Objective: People with schizophrenia have an increased risk of diabetes that may be independent of antipsychotics. Previous studies have explored the prevalence of a family history of type 2 diabetes (DM2) in schizophrenia. We hypothesized that parental DM2 is increased in probands with non-affective psychosis (NAP) compared to controls, and parental DM2 predicts comorbid diabetes in NAP, after controlling for potential confounders. Method: N = 217 patients with NAP and N = 67 controls were interviewed for a history of parental DM2. NAP was investigated as a predictor of parental DM2 in binary logistic regression models, controlling for age, sex, race, smoking, body mass index, socioeconomic status, and parental psychiatric history. Results: There was an increased prevalence of DM2 in the mother (30.0% vs 13.8%, p = 0.013) and in either the mother or father (44.5% vs 24.6%, p = 0.006) in patients with NAP versus controls. After accounting for potential confounders, NAP was associated with significant increased odds of parental DM2 (OR = 2.80, 95% CI 1.08-7.23, p = 0.034). Parental DM2 was also associated with increased odds of comorbid DM2 in NAP (OR = 3.67, 95% CI 1.58-8.56, p = 0.003). Conclusions: We replicated an association of an increased prevalence of parental DM2 in patients with NAP. Parental DM2 was also an independent predictor of comorbid DM2 in these patients. These associations may be due to shared environmental or genetic risk factors, or gene by environment interactions. Given risks of incident diabetes with antipsychotic treatment, screening for parental DM2 status is germane to the clinical care of patients with NAP.

Although there is great interest in the improving the ability to track patients' change over time in routine clinical care settings, no standardized transdiagnostic measure is currently available for busy clinicians to apply. The Clinical Global Impression (CGI) scales are simple measures widely used as outcomes in psychiatric clinical trials. However, the CGI suffers from poorly defined scoring anchors. Efforts to improve the anchors by enhancing the anchor descriptions have proven useful but are limited by being disease-specific, thereby acting as a barrier to the routine clinical adoption of the CGI. To inform the development of more broadly applicable CGI scoring anchors, we surveyed 24 clinical trial investigators, asking them to rank-order seven elements that inform their CGI-Severity (CGI-S) scoring. Symptom severity emerged as the most important element in determining CGI-S scores; the functional status of the patient emerged as a second element. Less importance was given to self-report symptom scores, staff observations, or side effects. Relative rankings of the elements' importance did not differ by investigators' experience nor time usually spent with patients. We integrated these results with published illness-specific CGI anchors to develop the Transdiagnostic CGI (T-CGI), which employs standardized scoring anchors applicable across psychiatric illnesses. Pending validity and reliability evaluations, the T-CGI may prove well-suited for inclusion in routine clinical settings and for incorporation into electronic medical records as a simple and useful measure of treatment efficacy.

Objective: Some reports suggest an increase in suicide ideations and behaviors in patients treated with antidepressants. This is an analysis of the impact of fluoxetine on suicide ideations in outpatients with minor depressive disorder. Methods: Research subjects were adult outpatients with minor depressive disorder (N=162), who received fluoxetine or placebo in a prospective, 12-week, double-blind randomized trial. The research participants were evaluated weekly with standard rating scales that included four suicide-related items: item 3 of the Hamilton Rating Scale for Depression (HRSD), item 18 of Inventory of Depressive Symptomatology (IDS-C), and items 15 and 59 of the Hopkins Symptom Checklist (SCL-90). Clinically significant intensification of suicide ideation was defined as an increase of ≥2 points on any of these items. Results: Overall 60/162 subjects (37%) had an increase of ≥1 point during treatment and 17/162 (10.5%) of ≥2 points on at least one suicide item, with 12/81 (14.8%) placebo and 5/81 (6.2%) fluoxetine-treated subjects having a ≥2 point gain. Of the study participants with baseline suicide ideation, 9/22 (40.9%) placebo and 3/24 (12.5%) fluoxetine treated had ≥2 point increase (p=0.04). Survival analysis revealed that subjects on placebo were significantly more likely (p=0.050) to experience a ≥2 point increase on one or more item, a difference that emerged early and continued throughout the 12-week trial. Conclusions: Compared to placebo, fluoxetine was not associated with a clinically significant increase in suicide ideation among adults with minor depressive disorder during 12 weeks of treatment.

Schizophrenia, bipolar disorder and major depressive disorder (MDD) have all been associated with aberrant blood cytokine levels; however, neither the pattern of cytokine alterations nor the impact of clinical status have been compared across disorders. We performed a meta-analysis of blood cytokines in acutely and chronically ill patients with these major psychiatric disorders. Articles were identified by searching the PubMed, PsycInfo and Web of Science, and the reference lists of these studies. Sixty-eight studies met the inclusion criteria (40 schizophrenia, 10 bipolar disorder and 18 MDD) for acutely ill patients. Forty-six studies met the inclusion criteria (18 schizophrenia, 16 bipolar disorder and 12 MDD) for chronically ill patients. Levels of two cytokines (interleukin- 6 (IL-6), tumor necrosis factor-α (TNF-α)), one soluble cytokine receptor (sIL-2R), and one cytokine receptor antagonist (IL-1RA) were significantly increased in acutely ill patients with schizophrenia, bipolar mania and MDD compared with controls (P < 0.01). Following treatment of the acute illness, IL-6 levels significantly decreased in both schizophrenia and MDD (P < 0.01); sIL-2R levels increased in schizophrenia; and IL-1RA levels in bipolar mania decreased. In chronically ill patients, the levels of IL-6 were significantly increased in schizophrenia, euthymic (but not depressed) bipolar disorder and MDD compared with controls (P< 0.01). The levels of IL-1β and sIL-2R were significantly increased in both chronic schizophrenia and euthymic bipolar disorder. Overall, there were similarities in the pattern of cytokine alterations in schizophrenia, bipolar disorder and MDD during acute and chronic phases of illness, raising the possibility of common underlying pathways for immune dysfunction. Effects of treatment on cytokines were more robust for schizophrenia and MDD, but were more frequently studied than for acute mania. These findings have important implications for our understanding of the pathophysiology and treatment of major psychiatric disorders.

