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Objective: Cognitive insight represents the capacity to self-reflect and consider external feedback when re-evaluating faulty beliefs. It is associated with specific cognitive capacities such as verbal memory, of which there is substantial evidence for sex differences in psychotic disorders. Like more general cognitive capacities, cognitive insight might too be modulated by sex differences.Method: One hundred and seventy-one first episode psychosis (FEP; 123 males, 48 females), and 203 multiple episode psychosis (MEP; 147 males, 56 females) participants completed the Beck Cognitive Insight Scale (BCIS). A two-way MANOVA was conducted on the three BCIS measures (self-reflectiveness, self-certainty, composite index) with sex (male, female) and illness stage (FEP, MEP) as factors, followed by two-way ANOVAs and a post hoc test of simple effects.Results: The only significant interaction to emerge was between sex and illness stage in self-certainty (F(1, 373) = 5.88, p = .016). A test of simple effects revealed that self-certainty group means were significantly different for males and females in FEP, where females had lower self-certainty than males (p = .053) but not during MEP (p = .119).Conclusion: Sex differences do not modulate cognitive insight in MEP, which may be attributable to females having greater positive symptom severity than males. In FEP however, results revealed that females were significantly less self-certain than males. Lower self-certainty relative to self-reflectiveness predicts treatment response in psychological interventions, and as such future FEP studies should explore sex differences in psychological interventions. [ABSTRACT FROM AUTHOR]

The authors reflect on how psychiatric disorders could be aggregates of rare or orphan diseases that share surface characteristics and how it may help in improving care for patients with orphan diseases. Topics include the European and American definitions of a rare disease, the possible adverse effects of rare diseases like physical and mental impairments, and the efforts to develop treatments in the U.S. since the passage of the Orphan Drug Act in 1983.

The article discusses the management of a 21-year-old male patient with first episode of psychosis. Topics mentioned include the symptoms displayed by the patient when he was brought to an emergency psychiatric clinic, the response of the patient with pharmacotherapy, the factors that need to consider when using pharmacogenetic variations, and the basis of maximum daily doses of antipsychotics.

The authors reflect on the implications of the neo-Kraepelin framework (NKF) for clinical practice and research. He says that the practice of psychiatry in the 18th and 19th centuries produced a rich literature through clinical descriptions. Frameworks produced by researcher Emile Kraepelin and psychoanalysis founder Sigmund Freud that shaped modern psychiatry are discussed. The repudiation of any theoretical framework of mental illnesses is considered a major theoretical foundation of the NKF.

Background: Specialized early intervention (EI) following a first episode of psychosis (FEP) are effective at reducing negative symptoms, although its trajectory warrants systematic assessment. However, findings are equivocal as to whether extended gains are made post 2 years of EI and whether there is additional benefit of extending EI for an additional 3 years. Methods: Data on 178 FEP patients, from a randomized controlled trial of a 3-year extension of EI service v. transfer to regular care following 2 years of EI service, were used for this report. Repeated measures analysis of variance were conducted separately for the initial 2 years of treatment in an EI service, and for the 3-year post-randomization to examine trajectories of negative symptoms over the two periods in the two arms of the study. Results: There were significant improvements in total negative symptoms over the first 2 years of EI F (4.612, 797.905) = 25.263, p < 0.001 and in domains of ' expressivity ' and ' motivation '. In the following 3 years, there were further significant improvements in negative symptoms F (4.318, 759.908) = 4.182, p = 0.002 with no difference between groups F (4.318, 759.908) = 1.073, p = 0.371. Changes in negative symptoms over the extension period were driven by expressivity F (4.01, 674.73) = 7.19, p < 0.01, but not motivation F (6.58, 1112.18) = 0.95, p = 0.46. Conclusion: Negative symptoms improve significantly over the first 2 years of EI. Subsequent amelioration was largely the result of expressivity. Motivation deficits remained stable. Extended EI offered no advantage over regular care post-randomization. [ABSTRACT FROM AUTHOR]

Introduction: Discontinuation of the initial oral antipsychotic prescribed for a first episode of psychosis (FEP) can derail outcome. Our objective was to examine the rate of and time to all-cause discontinuation of the first antipsychotic prescribed and the factors influencing such discontinuation.Methods: In a sample of 390 FEP patients, we estimated the rate of and time to discontinuation of the initial antipsychotic over a one-year period. The effects of a number of putative predictors of discontinuation were estimated using regression analyses.Results: Rate of discontinuation of the first antipsychotic was 72%, with no difference between the 3 investigated antipsychotics (olanzapine (73%), risperidone (68%) and aripiprazole (75%)), (χ2 (2) = 1.89, p = 0.388). Mean time to discontinuation was 7.2 (4.6) months and was not different among the three antipsychotics (Log-rank χ2 (2) = 0.257, p = 0.879). Binary logistic regression showed that higher positive and negative symptoms remission and baseline functioning were associated with lower rates of discontinuation (Nagelkerke R2 = 0.36, χ2 (10) = 66.9, p < 0.001). Multiple linear regression showed the same predictors, in addition to male gender and less weight gain per month of exposure to the initial antipsychotic, to be associated with longer time to discontinuation (adjusted R2 = 0.336, F (9, 219) = 13.8, p < 0.001).Conclusion: Discontinuation of the initial antipsychotic is a major concern in the course of treating FEP. Symptom relief, better functioning and lower side effects appear to be the major factors associated with continuing an antipsychotic medication. [ABSTRACT FROM AUTHOR]

