Validation of the Russian Version of the Positive and Negative Syndrome Scale (PANSS-Ru) and Normative Data.

Objective: The Positive and Negative Syndrome Scale (PANSS) is widely used to assess psychopathology. The Russian version (PANSSRu) has not been validated, and normative data for the Russian-speaking population currently do not exist. The aims of this study were to 1) complete linguistic validation for the PANSSRu, 2) perform psychometric validation of the Russian translation, and 3) present norms for the Russian and Belarusian population. Design: Validation and norms of the PANSS-Ru occurred in three stages-Stage I: linguistic validation; Stage II: psychometric validation of the translated version for 40 inpatients with schizophrenia and other psychoses; and Stage III: norms for 533 census-matched inpatients, outpatients, and healthy control subjects. Results: The rating criteria (PANSS-Ru), interview guide (SCI-PANSSRu), informant questionnaire (IQ-PANSS-Ru), and scoring form (PANSS QuikScore-Ru) were linguistically and psychometrically validated. Convergent validity between the PANSS subscale scores and total score with the Clinical Global Impressions-Severity Scale (CGI-S) were moderate (r=0.41-0.60) to high (r=0.61-0.80). Cronbach's α (0.88) verified internal consistency, and intra-class correlation coefficient (ICC) comparisons had a range of 0.83. Percentile normative data collected from 533 subjects are presented. Conclusion: This is the largest population-based study providing linguistic and psychometric validation of the PANSS-Ru. Normative data can provide clinicians with a benchmark of psychopathology and inform the efficacy of treatment interventions.

Sex differences in hedonic judgement of odors in schizophrenia cases and healthy controls.

The neurocircuitries subserving affective and olfactory processes overlap, are sexually dimorphic, and show disruptions in schizophrenia, suggesting their intersection may be a window on the core process producing psychosis. This study investigated diagnostic and sex differences in hedonic judgments of odors and smell identification in 26 schizophrenia cases and 27 healthy controls. Associations between olfaction measures and psychiatric symptoms were also examined. Cases and controls had similar identification accuracy of unpleasant odors, but cases were significantly less accurate in naming pleasant odors. In cases, greater negative symptom severity was related to abnormal hedonic judgments; specifically, higher pleasantness ratings for unpleasant odors and higher unpleasantness ratings for pleasant odors. Greater positive symptom severity was associated with lower pleasantness ratings for neutral odors. Regarding sex differences, male cases and female controls rated pleasant odors as significantly more unpleasant than male controls. Correlations between depression severity and pleasantness ratings of neutral odors were in opposite directions in male and female cases. These results suggest that a normal sexual dimorphism in the circuitry for hedonic odor judgments may interact with schizophrenia pathology, supporting the utility of olfactory hedonics as a sex-specific biomarker of this pathology.

Effects of Statins and Cholesterol on Patient Aggression: Is There a Connection?

Overview: Psychiatric adverse effects, including aggression, have been reported with the use of statin medications; however, there is little data to support or refute the theory that statins or low serum cholesterol do in fact increase a patient's risk of aggression. Objective: This study examined 1) statin use and increased aggression, measured by the requirement of either emergent psychiatric intervention referred to as "Code Green" (CG) or "Restraint and Seclusion" (RS) and 2) cholesterol level and increased aggression in psychiatric inpatients. Materials and Methods: Patient charts from January 1, 2011, to December 31, 2015 were reviewed. Statin therapy, lipid panel, and requirement of a psychiatric emergency code CG or RS were noted. Inpatients who did not receive cholesterol-lowering therapy were used as controls. Analyses of variance (ANOVAs) were used to examine the relationship between statin use and increased aggression. Results: Eleven (9.6%) patients receiving statins required a total of 57 CGs, and five (4.4%) required 27 RSs. Conversely, 33 (28.9%) patients not receiving statins required a total of 64 CGs, and 14 (12.3%) required 27 RSs. No statistically significant relationship between statin therapy and agitation was found as evidenced by a CG (F=0.068; p=0.795) or RS (F=0.001; p=1.000). A statistically significant relationship was found between total cholesterol level and requirement of a CG (F=1.435; p=0.029) or RS (F=2.89; p=0.000). Conclusion: It is evident that psychiatric inpatients with lower total cholesterol levels are at an increased risk for loss of behavioral control.

