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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.

ABSTRACT BACKGROUND: Few studies have examined the course of illness among severely depressed patients ascertained at first hospitalization. Using data from the Suffolk County Mental Health Project (SCMHP), we investigated the times to and predictors of the first full remission and the first relapse during a 4-year period in a first-admission cohort with major depressive disorder (MDD) with psychotic features.MethodThe cohort included 87 county-wide, first-admission patients with a longitudinal consensus diagnosis of MDD with psychotic features who were systematically followed over a 4-year period. We examined the associations of background, clinical and treatment factors, and time-varying indices of antidepressant (AD) and antipsychotic (AP) medication use to time to remission and relapse using Cox regression. RESULTS: By the 4-year follow-up, 60 respondents (69.0%) had achieved a period of full remission (median time of 22 weeks among remitters and 54 weeks in the full sample). In the multivariable analysis, longer time to remission was associated with longer latency between initial episode and hospitalization, lower pre-hospital Global Assessment of Functioning (GAF) score, and lack of insurance, but not use of medication. Twenty-six remitters (43.3%) relapsed (median time of 50 weeks among those who relapsed and 192 weeks among all remitters). None of the risk factors or time-varying medication variables was significantly associated with time to relapse.ConclusionOnly two-thirds of the sample had at least one full remission by 4 years, and almost half of them subsequently relapsed. Poorer pre-hospital resources predicted remission but not relapse. Medication use over the follow-up was not associated with remission or relapse. [ABSTRACT FROM AUTHOR]

Eating disorders are characterized by significant disturbances in eating patterns associated with negative attitudes toward one's body, weight, and shape. They are associated with an increased risk of mortality and morbidity as well as significant health, economic, and psychosocial burdens. Additionally, individuals with eating disorders often hesitate to seek treatment and symptoms may be difficult to ascertain without structured assessment. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Eating Disorders aims to enhance knowledge and increase the appropriate use of interventions for eating disorders, including anorexia nervosa, bulimia nervosa, and binge-eating disorder, thereby improving the quality of care and treatment outcomes. To this end, this evidence-based Performance in Practice tool can facilitate the implementation of a systematic approach to practice improvement for the care of individuals with eating disorders. This practice assessment activity can also be used in fulfillment of Continuing Medical Education and ABPN Continuing Certification, Improvement in Medical Practice., Competing Interests: The authors report no financial relationships with commercial interests., (Copyright © 2024 by the American Psychiatric Association.)

The goal of this article is to describe an integrated parallel process for the co-development of written and computable clinical practice guidelines (CPGs) to accelerate adoption and increase the impact of guideline recommendations in clinical practice. From February 2018 through December 2021, interdisciplinary work groups were formed after an initial Kaizen event and using expert consensus and available literature, produced a 12-phase integrated process (IP). The IP includes activities, resources, and iterative feedback loops for developing, implementing, disseminating, communicating, and evaluating CPGs. The IP incorporates guideline standards and informatics practices and clarifies how informaticians, implementers, health communicators, evaluators, and clinicians can help guideline developers throughout the development and implementation cycle to effectively co-develop written and computable guidelines. More efficient processes are essential to create actionable CPGs, disseminate and communicate recommendations to clinical end users, and evaluate CPG performance. Pilot testing is underway to determine how this IP expedites the implementation of CPGs into clinical practice and improves guideline uptake and health outcomes., (Copyright © The Authors 2023.)

