark Weiser.

At least 19 recordsLinked to original sources

Premorbid functioning trajectories and the one-year course of cognitive performance in first-episode psychosis: a cluster analysis in PSYSCAN.

BACKGROUND: We examined the course of cognitive performance in first-episode psychosis (FEP) compared to healthy controls (HC), and whether this varied across subgroups of patients defined by premorbid functioning (PMF) trajectories, using a clustering approach. METHODS: Data were collected in 302 FEP and 136 HC subjects participating in PSYSCAN (HEALTH.2013.2.2.1-2-FEP). K-means clustering (Euclidean distance) was used to cluster longitudinal trajectories of different PMF domains simultaneously. Since PMF was assessed retrospectively using the Premorbid Adjustment Scale (PAS), findings should be interpreted with caution, although PAS ratings have shown reasonable validity against prospective data. RESULTS: As expected, FEP showed impaired performance across all cognitive domains compared to HC. We identified four trajectories of PMF: a normal premorbid developmental trajectory (globally-normal, 21 %), stable intermediate PMF across domains (stable-intermediate, 29 %), stable poor or deteriorating PMF in the academic domain (normal-social/poor-academic, 29 %), and a globally impaired group with poor/deteriorating PMF across domains (globally-poor, 21 %). These clusters showed distinct levels of post-onset impairments in sustained visual attention, visual working memory and emotion recognition. CONCLUSIONS: This study confirms a positive association between PMF and cognitive performance in the early years following psychosis onset. It aligns with findings that individuals later diagnosed with schizophrenia already show developmental deficits/lags from childhood to early adolescence compared to normally developing children. As PMF can be considered a proxy for cognitive reserve, our results suggest that higher reserve acts as a buffer against cognitive decline and supports better performance on sustained visual attention, complex visual working memory, and aspects of emotion recognition.

Clustering↗

Insight into psychosis and quality of life.

BACKGROUND: Insight into having a psychotic disorder is often considered to be a positive characteristic that improves quality of life. However, the evidence regarding this controversy is mixed. The present study examined the relation between insight and quality of life. METHOD: One hundred thirty-one participants with a psychotic disorder (103 with schizophrenia, 28 with schizoaffective disorder) underwent an assessment of insight, psychotic symptoms, and quality of life. The relation between insight and quality of life was assessed using regression analyses. RESULTS: Contrary to our hypothesis, better insight into having a psychotic disorder was related to reduced emotional well-being (beta = .23, P < .01), lower vocational status (beta = .31, P < .01), and less economic satisfaction (beta = .27, P < .01). Insight into the need for taking medication was positively correlated with higher emotional well-being (beta = -.18, P < .05). No relation was found between insight and psychotic symptoms. DISCUSSION: In light of our findings, the potential importance of combining insight with mechanisms for coping is discussed.

Adaptation, Psychological↗

Premorbid intra-individual variability in intellectual performance and risk for schizophrenia: a population-based study.

BACKGROUND: Some, but not most, schizophrenia patients have below-average intelligence years before they manifest psychosis. However, it is not clear if those whose intelligence falls within-normal-range nevertheless have cognitive abnormalities. We examined the association between intra-individual variability in intellectual performance and risk for schizophrenia in individuals with normal IQ. METHODS: 555,326 adolescents, mandatory assessed by the Israeli Draft Board were followed up over 8 to 17 years for psychiatric hospitalization by means of the Israeli National Psychiatric Hospitalization Case Registry. Data were available on 4 intelligence sub-tests, and on behavioral and psychosocial variables. Variability was computed from the variance of the four intelligence tests' standardized scores. RESULTS: There was a significant monotonic association between increased intra-individual variability in intellectual performance and risk of schizophrenia in individuals with within-normal-range IQ. Individuals with the highest variability were 3.8 times more likely to have schizophrenia [95%CI: 2.32-6.08; p < 0.0001] compared with individuals with the lowest variability. This association held after controlling for the effects of potential confounders. CONCLUSIONS: Despite within-normal-range premorbid IQ, apparently healthy adolescents who will later on manifest schizophrenia, nevertheless have cognitive abnormalities such as increased variability across intellectual tasks, possibly related to frontal lobe abnormalities.

Adolescent↗

Advancing paternal age and autism.