Consistency checks to improve measurement with the Positive and Negative Syndrome Scale (PANSS).

International Society for CNS Clinical Trials and Methodology convened an expert working-group that assembled consistency/inconsistency flags for the Positive and Negative Syndrome Scale (PANSS). Twenty-four flags were identified and divided based on extent to which they represent error (Possibly, Probably, Very probably or definitely). The flags were applied to assessments derived from the NEWMEDS data repository and the CATIE clinical trial data. Almost 40% of ratings had at least one inconsistency flag raised and 10% had two. Application of flags to clinical rating can improve reliability and validity of trials.

The Symptoms of Trauma Scale (SOTS): Psychometric evaluation and gender differences with adults diagnosed with serious mental illness.

A new clinician rating measure, the Symptoms of Trauma Scale (SOTS), was administered to adult psychiatric outpatients (46 men, 47 women) with severe mental illness who reported a history of trauma exposure and had recently been discharged from inpatient psychiatric treatment. SOTS composite severity scores for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, posttraumatic stress disorder (PTSD), complex PTSD (cPTSD), and total PTSD/cPTSD severity had acceptable internal consistency reliability. SOTS scores' construct and convergent validity was supported by correlations with self-report measures of childhood and adult trauma history and PTSD, dissociation, and anger symptoms. For men, SOTS scores were associated with childhood sexual and emotional abuse and self-reported anger problems, whereas for women SOTS scores were most consistently and strongly associated with childhood family adversity and self-reported PTSD symptoms. Results provide preliminary support for the reliability and validity of the SOTS with adults with severe mental illness and suggest directions for replication, measure refinement, and research on gender differences.

Physician Prescribing Practices of Vitamin D in a Psychiatric Hospital.

Vitamin D supplementation has become an increasingly popular prescribing practice, despite our limited knowledge of both the definition and degree of deficiency as well as the expected benefits or risks of exogenous administration. Many of the hypothesized benefits of vitamin D supplementation include a variety of improvements in mental health; however, these claims are not consistently or robustly supported by current research. In this paper, we provide a brief overview of what is currently known about vitamin D deficiency and about outcomes of supplementation as well as a summary of the data relative to prescribing practices for inpatients in an urban psychiatric hospital.

Transcending Psychosis: The Complexity of Comorbidity in Schizophrenia.

Schizophrenic illness encompasses diverse clinical phenomena and consists of unclear underlying pathogeneses. For the past century, the comorbidities in schizophrenia have drawn persistent interest and debate due to its high prevalence rate and a need for better management. However, its clinical and biological diversity continue to challenge both the practicing clinicians and researchers. Emerging clinical and research evidence in the past decade suggest a distinct biopsychosocial pathogenesis and unique clinical attributes in some comorbid disorders in patients with schizophrenia. In addition, current evidence also supports improved outcomes with specific assessment and treatment of these subgroup of schizophrenia. The recent changes in DSV-5 and shift in the NIMH focus towards the real world clinical practice and research provide increased impetus to explore the pathogeneses and treatment of schizophrenia with comorbid disorders.

Maximizing clozapine utilization while minimizing blood dyscrasias: evaluation of patient demographics and severity of events.

