Urbanicity has been repeatedly associated with increased incidence of schizophrenia. This article (a) presents results of a prospective study of urbanicity and schizophrenia in Ireland and (b) reviews the literature relating to urbanicity and schizophrenia. We prospectively compared incidence of schizophrenia and other psychoses in urban and rural catchment areas (over 4 years and 7 years, respectively) using face-to-face, DSM-III-R diagnostic interviews. Incidence of schizophrenia in males was higher in urban compared to rural areas, with an age-adjusted incidence rate ratio (IRR) of 1.92 (1.52–2.44) for males and 1.34 (1.00–1.80) for females. Incidence of affective psychosis was lower in urban compared to rural areas for males (IRR 0.48; 0.34–0.67) and females (IRR 0.60; 0.43–0.83). These findings are consistent with the literature, which provides persuasive evidence that risk for schizophrenia increases with urban birth and/or upbringing, especially among males. Register-based studies support this conclusion more consistently than studies using face-to-face diagnostic interviews, the difference being related to power. The mechanism of association is unclear but may relate to biological or social/environmental factors or both, acting considerably before psychotic symptoms manifest. There is a diversity of potential candidates, including air pollution, cannabis and social exclusion. Urbanicity may have a synergistic effect with genetic vulnerability. Future research is likely to focus on the relationship between urbanicity and neural maldevelopment, the possibility of rural protective factors (e.g. social capital, low social fragmentation), urbanicity in developing countries, cultural variables and geographical location, and associations between urbanicity and other disorders (e.g. affective psychosis).

Background The critical period hypothesis proposes that deterioration occurs aggressively during the early years of psychosis, with relative stability subsequently. Thus, interventions that shorten the duration of untreated psychosis (DUP) and arrest early deterioration may have long-term benefits. Aims To test the critical period hypothesis by determining whether outcome in non-affective psychosis stabilises beyond the critical period and whether DUP correlates with 8-year outcome; to determine whether duration of untreated illness (DUI) has any independent effect on outcome. Method We recruited 118 people consecutively referred with first-episode psychosis to a prospective, naturalistic cohort study. Results Negative and disorganised symptoms improved between 4 and 8 years. Duration of untreated psychosis predicted remission, positive symptoms and social functioning at 8 years. Continuing functional recovery between 4 and 8 years was predicted by DUI. Conclusions These results provide qualified support for the critical period hypothesis. The critical period could be extended to include the prodrome as well as early psychosis.

INTRODUCTION:Substance misuse (SM) (drug/alcohol dependence or abuse) in psychotic illness is an increasingly recognized problem. We aimed to estimate the prevalence and examine the influence of SM on age at onset of psychosis and psychopathology among patients with first-episode psychosis.METHOD:One hundred seventy-one consecutive patients with first-episode psychosis were assessed. SM, age of onset of psychosis and psychopathology were determined using valid instruments.RESULTS:Seventy-seven (46%) patients had a lifetime history of SM and were predominately males, had more positive symptoms, and in the majority of cases (84%), started misusing substances before the onset of psychosis (SM-BP). There was no difference in age of onset between patients with SM-BP and the rest of the sample.CONCLUSION:Lifetime history of SM is common and may influence psychopathology, but does not appear to influence or bring forward the age at onset of psychotic symptoms.

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AbstractObjective: To examine the variables that influence of duration of untreated psychosis (DUP) prior to presentation in persons with a first episode of psychosis.Method: Prospective examination of consecutive first presentations with DSM-IV psychosis attending a community based psychiatric service.Results: One hundred and seventy-one patients had an average duration of untreated psychosis of 18 months and a median of five months. The mean duration of untreated mania was 1.5 months, median 0.75 months. DUP was predicted by social withdrawal and diagnosis in the total group and by prodrome in the schizophrenia/schizophreniform group. DUP was not associated with age at onset of psychosis, educational years or living status.Conclusions: There are significant differences in DUP between diagnostic groups. Increased social withdrawal is associated with a longer DUP.