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Competing Interests: J.A. is a member of the Platform for AI Ethics, Netherlands Institute for Standardization (NEN), member of the NEN 7542 workgroup on standardization of medication process data and contract reviewer for the European Commission. S.A.-A. has received consulting fees from AstraZeneca, Agilent Biotechnologies, and Diazyme. A.D.B. has received grants or contracts from NIH and NSF, payment or honoraria from Adelphi University, and travel support from Microsoft. A.J.B. is a cofounder of and consultant to Personalis and NuMedii; consultant to Mango Tree Corporation, and in the recent past, Samsung, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, and Merck, and Roche; is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Meta (Facebook), Alphabet (Google), Microsoft, Amazon, Snap, 10x Genomics, Illumina, Regeneron, Sanofi, Pfizer, Royalty Pharma, Moderna, Sutro, Doximity, BioNtech, Invitae, Pacific Biosciences, Editas Medicine, Nuna Health, Assay Depot, and Vet24seven, and several other non–health-related companies and mutual funds; and has received honoraria and travel reimbursement for invited talks from Johnson and Johnson, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, and many academic institutions, medical or disease specific foundations and associations, and health systems. A.J.B. receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. A.J.B.'s research has been funded by NIH, Peraton (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governor's Office of Planning and Research, California Institute for Regenerative Medicine, L'Oreal, and Progenity. A.B.C. has received consulting fees from Invitae Corporation. J.K.C. has received grants or contracts from the Office of Rural Health and Office of Healthcare and Equity, VHA. P.L.E. has received grants or contracts from NLM, NIAAA, and NCATS. Oluseyi Fayanju has received grants or contracts from GetSmarter. L.J.F. serves as a consultant to the American Psychiatric Association, has received travel support in relation to that role, and has also received grant support from NIMH. B.R.J. has received stock or stock options from Consent Vault, LLC. V.N.-J. occupies leadership or fiduciary roles with the Academy of Breastfeeding Medicine and West Central Illinois Breastfeeding Task Force. Ross Koppel has received consulting fees from advisors who contemplate investment in EHR companies, payment or honoraria from University at Buffalo, payment for expert testimony from the U.S. Department of Justice, stock or stock options from TrekIT, and occupies editor roles with the Journal of Applied Clinical Informatics and the International Journal of Medical Informatics. B.K. has received payment or honoraria from the Fall DeVos Medical Ethics Colloquy, and travel support to attend CSHI and AMIA conferences. C.U.L. has received royalties or licenses from Springer, has participated in a Data Safety monitoring board conducted by Lipika Samal at Harvard, and has received stock or stock options from Markel and Celanese. Z.C.L. has received consulting fees from Atrius Health, travel support from the University of Washington, Atrius Health, and Jackson Health System. R.J.M. has supported the present manuscript as a Texas Health Resources Clinical Scholar, has received grants or contracts from the Centers for Disease Control and Prevention, Sergey Brin Family Foundation, and Verily Life Sciences, payment or honoraria from Clinical Infectious Diseases, and occupies a leadership role with the Infectious Diseases Society of America. E.R.M. has received grants or contracts from the National Institute on Drug Abuse, the American Medical Association, and the Agency for Healthcare Research and Quality. A.B.N. has received grants or contracts from Royal Phillips and Eli Lilly, consulting fees from Intuity Medical, Roche, Eli Lilly, Sanofi, Greenberg Traurig, and Medtronic, payment or honoraria from The Doctors Company and TCOYD, and payment for expert testimony from AMFS. L.L.N. has received grants or contracts from GetPreCiSe, Florida State University, AHRQ, Baptist Memorial Healthcare Corporation, IBM Watson Health, and NIH/NIDDK. Deepti Pandita has received travel support from AMIA, has a patent pending with WellPulse app, and is a board member of AMIA. Raghuveer Puttagunta is a board member of Pennsylvania Medical Society. Angela Ryan is a member of AMIA and vice chair of the Australasian Institute of Digital Health. K.M.R. occupies a leadership role with the Society of Hospital Medicine Public Policy Committee. Neda Ratanawongsa occupies a leadership role with the San Francisco General Foundation. K.A.S. has received grants from Meds360 and Anonymous Foundation, honoraria from Stanford, travel support from the Society of Family Planning, and is a volunteer board member of the Society of Family Planning. Vignesh Subbian has received a grant from the National Science Foundation and occupies a leadership role with the AMIA ELSI Working Group. Ida Sim is a scientific advisor with Myovant Sciences. A.S. has received grants from NCATS Chicago Institute for Translational Medicine and PCORI Capricorn CRN, occupies leadership roles with the American Medical Informatics Association and IEEE Standards Association, and owns stock from Pfizer, Moderna, and J.B.S. holds leadership roles in AMIA and in the American College of Medical Informatics (ACMI), has received research funding from NIH and the Greenwall Foundation, and honoraria or consulting fees from the University of Kentucky, the University of Wisconsin, and the Icahn Mount Sinai School of Medicine. Peter Winkelstein has received a grant or contract from CTSA. J.X. has participated on a Data Safety Monitoring Board or Advisory Board with AfaSci, Inc. and Develo. C.Z. has received grants or contracts from CVS Foundation and Ariadne Labs, royalties, or licenses from UpToDate, consulting fees from Blue Cross Blue Shield of Massachusetts, and occupies leadership or fiduciary roles with the American Heart Association, Society for Maternal Fetal Medicine, and ACOG.