The aim of this study was to determine whether patient characteristics such as age, sex, race/ethnicity, and frequency of monitoring play a role in clozapine-related blood dyscrasias. This study examined all neutropenic events to identify any potential demographic qualities that may pose increased risk to individuals receiving clozapine treatment in accordance with the FDA guidelines released in 2005. These guidelines required the addition of absolute neutrophil count (ANC) tests in addition to white blood cell (WBC) counts to regular monitoring and a reduction in the frequency of testing to once monthly after 1 year of satisfactory WBC counts and ANCs. The previous schedule neither included ANC testing nor allowed for further reductions in the frequency of testing after 1 year, with patients continuing to be tested every 2 weeks indefinitely. This is a retrospective, closed chart review of all patients who received clozapine at the State Psychiatric Center and experienced a leukopenic/neutropenic event and/or who had a substantial drop in WBC/ANC from January 2009 to December 2011. A subset of patients who were identified as achieving 'non-rechallengeable' status with either an ANC and/or WBC threshold value from 2001 to 2014 were also examined. This protocol was approved by the New York State Psychiatric Institute Institutional Review Board. A total of 193 patients were included in the study. Males experienced more total events at 6.4 events per person compared with 5.2 events per woman. White patients had 6.5 total events per person compared with 4.2 total events per Black patient; however, Black patients experienced more moderate leukopenia/granulocytopenia events compared with Whites. Regardless of race or ethnicity, patients in the 40-49-year age range had the most events at 8.1 events per person and also presented with the highest number of moderate leukopenia/granulocytopenia events as did those scheduled for weekly monitoring. Conversely, the majority of patients with no recorded events were female and either 20-29 or 60-69 years of age. In total, 16 patients were exclusively designated as non-rechallengeable from 2001 to 2014 and only had one single blood event prompting this clozapine monitoring status. Of these 16 patient events, seven were White males, eight were White females, and one was a Black female with roughly 40% of those patients in the 50-59-year age group. Currently published predictions on possible demographic risk groups may not reflect clinical experience and may pose unnecessary treatment barriers in the provision of clozapine. Although the healthcare team should be aware of the possible demographic predictors of blood dyscrasias when using clozapine, treatment goals and monitoring strategies must be individualized to ensure successful clozapine therapy.

Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.

Report on ISCTM Consensus Meeting on Clinical Assessment of Response to Treatment of Cognitive Impairment in Schizophrenia.

If treatments for cognitive impairment are to be utilized successfully, clinicians must be able to determine whether they are effective and which patients should receive them. In order to develop consensus on these issues, the International Society for CNS Clinical Trials and Methodology (ISCTM) held a meeting of experts on March 20, 2014, in Washington, DC. Consensus was reached on several important issues. Cognitive impairment and functional disability were viewed as equally important treatment targets. The group supported the notion that sufficient data are not available to exclude patients from available treatments on the basis of age, severity of cognitive impairment, severity of positive symptoms, or the potential to benefit functionally from treatment. The group reached consensus that cognitive remediation is likely to provide substantial benefits in combination with procognitive medications, although a substantial minority believed that medications can be administered without nonpharmacological therapy. There was little consensus on the best methods for assessing cognitive change in clinical practice. Some participants supported the view that performance-based measures are essential for measurement of cognitive change; others pointed to their cost and time requirements as evidence of impracticality. Interview-based measures of cognitive and functional change were viewed as more practical, but lacking validity without informant involvement or frequent contact from clinicians. The lack of consensus on assessment methods was viewed as attributable to differences in experience and education among key stakeholders and significant gaps in available empirical data. Research on the reliability, validity, sensitivity, and practicality of competing methods will facilitate consensus.

The Symptoms of Trauma Scale (SOTS): An Initial Psychometric Study.

The Symptoms of Trauma Scale (SOTS) is a 12-item, interview-based, clinician-rated measure that assesses the severity of a range of trauma-related symptoms. This pilot study evaluated its use and psychometric properties in an outpatient setting that provides treatment to survivors of chronic interpersonal trauma. Thirty participants completed self-report measures of posttraumatic stress symptoms, depression, dissociation, self-esteem, and affect dysregulation; the participants also participated separately in a semistructured interview based on the SOTS conducted by 2 trained interviewers. SOTS composite severity scores for DSM-IV posttraumatic stress disorder (PTSD) and complex PTSD (cPTSD), DSM-5 PTSD, and PTSD dissociative subtype, and total traumatic stress symptoms generally had acceptable internal consistency and interrater reliability. Evidence of convergent, discriminant, criterion, and construct validity was found for the SOTS composite PTSD scores, although potential limitations to validity that require further research and refinement of the measure were identified for the SOTS total and DSM-IV cPTSD scores and the hyperarousal, affect dysregulation, and dissociation items. Interviewers and interviewees described the interview as efficient, informative, and well tolerated. Implications for clinical practice and research to refine the SOTS are discussed.

Impairment in emotional modulation of attention and memory in schizophrenia.