CONTEXT: Maternal and paternal ages are associated with neurodevelopmental disorders. OBJECTIVE: To examine the relationship between advancing paternal age at birth of offspring and their risk of autism spectrum disorder (ASD). DESIGN: Historical population-based cohort study. SETTING: Identification of ASD cases from the Israeli draft board medical registry. PARTICIPANTS: We conducted a study of Jewish persons born in Israel during 6 consecutive years. Virtually all men and about three quarters of women in this cohort underwent draft board assessment at age 17 years. Paternal age at birth was obtained for most of the cohort; maternal age was obtained for a smaller subset. We used the smaller subset (n = 132 271) with data on both paternal and maternal age for the primary analysis and the larger subset (n = 318 506) with data on paternal but not maternal age for sensitivity analyses. MAIN OUTCOME MEASURES: Information on persons coded as having International Classification of Diseases, 10th Revision ASD was obtained from the registry. The registry identified 110 cases of ASD (incidence, 8.3 cases per 10 000 persons), mainly autism, in the smaller subset with complete parental age data. RESULTS: There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age. CONCLUSIONS: Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting.

Adult↗

Premorbid intellectual functioning and risk of schizophrenia and spectrum disorders.

Evidence from longitudinal studies indicates that lower IQ score in childhood and early adolescence increases risk of schizophrenia and schizophrenia spectrum disorders (SSD). This study investigated the association between premorbid IQ and risk of SSD in a population-based cohort of 17-year-old conscripts. Fifty four thousand males assessed by the Israeli Draft Board during two consecutive years were followed by means of the Israeli National Psychiatric Hospitalization Case Registry for up to 11 years. Tests of verbal and non-verbal reasoning, mathematical knowledge and instructions comprehension and several psychosocial variables were recorded by the Draft Board. Risk for SSD increased with decreasing IQ score. Only poorer non-verbal reasoning conferred a significant increased risk for SSD after taking into account general intellectual ability. IQ was not associated with age of onset. These results confirm the importance of low intellectual functioning as a risk factor for SSD. This is unlikely to be due to prodrome.

Adolescent↗

Effectiveness of sildenafil in treating erectile dysfunction in PTSD patients: a double-blind, placebo-controlled crossover study.

OBJECTIVE: Post Traumatic Stress Disorder (PTSD) is known to be associated with Erectile Dysfunction (ED). Sildenafil citrate was shown to be effective treatment for ED among different clinical populations. However, to date, no placebo-controlled trial has assessed sildenafil's effectiveness for treating ED in PTSD patients. The goal of the present study was to address this question using a double-blind placebo controlled crossover design. METHODS: A four-week double-blind crossover trial of sildenafil (50 mg up to 100 mg per usage) versus placebo was conducted on 21 outpatients diagnosed with chronic PTSD accompanied by ED. Erectile function was assessed biweekly using the International Inventory of Erectile Function (IIEF). Depressive symptoms, PTSD symptoms and subjective well-being scores were assessed as well. RESULTS: Analysis of IIEF scores revealed a main effect of treatment phase (E = 33.361, df =2, P < 0.000). Pairwise comparisons showed that sildenafil IIEF scores (mean = 45.19 +/- 15.05) were significantly higher compared to baseline scores (mean = 20.00 +/- 12.32, P = 0.000) and placebo scores (mean = 33.04 +/- 12.99). Compared to placebo, a significant improvement was also observed during the sildenafil phase in erectile function, orgasmic function and sexual desire. There was no significant change in depression, PTSD symptoms or subjective well-being. CONCLUSION: The results of this study suggest that sildenafil citrate treatment for ED in PTSD patients was accompanied with improvement of ED symptoms and was found to be significantly better than placebo. Nevertheless, this effect should be considered marginal since patients still meet the criteria of ED after treatment. Larger, parallel group studies are warranted.

Adolescent↗

Personal and interpersonal perceived control and the quality of life of persons with severe mental illness.

Studies have been carried out to explore the impact of sense of control on the outcome of persons with severe mental illness (SMI). However, few studies have compared the differential effects of perceived personal control (control of the self) and perceived interpersonal control (the control of significant others). In the present study, we investigated the relations between perceived personal and perceived interpersonal control and different domains of quality of life (QOL) of persons with SMI. Measures of perceived personal and interpersonal control and QOL were administered to 145 participants with a diagnosis of SMI (schizophrenia, affective disorders, anxiety disorders, personality disorders). The results showed personal control to be positively related to various domains of QOL (beta = .28-.31, p < 0.001-0.01) while interpersonal control was negatively related to the physical domain of QOL (beta= -.20, p < 0.05). Theoretical, empirical, and clinical implications of the distinction between personal and interpersonal control for persons with SMI are discussed.