Schizophrenia is associated with significant health, social, occupational, and economic burdens, including increased mortality. Despite extensive and robust research on the treatment of individuals with schizophrenia, many individuals with the illness do not currently receive evidence-based pharmacological and nonpharmacological treatments. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia, Third Edition, aims to enhance knowledge and increase the appropriate use of interventions for schizophrenia, thereby improving the quality of care and treatment outcomes. To this end, this evidence-based Performance in Practice tool can facilitate the implementation of a systematic approach to practice improvement for the care of individuals with schizophrenia. This practice assessment activity can also be used in partial fulfillment of Continuing Medical Education and Maintenance of Certification, part IV, requirements, which can also satisfy requirements for the Centers for Medicare & Medicaid Services Merit-based Incentive Payment System program., Competing Interests: The authors report no financial relationships with commercial interests., (Copyright © by the American Psychiatric Association.)

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke's R 2  = 0.032; liability R 2  = 0.017; P < 10 -52 ), Latino (Nagelkerke's R 2  = 0.089; liability R 2  = 0.021; P < 10 -58 ), and European individuals (Nagelkerke's R 2  = 0.089; liability R 2  = 0.037; P < 10 -113 ), further highlighting the advantages of incorporating data from diverse human populations.

(Reprinted with permission from The American Journal of Psychiatry 2020; 177:868-872)., (Copyright © 2020 by the American Psychiatric Association.)