The authors examine some of the factors that are likely to differ between controls and people with psychiatric diagnoses and that have impact on commonly measured neural outcomes. Topics include psychotropic medications as a potential confound in studies on the neurobiological correlates of psychiatric disorders, the impact of major classes of psychotropic medications on brain structure and function, and weight as a confounding factor when studying brain measures in psychiatric populations.

The article discusses ways on how to address the impact of digital technology on the delivery of mental health care services during COVID-19 pandemic. Topics mentioned include the importance of informed consent and ethics, the need to hire personnel to monitor mentally ill patients who prefer in-person contact with service providers, and the key components of electronic interventions and virtual method of care delivery.

Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ɛ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ɛ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments. Using a virtual navigation task developed in-house, specifically designed to assess spatial versus non-spatial strategies, the current study is the first to differentiate functional and structural differences within APOE ɛ4 allele carriers. APOE ɛ4 allele carriers that predominantly use non-spatial strategies have decreased fMRI activity in the hippocampus and increased atrophy in the hippocampus, entorhinal cortex, and fimbria compared to APOE ɛ4 allele carriers who use spatial strategies. In contrast, APOE ɛ4 allele carriers who use spatial strategies have grey matter levels comparable to non-APOE ɛ4 allele carriers. Furthermore, in a leave-one-out analysis, grey matter in the entorhinal cortex could predict navigational strategy with 92% accuracy. [ABSTRACT FROM AUTHOR]

Aim Duration of untreated psychosis ( DUP) has been associated with negative symptoms in several studies; however, longitudinal findings have been inconsistent. No previous study has accounted for active psychosis after presentation, although this could impact on outcomes in a manner similar to DUP. Methods We measured Scale for the Assessment of Positive Symptoms at frequent intervals during the 12 months after initial presentation to determine the active psychosis duration for 230 individuals with first-episode psychosis. This duration was added to DUP prior to presentation to create a new variable, duration of active psychosis ( DAP). Negative symptoms were divided into expressivity and motivation/pleasure domains as measured by Scale for the Assessment of Negative Symptoms ( SANS). The relationship of DUP and DAP with negative symptoms at 24-month follow up was determined and confounders controlled for using regression analysis. Results When DUP and DAP were compared as binary variables with long and short groups, 25.2% of individuals had differing category membership. DAP had a significant uncorrected association with both expressivity domain and motivation/pleasure domains at 24 months; however, relationship with DUP was not significant. DAP remained a significant predictor of 24-month expressivity domain after controlling for potential confounders. Conclusions Active psychosis after presentation is substantial, which is a limitation of DUP studies if active psychosis is considered as the key factor within DUP. DAP is a better predictor of negative symptoms than DUP at 2-year follow up, which suggests this concept requires further research. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Progress of negative symptoms over the initial 5 years of a first episode of psychosis" which was published in 14 March, 2018 issue of the perodical.

Attention Deficit/Hyperactivity Disorder (ADHD) has been associated with atypical patterns of neural activity measured by electroencephalography (EEG). However, the identification of EEG diagnostic biomarkers has been complicated by the disorder's heterogeneity. The objective of this review was to synthesize the literature investigating EEG variation in patients diagnosed with ADHD, addressing the following questions: 1) Are the diagnostic ADHD subtypes associated with different EEG characteristics? 2) Are EEG measures correlated with ADHD traits and/or symptom severity? and 3) Do classification techniques using EEG measures reveal different clinical presentations of ADHD? Outcomes highlight the potential for electrophysiological measures to provide meaningful insights into the heterogeneity of ADHD, although direct translation of EEG biomarkers for diagnostic purposes is not yet supported. Key measures that show promise for the discrimination of existing ADHD subtypes and symptomatology include: resting state and task-related modulation of alpha, beta and theta power, and the event-related N2 and P3 components. Prescriptions are discussed for future studies that may help to bridge the gap between research and clinical application. • Electrophysiology provides meaningful insight into the heterogeneity of ADHD. • Attentional, inhibitory control, and resting tasks are compared in ADHD subtypes. • Power spectrum and event-related potential analyses are related to ADHD symptoms. • EEG shows promise for the discovery of novel subgroups of ADHD. [ABSTRACT FROM AUTHOR]

The authors highlight some of the assumptions and limitations of neuroscience to underscore the potential value of a skeptical approach to neuroscience in psychiatric training and practice. Topics mentioned include conceptualization of chemical reactions at various levels, the National Institute of Mental Health Research Domain Criteria project, and the significance of limitations of neuroscience to psychiatry.