Adult↗

Effects of season of birth on autism spectrum disorders: fact or fiction?

OBJECTIVE: This study attempted to examine the relationship between month and season of birth and risk for autism spectrum disorders. METHOD: The cohort included all Jewish individuals born in Israel over 5 consecutive years (N=311,169) and assessed by the Israeli Draft Board as part of the mandatory assessment of eligibility for military service conducted at age 17. The outcome of autism spectrum disorders was ascertained from the Draft Board Medical Registry, which contains information about medical and psychiatric disorders for this population of adolescents. RESULTS: There was no association between month or season of birth and the prevalence of autistic spectrum disorders. CONCLUSIONS: The findings from this historical, population-based cohort study do not support an association between season of birth and autistic spectrum disorders.

Adolescent↗

Poor premorbid school performance is associated with later cigarette smoking among schizophrenia patients.

Schizophrenia patients who smoke have been postulated to have genetically mediated dysfunctional nicotinic neurotransmission. We hypothesized that this nicotinic dysfunction would manifest as poorer school performance in adolescence, before the onset of illness, in smoking compared with non-smoking schizophrenia patients. Over a 31-year follow-up period, 100 (65 men) cohort members of the Northern Finland 1966 Birth Cohort were hospitalized and diagnosed with DSM-III-R schizophrenia. The information on school performance was obtained at the end of compulsory schooling at age 16 years. The information on smoking habits was gathered from a questionnaire mailed to cohort members at the age of 31 years. Compared with non-smoking schizophrenia patients, schizophrenia patients who smoked in adulthood had lower overall mean grades, lower mean grades in combined mathematical subjects, and lower grades in music. Poor school performance might represent premorbid nicotinergic dysfunction associated with cognitive deficits in future smokers among schizophrenia patients compared with those who remained non-smokers.

Adult↗

Comments on risk for schizophrenia.

Recent developments have significantly furthered understanding of genetic and environmental factors affecting risk for schizophrenia. Environmental effects, such as immigration, living in a city, and substance abuse have been found to be associated with later schizophrenia. Although the highest risk for schizophrenia is still having a monozygotic twin with schizophrenia (50%), the candidate genes claimed to be associated to date only yield a very small excess risk and all of these effects (environmental and genetics) increase the risk for schizophrenia by only 2-3 fold. Thus, given the low prevalence of the disorder in the general population (0.5-1%), they are not practical in predicting future illness. One possible strategy to make the currently known risk factors for schizophrenia more useful clinically is based on findings indicating that many of the genetic and environmental risks cited above are not specific for schizophrenia, but increase risk for psychopathology in general. As up to 50% of the general population will be affected during their lifetime by a condition defined in DSM IV as psychopathology, due to this much higher base rate, factors increasing risk by 2-3 fold might become clinically relevant.

Emigration and Immigration↗

Association between functioning in adolescence prior to first admission for schizophrenia and affective disorders and patterns of hospitalizations thereafter.

BACKGROUND: Kraepelin and Blueler suggested that subtle manifestations of schizophrenia are present in some persons for many years before formal diagnosis and that the severity of these is associated with outcomes in schizophrenia. Empirical support for this hypothesis comes primarily from small samples using retrospectively collected data. AIMS: We tested this hypothesis, for the first time, using a population-based cohort. METHOD: The Israeli Draft Board Registry, which contains measures of intellectual and behavioral functioning for the unselected population of 17-year-olds, was merged with the National Psychiatric Hospitalization Case Registry that contains data on all psychiatric hospitalizations. The database was used to identify adolescents assessed by the draft board at least 1 year prior to their first hospitalization for schizophrenia (n=996) or affective disorder (n=335). RESULTS: Poorer social functioning and organizational ability prior to first admission were associated with more days per year in the hospital for the male schizophrenia group. There were no significant correlations between days per year in the hospital and any of the behavioral functioning measures for the affective group. Among females the higher the previous level of intellectual functioning the fewer the days per year in the hospital in both the schizophrenia group and affective groups. For males no such correlations were evident. The comparisons between patients who had one as opposed to more than one admission found that in both diagnostic groups female patients with one admission had higher pre-first hospitalization intellectual functioning. CONCLUSIONS: Gender and disease specific premorbid deficits have may have differential prognostic value for outcomes in schizophrenia and affective disorders.