Background: Psychosis is a risk factor for aging-related conditions and early mortality. Little is known about the age-specific risk of objectively measured physical functional limitations among individuals with serious mental illness., Methods: The Suffolk County Mental Health Project is a prospective study of individuals hospitalized for the first time for psychosis. To assess physical functioning at midlife and to identify emerging risk factors for older-age changes, 101 participants with schizophrenia (mean age = 47.2, SD = 8.0 years; 41.6% female) and 112 participants with other psychoses (mean age = 48.2, SD = 9.5 years; 45.5% female) were assessed for chair-rise and balance limitations 20 years after diagnosis. A never-psychotic comparison group of 237 age/sex/geographically matched community controls was similarly assessed (mean age = 50.3, SD = 8.8 years; 44.7% female). Logistic regression was used to examine group differences in prevalence of poor performance and demographic, medical, and treatment correlates., Results: Chair-rise limitations (45.5% [35.8-55.3]) and balance limitations (17.2% [9.8-24.5]) were common in individuals with schizophrenia. Prevalence of chair-rise limitations was higher in schizophrenia (46.3%) than in other psychotic disorders (31.9%) and never-psychotic group (22.1%), whereas risk of balance limitations was higher in schizophrenia (17.2%) compared with never-psychotic controls (8.1%). Schizophrenia was a significant risk factor for chair-rise (adjusted odds ratio = 3.01 [1.79-5.08], p < .001) and balance limitations (adjusted odds ratio = 2.63, [1.25-5.51], p = .010). Multivariable analysis of symptom severity found avolition was associated with chair-rise limitations, but not balance, independent of diagnosis., Conclusion: Physical limitations are crucial because they identify existing problems with mobility and portend an increased risk of disability and death. Because participants with schizophrenia were at increased risk of physical limitations, assessments of chair-rise and balance limitations may be critical to monitoring individuals with psychosis., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: It remains uncertain whether people with psychotic disorders experience progressive cognitive decline or normal cognitive aging after first hospitalization. This information is essential for prognostication in clinical settings, deployment of cognitive remediation, and public health policy., Objective: To examine long-term cognitive changes in individuals with psychotic disorders and to compare age-related differences in cognitive performance between people with psychotic disorders and matched control individuals (ie, individuals who had never had psychotic disorders)., Design, Setting, and Participants: The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Cognitive functioning was assessed 2 and 20 years later. Patients were recruited from the 12 inpatient facilities of Suffolk County, New York. At year 20, the control group was recruited by random digit dialing and matched to the clinical cohort on zip code and demographics. Data were collected between September 1991 and July 2015. Analysis began January 2016., Main Outcomes and Measures: Change in cognitive functioning in 6 domains: verbal knowledge (Wechsler Adult Intelligence Scale-Revised vocabulary test), verbal declarative memory (Verbal Paired Associates test I and II), visual declarative memory (Visual Reproduction test I and II), attention and processing speed (Symbol Digit Modalities Test-written and oral; Trail Making Test [TMT]-A), abstraction-executive function (Trenerry Stroop Color Word Test; TMT-B), and verbal fluency (Controlled Oral Word Association Test)., Results: A total of 705 participants were included in the analyses (mean [SD] age at year 20, 49.4 [10.1] years): 445 individuals (63.1%) had psychotic disorders (211 with schizophrenia spectrum [138 (65%) male]; 164 with affective psychoses [76 (46%) male]; 70 with other psychoses [43 (61%) male]); and 260 individuals (36.9%) in the control group (50.5 [9.0] years; 134 [51.5%] male). Cognition in individuals with a psychotic disorder declined on all but 2 tests (average decline: d = 0.31; range, 0.17-0.54; all P < .001). Cognitive declines were associated with worsening vocational functioning (Visual Reproduction test II: r = 0.20; Symbol Digit Modalities Test-written: r = 0.25; Stroop: r = 0.24; P < .009) and worsening negative symptoms (avolition: Symbol Digit Modalities Test-written: r = -0.24; TMT-A: r = -0.21; Stroop: r = -0.21; all P < .009; inexpressivity: Stroop: r = -0.22; P < .009). Compared with control individuals, people with psychotic disrders showed age-dependent deficits in verbal knowledge, fluency, and abstraction-executive function (vocabulary: β = -0.32; Controlled Oral Word Association Test: β = -0.32; TMT-B: β = 0.23; all P < .05), with the largest gap among participants 50 years or older., Conclusions and Relevance: In individuals with psychotic disorders, most cognitive functions declined over 2 decades after first hospitalization. Observed declines were clinically significant. Some declines were larger than expected due to normal aging, suggesting that cognitive aging in some domains may be accelerated in this population. If confirmed, these findings would highlight cognition as an important target for research and treatment during later phases of psychotic illness.

Objective: At first hospitalization, a long duration of untreated psychosis (DUP) predicts illness severity and worse treatment outcomes. The mechanism of this association, however, remains unclear. It has been hypothesized that lengthy untreated psychosis is toxic or that it reflects a more severe form of schizophrenia. Alternatively, the association may be an artifact of lead-time bias. These hypotheses are tested in a longitudinal study of schizophrenia with 2,137 observations spanning from childhood to 20 years after first admission., Methods: Data were from the Suffolk County Mental Health Project. The cohort included 287 individuals with schizophrenia or schizoaffective disorder. DUP was defined as days from first psychotic symptom to first psychiatric hospitalization. Psychosocial function was assessed using the Premorbid Adjustment Scale and the Global Assessment of Functioning Scale. Psychosocial function trajectories were estimated using multilevel spline regression models adjusted for gender, occupational status, race, and antipsychotic medication., Results: Both long- and short-DUP patients experienced similar declines in psychosocial function, but declines occurred at different times relative to first admission. Long-DUP patients experienced most of these declines prior to first admission, while short-DUP patients experienced declines after first admission. When psychosocial function was analyzed relative to psychosis onset, DUP did not predict illness course., Conclusions: The association between DUP and psychosocial function may be an artifact of early detection, creating the illusion that early intervention is associated with improved outcomes. In other words, DUP may be better understood as an indicator of illness stage than a predictor of course.

Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnosis and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β = 0.21), greater illness severity (β = 0.28), and worse cognition (β = -0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a tool for diagnosis and treatment planning.

Background: Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood., Methods: Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis., Results: CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 × 10 -5 ). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden., Conclusions: CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Research on a putative link between apolipoprotein-ε4 allele (APOE-ε4) and schizophrenia has been inconclusive. However, prior studies have not investigated the association between APOE-ε4 and symptom trajectories, nor has the existing literature taken into account the potentially moderating effect of age in genetic association studies., Methods: The association between APOE-ε4 and four symptom dimensions was investigated in a longitudinal study of 116 individuals with schizophrenia initially assessed during their first admission for psychosis and evaluated five times over the following 20years. A meta-analysis identified 29 case-control studies of APOE-ε4 allele frequency in schizophrenia, which were analyzed using random-effects meta-regression to test the potentially moderating effect of age., Results: Longitudinal models identified a specific association between APOE-ε4 and symptom trajectories, showing that APOE-ε4 portends worsening severity of hallucinations and delusions in late adulthood among people with schizophrenia, at a rate of a 0.46 standard deviation increase per decade. Meta-analysis showed a significant effect of age: the association between APOE-ε4 and schizophrenia was not detectable in younger people but became pronounced with age, such that APOE-ε4 increased the odds of diagnosis by 10% per decade., Conclusions: Taken together, the meta-analysis and longitudinal analysis implicate APOE-ε4 as an age-related risk factor for worsening hallucinations and delusions, and suggest APOE-ε4 may play an age-mediated pathophysiological role in schizophrenia. The presence of an APOE-ε4 allele may also identify a subgroup of patients who require intensive monitoring and additional targeted interventions, especially in mid-to late-life., (Copyright © 2018 Elsevier B.V. All rights reserved.)

(Reprinted with permission from Am J Psychiatry 2018; 175:86-90) ., (Copyright © 2019 by the American Psychiatric Association.)

(Reprinted with permission from American Journal of Psychiatry 2016; 173:543-546)., (Copyright © 2017 by the American Psychiatric Association.)

This report highlights findings from the Study of Psychiatrists' Use of Informational Resources in Clinical Practice, a cross-sectional Web- and paper-based survey that examined psychiatrists' comfort using computers and other electronic devices in clinical practice. One-thousand psychiatrists were randomly selected from the American Medical Association Physician Masterfile and asked to complete the survey between May and August, 2012. A total of 152 eligible psychiatrists completed the questionnaire (response rate 22.2 %). The majority of psychiatrists reported comfort using computers for educational and personal purposes. However, 26 % of psychiatrists reported not using or not being comfortable using computers for clinical functions. Psychiatrists under age 50 were more likely to report comfort using computers for all purposes than their older counterparts. Clinical tasks for which computers were reportedly used comfortably, specifically by psychiatrists younger than 50, included documenting clinical encounters, prescribing, ordering laboratory tests, accessing read-only patient information (e.g., test results), conducting internet searches for general clinical information, accessing online patient educational materials, and communicating with patients or other clinicians. Psychiatrists generally reported comfort using computers for personal and educational purposes. However, use of computers in clinical care was less common, particularly among psychiatrists 50 and older. Information and educational resources need to be available in a variety of accessible, user-friendly, computer and non-computer-based formats, to support use across all ages. Moreover, ongoing training and technical assistance with use of electronic and mobile device technologies in clinical practice is needed. Research on barriers to clinical use of computers is warranted.

