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Schizophrenia (SCZ) is the archetypal severe mental illness and one of the most deeply characterized human genetic traits. Like most common diseases SCZ is highly polygenic, and as such its genetic liability can be summarized at the individual level by a polygenic risk score (PRS). Polygenic risk scores are a cornerstone of the precision medicine vision, as it is widely anticipated they will come to serve as biomarkers of disease and poor outcomes in real-world clinical practice. However, to date, few studies have assessed their actual prognostic value relative to current standards-of-care. SCZ is an ideal test case towards this end because the predictive power of the SCZ PRS exceeds that of most other common diseases. Here, we analyzed clinical and genetic data from two multi-ethnic cohorts totaling 8,541 adults with SCZ and related psychotic disorders, assessing whether the SCZ PRS improves poor outcome prediction relative to clinical features captured in a standard psychiatric interview. For all outcomes investigated, the SCZ PRS did not improve the performance of predictive models, an observation that was generally robust to divergent case definitions and ancestral backgrounds of study participants. These findings demonstrate the limited potential of even the most powerful contemporary polygenic risk scores as a tool for individualized outcome prediction.

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10−8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.

A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47 005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5-3.0 Mb) at 22q11.2--the reciprocal of the well-known, risk-inducing deletion of this locus--are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia.

IntroductionThe advances and massification of technology have allowed new developments in effective assessment methodologies for the evaluation of cognitive functions and associated functions of several brain systems and structures. Computerized test batteries have become more robust alternatives to paper-and-pencil test batteries and useful tools for research in several scientific domains, including psychiatry, psychology, genetics and neurosciences.AimsTo validate and disseminate the Portuguese PennCNP battery for clinical and non-clinical studies.ObjectivesTo translate and provide preliminary psychometric data of the Portuguese PennCNP tests in 9 neurocognitive domains.MethodThe PennCNB (Gur et al., 2010) was translated and administered to a sample of 120 Portuguese participants from the general population.ResultsFindings on the internal consistency and performance (speed and accuracy) are presented for the 19 tasks included in the PennCNB, in addition to results of correlation analysis within tests on the same domain for criterion validity, and gender sensitivity analysis.ConclusionComputerized assessment provides efficient and reliable results, based on performance of abstract.Objective and simple tasks that cover a vast range of cognitive functionsThe administration requires minimal training and provides a quick and automated scoring procedure, with great utility in several research and clinical fields. The availability of a test battery suitable for a large number of Portuguese native-speakers worldwide is of added value, since the translation of measures to several languages allows creating more extensive normative samples and direct results comparability in future research, including transnational or cross-cultural studies and clinical trials.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The authors demonstrate the role that research can play in the development of an academic department of psychiatry.The authors explore the challenges and achievements in the transition of one department from a strong clinically- and educationally-centered department to one with an equally strong research focus.The department significantly expanded and improved its research, educational role, and contribution to its medical school.Leading departments of psychiatry in the United States have extremely strong research divisions. The research enterprise brings a critical academic identity to the institution and a stronger reputation and differentiates the department within the health-delivery system. However, for a department developing a research program, the frontline clinicians, staff, and students may see research as an imposition on patients and a distraction from the perceived primary mission, and they may be concerned about how they will be perceived as the institution changes its identity.