Adolescent↗

Elaboration on premorbid intellectual performance in schizophrenia: premorbid intellectual decline and risk for schizophrenia.

CONTEXT: Consistent evidence indicates that some, but not most, patients with schizophrenia have below-average intelligence years before they manifest psychosis. However, it is not clear whether this below-average premorbid intelligence is stable or progressive. OBJECTIVE: To examine whether increased risk for schizophrenia is associated with declining intellectual performance from childhood through adolescence. DESIGN: Historical cohort study of an entire population using record linkage for psychiatric hospitalization during an 8- to 17-year follow-up period. SETTING: Mandatory assessment by the draft board of Israeli conscripts. PARTICIPANTS: Population-based cohort of 555 326 adolescents born in Israel. Data were available on 4 intelligence subtests as well as on reading and spelling abilities and on behavioral and psychosocial variables. A regression-based approach was used to assess the discrepancy between actual IQ at age 17 years and estimated IQ during childhood based on reading and spelling abilities. MAIN OUTCOME MEASURES: Hospitalization for schizophrenia (as per the International Statistical Classification of Diseases, 10th Revision criteria). RESULTS: Lower-than-expected IQ at age 17 years was associated with increased risk for later hospitalization for schizophrenia. Results were held after controlling for potential confounders. For 75% of patients with schizophrenia with low actual IQ (<85) at age 17 years and for 23% of patients with actual IQ within the normal range (> or =85), actual IQ was 10 or more points lower than expected. Lower-than-expected IQ was not associated with bipolar disorder or with depression or anxiety disorder. CONCLUSIONS: Indirect evidence suggests that intellectual deterioration from childhood through adolescence is associated with increased risk for schizophrenia. Despite within-normal-range premorbid IQ scores, apparently healthy adolescents who will later manifest schizophrenia nevertheless have intellectual decline.

Adolescent↗

Paternal age and intelligence: implications for age-related genomic changes in male germ cells.

BACKGROUND: A robust association between advancing paternal age and schizophrenia risk is reported, and genetic changes in the germ cells of older men are presumed to underlie the effect. If that is so, then the pathway may include effects on cognition, as those with premorbid schizophrenia are reported to have lower intelligence. There are also substantial genetic influences on intelligence, so de novo genetic events in male germ cells, which accompany advancing paternal age, may plausibly influence offspring intelligence. OBJECTIVE: An association of paternal age with IQ in healthy adolescents may illuminate the mechanisms that link it to schizophrenia. METHOD: We examined the association of paternal age and IQ scores using the Israeli Army Board data on 44 175 individuals from a richly described birth cohort, along with maternal age and other potential modifiers. RESULTS: A significant inverted U-shaped relationship was observed between paternal age and IQ scores, which was independent from a similar association of IQ scores with maternal age. These relationships were not significantly attenuated by controlling for multiple possible confounding factors, including the other parent's age, parental education, social class, sex and birth order, birth weight and birth complications. Overall, parental age accounted for approximately 2% of the total variance in IQ scores, with later paternal age lowering non-verbal IQ scores more than verbal IQ scores. CONCLUSION: We found independent effects of maternal and paternal age on offspring IQ scores. The paternal age effect may be explained by de novo mutations or abnormal methylation of paternally imprinted genes, whereas maternal age may affect fetal neurodevelopment through age-related alterations in the in-utero environment. The influence of late paternal age to modify non-verbal IQ may be related to the pathways that increase the risk for schizophrenia in the offspring of older fathers.

Cohort Studies↗

Time for a shift in focus in schizophrenia: from narrow phenotypes to broad endophenotypes.

Many manifestations of mental illness, risk factors, course and even response to treatment are shared by several diagnostic groups. For example, cognitive and social impairments are present to some degree in most DSM and ICD diagnostic groups. The idea that diagnostic boundaries of mental illness, including schizophrenia, have to be redefined is reinforced by recent findings indicating that on the one hand multiple genetic factors, each exerting a small effect, come together to manifest as schizophrenia, and on the other hand, depending on interaction with the environment, the same genetic variations can present as diverse clinical phenotypes. Rather than attempting to find a unitary biological explanation for a DSM construct of schizophrenia, it would be reasonable to deconstruct it into the most basic manifestations, some of which are common with other DSM constructs, such as cognitive or social impairment, and then investigate the biological substrate of these manifestations.

Cognition Disorders↗

Interpreting the association between cannabis use and increased risk for schizophrenia.