Several studies have reported differences between African Americans and Caucasians in relative proportion of psychotic symptoms and disorders, but whether this reflects racial bias in the assessment of psychosis is unclear. The purpose of this study was to examine the distribution of psychotic symptoms and potential bias in symptoms assessed via semi-structured interview using a cohort of 3,389 African American and 5,692 Caucasian participants who were diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. In this cohort, the diagnosis of schizophrenia was relatively more common, and the diagnosis of bipolar disorder and schizoaffective disorder-bipolar type was less relatively common, among African Americans than Caucasians. With regard to symptoms, relatively more African Americans than Caucasians endorsed hallucinations and delusions symptoms, and this pattern was striking among cases diagnosed with bipolar disorder and schizoaffective-bipolar disorder. In contrast, the relative endorsement of psychotic symptoms was more similar among cases diagnosed with schizophrenia and schizoaffective disorder-depressed type. Differential item function analysis revealed that African Americans with mild psychosis over-endorsed "hallucinations in any modality" and under-endorsed "widespread delusions" relative to Caucasians. Other symptoms did not show evidence of racial bias. Thus, racial bias in assessment of psychotic symptoms does not appear to explain differences in the proportion of symptoms between Caucasians and African Americans. Rather, this may reflect ascertainment bias, perhaps indicative of a disparity in access to services, or differential exposure to risk factors for psychosis by race. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objective: For many clinical questions in psychiatry, high-quality evidence is lacking. Credible practice guidelines for such questions depend on transparent, reproducible, and valid methods for assessing expert opinion. The objective of this study was to develop and demonstrate the feasibility of a method for assessing expert opinion to aid in the development of practice guidelines by the American Psychiatric Association (APA)., Methods: A "snowball" process initially soliciting nominees from three sets of professional leaders was used to identify experts on a guideline topic (psychiatric evaluation). In a Web-based survey, the experts were asked to rate their level of agreement that specific assessments improve specific outcomes when they are included in an initial psychiatric evaluation. The experts were also asked about their own practice patterns with respect to the doing of the assessments. The main outcome measures are the following: number of nominated experts, number of experts who participated in the survey, and number and nature of quantitative and qualitative responses., Results: The snowball process identified 1,738 experts, 784 (45 %) of whom participated in the opinion survey. Participants generally, but not always, agreed or strongly agreed that the assessments asked about would improve specified outcomes. Participants wrote 716 comments explaining why they might not typically include some assessments in an initial evaluation and 1,590 comments concerning other aspects of the topics under consideration., Conclusions: The snowball process based on initial solicitation of Psychiatry's leaders produced a large expert panel. The Web-based survey systematically assessed the opinions of these experts on the utility of specific psychiatric assessments, providing useful information to substantiate opinion-based practice guidelines on how to conduct a psychiatric evaluation. The considerable engagement of respondents shows promise for using this methodology in developing future APA practice guidelines.

Importance: Established nosology identifies schizoaffective disorder as a distinct category with boundaries separating it from mood disorders with psychosis and from schizophrenia. Alternative models argue for a single boundary distinguishing mood disorders with psychosis from schizophrenia (kraepelinian dichotomy) or a continuous spectrum from affective to nonaffective psychosis., Objective: To identify natural boundaries within psychotic disorders by evaluating associations between symptom course and long-term outcome., Design, Setting, and Participants: The Suffolk County Mental Health Project cohort consists of first-admission patients with psychosis recruited from all inpatient units of Suffolk County, New York (72% response rate). In an inception cohort design, participants were monitored closely for 4 years after admission, and their symptom course was charted for 526 individuals; 10-year outcome was obtained for 413., Main Outcomes and Measures: Global Assessment of Functioning (GAF) and other consensus ratings of study psychiatrists., Results: We used nonlinear modeling (locally weighted scatterplot smoothing and spline regression) to examine links between 4-year symptom variables (ratio of nonaffective psychosis to mood disturbance, duration of mania/hypomania, depression, and psychosis) and 10-year outcomes. Nonaffective psychosis ratio exhibited a sharp discontinuity-10 days or more of psychosis outside mood episodes predicted an 11-point decrement in GAF-consistent with the kraepelinian dichotomy. Duration of mania/hypomania showed 2 discontinuities demarcating 3 groups: mania absent, episodic mania, and chronic mania (manic/hypomanic >1 year). The episodic group had a better outcome compared with the mania absent and chronic mania groups (12-point and 8-point difference on GAF). Duration of depression and psychosis had linear associations with worse outcome., Conclusions and Relevance: Our data support the kraepelinian dichotomy, although the study requires replication. A boundary between schizoaffective disorder and schizophrenia was not observed, which casts further doubt on schizoaffective diagnosis. Co-occurring schizophrenia and mood disorder may be better coded as separate diagnoses, an approach that could simplify diagnosis, improve its reliability, and align it with the natural taxonomy.