The gap junction subunit connexin permits direct intercellular exchange of ions and molecules including glutamate, and plays an important role in the central nervous system. The connexin 40 (Cx40) and connexin 50 (Cx50) genes are located on chromosome 1q21.1, a region strongly linked with schizophrenia. These lines of evidence suggest that Cx40 and Cx50 may play a role in schizophrenia.Using an allele-specific PCR assay, four polymorphisms each were genotyped for Cx40 and Cx50 in 190 Caucasian patients with schizophrenia and 190 controls matched for sex, age and ethnicity. Following up, Cx50 rs989192 and rs4950495 were investigated in 99 Canadian and 163 Portuguese trios and nuclear families with schizophrenia probands. Hardy-Weinberg equilibrium and linkage disequilibrium (LD) block identification was carried out with HaploView, and association analysis for alleles and haplotypes with a permutation test of 10 000 simulations was carried out using the UNPHASED software program.Distributions of genotype frequencies of all markers were in Hardy-Weinberg equilibrium in Caucasian patients, controls and families. One rs989192-rs4950495 LD block was found in patients but not in controls. We found a significant association between the Cx50 rs989192-rs4950495 haplotype and schizophreniay (chi(2) = 29.55, p0.01). The A-C haplotype had a higher frequency in patients (chi(2) = 7.153, p0.01). Family studies also showed that the A-C haplotype was transmitted more often to patients with schizophrenia (chi(2) = 8.43, p0.01). No association of Cx40 with schizophrenia was found for allele, genotype or haplotype analyses.Our matched case-control and family study indicate that Cx50, but not Cx40, may play a role in the genetic susceptibility to schizophrenia.

We previously performed a genome-wide linkage scan in Portuguese schizophrenia families that identified a risk locus on chromosome 5q31-q35. This finding was supported by meta-analysis of 20 other schizophrenia genome-wide scans that identified 5q23.2-q34 as the second most compelling susceptibility locus in the genome. In the present report, we took a two-stage candidate gene association approach to investigate a group of gamma-aminobutyric acid (GABA) A receptor subunit genes (GABRA1, GABRA6, GABRB2, GABRG2, and GABRP) within our linkage peak. These genes are plausible candidates based on prior evidence for GABA system involvement in schizophrenia. In the first stage, associations were detected in a Portuguese patient sample with single nucleotide polymorphisms (SNPs) and haplotypes in GABRA1 (P=0.00062-0.048), GABRP (P=0.0024-0.042), and GABRA6 (P=0.0065-0.0088). The GABRA1 and GABRP findings were replicated in the second stage in an independent German family-based sample (P=0.0015-0.043). Supportive evidence for association was also obtained for a previously reported GABRB2 risk haplotype. Exploratory analyses of the effects of associated GABRA1 haplotypes on transcript levels found altered expression of GABRA6 and coexpressed genes of GABRA1 and GABRB2. Comparison of transcript levels in schizophrenia patients and unaffected siblings found lower patient expression of GABRA6 and coexpressed genes of GABRA1. Interestingly, the GABRA1 coexpressed genes include synaptic and vesicle-associated genes previously found altered in schizophrenia prefrontal cortex. Taken together, these results support the involvement of the chromosome 5q GABAA receptor gene cluster in schizophrenia, and suggest that schizophrenia-associated haplotypes may alter expression of GABA-related genes.

Large and rare copy number variants (CNVs) at several loci have been shown to increase risk for schizophrenia. Aiming to discover novel susceptibility CNV loci, we analyzed 6882 cases and 11 255 controls genotyped on Illumina arrays, most of which have not been used for this purpose before. We identified genes enriched for rare exonic CNVs among cases, and then attempted to replicate the findings in additional 14 568 cases and 15 274 controls. In a combined analysis of all samples, 12 distinct loci were enriched among cases with nominal levels of significance (P < 0.05); however, none would survive correction for multiple testing. These loci include recurrent deletions at 16p12.1, a locus previously associated with neurodevelopmental disorders (P = 0.0084 in the discovery sample and P = 0.023 in the replication sample). Other plausible candidates include non-recurrent deletions at the glutamate transporter gene SLC1A1, a CNV locus recently suggested to be involved in schizophrenia through linkage analysis, and duplications at 1p36.33 and CGNL1. A burden analysis of large (>500 kb), rare CNVs showed a 1.2% excess in cases after excluding known schizophrenia-associated loci, suggesting that additional susceptibility loci exist. However, even larger samples are required for their discovery.

We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611–rs10043986, r2 = 0.008; rs10043986–rs4704591, r2 = 0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case–control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.04–1.18, P = 8.2 × 10−4 and rs4704591, OR = 1.07, 95% CI = 1.03–1.11, P = 3.0 × 10−4). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR = 1.11, 95% CI = 1.03–1.17, P = 0.0026 and rs4704591, OR = 1.07, 95% CI = 1.02–1.11, P = 0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted.