This research attempts to explore empirically the relationship between lack of illness and neuropsychological performance in a group of chronic schizophrenic subjects. Thirty one chronic schizophrenics were administered the recently developed Scale to Assess Unawareness of Mental Disorder (SUMD) and 3 neuropsychological tests that have demonstrated ability to assess frontal lobe performance: the Wisconsin Card Sorting Test (WCST), Verbal Fluency Test and Trails A and B. The number of categories completed and the percent perseverative responses on the WCST were found to significantly correlate with lack of illness awareness as measured by the SUMD. These two WCST variables were also able to significantly discriminate between subjects of high versus low awareness. A discriminant function analysis found that a linear combination of WCST percent perseverative responses and symptom severity could successfully categorize 84% of the aware versus unaware subjects. These results are taken to support the hypothesis that at least in some of its manifestations lack of awareness among chronic schzophrenics has an organic etiology probably mediated by the frontal lobes.

Background: Neurological soft signs (NSS) are well described among patients with schizophrenia, the neurology of other psychoses is relatively unexplored and few comparative studies have prospectively examined these signs in first-episode patients,Methods: We assessed neurological functioning in 242 patients presenting with a first episode of psychosis (in accordance with DSM-IV diagnosis) using the Condensed Neurological Examination (CNE). We sought to determine whether NSS were specific to patients with schizophrenia, bipolar affective disorder and other forms of psychosis. We also examined the factors associated with and predictive of neurodysfunction at first presentation and at 4 year follow-up.Results: NSS were not specific to any diagnostic group. Neurological functioning was closely associated with psychopathology and mixed-handedness at first presentation. At follow-up there was a statistically significant improvement in neurological functioning. Persistent neurodysfunction at this stage was related to enduring negative symptoms and associated with poorer outcome.Discussion: Schizophrenia and bipolar disorder are indistinguishable in terms of neurodysfunction at presentation. At presentation and 4 years NSS closely parallel psychopathology and mixed-handedness indicating that NSS may be a function of these factors or possibly an independent factor operates equally upon both symptoms and neurological function. (c) 2006 Elsevier B.V. All rights reserved.

OBJECTIVE:The objective of this study was to determine the stability of a diagnosis of psychosis four years after the first-episode diagnosis.METHODS:The study was a prospective four-year follow-up study (1995 to 1999) of 147 patients with schizophrenia, affective disorder, and other psychoses who presented with a first episode of psychosis in an epidemiologic catchment area in Ireland. All diagnoses were made on the basis of the Structured Clinical Interview for DSM-IV.RESULTS:One quarter of the patients evidenced a change in diagnosis at follow-up. The most common change was to a diagnosis of schizophrenia. The positive predictive values of schizophrenia and bipolar affective disorder were 97 percent and 80 percent, respectively. Fewer years spent in education, lower levels of initial psychopathology, and presence of comorbid alcohol or substance abuse were associated with change in diagnosis at follow-up.CONCLUSIONS:Among the diagnoses studied, schizophrenia was the most stable diagnosis after four years. The greatest instability occurred in the categories of drug-induced psychosis and psychosis not otherwise specified.

OBJECTIVE:To map the development of insight in the 4 years after presentation with first-episode schizophrenia and schizophreniform disorder and to determine the effects of evolving insight on depression and the likelihood of attempted suicide.METHOD:We assessed 101 individuals at presentation, 6 months and 4 years. We measured insight, including recognition of mental illness, recognition of need for treatment and ability to relabel psychotic symptoms. We measured depression and recorded all suicide attempts.RESULTS:Insight improved with time. Recognition of mental illness at 6 months predicted depression and attempted suicide at 4 years.CONCLUSION:Six months after presentation, the greater the acknowledgement by people that they had a mental illness, the more depressed they were at 4 years and the greater the likelihood that they would attempt suicide by 4 years. This may have implications for disclosure of diagnosis.