Background: Prior studies of common disorders in community-dwelling adults identified internalizing and externalizing spectra of mental illness. We investigated the placement of schizophrenia and schizotypal personality disorder in this framework and tested the validity of the resulting organization in a clinical population., Methods: The data came from the Suffolk County Mental Health Project cohort (N = 628), which consists of first-admission patients with psychosis recruited from inpatient units throughout Suffolk County, NY (72% response rate). The sample was reassessed multiple times over the following 10 years. Complete diagnostic data were available for 469 participants. Mental health professionals diagnosed 11 target conditions based on semistructured clinical interviews, review of medical records, and reports of significant others. Two validators were included: family history of schizophrenia and 10-year illness course., Results: Confirmatory factor analysis revealed that the The Diagnostic and Statistical Manual of Mental Disorders-IV grouping of conditions fit the data poorly. The best alternative classification consisted of three clusters: internalizing, externalizing, and schizophrenic. Both validators supported the coherence and distinctiveness of the schizophrenic cluster., Conclusions: We replicated internalizing and externalizing spectra in a clinical population, identified a schizophrenic spectrum, and provided initial evidence of its validity. These findings suggest that schizotypal personality disorder may be better placed with schizophrenia, antisocial conditions with substance use disorders, and major depression with anxiety disorders.

Objective: Diagnostic shifts have been prospectively examined in the short term, but the long-term stability of diagnoses has rarely been evaluated. The authors examined diagnostic shifts over a 10-year follow-up period., Method: A cohort of 470 first-admission patients with psychotic disorders was systematically assessed at baseline and at 6-month, 2-year, and 10-year follow-ups. Longitudinal best-estimate consensus diagnoses were formulated after each assessment., Results: At baseline, the diagnostic distribution was 29.6% schizophrenia spectrum disorders, 21.1% bipolar disorder with psychotic features, 17.0% major depression with psychotic features, 2.4% substance-induced psychosis, and 27.9% other psychoses. At year 10, the distribution changed to 49.8%, 24.0%, 11.1%, 7.0%, and 8.1%, respectively. Overall, diagnoses were changed for 50.7% of study participants at some point during the study. Most participants who were initially diagnosed with schizophrenia or bipolar disorder retained the diagnosis at year 10 (89.2% and 77.8%, respectively). However, 32.0% of participants (N=98) originally given a non-schizophrenia diagnosis had gradually shifted to a schizophrenia diagnosis by year 10. The second largest shift was to bipolar disorder (10.7% of those not given this diagnosis at baseline). Changes in the clinical picture explained many diagnostic shifts. In particular, poorer functioning and greater negative and psychotic symptom ratings predicted a subsequent shift to schizophrenia. Better functioning and lower negative and depressive symptom ratings predicted the shift to bipolar disorder., Conclusions: First-admission patients with psychotic disorders run the risk of being misclassified at early stages in the illness course, including more than 2 years after first hospitalization. Diagnosis should be reassessed at all follow-up points.

Objectives: To determine whether switching from depression to mania is part of the natural history of bipolar illness or results from antidepressant (AD) treatment by examining bipolar patients with psychosis early in their illness course., Methods: A multi-facility cohort of 123 first-admission inpatients, aged 15-60 years, with DSM-IV bipolar disorder (BD) with psychotic features, was followed for four years, and 76 individuals experienced at least one episode of depression. Frequency of and risk factors for switches from depression to mania, time to switch, and duration of the subsequent manic episode were examined in relation to AD use (with anti-manic and/or antipsychotic medications)., Results: The 76 respondents experienced 113 depressive episodes. Those prescribed ADs had more depressive episodes and spent more time depressed than non-users. A total of 23 depressive episodes in 17 respondents ended in a manic/hypomanic/mixed episode (20%). The time to switch and duration of the subsequent manic episode were not significantly different for the seven respondents and nine episodes involving AD treatment versus the 10 respondents and 14 episodes without ADs. None of the risk factors (age of onset