The search for DNA alterations that cause human disease has been an area of active research for more than 50 years, since the time that the genetic code was first solved. In the absence of data implicating chromosomal aberrations, researchers historically have performed whole genome linkage analysis or candidate gene association analysis to develop hypotheses about the genes that most likely cause a specific phenotype or disease. Whereas whole genome linkage analysis examines all chromosomal locations without a priori predictions regarding what genes underlie susceptibility, candidate gene association studies require a researcher to know in advance the genes that he or she wishes to test (based on their knowledge of a disease). To date, very few whole genome linkage studies and candidate gene studies have produced results that lead to generalizable findings about common diseases. One factor contributing to this lack of results has certainly been the previously limited resolution of the techniques. Recent technological advances, however, have made it possible to perform highly informative whole genome linkage and association analyses, as well as whole genome transcription (transcriptome) analysis. In addition, for the first time we can detect structural DNA aberrations throughout the genome on a fine scale. Each of these four approaches has its own strengths and weaknesses, but taken together, the results from an integrated analysis can implicate highly promising novel candidate genes. Here, we provide an overview of the integrated methodology that we have used to combine high-throughput genetic and functional genomic data with bioinformatics data that have produced new insights into the potential biological basis for schizophrenia. We believe that the potential of this combined approach is greater than that of a single mode of discovery, particularly for complex genetic diseases.

Schizophrenia is a common, multigenic psychiatric disorder. Linkage studies, including a recent meta-analysis of genome scans, have repeatedly implicated chromosome 8p12-p23.1 in schizophrenia susceptibility. More recently, significant association with a candidate gene on 8p12, neuregulin 1 (NRG1), has been reported in several European and Chinese samples. We investigated NRG1 for association in schizophrenia patients of Portuguese descent to determine whether this gene is a risk factor in this population. We tested NRG1 markers and haplotypes for association in 111 parent-proband trios, 321 unrelated cases, and 242 control individuals. Associations were found with a haplotype that overlaps the risk haplotype originally reported in the Icelandic population ("Hap(ICE)"), and two haplotypes located in the 3' end of NRG1 (all P0.05). However, association was not detected with Hap(ICE) itself. Comparison of NRG1 transcript expression in peripheral leukocytes from schizophrenia patients and unaffected siblings identified 3.8-fold higher levels of the SMDF variant in patients (P=0.039). Significant positive correlations (P0.001) were found between SMDF and HRG-beta 2 expression and between HRG-gamma and ndf43 expression, suggesting common transcriptional regulation of NRG1 variants. In summary, our results suggest that haplotypes across NRG1 and multiple NRG1 variants are involved in schizophrenia.

We have studied 24 families with multiple affected members with bipolar disorder to test the hypothesis that in those families clinically showing genetic anticipation [Macedo et al., 1999] we would find large repeat expansions. The families meeting inclusion criteria had a minimum of two affected members over two generations and showed marked anticipation both in terms of age of onset and disease severity. We used the repeat expansion detection (RED) method to test patients (n = 24) and controls from these families and unrelated controls (n = 53). We also genotyped patients and family members from two families with large expansions at the known expansion loci on chromosomes 13, 17, and 18. The RED method revealed a higher number of large expansions in patients compared with controls (t-test; P0.0055: Mann-Whitney U; P = 0.02). The patients with the largest expansions were typed at the specific loci on chromosomes 13, 17, and 18 and the chromosome 18 expansion locus segregated with disease in one family, and a second family showed segregation with the expansion located at the SCA8 locus on chromosome 13. Genetic anticipation had been analyzed in this cohort of families, with correction for potential ascertainment bias, possible proband effects, cohort effects, regression to the mean, gender effects, and maternal vs. paternal transmission. None of these potential confounds appeared to account for the observed anticipation. We also identified that the presence of large expansions in affected family members derives primarily from two families from the genetically isolated Azores population. One family shows segregation with the chromosome 18 locus, whereas the other family segregates with expansions at the SCA8 locus. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:854-857, 2000.