The author examines the reason behind the perception that mental illness is like any other illness, its consequences and the evidence to support or refute its continued justification. Topics discussed include a position believed to best fit the present state of knowledge and clinical realities and public perceptions of mental illnesses and detailed examination of the comparison between type 2 diabetes and mental disorders particularly schizophrenia, other psychoses and depression.

The article presents a study conducted by the authors on impact of environmental factors over hyperactivity disorder. Topics discussed include information on studies conducted over DNA methylation and histone acetylation; impact of hyper methylation and hypo methylation over gene expression; and positive impact of chromatin remodeling.

The author comments on pieces of evidence for medium range cognitive impairment (MeRCI) hypothesis for psychosis formation from epidemiological studies and latest molecular genetic developments. Topics covered include the difficulty to understand delusions and psychotic symptoms within a simple framework, a proposal that delusions may emerge under MeRCI and factors driving psychosis in individuals.

Abstract: Objective: Previous findings indicate that women with Bulimia Nervosa (BN), when compared to women with no eating disorder (NED), tend to display elevated methylation in the promoter region of the DRD2 gene. The preceding would be compatible with evidence of generally reduced dopamine activity in people with BN. However, altered DNA methylation has also been associated with adverse environmental exposures (such as to childhood abuse) and with psychiatric disturbances (such as Borderline Personality Disorder: BPD). In this study, we examined the extent to which DRD2 methylation was associated with the presence or absence of a bulimic eating disorder, to childhood abuse exposure, or to comorbid BPD. Method: Women with a bulimia-spectrum disorder (BSD) and women with NED were assessed for childhood traumata, eating-disorder symptoms and BPD, and provided blood samples for methylation analyzes. Results: BSD and NED groups did not differ as to mean percent DRD2 promoter methylation. However, among the women with a BSD, those with BPD showed small, but significant increases in DRD2 methylation levels compared to women with NED (as indicated by Hochberg's post-hoc tests). Similarly, women with a BSD who reported a history of childhood sexual abuse showed a trend-level elevation of DRD2 methylation compared to our NED group. Discussion: Our findings imply that, in people with a BSD, increased methylation of the DRD2 gene promoter may be more strongly characteristic of comorbid psychopathology than it is a global correlate of the eating disorder per se. We discuss theoretical implications of our findings. [Copyright &y& Elsevier]

Objective: Diagnostic stability is an important indicator of the reliability and validity of psychiatric diagnoses and has implications in clinical practice and research. While several studies have investigated the diagnostic stability of first-episode psychosis (FEP) disorders, less is known about psychiatric comorbidity in FEP and the persistence of such comorbid conditions over time. Our study aimed to confirm the diagnostic stability of FEP disorders and determine the variation in persistence of comorbid substance use disorders (SUDs), mood disorders, and anxiety disorders over 1 year. Method: The Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition was conducted at first presentation and repeated after 1 year (or reconstructed) for 214 FEP patients at the Prevention and Early Intervention Program for Psychoses-Montreal. Results: Psychotic disorder diagnoses were retained by 76.2% of patients at 1 year, schizophrenia being the most stable diagnosis (92.1%). Most diagnostic shifts were to schizophrenia and schizophrenia spectrum disorders. Comorbid SUDs, anxiety disorders, and mood disorders persisted for 50.7%, 64.0%, and 16.7% of patients, respectively. Many new cases of each of these disorders also emerged at 1-year follow-up. Conclusions: These findings demonstrate the stability of primary psychotic disorder diagnoses and greater fluidity of comorbid psychiatric diagnoses, with anxiety disorders persisting as comorbid conditions more than mood disorders and SUDs. These results highlight the importance of repeating a structured diagnostic assessment longitudinally, especially for consideration of comorbid conditions. [ABSTRACT FROM AUTHOR]

The author reflects on the misleading effects of simple and the complex theories in psychiatry. He states that more than 3000 different forms of attention-deficit/hyperactivity disorder (ADHD) can be defined by combining the 18 items listed in the the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). To identify genetic and environmental risk factors which correlates with psychiatric disorders, endophenotype approach is used in many empirical studies.