Objective: This study examined the patterns and predictors of medication use and 24-month course/outcome in first-admission patients with major depressive disorder with psychotic features (MDD/P)., Method: An epidemiological sample of 87 first-admission patients with research diagnoses of MDD/P received intensive clinical assessments at baseline and at 6- and 24-month follow-ups and telephone assessments at 3-month intervals. Use of medications (antidepressant [AD], antipsychotic [AP], and antimanic agents) was determined from self-reports corroborated by external sources where possible. Outcome was assessed with the Global Assessment of Functioning and consensus evaluations of illness course and time in remission., Results: More patients received APs (77.0%) than ADs (57.5%) at discharge, with almost half (49.4%) receiving these in combination. At 24-month follow-up, 40.2% reported using no medications; 39.1% used ADs, and 32.2% used APs. Only early AD use predicted regular AD use during the 6- to 24-month follow-up. A minority (29%) achieved functional recovery (Global Assessment of Functioning score > or = 71) by 24 months. Although about 60% of the sample achieved a period of complete remission by 24 months, only about 40% had a sustained remission for at least 19 months. Medication use was not predictive of these outcome measures. There was little evidence that changes in medication, augmentation strategies, or electroconvulsive therapy was used to reduce symptoms during the 24-month follow-up. Fewer than half of our subjects received a MDD/P clinical diagnosis at discharge, which appeared to influence medication use patterns over the 24-month follow-up., Conclusions: These findings suggest that for most of these patients with MDD/P, outcome was suboptimal for both functional and syndromal recovery. The lack of an association between medication use and outcome suggests that medication changing and augmentation strategies, electroconvulsive therapy use, and/or strategies to improve medication adherence might be considered in the treatment of patients with MDD/P who remain low functioning and symptomatic even while receiving pharmacotherapy. Finally, our findings highlight the need for routine systematic diagnostic procedures to ensure appropriate diagnosis and treatment of MDD/P at first admission as well as the need for replication of our findings in a more contemporary sample.

The staff of the American Psychiatric Association (APA), the American Psychiatric Institute for Research and Education (APIRE), and a national panel of experts in bipolar disorder and practice guideline development have collaborated to generate a set of quality of care indicators for the pharmacologic and psychosocial treatment of bipolar disorder. The indicators were derived from APA's evidence-based Practice Guideline for the Treatment of Patients with Bipolar Disorder, 2002 (1) and the Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder, 2000 (2) These quality indicators can be used for quality monitoring, benchmarking, and quality improvement efforts across health plans, systems of care, and health care providers to improve quality and outcomes of care for patients with bipolar disorder.

Knowing the long-term outcomes of schizophrenia and stability of a schizophrenia diagnosis are important from a clinical standpoint as well as essential to future research on diagnostic classifications and outcome. As in prior research on schizophrenia, prospectively designed long-term studies over the past 30 years find that the predominant course of illness includes chronically poor functioning, with little evidence of long-term improvement. Mortality due to suicide is significant at about 10% over 10-year periods of follow-up. Within studies, outcome domains are interrelated, and the relatively consistent predictors of poorer outcome include family history of schizophrenia, insidious onset, poor premorbid functioning, severity of negative symptoms, and severity and duration of untreated psychosis. Residing in a developed rather than a developing country is also associated with a poorer long-term course. The diagnostic stability of schizophrenia is less well studied. The positive predictive value exceeds 90%, and preliminary findings from the 10-year follow-up of the Suffolk County Mental Health Project cohort have found that the agreement across time increased from k = .52 (baseline to 10 years) to k = .76 (6 or 24 months to 10 years). After discussing several limitations of the existing body of research, we suggest that future studies incorporate more "modifiable" risk factors into the assessment battery that could potentially be used as building blocks in experimental intervention designs.