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. BD subtypes 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 factors contributing to the combination of symptoms within a given patient are poorly understood. Methods. Rare, large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis], 1436 BD II, 579 SAB) and 8656 controls. Measures of CNV burden were integrated with polygenic risk scores (PRS) for schizophrenia (SCZ) to evaluate the relative contributions of rare and common variants to psychosis risk. Results. CNV burden did not differ relative to controls in BD when treated as a single diagnostic entity. Burden in SAB was increased relative to controls (p-value = 0.001), BD I (p-value = 0.0003) and BD II (p-value = 0.0007). Burden and SCZ PRS were increased in SAB compared to BD I with psychosis (CNV p-value = 0.0007, PRS p-value = 0.004) and BD I without psychosis (CNV p-value = 0.0004, PRS p-value = 3.9 × 10−5). Within BD I, psychosis was associated with increased SCZ PRS (p-value = 0.005) 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.

BACKGROUND: Cancer-related fatigue (CRF) is a prevalent and debilitating symptom experienced by cancer survivors, yet treatment options for CRF are limited. In this study, we evaluated the efficacy of weekly Swedish massage therapy (SMT) versus an active control condition (light touch [LT]) and waitlist control (WLC) on persistent CRF in breast cancer survivors. METHODS: This early phase, randomized, single-masked, 6-week investigation of SMT, LT, and WLC enrolled 66 female stage 0-III breast cancer survivors (age range, 32-72 years) who had received surgery plus radiation and/or chemotherapy/chemoprevention with CRF (Brief Fatigue Inventory > 25). The primary outcome was the Multidimensional Fatigue Inventory (MFI), with the National Institutes of Health PROMIS Fatigue scale secondary. RESULTS: Mean baseline MFI scores for 57 evaluable subjects were 62.95 for SMT, 55.00 for LT, and 60.41 for WLC. SMT resulted in a mean (standard deviation) 6-week reduction in MFI total scores of −16.50 (6.37) (n = 20) versus −8.06 (6.50) for LT (n = 20) and an increase of 5.88 (6.48) points for WLC (n = 17) (treatment-by-time P <.0001). The mean baseline PROMIS Fatigue scores were SMT, 22.25; LT, 22.05; and WLC, 23.24. The mean (standard deviation) reduction in PROMIS Fatigue scores was −5.49 (2.53) points for SMT versus −3.24 (2.57) points for LT and −0.06 (1.88) points for WLC (treatment-by-time P =.0008). Higher credibility, expectancy, and preference for SMT than for LT did not account for these results. CONCLUSION: SMT produced clinically significant relief of CRF. This finding suggests that 6 weeks of a safe, widely accepted manual intervention causes a significant reduction in fatigue, a debilitating sequela for cancer survivors. Cancer 2018;124:546-54. © 2017 American Cancer Society.

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 R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations.

A multidisciplinary expert review of key issues and future directions from the conference “Controversial labels and clinical uncertainties: psychogenic disorders, conversion disorder, and functional symptoms.” On October 9 and 10, 2015, a conference entitled “Controversial labels and clinical uncertainties: psychogenic disorders, conversion disorder, and functional symptoms” was held at the Center for Ethics, Emory University, Atlanta, GA, USA. This conference brought together a select group of 30 distinguished thought leaders and practitioners, including ethicists, researchers, clinicians, humanities scholars, and advocates to discuss the unique challenges and controversies related to the diagnosis, treatment, and stigma for patients with what is currently recognized as functional (“psychogenic”) neurological disorders. Our group of experts explored the conflicts and ethical tensions within health care that must be addressed in order to advance care for these disorders. What follows is a reflection on the conversations between conference attendees outlining key challenges and value conflicts in the diagnosis and treatment of patients with functional disorders. With this report, we aim to provide a roadmap for reducing stigma and improving care for functional neurological disorders (FND). A path forward would involve (1) setting a multifactorial research agenda that equally prioritized access to effective psychotherapy as well as identification of novel biomarkers; (2) empowering patients with FND to be heard and to drive changes in care; and (3) reducing isolation for clinicians by providing formal training and setting up multidisciplinary care teams and support networks.

Complementary and integrative strategies are widely used by families with children who have mental health diagnoses. The therapies used by these children include herbs, dietary supplements, massage, acupuncture, meditation, and naturopathy. The literature on efficacy of complementary and alternative approaches is of limited value, and studies are needed to test efficacy and safety. Interpretation of complementary and integrative health care studies for symptomatic management of mental health conditions is hampered by study design and methodological limitations. Well-designed, adequately powered, and suitably controlled clinical trials on promising complementary and integrative modalities are needed for children and adolescents with psychiatric conditions.

The Genomic Psychiatry Cohort (GPC) is a longitudinal resource designed to provide the necessary population-based sample for large-scale genomic studies, studies focusing on Research Domain Criteria (RDoC) and/or other alternate phenotype constructs, clinical and interventional studies, nested case-control studies, long-term disease course studies, and genomic variant-to-phenotype studies. We provide and will continue to encourage access to the GPC as an international resource. DNA and other biological samples and diagnostic data are available through the National Institute of Mental Health (NIMH) Repository. After appropriate review and approval by an advisory board, investigators are able to collaborate in, propose, and co-lead studies involving cohort participants.