Abstract: Both medication non-adherence and co-morbid cannabis abuse are associated with poor clinical outcome in first episode psychosis (FEP). The nature of interaction between adherence to medication and continued cannabis use remains unexplored. The objectives of this study were to examine variation in medication adherence associated with cessation or continuation of cannabis use, and to determine the impact of interaction between cannabis use and adherence to medication on symptom outcome at 12months. From a consecutive patient cohort (N=192) with a DSM-IV diagnosis of a FEP, 62 patients who met DSM-IV criteria for a currently active cannabis abuse disorder were followed up for one year. Complete data on repeated measures of medication adherence, symptoms, and cannabis use were available for 48 of the 62 patients. Twenty-eight patients (58.7%) continued while 20 (41.2%) stopped cannabis use after entering treatment. While both groups were relatively non-adherent at six months, 25/28 (92%) of the former group became adherent compared to 8/20 (40%) of those who stopped cannabis use (p <.01). While there was no overall effect of continued cannabis use on symptom levels at 12months, after controlling for medication adherence patients with continuous cannabis use had significantly higher level of symptoms (F(1,30)=2.74, p =0.03). FEP patients with an active cannabis use disorder may make a choice of either stopping cannabis and not taking medications or continuing cannabis but becoming more adherent to medications, adherence to medication appears to help both groups but continuous users remain at higher risk of poor symptom outcome even while on medication. [Copyright &y& Elsevier]

The authors offer information on the concept of publication bias and the dangers associated with it in terms of harming the health of millions of people. The ethical duty of researchers is to publish both positive and negative outcomes in an equitable manner without any form of bias. Several challenges faced by researchers in preventing publication bias and ways in which they can be overcome are highlighted. All journals must promote publication of high-quality negative studies.

As a relatively large body of research has been published up to now, it may be informative to explore whether the use of endophenotypes has produced consistent findings in attention-deficit hyperactivity disorder (ADHD). We reviewed the results of genetic studies investigating associations between putative susceptibility genes for ADHD and neuropsychological traits relevant for this disorder. A PubMed database search identified 47 studies. Most of them ( n = 36) examined a single candidate gene, while seven studies examined two or three genes and only four studies examined 10 genes or more. The most investigated genes were DRD4, DAT1, COMT, MAOA, and DBH. Regarding DRD4, association of high reaction time variability with the 7-R allele absence appears to be the most consistent result. Speed of processing, set shifting, and cognitive impulsiveness were less frequently investigated, but seem to be altered in the 7-R allele carriers. Regarding DAT1, majority of studies reported negative results indicating that this gene may have a modulating effect rather than direct influence on cognitive functioning. The other genes were investigated in fewer studies, and the reported findings need to be replicated. The principal methodological issues that could represent confounding factors and may explain conflicting results are discussed. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

The author discusses his proposal to deconstruct the mental health crisis into 2 pieces namely biological psychiatry and mental health. He references an editorial by Z. Merali and H. Anisman where they present 3 key points on the crisis in biological psychiatry such as big pharmaceutical companies withdrawing from the field, failure of advanced technologies to provide clinical utility in psychiatry and little progress made in identifying biomarkers for mental disorders.

Association between 5-HTTLPR polymorphism and development of acute and persistence of chronic posttraumatic stress disorder (PTSD) was prospectively investigated. DNA was extracted from 41 motor-vehicle accident victims evaluated for development and persistence of PTSD, 1 and 12 months posttrauma. At Time 1, a nonsignificant trend for higher acute PTSD rate in ll homozygotes (82%) was observed compared to those with ss and sl genotypes (50%). At Time 2, higher chronic PTSD rate was found in ll homozygotes (55%) compared to those with ss and sl genotypes (20%), with an odds ratio of 4.8 (95% CI = 1.09–21.22). Contrary to previous findings, these data are suggestive of a protective role for the s allele of 5-HTTLPR in chronic PTSD. [ABSTRACT FROM AUTHOR]

The article focuses on molecular genetics which is considered the new trend in the genetics of psychiatric disorders. Various research indicate that one out of every six papers published on schizophrenia, bipolar disorder or autism refers to genetics. With technological advances like genomic hybridization arrays allowed cytogeneticists to go beyond the microscopic level of resolution and to detect chromosomal rearrangements.

The article discusses the mental wellness of Aboriginal communities in Canada. Topics covered include the European colonization in the areas in the 16th century and the death of most people due to infectious diseases. Also mentioned is the assimilation of different cultures in the communities in the mid 1850s.

Summary: The present study assessed the modulating effect of education level on cortisol reactivity to the Trier Social Stress Test (TSST) in a sample of 101 middle-aged adults (22 males, 79 females) between the ages of 50 and 65. The TSST involves a public speech and mental arithmetic task in front of an audience. No previous studies have assessed whether education level can have an impact on cortisol reactivity to this psychosocial stressor. It is plausible that greater exposure to academia may impact how one perceives and responds to the demands of the speech and arithmetic task. Should education have an impact on cortisol reactivity to the TSST, future studies will be required to control for this factor in order to reduce both statistical error and false interpretations. In addition to completing the TSST, participants were administered a battery of neurocognitive tests and personality questionnaires, including a report on education level (i.e. number of years total and degree: High School, Junior College, Technical, University). Results showed that adults with post-secondary education above Junior College tended to secrete higher cortisol levels overall, as measured by total area under the curve. However, it was the group with lower educational attainment who showed a greater stress response specific to the TSST, as measured by percentage increase in cortisol from pre- to post-TSST. Analyses also found that higher educated adults performed better than their less educated peers on verbal fluency. Considering that the TSST is an oral task, it is suggested that middle-aged individuals with a lower level of education may find the TSST more stressful due to lower verbal capacity, which may lead to an increased cortisol response to the TSST when compared to individuals with a higher level of education. [Copyright &y& Elsevier]