Expansion at a recently identified unstable trinucleotide repeat on chromosome 13q21 has been reported as the molecular cause for spinocerebellar ataxia type 8 (SCA8). The trinucleotide repeat, which consists of a [CTA]n repeat and adjacent [CTG]n repeat, was reported to have a pathogenic range of 107-127 CTG repeats (or 110-130 combined CTA and CTG repeats) in a large ataxia kindred. This repeat region was also cloned by our group from a bipolar affective disorder (BPAD) patient, who has approximately 600 combined repeats, and large alleles (100 repeats) were reported to be present in 0.7% of controls and 1.5% of major psychosis patients (n = 710 and n = 1,120, respectively). We have followed up these findings by screening three new samples of BPAD and schizophrenia (SCZ) patients and controls, including 272 individuals from 14 BPAD families from Sweden, 130 individuals from 32 SCZ and BPAD families/trios from the Azores Islands, and 206 SCZ individuals from the United Kingdom and Ireland, and 219 matched controls. We found large repeat alleles above the SCA8 pathogenic range in individuals from 3 of 32 Azorean pedigrees and in 1 of 206 SCZ individuals from the United Kingdom, and repeat alleles within the SCA8 pathogenic range in 1 of 14 Swedish families. Although the rarity of major psychosis patients carrying the SCA8 expansion mutation would require a much larger sample size to reach statistical significance, these results support the previously reported observation of increased occurrence of large repeats at SCA8 in major psychosis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:873-876, 2000.

A functional polymorphism in the coding region of the catechol O-methyltransferase (COMT) gene has been reported in previous studies to be associated with obsessive compulsive disorder (OCD), particularly in males [Karayiorgou et al., 1997, 1999]. Using a family-based population analysis, we attempted to replicate these findings in a group of 72 OCD patient/parent trios collected from Buffalo, New York, and Toronto, Canada. Analysis of allele and genotype frequencies using the haplotype relative risk (HRR) and transmission disequilibrium test (TDT) did not identify an association between a particular allele and OCD as had been previously reported. Furthermore, no evidence was found to support the findings of a gender-based association for COMT when the patients and the parents of the same gender were compared. However, our genotype results (n = 72) demonstrate a tendency for association between homozygosity at the COMT locus and OCD (homozygosity analysis: chi(2) = 5.66, P = 0.017; genotypic analysis: chi(2) = 5.78, P = 0.056). Although these findings do not replicate the previous reports, they do provide limited support to demonstrate a trend for homozygosity at the COMT locus in the OCD patients and, in turn, further implicate a potential role for COMT in the genetic etiology of OCD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:721-724, 2000.

Obsessive-compulsive disorder (OCD) and serotonin reuptake inhibitors became inextricably joined with the discovery of their effectiveness for the treatment of OCD in 1969 and 1976. The specificity of response of OCD to serotonin reuptake inhibitors has provided an important platform for the exploration of the neurobiology of OCD. This knowledge has come from many different areas of investigation, including neuroimaging, neuroimmunology and pharmacologic challenge studies. As the research into the pharmacologic treatment of OCD has progressed, a number of serotonin reuptake inhibitors have been approved and marketed for the treatment of OCD. These agents include clomipramine, sertraline, paroxetine, fluoxetine, and fluvoxamine. Because these agents share the same mechanism of action (serotonin reuptake inhibition), choosing which agent to use must be based on other parameters. These include differences in efficacy, dosing, and side-effect profile. Citalopram, a newly marketed selective serotonin reuptake inhibitor could offer some advantages over those agents currently marketed. Theoretically, it should also be effective in the treatment of OCD. In treating depression, it has been shown to have minimal side-effects, low risk of withdrawal symptoms, and little possibility of interaction with other agents.