Recent longitudinal studies from Sweden, the Netherlands, New Zealand, and Israel report that cannabis use during childhood and adolescence doubles the risk of later appearance of psychosis or schizophrenia. These data have been interpreted as indicating that cannabis has a causal effect along the pathway to psychosis. In this paper, we will offer an alternative explanation of these data. Recent investigations of patients with schizophrenia found increased density of cannabinoid receptors in the dorso-lateral prefrontal cortex and the anterior cingulate cortex. Others reported higher levels of endogenous cannabinoids in the blood and cerebrospinal fluid of patients; these findings were independent of possible cannabis use. Several genetic studies have reported an association between genes encoding the cannabinoid receptor and schizophrenia. Thus, an alternative explanation of the association between cannabis use and schizophrenia might be that pathology of the cannabinoid system in schizophrenia patients is associated with both increased rates of cannabis use and increased risk for schizophrenia, without cannabis being a causal factor for schizophrenia.

Humans↗

Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study.

OBJECTIVE: The prevalence of cigarette smoking among schizophrenia patients is significantly higher than in the general population; this may reflect self-medication of symptoms and/or adverse effects of neuroleptics. The authors examined the prevalence of cigarette smoking in apparently healthy adolescents later hospitalized for schizophrenia. METHOD: Each year, a random sample of male Israeli military recruits, who have been screened and found not to be suffering from major psychopathology, complete a smoking questionnaire. Through the Israeli National Psychiatric Hospitalization Case Registry, 14,248 of these adolescents were followed to determine later psychiatric hospitalization. RESULTS: Of the 14,248 adolescents assessed, 4,052 (28.4%) reported smoking at least one cigarette a day. Over a 4-16-year follow-up, the prevalence of schizophrenia in the entire cohort was 0.3% (N=44). Smokers were at greater risk for later schizophrenia; the adjusted relative risk was 1.94, and the 95% confidence interval (CI) was 1.05-3.58. The number of cigarettes smoked was significantly associated with the risk for schizophrenia. Compared to nonsmokers, adolescents who smoked 1-9 cigarettes/day were 1.38 times (95% CI=0.48-4.00) as likely to be hospitalized later for schizophrenia, and adolescents who smoked 10 cigarettes/day or more were 2.28 times (95% CI=1.19-4.34) as likely; the latter difference was statistically significant. CONCLUSIONS: Taken together with the existing data on abnormalities in nicotinic transmission in patients and their relatives, this higher prevalence of smoking in future schizophrenia patients, before the onset of their illness, might indicate that impaired nicotinic neurotransmission is involved in the pathophysiology of schizophrenia.

Adolescent↗

Body mass index and future schizophrenia in Israeli male adolescents.

BACKGROUND: Compared with the general population, individuals suffering from schizophrenia are more likely to be overweight, a finding attributed to the effect of antipsychotic medications, poor nutrition, and sedentary lifestyle. As evidence accumulates indicating that some aspects of the illness manifest before the onset of psychosis and establishment of the diagnosis, it has been suggested that increased weight, like other metabolic dysfunctions, might precede active illness. METHOD: Data on height and weight of 203,257 male adolescents assessed by the Israeli Draft Board, and followed for 2-6 years for later hospitalization for schizophrenia using the Israeli National Psychiatric Hospitalization Case Registry, were analyzed. RESULTS: From the entire cohort, 309 (0.15%) were later hospitalized for schizophrenia (ICD-10). After removing adolescents with evidence of illness before or within 1 year of the Draft Board assessment, 204 future schizophrenia patients were available for analysis. Compared with the rest of the cohort, future schizophrenia patients had lower body mass indexes (21.24 +/- 3.3 kg/m2 vs. 21.77 +/- 3.5 kg/m2; F = 4.682, df = 1, p = .03) and weighed slightly but significantly less (64.2 +/- 11.6 kg vs. 66.3 +/- 12.0 kg; F = 6.615, df = 1, p = .01). The mean height of the future patients did not differ significantly from the mean height of the remaining cohort (173.63 +/- 6.7 cm vs. 174.40 +/- 6.9 cm; F = 2.520, df = 1, p = .112). When reanalyzing the data, controlling for physical activity and socioeconomic status, the differences between the groups remained significant. CONCLUSION: Before the onset of illness, future schizophrenia patients are not heavier compared with their peers. This implies that the increased weight of patients with schizophrenia is related to illness effects, including the effects of antipsychotic medication.

Adolescent↗