We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region (3′-UTR) of the SLC6A3 gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of SLC6A3, as indicated by a significant (p=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.Neuropsychopharmacology (2007) 32, 1370–1376. doi:10.1038/sj.npp.1301240; published online 25 October 2006 [ABSTRACT FROM AUTHOR]

Previous research has suggested that there may be overlap between schizophrenia and attention-deficit hyperactivity disorder (ADHD). The relationship between schizotypal personality traits, ADHD features and polymorphisms was evaluated in dopamine-related genes. Thirty-one healthy, Caucasian men completed the Rust Inventory of Schizotypal Cognitions (RISC) and the ADHD Self-Report Scale (ASRS). Catechol-O-methyltransferase (COMT) Val158Met, dopamine receptors of the D3 type (DRD3) Ser9Gly, DRD4 variable number of tandem repeats (VNTR), and SLC6A3 VNTR polymorphisms were analyzed. RISC score was correlated with ASRS score ( r = 0.54, P = 0.003). COMT Met homozygotes had higher ASRS scores than Val homozygotes ( P = 0.005). These findings are consistent with evidence of overlap between schizophrenia and ADHD and support an involvement of COMT genotype in ADHD features. [ABSTRACT FROM AUTHOR]

The article describes the treatment of first-episode psychosis in an 18-year-old woman with autism-spectrum disorder and intellectual deficiency. Topics include the response of the patient to antipsychotic medication, two intramuscular injections of loxapine received by the patient after trying to assault a nurse, and reduction in the patient's psychotic symptomatology after five days of treatment.

Objective: It is suggested that schizophrenic patients who respond to neuroleptic medication and those who do not might differ with respect to their pathogenesis. In particular, it has been proposed that genetic factors may contribute to treatment response and/or outcome. In order to test this hypothesis, we compared the pattern of familial aggregation of schizophrenia related disorders in schizophrenic patients who are either responders (R) or nonresponders (NR) to typical neuroleptics.Method: R (n=36) or NR (n=35) patients to typical neuroleptics and healthy controls (n=63) were recruited. At least one key informant relative of each proband was interviewed blind as to the status of the proband using the Family Interview for Genetic Studies. Morbid risk for schizophrenia and cluster A personality disorders and family loading score for schizophrenia were examined in first- and second-degree relatives of these probands.Results: First-degree relatives of NR patients were at a significantly higher risk for schizophrenia (MR=8.84), compared, respectively, to relatives of controls (MR=1.52) or relatives of R patients (MR=2.45). The same pattern was observed in second-degree relatives. Family loading score for schizophrenia in first- and second-degree relatives was significantly higher in NR compared to R patients.Conclusions: Schizophrenic patients who do not respond to typical neuroleptics may suffer from a more familial form of schizophrenia compared to patients who are responders. [ABSTRACT FROM AUTHOR]

Genetics has captured the imagination of the public, the interest of the media and a large place in the sciences. Since the discovery of the structure of DNA by Watson and Crick, the double helix has epitomized the main dogma of genetics: everything from the tiniest details of the human body to the most complex of behaviours is encoded in the genes. This belief has been strengthened by the tremendous success that has been achieved in cloning more than 1000 genes that cause simple Mendelian disorders. However, for complex disorders, particularly psychiatric conditions, the search for genes has been frustrating and has not yielded definitive results, although claims of gene discoveries are made regularly. In this article, we discuss the possible causes for these difficulties, along with some directions that may help in reducing these problems. We also consider the implications of psychiatric genetic research for individual and public health. [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]

An increased incidence of schizophrenia has been associated with several perinatal insults, most notably maternal infection during pregnancy and perinatal hypoxia. This study used a rat model to directly test if maternal exposure to bacterial endotoxin (lipopolysaccharide, LPS) during pregnancy alters behaviors relevant to schizophrenia, in offspring at adulthood. The study also tested if postnatal anoxia interacted with gestational LPS exposure to affect behavior. At adulthood, offspring from dams administered LPS on days 18 and 19 of pregnancy showed significantly increased amphetamine-induced locomotion, compared to offspring from saline-treated dams. A period of anoxia on postnatal day 7 had no effect on amphetamine-induced locomotion and there was no interaction between effects of gestational LPS and postnatal anoxia on this behavior. Offspring from LPS-treated dams also showed enhanced acoustic startle responses as adults, compared to offspring from saline-treated dams. In offspring tested for pre-pulse inhibition (PPI) of acoustic startle and for apomorphine modulation of PPI, no effects of either gestational LPS or of postnatal anoxia and no interactions between LPS and anoxia were observed. It is concluded that maternal LPS exposure during pregnancy in the rat may be a useful model to study mechanisms responsible for effects of maternal infection on behaviors relevant to schizophrenia, in offspring. [Copyright &y& Elsevier]