Molecular genetic studies of psychiatric disorders must face the possibility that despite the significant contribution of genetic factors to the expression of syndromes like schizophrenia, these syndromes may be a heterogeneous collection of genetic and non-genetic illnesses. These illnesses may be etiologically distinct from each other and still share many clinical features in common. Linkage studies of families with multiple affected members tend to favor the selection of genetic forms of a syndrome but can still represent a heterogeneous set of different genetic illnesses. To limit the potential genetic heterogeneity of a study sample, we selected a population that was geographically isolated and was historically relatively genetically homogeneous. We then assessed the relative level of homogeneity utilizing a surname analysis of the population of the Azores, mainland Portugal, rural USA, and urban USA. The average number of families with the same last name corrected for population size in the Azores is 30.88, in Coimbra it is 21.42, compared to 1.13 in a rural American population and 0.38 in an urban American population. The results of this analysis indicate that the Azores have the highest degree of homogeneity, and mainland Portugal has a high degree of homogeneity.

In spite of significant advances in the development of behavioral and pharmacologic strategies for the treatment of obsessive compulsive disorder, little is known about the comparative efficacy and safety of those treatments. In addition, questions about the dose and duration in maintenance treatment remain unknown. This article reviews current issues in the pharmacologic management of patients with obsessive compulsive disorder.

In this study, 16 patients with obsessive-compulsive disorder (OCD) who had partially improved during at least 6 months of treatment with clomipramine were sequentially treated with triiodothyronine and lithium carbonate in an 8-week double-blind cross-over study. Both triiodothyronine and lithium carbonate have been reported to be efficacious in open trials as adjunctive agents when combined with tricyclics in the treatment of OCD and depressed patients. However, in our controlled study, OCD and depressive symptoms, as assessed by standardized rating scales in the patient group as a whole, did not significantly change after either adjuvant treatment. Further analysis on an individual patient basis revealed that neither adjuvant medication was associated with a clinically meaningful change (greater than 25%) in OCD symptoms. However, lithium, but not triiodothyronine, adjuvant therapy was associated with a 25% or greater reduction in depression scores in 44% of the patients. This controlled study lends further support to the contention that OCD may represent a disorder with characteristics distinct from affective disorders.

Obsessive-compulsive disorder (OCD) has recently been recognized as a relatively common disorder, affecting one in 40 individuals in the United States. OCD has also been demonstrated to be at least partially drug-responsive, although fewer than 20 adequate, fully controlled treatment trials in OCD patients have been reported, all in the last decade. The partially selective serotonin (5-hydroxytryptamine, 5-HT) uptake inhibitor clomipramine has been the most studied drug and uniformly has been found to be of some benefit in patients with OCD. Several recent controlled trials with other, more highly selective 5-HT uptake inhibitors have also shown these drugs to be more effective than placebo. More recently, preliminary data from several studies have questioned whether buspirone, an azapirone with prominent 5-HT-related anxiolytic and possible antidepressant properties, may have direct therapeutic effects in OCD patients or may be a useful adjunct when used in combination with the selective 5-HT uptake inhibitor fluoxetine. These studies are reviewed briefly and evaluated in the context of investigations that used other drugs with serotonergic actions either alone or in combination with selective 5-HT uptake inhibitors in OCD patients.

Ten patients with DSM-III-R obsessive-compulsive disorder (OCD) who were being treated chronically with clomipramine (270 +/- 20 mg/day) were studied to determine the minimum dose of clomipramine needed to maintain therapeutic benefit. These 10 patients were among the 17 of 18 patients recently reported to develop a return of OC symptoms following discontinuation of clomipramine under double-blind, placebo-controlled conditions. Each patient was rated twice--open and double-blind--at both initial and minimum doses of clomipramine, using the following three OC measures: the Yale-Brown Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health-Obsessive Compulsive Scale (NIMH-OC), and the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH Global OC Scale). Gradual, open dosage reduction resulted in a mean dosage of 165 +/- 19 mg/day, a reduction of 105 mg/day (approximately 40%, t = 5.55, p less than .001). This decrease in dose was accompanied by no significant change in the three OC measures, as determined by paired t-test. These results suggest that even though OCD patients were not able to discontinue medication completely, they were able to do well at lower doses than those used initially in treatment of the disorder.