Individuals with epilepsy are at increased risk of having psychotic symptoms that resemble those of schizophrenia. More controversial and less searched is if schizophrenia is a risk factor for epilepsy. Here we review overlapping epidemiological, clinical, neuropathological and neuroimaging features of these two diseases. We discuss the role of temporal and other brain areas in the development of schizophrenia-like psychosis of epilepsy. We underline the importance of ventricular enlargement in both conditions as a phenotypic manifestation of a shared biologic liability that might relate to abnormalities in neurodevelopment. We suggest that genes implicated in neurodevelopment may play a common role in both conditions and speculate that recently identified causative genes for partial complex seizures with auditory features might help explain the pathophysiology of schizophrenia. These particularly include the leucine-rich glioma inactivated (LGI) family gene loci overlap with genes of interest for psychiatric diseases like schizophrenia. Finally, we conclude that LGI genes associated with partial epilepsy with auditory features might also represent genes of interest for schizophrenia, especially among patients with prominent auditory hallucinations and formal thought disorder.

ResumenTener un diagnóstico de esquizofrenia es un factor de riesgo para el ingreso no voluntario en la asistencia hospitalaria psiquiátrica, pero tenemos una comprensión limitada de por qué algunos pacientes precisan un ingreso no voluntario y otros no. Intentamos identificar los predictores del ingreso no voluntario en el primer episodio de esquizofrenia. Utilizamos instrumentos validados para evaluar las variables clínicas y sociodemográficas en todos los pacientes (n = 78) con primer episodio de esquizofrenia de un área geográfica definida ingresados en un hospital psiquiátrico de Dublín durante un periodo de 4 años. No se pudo distinguir a los pacientes no voluntarios (n = 17) de los voluntarios (n = 61) de acuerdo con la edad, el género, la situación de convivencia, el estado civil, el abuso de drogas o la duración de la psicosis no tratada. Ni los síntomas positivos ni los negativos fueron predictores útiles del tipo de ingreso. La falta de insight fue un fuerte predictor del ingreso de tipo no voluntario.

This study aimed to identify the incidence and clinical correlates of aggression and violence in first episode psychosis. We prospectively recruited subjects with a first episode of DSM-psychosis presenting from a geographically defined catchment area to a secondary referral psychiatric service over a four-year period (n=157). We used the Modified Overt Aggression Scale to retrospectively assess aggression (a hostile or destructive mental attitude, including verbal aggression, physical aggression and/or violence) and violence (the exercise of physical force), blind to diagnosis. One in three patients with psychosis was aggressive at the time of presentation. One patient in 14 engaged in violence that caused, or was likely to cause, injury to other people. Aggression was independently associated with drug misuse (odds ratio (OR) 2.80, 95% confidence interval 1.12–6.99) and involuntary admission status (OR=3.62, 95% CI 1.45–9.01). Violence in the week prior to presentation was associated with drug misuse (OR=2.75, CI 1.04–7.24) and involuntary admission status (OR=3.21, CI 1.21–8.50). Violence in the week following presentation was associated with poor insight (OR 2.97, CI 1.03–8.56) and pre-contact violence (OR 3,82, CI 1.34–10.88). In patients with schizophrenia, violence in the week following presentation was associated with drug misuse (OR=7.81, CI 1.33–45.95) and high psychopathology scores (OR=20.59, CI 1.66–254.96). Overall, despite a high rate of verbal aggression, physical violence towards other people is uncommon in individuals presenting with first episode psychosis.