The effects of adrenergic and corticosteroid hormonal systems on emotional memory were measured in 64 young men. Placebo, propranolol (40 or 80 mg; beta Mocker), or metyrapone (corticosteroid synthesis inhibitor) was administered before the viewing of a story composed of emotional and neutral segments. Short- and long-term declarative memory for the story was assessed. Propranolol 40 mg had no effects on declarative memory. Propranolol 80 mg impaired short- and long-term declarative memory for emotionally arousing material. Metyrapone did not impair short-term declarative memory but impaired long-term declarative memory for emotionally arousing and neutral material. Results demonstrate that adrenergic and corticosteroid hormonal systems differentially affect declarative memory for emotionally arousing and neutral material, and suggest that interactions between adrenal hormonal systems modulate emotionally arousing declarative memory in humans. [ABSTRACT FROM AUTHOR]

Prepulse inhibition (PPI) of the acoustic startle response (ASR) is a form of sensorimotor gating, defined as an inhibition of the startle response when a low intensity stimulus, the prepulse, precedes the startling stimulus. Deficits in PPI have been reported in schizophrenia and other psychiatric/neurological disorders, and correlate with symptom severity in schizophrenia, suggesting that deficient PPI per se or abnormalities in neural circuits regulating PPI may cause some symptoms of schizophrenia. If so, then genes conferring reduced PPI may contribute toward genetic vulnerability to schizophrenia. Studies with selectively bred rodent strains indicate that PPI is under genetic control; however, the identity of the relevant genes is unknown. The current study used recombinant congenic mouse strains derived from C57BL/6J and A/J parents to assess genetic variability in PPI and in ASR and to identify provisional quantitative trait loci (QTLs) modulating these phenotypes. Significant between-strain differences in ASR and in PPI at each of several prepulse intensities (75, 80, 85, 90, 95 dB) were found. Correlations between PPI at the various prepulse intensities were highly significant, suggesting appreciable overlap in genetic regulation of PPI across prepulse intensities. Five QTLs (chromosomes 3, 5, 7, 16) associated with PPI across all prepulse intensities, but not with ASR, were identified. Two additional QTLs (chromosomes 2, 11) associated with both PPI and ASR were found. Fifteen QTLs were associated with ASR alone. Data on genotypes of informative congenic strains were used to support probable involvement of loci modulating PPI and to narrow the probable chromosomal location of QTLs. If confirmed, these QTLs may suggest candidate genes directing novel mechanisms for regulation of PPI [Copyright &y& Elsevier]

Examines the genetics of schizophrenia from animal models to clinical studies. Role of family, twin and adoption studies in the pathogenesis of schizophrenia; Symptoms of schizophrenia; Behavioral trait for schizophrenia.

To determine whether two groups of schizophrenic patients representing the two extremes of the neuroleptic response-spectrum (consistent responders vs. consistent nonresponders) differ with respect to their neuropsychological profile. Neuroleptic-responder (R; n=36) and -nonresponder (NR; n=39) schizophrenic patients were recruited according to a priori defined criteria of responsiveness to typical neuroleptics. Seven neuropsychological domains were assessed and compared between groups: attention-vigilance, abstraction-flexibility, spatial organization, visual-motor processing, visual memory, verbal abilities, and verbal memory and learning. All measures were standardized using the scores of 36 healthy volunteers. NR schizophrenic patients performed worse in all neuropsychological domains compared to normal controls and R schizophrenic patients. However, only performances on visual memory, verbal abilities, and verbal memory and learning were significantly poorer in NR compared to R patients. Only the latter domain significantly differentiated NR patients from the other two groups. R patients performed at an intermediate level in all domains. This report of differences in neuropsychological profile between neuroleptic-responder and -nonresponder schizophrenic patients adds to the growing evidence supporting the value of distinguishing schizophrenic patients on the basis of their therapeutic response to neuroleptics. [ABSTRACT FROM AUTHOR]

Persistent negative symptoms (PNS) are linked to poor functional outcomes and may be primary or caused by secondary factors. Although several studies have examined PNS in first-episode psychosis (FEP), a comparison with a data-driven approach is lacking. Here, we compared clinically defined PNS subgroups with class trajectories identified through latent growth modeling (LGM). Patients admitted to an early intervention service (N = 392) were classified as PNS (n = 105), secondary PNS (sPNS; n = 74), or non-PNS (n = 213) based on longitudinal data collected six to twelve months after admission. LGM was used to stratify patients based on similar negative symptom course over the same time period. Using multiple linear regression, we assessed the utility of both approaches in predicting Social and Occupational Functioning Assessment Scale (SOFAS) scores at two-year follow-up. Three negative symptom trajectories were identified: low and remitting (LR; n = 158), moderate and improving (MI; n = 163) and delayed partial response (DR; n = 71). Most non-PNS patients followed the LR trajectory, while patients with PNS or sPNS were generally divided between MI and DR. Both PNS classification and trajectory membership were significant predictors of two-year functional outcomes; the DR and MI trajectories predicted greater increases in SOFAS scores (DR: b = -19.14; MI: b = -11.54) than either sPNS (b = -9.19) or PNS (b = -6.46). These findings demonstrate that combining PNS and symptom-based stratification can predict functional outcomes more accurately than either taxonomy alone. Such a combined approach could yield significant advances in developing more targeted interventions for patients at risk for poor functional outcomes. [ABSTRACT FROM AUTHOR]