Emotion plays a critical role in cognition and goal-directed behavior via complex interconnections between the emotional and motivational systems. It has been hypothesized that the impairment in goal-directed behavior widely noted in schizophrenia may result from defects in the interaction between the neural (ventral) emotional system and (rostral) cortical processes. The present study examined the impact of emotion on attention and memory in schizophrenia. Twenty-five individuals with schizophrenia related psychosis and 25 healthy control subjects were administered a computerized task in which they were asked to search for target images during a Rapid Serial Visual Presentation of pictures. Target stimuli were either positive or negative, or neutral images presented at either 200ms or 700ms lag. Additionally, a visual hedonic task was used to assess differences between the schizophrenia group and controls on ratings of valence and arousal from the picture stimuli. Compared to controls, individuals with schizophrenia detected fewer emotional images under both the 200ms and 700ms lag conditions. Multivariate analyses showed that the schizophrenia group also detected fewer positive images under the 700ms lag condition and fewer negative images under the 200ms lag condition. Individuals with schizophrenia reported higher pleasantness and unpleasantness ratings than controls in response to neutral stimuli, while controls reported higher arousal ratings for neutral and positive stimuli compared to the schizophrenia group. These results highlight dysfunction in the neural modulation of emotion, attention, and cortical processing in schizophrenia, adding to the growing but mixed body of literature on emotion processing in the disorder.

Exploring the potential effect of polypharmacy on the hematologic profiles of clozapine patients.

INTRODUCTION: Clozapine, an atypical antipsychotic with documented efficacy in the management of treatment-resistant schizophrenia, is associated with the risk of adverse hematological outcomes. Of particular concern are reductions in white blood cells (WBC) and absolute neutrophil counts (ANC). Individuals who display moderate leukopenia (3000/mm(3) > WBC ≥ 2000/mm) upon initiation of clozapine therapy are at increased risk of developing agranulocytosis, defined as an ANC less than 500/mm. Complications of agranulocytosis can be severe and include increased risk of infection and mortality. OBJECTIVES: The primary objective of this study was to examine data on clozapine recipients who experienced adverse drug reactions (ADRs) related to decreases in WBC or ANC and ascertain whether other drugs and/or drug interactions had played a role. The analysis included multiple classes of medications. METHODS: A retrospective chart review was performed of open and closed medical records of all inpatient recipients of clozapine at a state psychiatric center between January 1, 2004 and June 30, 2011. Laboratory records of patients prescribed clozapine were examined for abnormal WBC counts or ANC. A hematological ADR was considered to have occurred if there was a substantial drop in either WBC or ANC or mild or moderate leukopenia or granulocytopenia. Each episode was analyzed for medications that might have contributed to the ADR. Data were collected for all scheduled and STAT medications started at any point during the clozapine patient's hospitalization. The following seven medication groups, based on the Therapeutic Classification System of the American Hospital Formulary System (AHFS), were chosen for analysis because they were consistently used in the majority of the patient population: antihistamines, anti-infectives, autonomic agents, cardiovascular agents, antipsychotics, vitamins, and gastrointestinal agents. Pearson correlation coefficients were calculated to identify associations between the presence of hematological ADRs and medications administered concomitantly with clozapine. RESULTS: The following significant correlation coefficients were found between the use of a class of medications and the occurrence of a hematological ADR: antiinfective agents 0.409 (p < 0.01), gastrointestinal agents 0.329 (p < 0.01), and autonomic agents 0.309 (p < 0.01). In the subset of patients who were prescribed a proton-pump inhibitor or ranitidine concomitantly with clozapine, 24/26 (96%) experienced a hematological ADR. CONCLUSIONS: Autonomic agents, anti-infective agents, and proton pump inhibitors and other gastrointestinal agents were all associated with hematological ADRs when co-prescribed with clozapine. Medications from these classes should be initiated cautiously in patients being treated with clozapine to avoid precipitous drops in ANC or WBC that may increase the risk of agranulocytosis.

Pharmacotherapy of cognitive deficits in schizophrenia.

While second-generation antipsychotics treat negative as well as positive symptoms, recovery for persons with schizophrenia remains elusive, in part because there are no FDA-approved medications that treat the cognitive deficits of schizophrenia (CDS). Recent work has identified agents that, when added to antipsychotics, improve cognition in schizophrenia. This work and hypothesized mechanisms of action will be reviewed.