Linkage disequilibrium and haplotype structure of five GABA A receptor subunit genes investigated for association with schizophrenia

Involvement of the brain serotonin (5-HT) neurotransmitter system in obsessive-compulsive disorder (OCD) was originally suggested on the basis of therapeutic effects found with the semiselective serotonin uptake inhibitor, clomipramine. More recent studies directly comparing clomipramine with non-selective or norepinephrine-selective uptake inhibitors, such as desipramine or nortriptyline, as well as studies with new, more selective serotonin uptake inhibitors, including fluvoxamine and fluoxetine, have supported that hypothesis. Clomipramine's antiobsessional effect has been augmented with the serotonin precursor, L-tryptophan, or with lithium, which has prominent serotonergic effects. Patients whose OCD symptoms improved on clomipramine worsened when the drug was discontinued (regardless of duration of therapy) and improved when clomipramine was reinstituted. OCD symptoms also worsened when metergoline, a 5-HT antagonist, was given to patients who had improved with clomipramine. Metergoline given alone had no effect. Administration of m-chlorophenylpiperazine (m-CPP), a 5-HT receptor agonist, to untreated OCD patients increased their anxiety, depression, and dysphoria, and exacerbated their OC symptoms. After 4 months of clomipramine therapy, m-CPP failed to produce the same behavioural effects, suggesting an alteration of a 5-HT subsystem (possibly downregulation of some 5-HT receptors). The data reviewed suggest an important role for an abnormal brain 5-HT subsystem in patients with OCD.

Objectives To investigate the symptom dimensions of psychosis using factor analyses/FA of lifetime symptoms of a sample of Portuguese psychotic patients. Method FA of the OPCRIT items (56 signs and symptoms) of 684 patients - Schizophrenia/Sz (73.8%), Other non-organic psychotic disorders/ONPD (6.0), Schizoaffective disorders/SzA (1.4%), Bipolar disorders/BP (18.1%) and Severe depression with psychosis/SDP (.8%) – assessed with the Diagnostic Interview for Genetic Studies. Delusions of poverty, guilty delusions, nihilistic delusions, primary delusional perception, and somnolence, problems with appetite and weight and grandiosity were excluded from the final solution, as each were present in less than 10% of patients and did not load at any factor. Results Following the Kaiser and the Cattel's Scree Plot criteria, a four factors structure was selected, which explained variance (EV) was of 60.25%. Based on items content, the meaningful four factors were denominated as follows: F1 Depression (EV 21.77%; a=.97); F2 Mania (5.72%; a=.97); F3 Delusions and hallucinations (2.97%; a=.92); F4 Disorganization and Negative symptoms (2.07%; a=.90). Mann-Whitney U tests revealed that the symptom dimensions that distinguished better between Dx categories were Delusions and hallucinations (only SDP vs. BP and Sc vs. SzA did not significantly differ) and Disorganization and Negative symptoms (only SDP vs. BP and SDP vs. ONPD did not significantly differ), with Sz patients presenting the highest scores. Conclusions This factorial structure is in accordance with other reports. Given the Schizophrenia (Sz) and Bipolar disorder (BP) heterogeneity and overlap, the present study contribute to phenotypic refinement and formulation of alternative psychosis phenotypes.

Aim:To investigate the role of perfectionism in the development of disordered eating behaviours.Method:382 female university students completed the Hewitt & Flett MPS and the EAT-40 at baseline, one year after (T1) and two years later (T2).Results:Perfectionism at baseline was significantly associated with long-term abnormal eating attitudes/behaviours. Self-Oriented Perfectionism (SOP) and Socially Prescribed Perfectionism (SPP) were significant predictors of disordered eating behaviours. SOP at baseline was predictive of diet concerns, at T1 and T2. Baseline SPP was correlated with overall eating disturbance at T1 and T2. Regression analysis revealed that only SPP was a significant predictor of bulimic behaviours and social pressure to eat at T1, but not at T2.Conclusion:Our findings contribute to a more clear understanding of the association between perfectionism and eating disorders. SOP and SPP were prospectively associated with abnormal eating attitudes/behaviours and SOP was found to be predictive of diet concerns.