Hallucinations are a core feature of psychosis, and their severity during the acute phase of illness is associated with a range of poor outcomes. Various clinical and sociodemographic factors may predict hallucinations and other positive psychotic symptoms in first episode psychosis (FEP). Despite this, the precise factors associated with hallucinations at first presentation to an early intervention service have not been extensively researched. Through detailed interviews and chart reviews, we investigated sociodemographic and clinical predictors in 636 minimally-medicated patients who entered PEPP-Montréal, an early intervention service for FEP, between 2003 and 2018. Hallucinations were measured using the Scale for the Assessment of Positive Symptoms (SAPS), while negative symptoms were assessed using the Scale for the Assessment of Negative symptoms (SANS). Depressive symptoms were evaluated through the Calgary Depression Scale for Schizophrenia (CDSS), and anxiety symptoms via the Hamilton Rating Scale for Anxiety (HAS). A majority (n = 381, 59.9 %) of the sample presented with clinically significant hallucinations (SAPS global hallucinations score ≥ 3) at program entry. These patients had an earlier age at onset, fewer years of education, and a higher severity of delusions, depression and negative symptoms than those without clinical-level hallucinations. These results suggest that individuals with clinically significant hallucinations at admission tend to be younger and have a greater overall symptom burden. This makes it especially important to monitor hallucinations alongside delusions, depression and negative symptoms in order to identify who might benefit from targeted interventions. The implications of these findings for early intervention and person-centered care are discussed. [ABSTRACT FROM AUTHOR]

Purpose: Cross-cultural psychosis research has typically focused on a limited number of outcomes (generally symptom-related). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to fundamental treatment processes like trust. Addressing this gap, we studied two similar first-episode psychosis programs in Montreal, Canada, and Chennai, India. We hypothesized higher trust in healthcare institutions and providers among patients and families in Chennai at baseline and over follow-up. Methods: Upon treatment entry and at months 3, 12 and 24, trust in healthcare providers was measured using the Wake Forest Trust scale and trust in the healthcare and mental healthcare systems using two single items. Nonparametric tests were performed to compare trust levels across sites and mixed-effects linear regression models to investigate predictors of trust in healthcare providers. Results: The study included 333 patients (Montreal = 165, Chennai = 168) and 324 family members (Montreal = 128, Chennai = 168). Across all timepoints, Chennai patients and families had higher trust in healthcare providers and the healthcare and mental healthcare systems. The effect of site on trust in healthcare providers was significant after controlling for sociodemographic characteristics known to impact trust. Patients' trust in doctors increased over follow-up. Conclusion: This study uniquely focuses on trust as an outcome in psychosis, via a comparative longitudinal analysis of different trust dimensions and predictors, across two geographical settings. The consistent differences in trust levels between sites may be attributable to local cultural values and institutional structures and processes and underpin cross-cultural variations in treatment engagement and outcomes. [ABSTRACT FROM AUTHOR]

Background: Data from high-income countries (HICs) show a high risk of suicidal thoughts and behaviors (STBs) in first-episode psychosis (FEP). It is unknown, however, whether rates and associated factors differ in low- and middle-income countries (LMICs). Aims: We therefore aimed to compare the 2-year course of STBs and associated factors in persons with FEP treated in two similarly structured early intervention services in Chennai, India and Montreal, Canada. Method: To ensure fit to the data that included persons without STBs and with varying STBs' severity, a hurdle model was conducted by site, including known predictors of STBs. The 2-year evolution of STBs was compared by site with mixed-effects ordered logistic regression. Results: The study included 333 FEP patients (168 in Chennai, 165 in Montreal). A significant decrease in STBs was observed at both sites (OR = 0.87; 95% CI [0.84, 0.90]), with the greatest decline in the first 2 months of follow-up. Although three Chennai women died by suicide in the first 4 months (none in Montreal), Chennai patients had a lower risk of STBs over follow-up (OR = 0.44; 95% CI [0.23, 0.81]). Some factors (depression, history of suicide attempts) were consistently associated with STBs across contexts, while others (gender, history of suicidal ideation, relationship status) were associated at only one of the two sites. Conclusions: This is the first study to compare STBs in FEP between two distinct geo-sociocultural contexts (an HIC and an LMIC). At both sites, STBs reduced after treatment initiation, suggesting that early intervention reduces STBs across contexts. At both sites, for some patients, STBs persisted or first appeared during follow-up, indicating need for suicide prevention throughout follow-up. Our study demonstrates contextual variations in rates and factors associated with STBs. This has implications for tailoring suicide prevention and makes the case for more research on STBs in FEP in diverse contexts. [ABSTRACT FROM AUTHOR]