Zonisamide-induced psychosis in a patient with bipolar disorder and narcolepsy.

Zonisamide is an anticonvulsant used as an adjunctive treatment for partial seizures. It has also been used off-label for treatment of mania. Abdoh et al recently reported a very interesting case of psychosis induced by zonisamide. We too observed a case of psychosis induced by zonisamide in a 34-year-old female with bipolar disorder and narcolepsy.

Integrating psychopharmacology and cognitive remediation to treat cognitive dysfunction in the psychotic disorders.

Cognitive deficits are a prominent and enduring aspect of schizophrenia, which pose a significant barrier to achieving functional goals. The most promising intervention for treating cognitive impairment is cognitive remediation (CR), a behaviorally based therapy associated with medium effect sizes for cognitive and functional outcomes. However, there is a sizeable group of nonresponders whose CR outcomes become limited when the therapeutic approach fails to address individual differences in baseline cognition, motivation variables, and the extent to which CR offers opportunities for generalization. This speaks to a need to develop cognitive interventions that are both personalized and scalable. Emerging data suggest that specific pharmacological agents have the potential to enhance and accelerate behaviorally based CR effects. This article will review the rationale and preliminary evidence to support combining CR and pharmacotherapy. We will review crucial aspects of cognitive interventions that offer the most promise for improving not only cognitive outcomes, but also for enhancing improvement in real-world functioning. Finally, we will address methodological issues to be considered for future research on combined pharmacological and CR interventions.

Hematologic impact of antibiotic administration on patients taking clozapine.

OBJECTIVE: The purpose of this study was to determine if the drop in white blood cell/absolute neutrophil count for clozapine patients on antibiotics is a normal response to the resolution of infection or if the concurrent administration resulted in an abnormal drop in blood counts and further reduction of white blood cell/absolute neutrophil below baseline prior to infection. DESIGN: This was a retrospective record review of all patients who received clozapine and antibiotics concurrently between June 30, 2010, and June 30, 2011. SETTING: Subjects included inpatients on clozapine therapy at a state psychiatric facility. PARTICIPANTS: This protocol was approved by the Institutional Review Board of record. A total of 42 patients prescribed 93 antibiotic regimens were found to meet all of the above requirements. MEASUREMENTS AND METHODS: Medications were placed into distinct groups based on approved use and mechanism of action. Pearson Correlation Coefficients were utilized and were found to be 0.409 (p<0.01), indicating that a statistically significant relationship existed between the use of systemic antibiotics and alterations in hematologic parameters. RESULTS: Each regimen was classified by specific agent as well as whether the final white blood cell/absolute neutrophil was above or below the baseline established for each patient. CONCLUSION: Antibiotics have been identified as one category of medications that may cause decreased white blood cell/absolute neutrophil counts when combined with clozapine. Our study supports the use of either ciprofloxacin or moxifloxacin as agents that may have less risk of reductions in white blood cell/absolute neutrophil counts than are seen with penicillins, cephalosporins, and other antibiotics that may ultimately require interruption or discontinuation of clozapine therapy.

Long-term impact of web-based tools, leadership feedback, and policies on inpatient antipsychotic polypharmacy.

This column describes a series of interventions to decrease antipsychotic polypharmacy in the New York State Office of Mental Health (NYSOMH) network of psychiatric hospitals. Phase 1 consisted of implementation of the Psychiatric Services Clinical Knowledge Enhancement System (PSYCKES), a Web-based application supporting clinical decision making and quality improvement, and a policy requiring approval by NYSOMH's medical director to prescribe more than two antipsychotics per patient. In phase 2 hospital leaders received feedback from the office of the medical director identifying specific patients on polypharmacy. In phase 3, access to PSYCKES continued, but the prior-approval policy and feedback were discontinued. Polypharmacy decreased significantly during phase 1, from 16.9 to 9.7 inpatients per 1,000, and decreased further in phase 2, to 3.9 inpatients per 1,000. In phase 3 the prevalence of antipsychotic polypharmacy remained low at six-month follow-up (3.1 inpatients per 1,000), despite the ending of state-level oversight. On long-term follow-up, polypharmacy increased, eventually rising to 9.2 inpatients per 1,000 after 36 months, but remained well below baseline levels.