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Objective: To test whether duration of untreated psychosis (DUP) < 3 months, recommended by the World Health Organization/International Early Psychosis Association, enhances the effects of an extended early intervention service (EEIS) on symptom remission. Method: We examined data from a randomized controlled trial in which patients who received 2 years of treatment in EIS for psychosis were subsequently randomized to either 3 years of EEIS or 3 years of regular care (RC). Using a DUP cut‐off ≤ 12 weeks (approximately < 3 months), patients were split into two groups. Length of positive, negative and total symptom remission were the outcomes. Results: Patients (N = 217) were mostly male (68%) with schizophrenia spectrum disorder (65%); 108 (50%) received EEIS (58 had DUP ≤12 weeks; 50 had DUP >12 weeks). Interaction between treatment condition (EEIS vs. RC) and DUP cut‐off ≤ 12 weeks was only significant in multiple linear regression model examining length of negative symptom remission as the outcome (adjusted β = 36.88 [SE = 15.88], t = 2.32, P = 0.02). EEIS patients with DUP ≤12 weeks achieved 25 more weeks of negative symptom remission than EEIS patients with DUP >12 weeks. Conclusion: Having a short DUP may be critical in deriving long‐term benefits from EIS for psychosis, including EEIS settings. This work empirically supports policy recommendations of reducing DUP <3 months. [ABSTRACT FROM AUTHOR]

Objective: The experience of pre‐onset subthreshold psychotic symptoms (STPS, signifying a clinical high‐risk state) in first episode psychosis (FEP) predicts poorer outcomes during treatment, possibly through differential adherence to medication. We explored whether adherence differs between FEP patients with and without pre‐onset STPS. Methods: Antipsychotic medication adherence was compared in 263 STPS+ and 158 STPS− subjects in a specialized early intervention program for FEP. Data were gathered from a larger observational study conducted between 2003 and 2016. STPS status, sociodemographic, and baseline clinical variables were tested as predictors of non‐adherence using univariate and multivariate logistic regressions. Time to onset of non‐adherence was analyzed using Kaplan–Meier curves. The same predictors were tested as predictors of time to onset of non‐adherence using Cox regression models. Results: Medication non‐adherence was higher in STPS+ participants (78.9% vs. 68.9%). STPS status (OR 1.709), substance use disorder (OR 1.767), and milder positive symptoms (OR 0.972) were significant baseline predictors of non‐adherence. Substance use disorder (HR 1.410), milder positive symptoms (HR 0.990), and lack of contact between the clinical team and relatives (HR 1.356) were significant baseline predictors of time to non‐adherence. Conclusion: FEP patients who experience pre‐onset STPS are more likely to be non‐adherent to antipsychotic medication over 2 years of intervention. FEP programs should routinely evaluate pre‐onset symptomatology to deliver more personalized treatments, with emphasis on engaging both patients and family members from the beginning of care. [ABSTRACT FROM AUTHOR]

Background: A history of childhood symptoms of inattention-hyperactivity is often reported in first episode psychosis (FEP) as is cannabis use. In the general population childhood ADHD predicts future cannabis use but the relationship has not been tested in FEP.Method: Parents of patients with a first episode of psychosis (n=75) retrospectively assessed their affected child for symptoms of early-life disorders, namely, attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD) using the Child Behaviour Checklist (CBCL). Assessments were made prospectively of cannabis use over two years following a FEP and of SCID diagnosis of cannabis-use disorder.Results: Childhood hyperactivity-inattention symptoms predicted inability to maintain abstinence from cannabis following treatment (Wald=8.4, p=.004) and lifetime cannabis-use diagnosis (Wald=5.3, p=.022) in a logistic regression controlling for relevant covariates including symptoms of CD and ODD from ages 12 to 18. When the symptom of inattention was considered in place of the hyperactivity-inattention syndrome it predicted cannabis-use diagnosis (Wald=6.4, p=.011) and persistent abstinence from cannabis (Wald=5.3, p=.021). Symptoms of CD and ODD did not predict cannabis use when hyperactivity-inattention symptoms were controlled for.Conclusions: Symptoms of childhood inattention-hyperactivity predict subsequent cannabis use in FEP. [ABSTRACT FROM AUTHOR]

Objective: To determine to what extent the clinical response to methylphenidate (MPH) is affected by psychiatric comorbidities in children diagnosed with attention-deficit hyperactivity disorder (ADHD).Methods: Children (n = 267) aged 6 to 12 years diagnosed with ADHD participated in a double-blind, placebo-controlled, 2-week medication trial of MPH. Children were assessed using parent and teacher ratings and laboratory measures. Clinical response to MPH was determined by integrating all obtained measures.Results: Meeting criteria for conduct disorder (CD) was 27.7% of children, 40.8% for oppositional defiant (ODD), 47.2% for anxiety, and 7.9% for depressive disorders. The presence of CD or ODD was associated with good response to MPH. In contrast, children diagnosed with only comorbid anxiety were more likely to receive poor response rating independent of age, sex, or socioeconomic status. Low family income was found to be predictive of good response to MPH.Conclusions: The response to MPH in children with ADHD may be dependent on the type of comorbid disorder present.Clinical Trial Registration Number: NCT00483106. [ABSTRACT FROM AUTHOR]

Background: We reviewed systematically the results of genetic studies investigating associations between putative susceptibility genes for attention-deficit hyperactivity disorder (ADHD) and neuropsychological traits relevant for this disorder. Methods: We identified papers for review through the PubMed database. Results: Twenty-nine studies examined 10 genes (DRD4, DAT1, COMT, DBH, MAOA, DRD5, ADRA2A, GRIN2A, BDNF and TPH2) in relation to neuropsychological traits relevant for ADHD. For DRD4, the continuous performance test (CPT) and derived tasks were the most used tests. Association of high reaction time variability with the 7-repeat allele absence appears to be the most consistent result and seems to be specific to ADHD. Speed of processing, set-shifting and cognitive impulsiveness were less frequently investigated but seem to be altered in the 7-repeat allele carriers. No effect of genotype was found on response inhibition (the stop and go/no-go tasks). For DAT1, 4 studies provide conflicting results in relation to omission and commission errors from CPT and derived tasks. High reaction time variability seems to be the most replicated cognitive marker associated with the 10-repeat homozygosity. The other genes have attracted fewer studies, and the reported findings need to be replicated. Limitations: Although we aimed to perform a formal meta-analysis, this was not possible because the number of studies using the same neurocognitive endophenotypes was limited. We referred only minimally to the various theoretical frameworks in this field of research; more detail would have been beyond the scope of our systematic review. Finally, sample sizes in most of the studies we reviewed were small. Thus, some negative findings could be attributed to a lack of statistical power, and positive results should be considered preliminary until they are replicated in extended samples. Conclusion: Several methodological issues, including measurement errors, developmental changes in cognitive abilities, sex, psychostimulant effects and presence of comorbid conditions, represent confounding factors and may explain conflicting results. [ABSTRACT FROM AUTHOR]

BACKGROUND: Low-function alleles of the serotonin transporter promoter polymorphism (5HTTLPR) have been linked to various psychopathological entities, especially in individuals exposed to prior stressors. In women with bulimic syndromes, we explored associations with personality pathology of 5HTTLPR and prior sexual or physical maltreatment. METHODS: Ninety-two women with bulimic syndromes were genotyped for 5HTTLPR short (S) and long (L(G) and L(A)) alleles and were then assessed for eating symptoms, dimensional personality disturbances, history of sexual or physical abuse and borderline personality disorder (BPD). RESULTS: With a classification based on a biallelic model of 5HTTLPR (i.e., presence or absence of at least 1 S-allele copy), multiple regression analyses indicated significant proportions of variance in stimulus seeking and insecure attachment to be explained by abuse x genotype interaction effects, with greater psychopathology always occurring in S-allele carriers who had been abused. Likewise, a logistic regression analysis linked BPD to significant main effects of genotype and abuse. Analyses that aggregated carriers according to a triallelic model of 5HTTLPR (i.e., presence or absence of at least 1 copy of a presumably low-function S or LG allele) produced similar patterns but no statistically significant effects. CONCLUSIONS: Traits such as sensation seeking and insecure attachment are, on average, elevated in 5HTTLPR S-allele carriers with bulimic syndromes who report prior physical or sexual maltreatment. These results add to the literature associating pronounced psychopathological manifestations, with conjoint effects of stress and the 5HTTLPR polymorphism. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether children with attention-deficit hyperactivity disorder (ADHD) and learning disabilities respond differently to methylphenidate (MPH) compared with children with ADHD only. METHODS: We conducted a prospective, double-blind, placebo-controlled, randomized, 2-week crossover trial of MPH, during which response to MPH was assessed. Learning ability was appraised using the Wide Range Achievement Test, Revised (WRAT-R), for English-speaking students and the Test de rendement pour francophones for French-speaking students. The study was conducted at the Douglas Hospital, a McGill University-affiliated teaching hospital in Montréal. Ninety-five children, aged 6-12 years, who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria for ADHD participated in the study, which ran from 2001 to 2004. The outcome measure used was the Consensus Clinical Response, an indicator of the degree of clinical improvement shown when taking MPH. RESULTS: The proportion of children with learning disabilities who responded to MPH (55%) was significantly smaller (chi(2)1 = 4.5, p = 0.034) than the proportion of children without learning disabilities who responded adequately to MPH (75%). This difference was mainly because of children with mathematics disability being particularly unresponsive to MPH (chi(2)1 = 4.5, p = 0.034). Children with reading disability did not show this pattern of poor response (chi(2)1 = 1.0, p = 0.33). CONCLUSION: Children with ADHD and comorbid learning disability tended to respond more poorly to MPH. In particular, children with disability in mathematics responded less to MPH than those without disability in mathematics. Additional therapy may be indicated for this group of patients. [ABSTRACT FROM AUTHOR]

This paper describes a research program intended to provide a better understanding of the influence of several putative risk factors for schizophrenia on child development and psychosis. Two related components of the overall program are described: the retrospective EnviroGen projects, which use a variety of putative risk factors to explain variance in several dimensions of schizophrenia and in psychotic symptoms in community controls, and Project Ice Storm, which prospectively examines the effects of prenatal maternal stress in the children of women who were exposed to the 1998 Quebec ice storm during their pregnancies. The EnviroGen projects have been successful in explaining variance in several dimensions of illness, including premorbid adjustment and severity of dissociative symptoms. Project Ice Storm has demonstrated the noxious effects of prenatal stress on cognitive and language development in children. We have also found that 'ice storm children' exposed in specific weeks of gestation show greater dermatoglyphic asymmetry, as has been reported for samples of patients with schizophrenia. In both studies, prenatal maternal stress has been associated with more severe childhood behaviour problems. The combination of retrospective and prospective studies is a rich source of triangulated results providing information about developmental psychopathology. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Genetic and nonshared environmental factors (experienced by 1 family member to the exclusion of the others) have been strongly implicated in the causes of attention-deficit hyperactivity disorder (ADHD). Pregnancy, labour/delivery and neonatal complications (PLDNC) have often been associated with ADHD; however, no investigations aimed at delineating the shared or nonshared nature of these factors have been reported. We aimed to identify those elements of the PLDNC that are more likely to be of a nonshared nature. METHODS: We used an intrafamily study design, comparing the history of PLDNC between children diagnosed with ADHD, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and their unaffected siblings. Children with ADHD were recruited from the outpatient, day-treatment program of the Child Psychiatry Department, Douglas Hospital, Montreal. The unaffected sibling closest in age to the child with ADHD was used as a control. The history of PLDNC was assessed using the Kinney Medical and Gynecological Questionnaire and the McNeil-Sjostrom Scale for both children with ADHD and their siblings. Seventy children with ADHD along with 50 of their unaffected siblings agreed to participate in the study. Child Behavior Checklist (CBCL), Continuous Performance Test (CPT) and Restricted Academic Situation Scale (RASS) scores were also used as measures of ADHD symptoms in children with ADHD. RESULTS: The children with ADHD had significantly higher rates of neonatal complications compared with their unaffected siblings (F4,196 = 3.67, p < 0.006). Furthermore, neonatal complications in the children with ADHD were associated with worse CBCL total and externalizing scores and with poorer performance on the CPT. CONCLUSIONS: These results suggest that neonatal complications are probably a nonshared environmental risk factor that may be pathogenic in children with ADHD. [ABSTRACT FROM AUTHOR]

BACKGROUND: A short (s) allele in the promoter region of the 5-hydroxytryptamine (5-HT) transporter gene (5HTTLPR) has been associated with low transcription of the 5-HT transporter protein, and with clinical manifestations including impulsivity, affective disorder, and bulimia nervosa. METHODS: We studied implications of the 5HTTLPR s allele for eating symptoms, psychopathologic traits, and platelet [3H-] paroxetine binding in 59 women with bulimia spectrum syndromes. RESULTS: Compared with those without it, carriers of the s allele of 5HTTLPR showed significantly more affective instability, behavioral impulsivity, interpersonal insecurity, comorbid borderline personality disorder (BPD), and lower density (Bmax) of paroxetine-binding sites. CONCLUSIONS: Our results suggest that proneness to impulsivity, affective dysregulation, and reduced central 5-HT reuptake may (in part) be codetermined by the 5HTTLPR polymorphism. However, given inconsistent 5HTTLPR expression in different populations, we speculate that we may be observing a phenotype (i.e., eating disorder)-dependent manifestation. 2004 by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To review the results of genetic studies investigating dopamine-related genes in attention-deficit hyperactivity disorder (ADHD). DATA SOURCES: Papers (association/linkage, meta-analyses and animal model studies) were identified through searches of the PubMed database and systematically reviewed. DATA SYNTHESIS: Consistent results from molecular genetic studies are pointing strongly to the possible link between 2 specific genes, the dopamine transporter (SLC3A6) and the dopamine receptor 4 (DRD4), and ADHD. CONCLUSIONS: The implication of SLC6A3 and DRD4 genes in ADHD appears to be one of the most replicated in psychiatric genetics and strongly suggests the involvement of the brain dopamine systems in the pathogenesis of ADHD. However, more work is required to further these findings by genotype-to-phenotype correlations and identify the functional allelic variants/mutations that are responsible for these associations. The role of other dopamine genes, which may have smaller effects than SLC6A3 and DRD4, needs also to be determined. [ABSTRACT FROM AUTHOR]

The schizophrenia phenotype is heterogeneous with respect to clinical presentation, long-term response to medication, and outcome, possibly reflecting genetic heterogeneity and/or the presence of modifier genes. Compared to non-responders, schizophrenic patients who are responders to neuroleptic medications are characterized by a high female/male ratio, a better longterm outcome and more frequently disturbed dopamine neurotransmission. In this study, we compared two groups of schizophrenic patients selected on the basis of their long-term response to neuroleptics (excellent responders and non-responders) and a group of healthy volunteers, with regard to a missense mutation (677C→T) in the methylenetetrahydrofolate reductase (MTHFR) gene. This polymorphism was chosen because it is functional5 and was previously associated with schizophrenia. The present study revealed a significant association between schizophrenia and allele T of this gene. This association was entirely due to an over-representation of allele T in responder patients compared to controls; nonresponder patients did not differ from controls. Genotype TT was more frequent in responder patients compared to controls, thus replicating the findings of Arinami et al. These results strongly suggest that the MTHFR gene is involved in the pathogenesis of schizophrenia characterized by a rapid and sustained therapeutic response to typical neuroleptics and/or a good long-term prognosis/favorable therapeutic outcome. [ABSTRACT FROM AUTHOR]

Several studies have indicated that patients with bipolar disorder (BD) who respond well to lithium prophylaxis constitute a biologically distinct subgroup. Lithium is thought to stablize mood by acting at the phosphoinositide cycle. We have investigated a polymorphism located in the gene (PLCG1) that codes for a γ-1 isozyme of phospholipase (PLC), an enzyme that plays an important role in the phosphoinositide second messenger system. A population-based association study and a family-based linkage study were carried out on patients who were considered excellent responders to lithium prophylaxis. Response to lithium was evaluated prospectively with an average follow-up of 14.4 ± 6.8 years. The PLCG1 polymorphism was investigated in 136 excellent lithium responders and 163 controls. In addition, the segregation of this marker was studied in 32 families ascertained through lithium-responsive bipolar probands. The allele distributions between lithium-responsive bipolar patients and controls were different, with a higher frequency of one of the PLCG1 polymorphisms in patients (χ² = 8.09; empirical P=0.033). This polymorphism, however, confers only a small risk (OR = 1.88, CI 1.19-3.00). Linkage studies with the same marker yielded modest support for the involvement of this gene in the pathogenesis of BD when unilineal families were considered (Max LOD=1.45; empirical P=0.004), but not in the whole sample. Our results provide preliminary evidence that a PLC isozyme may confer susceptibility to bipolar disorder, probably accounting for a fraction of the total genetic variance. Whether this polymorphism is impli- cated in the pathogenesis of BD or in the mechanism of lithium response remains to be determined. [ABSTRACT FROM AUTHOR]