Despite their acknowledged value, patient-reported outcome measures (PROMs) are infrequently used in psychosis, particularly in low-and middle-income countries. We compared ratings on two single-item PROMs, Self-Rated Health (SRH) and Self-Rated Mental Health (SRMH), of persons receiving similar early psychosis services in Chennai, India and Montreal, Canada. We hypothesized greater improvements in SRH and SRMH in the Chennai (compared to the Montreal) sample. Participants (Chennai N = 159/168 who participated in the larger study; Montreal N = 74/165 who participated in the larger study) completed the SRH and SRMH during at least two out of three timepoints (entry, months 12 and 24). Repeated measures proportional odds logistic regressions examined the effects of time (baseline to month 24), site, and relevant baseline (e.g., gender) and time-varying covariates (i.e., symptoms) on SRH and SRMH scores. SRH (but not SRMH) scores significantly differed between the sites at baseline, with Chennai patients reporting poorer health (OR: 0.33; CI: 0.18, 0.63). While Chennai patients reported similar significant improvements in their SRH (OR: 7.03; CI: 3.13; 15.78) and SRMH (OR: 2.29, CI: 1.03, 5.11) over time, Montreal patients only reported significant improvements in their SRMH. Women in Chennai (but not Montreal) reported lower mental health than men. Higher anxiety and longer durations of untreated psychosis were associated with poorer SRH and SRMH, while negative symptoms were associated with SRH. As hypothesized, Chennai patients reported greater improvements in health and mental health. The marked differences between health and mental health in Montreal, in contrast to the overlap between the two in Chennai, aligns with previous findings of clearer distinctions between mind and body in Western societies. Cross-context (e.g., anxiety) and context-specific (e.g., gender) factors influence patients' health perceptions. Our results highlight the value of integrating simple PROMs in early psychosis. [ABSTRACT FROM AUTHOR]

Purpose: To study the impact of supervised antipsychotic medication discontinuation on clinical and functional outcomes in first-episode psychosis (FEP) in two different cultural environments. Method: FEP patients(N = 253), treated in two early intervention services (Montreal, Canada and Chennai, India) for 2 years, were assessed for medication use, positive and negative symptom remission and social–occupational functioning at regular intervals. Results: Between months 4 and 24 of treatment, 107 patients discontinued medication ('Off'group) as compared to 146 who stayed on medication ('On'group). Medication discontinuation was higher in Chennai as compared to Montreal (n = 80, 49.07% vs n = 27, 16.87%; χ2 37.80, p < 0.001), with no difference in time to discontinuation [Means(SDs) = 10.64(6.82) and 10.04(5.43), respectively, p = 0.71). At month 24 (N = 235), there were no differences in the rate of positive symptom remission between the on and Off groups (81.5 vs 88.0%, respectively) at both sites. The rate of negative symptom remission was lower among patients in the On compared to the Off group (63.2 vs 87.9%, respectively, χ2 = 17.91, p < 0.001), but only in Montreal (55.4% vs 80.0%, respectively, χ2 = 4.12, p < 0.05). Social and Occupational Functioning Assessment Scale scores were equally high in both Off and On medication groups in Chennai [Means (SDs) = 79.43(12.95) and 73.59(17.63), respectively] but higher in the Off compared to the On group in Montreal Means (SDs) = 77.47(14.97) and 64.94(19.02), respectively; Time × site interaction F = 3.96(1,217), p < 0.05]. Medication status (On–Off) had no impact on the outcomes, independent of other variables known to influence outcomes. Conclusion: Certain cultural environments and patient characteristics may facilitate supervised discontinuation of antipsychotic medication following treatment of an FEP without negative consequences. [ABSTRACT FROM AUTHOR]

The author discusses the 1000 Genomes Project, which revealed the occurrence of harmful, rare genetic variants at several loci, and highlights the association between such rare variants and psychiatric phenotypes. He expects that psychiatric investigators will study harmful variants in patients with specific disorders, and opines that a reverse phenotypic mapping program may help in creating a biologically rooted psychiatric classification by using rare genetic variants as anchors.

In this article the author discuses the use of anti-depression drug, Clozapine in the treatment of mental illnesses like Schizophrenia. Reportedly, its enhanced benefits have been shown in many cases relating to patients diagnosed with refractory Schizophrenia, responding poorly to other antipsychotic medications. Clozapine is stated to be the only antipsychotic medication successfully used in treating the craving for drugs of abuse.