There is enduring debate about the validity of subjective measures of quality of life derived from people with psychiatric disorders and particularly from those with psychosis. We evaluated patients with established psychosis 4 years after their first episode. We compared subjective and objective measures of quality of life and evaluated the influence of insight on the individual's interpretation of their quality of life. Subjective measures of quality of life were derived using the World Health Organization Quality of Life Scale—Brief Version, and objective measures of quality of life were derived using the Quality of Life Scale by Heinrichs et al. We measured Insight using the Insight Scale. There were robust correlations between subjective and objective assessments of quality of life. This was most marked for psychological symptoms. Self-report measures are valid and should form part of the overall assessment of quality of life among patients with psychotic disorders.

Research literature supports the notion that more people diagnosed with schizophrenia are born during the winter months than other seasons [O'Hare A, Walsh D, Torrey F. Seasonality of schizophrenia births in Ireland. Br J Psychiatry 1980;137:74–7; Pulver AE, Stewart W, Carpenter WT, Jr., Childs B. Risk factors in schizophrenia: season of birth in Maryland, USA. Br J Psychiatry 1983;143:389–96.]. Researchers have postulated that this surge in winter-birth schizophrenia may be related to increases in viral infectious such as influenza and measles [Watson CG, Kucala T, Tilleskjor C, Jacobs L. Schizophrenic birth seasonality in relation to incidence of infectious diseases and temperature extremes. Arch Gen Psychiatry 1984;41:85–90; Mednick SA, Machon RA, Huttunen MO, Bonnett D. Adult schizophrenia following prenatal exposure to an influenza epidemic. Arch Gen Psychiatry 1988;45:189–92.]. However, data supporting significant relationships between infectious disease and schizophrenia incidence has been equivocal [Kendell R, Kemp I. Maternal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 1989;46:878–82; McGrath J, Castle D. Does influenza cause schizophrenia? A five year review. Aust N Z J Psychiatry 1995;29:23–31.]. The purpose of this study was to replicate and expand previous studies by examining seasonal and infectious disease influences on schizophrenia prevalence. It was hypothesized that: (1) there would be an increase in schizophrenia prevalence during the winter months; and (2) that a significant amount of variability in schizophrenia birthrates would be accounted for by rates of influenza and measles. A Georgia Medicaid database (N=746,615) and statewide infectious disease tables were used to identify correlations. Medicaid recipients were divided into schizophrenia (n=11,736) and non-schizophrenia (n=734,879) groups. A ratio of schizophrenic recipients to non-schizophrenic recipients was calculated for each birth cohort represented by each month of the year from 1948–1965. Multiple regression analyses indicated a significant relationship between winter season and schizophrenia incidence. However, neither influenza nor measles was predictive of schizophrenia prevalence. These findings were made using one of the largest sample of schizophrenic individuals in the literature to date. Limitations of the study are discussed, including the use of seasonal and prevalence correlations without data on patient linked maternal infections.

Background. Although patients with schizophrenia have increased rates of neurological soft signs, few studies have examined prospectively their trait or state characteristics in relation to psychopathology.Method. In a prospective study of 97 patients with first-episode schizophrenia (DSM-IV criteria) we assessed neurological soft signs and psychopathology at presentation and at 6 month follow-up for 73 cases. To establish whether soft signs were associated with variations in clinical state, neurological soft signs were measured using two validated examinations (Neurological Evaluation Scale and Condensed Neurological Examination); psychopathology was assessed using the Positive and Negative Syndrome Scale.Results. There was significant improvement in overall neurological function, primarily in motor-related and cortical signs, which were associated with improvement in psychopathology. Conversely, 'harder' signs were unrelated to improvement in psychopathology.Conclusions. Neurological soft signs in schizophrenia are heterogenous. Motor and cortical signs evidence state-like characteristics and vary with clinical course, while 'harder' signs evidence more static, trait-like characteristics in accordance with a neurodevelopmental basis.

The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms.This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified.Children with ADHD had significantly higher dimethylphosphate (DMP, 236.69 nmol/g cre. vs. 186.84 nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95 µg/g cre. vs. 16.55 µg/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24–0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13–1.05), indicating that 59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12–65.04).This study indicated a gene-environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose-response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected.