Features of schizophrenia following premorbid eating disorders.

OBJECTIVE: Eating disorders (ED) and schizophrenia are frequently comorbid and schizophrenia shares genetic susceptibility with anorexia. Many factors associated with schizophrenia can disrupt eating, but ED can present years before schizophrenia. If premorbid ED distinguishes a particular subtype of schizophrenia, then phenotypic features may differ between schizophrenia cases with and without premorbid ED. METHOD: This secondary analysis used data from an inpatient schizophrenia research study that comprehensively assessed life course psychiatric disorders (DIGS interview), intelligence (WAIS), global assessments of function (GAF) and assessed symptoms during medication-free and fixed dose neuroleptic phases (PANSS). RESULTS: Premorbid ED was identified in 27 of the 288 schizophrenia cases (9.4%). This group had more females than the group without premorbid ED (74.1% vs. 30%); premorbid ED was 5-fold more common in female than male cases (χ2 (17.9, P < .0001). Only the premorbid ED group had gustatory hallucinations. They also demonstrated significantly more severe psychotic and disorganization symptoms during medication-free and fixed dose treatment phases, despite similar negative symptoms and GAF scores, as other cases. The premorbid ED group had significantly better cognition overall, but relatively lower nonverbal than verbal intelligence. DISCUSSION: Premorbid ED may define a specific subtype of schizophrenia that is common in females. Their more severe psychotic symptoms and better IQ, despite similarly impaired function and negative symptoms as other cases, suggests a distinct pathophysiology. Premorbid ED should be considered in evaluating risk states for schizophrenia, and as a relevant phenotype for treatment resistant schizophrenia.

Normal sexual dimorphism in theory of mind circuitry is reversed in Schizophrenia.

The ability to mentalize, or theory of mind (ToM), is sexually dimorphic in humans and impaired in schizophrenia. This sex-stratified study probed cognitive (indexed by intelligence) and affective (indexed by olfactory tasks) contributions to ToM performance in 37 individuals with schizophrenia and 31 healthy controls. The schizophrenia group showed impairments in mental state identification and inferring intentions compared to controls. Higher intelligence was correlated with mental state identification and inferring intentions in healthy females, whereas better smell identification was associated with mental state identification in healthy males. Conversely, higher intelligence was associated with mental state identification and inferring intentions in schizophrenia males, while better smell identification was correlated with mental state identification in schizophrenia females. These findings suggest that for ToM circuitry, the cognitive influences in healthy females and affective influences in healthy males are reversed in schizophrenia and may be displaced to lower circuitries by disease pathology. Symptom associations with emotion and cognition are also dimorphic, plausibly due to similar pathology superimposed on normal sex-specific circuitries. Males appear to rely on limbic processing for ToM, and disruption to this circuitry may contribute to development of negative symptoms. These findings highlight the importance of utilizing sex-stratified designs in schizophrenia research.

Telomere length and early trauma in schizophrenia.

BACKGROUND: Childhood trauma is emerging as a risk factor for schizophrenia, but its mechanism with respect to etiology is unknown. One possible pathway is through leucocyte telomere length (LTL) shortening, a measure of cellular aging associated with trauma. This study examined early trauma and LTL shortening in schizophrenia and considered sex effects. METHODS: The early trauma inventory (ETI) was administered to 48 adults with DSM-5 schizophrenia and 18 comparison participants. LTL was measured using qPCR. OUTCOMES: Cases had significantly more global trauma (F=4.10, p<0.01) and traumatic events (F=11.23, p<0.001), but case and control groups had similar LTL (1.91±0.74 and 1.83±0.62: p=0.68). The association of early trauma and LTL differed by sex in cases and controls (Fisher's R: Z<0.05). Significant negative associations were shown in male cases and, conversely, in female controls. For example, physical punishment was associated LTL shortening in males' cases (r=-0.429, p<01). Only female controls showed significant telomere shortening in association with early trauma. INTERPRETATION: This data confirms the substantial excess of early trauma among schizophrenia cases. There were significant sex-differences in the relationship of the trauma to LTL, with only male cases showing the expected shortening. There were converse sex effects in the control group. Mean LTL was notably similar in cases and controls, despite the trauma-related shortening in male cases, cigarette smoking, older age and chronic illness of the cases. Factors may lengthen LTL in some schizophrenia cases. The converse sex differences in the cases are consistent with findings defective sexual differentiation in schizophrenia, consistent with other findings in the field.

Independence of diabetes and obesity in adults with serious mental illness: Findings from a large urban public hospital.

OBJECTIVE: There is limited research on metabolic abnormalities in psychotropic-naïve patients with serious mental illness (SMI). Our study examined metabolic conditions in a large, ethnically diverse sample of psychotropic-naïve and non-naïve adults with SMI at an urban public hospital. METHODS: In this cross-sectional study of 923 subjects, the prevalences of hyperglycemia meeting criteria for type 2 diabetes mellitus (T2DM) based on fasting plasma glucose and obesity defined by BMI and abdominal girth were compared across duration of psychotropic medication exposure. Multiple logistic regression models used hyperglycemia and obesity as dependent variables and age, sex, race/ethnicity, and years on psychotropics as independent variables. RESULTS: Psychotropic-naïve patients, including both schizophrenia and non-psychotic subgroups, showed an elevated prevalence of hyperglycemia meeting criteria for T2DM and a decreased prevalence of obesity compared to the general population. Obesity rates significantly increased for those on psychotropic medications more than 5 years, particularly for patients without psychosis (BMI: aOR = 5.23 CI = 1.44-19.07; abdominal girth: aOR = 6.40 CI = 1.98-20.69). Women had a significantly higher obesity rate than men (BMI: aOR = 1.63 CI = 1.17-2.28; abdominal girth: aOR = 3.86 CI = 2.75-5.44). Asians had twice the prevalence of hyperglycemia as whites (aOR = 2.29 CI = 1.43-3.67), despite having significantly less obesity (BMI: aOR = .39 CI = .20-.76; abdominal girth: aOR = .34 CI = .20-.60). Hispanics had a higher rate of obesity by BMI than whites (aOR = 1.91 CI = 1.22-2.99). CONCLUSIONS: This study showed disparities between obesity and T2DM in psychotropic-naïve patients with SMI, suggesting separate risk pathways for these two metabolic conditions.

Influence of early trauma on features of schizophrenia.

AIM: This proof-of-concept study examined if early trauma influences features of schizophrenia, consistent with hypothalamic-pituitary-adrenal (HPA) axis activation. METHODS: Early trauma and current perceived stress were assessed in 28 treated schizophrenia cases, along with salivary cortisol, brain volumes, cognition and symptoms. RESULTS: Early trauma predicted more positive (r = .66, P = .005) and dysthymia symptoms (r -.65, P = .007), but less negative symptoms (r = -.56, P = .023), as well as reduced whole brain volumes (r = .50, P = .040) and increased amygdala to whole brain volume ratios (r = .56, P = .018). Larger volume reductions accompanied cortisol levels: evening values predicted smaller whole brain and hippocampal volumes whereas afternoon levels only significantly predicted smaller brain volumes in women. Sex differences were demonstrated between early trauma and cognition, with better cognition in traumatized women than other women and no male effects. Current perceived stress was related to dysthymia (especially in women) and diminished sense of purpose and social drive (especially in men). CONCLUSIONS: These results suggest that early trauma and current stress impact features of schizophrenia, consistent with stress sensitization and increased dopamine activity for treatment refractory positive symptoms, as well as the cascade of increased morning cortisol, reduced brain volumes, and depressive and deficit symptoms. Conversely, cognitive deficits and negative symptoms may arise from a distinct diathesis. The sex differences accord with the literature on human HPA function and stress responses. Early trauma may be a stressor in the aetiopathophysiology of schizophrenia, particularly for cases with treatment refractory positive symptoms, and may guide future treatment development.

A Randomized Trial of Dialectical Behavior Therapy in High-Risk Suicidal Veterans.

OBJECTIVE: Despite advances in suicide prevention implemented throughout the US Department of Veterans Affairs (VA) including the hiring of Suicide Prevention Coordinators (SPCs) at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services, suicide by veterans remains a critical problem affecting 20 veterans daily. Few empirically based treatment strategies for suicide prevention for postdeployment military personnel exist. This study aimed to test whether dialectical behavior therapy (DBT), one of the few psychosocial treatments with proven efficacy in diminishing suicidal behavior in individuals with personality disorder, can be applied to veterans irrespective of personality diagnosis. METHODS: From January 2010 to December 2014, 91 nonpsychotic veterans at high risk for suicide (61 men, 30 women) were randomly assigned to a 6-month treatment trial at a veterans' medical center comparing standard DBT to treatment as usual (TAU) and followed for 6 months after trial completion. Primary outcome was suicide attempts, measured with the Columbia-Suicide Severity Rating Scale, and secondary outcomes were suicide ideation, depression, hopelessness, and anxiety. There were no exclusions pertaining to substance abuse, homelessness, or medical comorbidity. RESULTS: Both DBT and TAU resulted in improvements in suicidal ideation, depression, and anxiety during the course of the 6-month treatment trial that did not differ between treatment arms. Survival analyses for suicide attempts and hospitalizations did not differ between treatment arms. However, DBT subjects utilized significantly more individual mental health services than TAU subjects (28.5 ± 19.6 vs 14.7 ± 10.9, F1,77 = 11.60, P = .001). CONCLUSIONS: This study is the first to examine 6-month DBT in a mostly male, veteran population. Increased mental health treatment service delivery, which included enhanced monitoring, outreach, and availability of a designated SPC, did not yield statistically significant differences in outcome for veterans at risk for suicide in TAU as compared to the DBT treatment arm. However, both treatments had difficulty with initial engagement post-hospitalization. Future studies examining possible sex differences and strategies to boost retention in difficult-to-engage, homeless, and substance-abusing populations are indicated. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02462694.

Startle amplitude during unpleasant pictures is greater in veterans with a history of multiple-suicide attempts and predicts a future suicide attempt.

UNLABELLED: Recent studies demonstrate that veterans exhibit higher suicide risk compared with the general U.S. POPULATION: A prior suicide attempt is a well-documented predictor of suicide death. Despite increased attention to clinical risk factors of suicide and efforts to develop psychosocial interventions to reduce suicide risk, the underlying biological factors that confer this risk are not well understood. This study examined affect-modulated startle (AMS) during a series of intermixed unpleasant, neutral, and pleasant pictures in a sample of 108 demographically-matched veterans at low (passive ideators: n = 26) and high risk (active ideators: n = 29; single attempters: n = 28; and multiple attempters: n = 25) for suicide based on the Columbia Suicide Severity Rating Scale. An exploratory aim involved a longitudinal component in a subset of the high-risk sample that went on to participate in a randomized 6-month clinical trial. We investigated whether baseline AMS predicts a subsequent suicide attempt at 12-month follow-up. Compared with the other three groups, multiple attempters showed greater startle potentiation during unpleasant pictures and deficient overall startle habituation from early to later trials. The groups did not differ in startle during neutral or pleasant pictures, or self-reported picture valence. Greater startle during unpleasant pictures was associated with greater emotion dysregulation as measured by the Difficulties in Emotion Regulation Scale and a future suicide attempt assessed prospectively at 12-month follow-up. These findings suggest that startle potentiation during unpleasant pictures in multiple-suicide attempters is a promising psychophysiological biomarker of suicide risk and underscore the clinical importance of targeting emotion dysregulation in the treatment of patients at-risk for suicide.

Phenotypically distinct subtypes of psychosis accompany novel or rare variants in four different signaling genes.

BACKGROUND: Rare gene variants are important sources of schizophrenia vulnerability that likely interact with polygenic susceptibility loci. This study examined if novel or rare missense coding variants in any of four different signaling genes in sporadic schizophrenia cases were associated with clinical phenotypes in an exceptionally well-characterized sample. METHOD: Structured interviews, cognition, symptoms and life course features were assessed in 48 ethnically-diverse cases with psychosis who underwent targeted exome sequencing of PTPRG (Protein Tyrosine Phosphatase, Receptor Type G), SLC39A13 (Solute Carrier Family 39 (Zinc Transporter) Member 13), TGM5 (transglutaminase 5) and ARMS/KIDINS220 (Ankyrin repeat-rich membrane spanning protein or Kinase D-Interacting Substrate of 220kDa). Cases harboring rare missense coding polymorphisms or novel mutations in one or more of these genes were compared to other cases not carrying any rare missense coding polymorphisms or novel mutations in these genes and healthy controls. FINDINGS: Fifteen of 48 cases (31.25%) carried rare or novel missense coding variants in one or more of these genes. The subgroups significantly differed in important features, including specific working memory deficits for PTPRG (n=5); severe negative symptoms, global cognitive deficits and poor educational attainment, suggesting a developmental disorder, for SLC39A13 (n=4); slow processing speed, childhood attention deficit disorder and milder symptoms for TGM5 (n=4); and global cognitive deficits with good educational attainment suggesting neurodegeneration for ARMS/KIDINS220 (n=5). Case vignettes are included in the appendix. INTERPRETATION: Genes prone to missense coding polymorphisms and/or mutations in sporadic cases may highlight influential genes for psychosis and illuminate heterogeneous pathways to schizophrenia. Ethnicity appears less important at the level of genetic variability. The sequence variations that potentially alter the function of specific genes or their signaling partners may contribute to particular subtypes of psychosis. This approach may be applicable to other complex disorders.

Telephone based cognitive-behavioral screening for frontotemporal changes in patients with amyotrophic lateral sclerosis (ALS).

Our objective was to establish a valid and reliable battery of measures to evaluate frontotemporal dementia (FTD) in patients with ALS over the telephone. Thirty-one subjects were administered either in-person or by telephone-based screening followed by the opposite mode of testing two weeks later, using a modified version of the UCSF Cognitive Screening Battery. Equivalence testing was performed for in-person and telephone based tests. The standard ALS Cognitive Behavioral Screen (ALS-CBS) showed statistical equivalence at the 5% significance level compared to a revised phone version of the ALS-CBS. In addition, the Controlled Oral Word Association Test (COWAT) and Center for Neurologic Study-Lability Scale (CNS-LS) were also found to be equivalent at the 5% and 10% significance level, respectively. Similarly, the Mini-Mental State Examination (MMSE) and the well-established Telephone Interview for Cognitive Status (TICS) were also statistically equivalent. Equivalence could not be claimed for the ALS-Frontal Behavioral Inventory (ALS-FBI) caregiver interview and the Written Verbal Fluency Index (WVFI). In conclusion, our study suggests that telephone-based versions of the ALS-CBS, COWAT, and CNS-LS may offer clinicians valid tools to detect frontotemporal changes in the ALS population. Development of telephone based cognitive testing for ALS could become an integral resource for population based research in the future.

Parental age effects on odor sensitivity in healthy subjects and schizophrenia patients.

A schizophrenia phenotype for paternal and maternal age effects on illness risk could benefit etiological research. As odor sensitivity is associated with variability in symptoms and cognition in schizophrenia, we examined if it was related to parental ages in patients and healthy controls. We tested Leukocyte Telomere Length (LTL) as an explanatory factor, as LTL is associated with paternal age and schizophrenia risk. Seventy-five DSM-IV patients and 46 controls were assessed for detection of PEA, WAIS-III for cognition, and LTL, assessed by qPCR. In healthy controls, but not schizophrenia patients, decreasing sensitivity was monotonically related to advancing parental ages, particularly in sons. The relationships between parental aging and odor sensitivity differed significantly for patients and controls (Fisher's R to Z: χ(2) = 6.95, P = 0.009). The groups also differed in the association of odor sensitivity with cognition; lesser sensitivity robustly predicted cognitive impairments in patients (<0.001), but these were unassociated in controls. LTL was unrelated to odor sensitivity and did not explain the association of lesser sensitivity with cognitive deficits.Parental aging predicted less sensitive detection in healthy subjects but not in schizophrenia patients. In patients, decreased odor sensitivity strongly predicted cognitive deficits, whereas more sensitive acuity was associated with older parents. These data support separate risk pathways for schizophrenia. A parental age-related pathway may produce psychosis without impairing cognition and odor sensitivity. Diminished odor sensitivity may furthermore be useful as a biomarker for research and treatment studies in schizophrenia. © 2015 Wiley Periodicals, Inc.

Olfactory performance segregates effects of anhedonia and anxiety on social function in patients with schizophrenia.

BACKGROUND: Social dysfunction is common among individuals with schizophrenia. While often attributed to anhedonia, social dysfunction could also result from unrecognized anxiety. We examined the contributions of anhedonia and anxiety to social function using olfactory function to examine whether the domains had separate underpinnings. METHODS: We assessed anhedonia, anxiety and social function as well as olfactory function in well-characterized patients with schizophrenia or schizoaffective disorder and healthy controls. RESULTS: We included 56 patients and 37 controls in our study. Patients exhibited significantly higher levels of anhedonia and anxiety than controls, and the domains were highly correlated in patients. The combination of anhedonia and anxiety more strongly predicted social dysfunction than either measure alone. Smell identification was differentially related to the symptoms, with better performance predicting less anhedonia but more social fear in male patients. LIMITATIONS: The use of self-report measures precludes differentiation between recollected or recounted experience. Aside from smell identification and odour threshold, additional measures of olfaction may be considered for future studies. CONCLUSION: Anhedonia and anxiety were strongly correlated and both negatively impacted social function. The olfactory biomarker results support the conclusion that these domains are separate. Social function in patients with schizophrenia may improve with interventions for anxiety, even in the presence of marked negative symptoms.

Disagreement between therapist raters and independent evaluators in a controlled clinical trial of interpersonal psychotherapy for depressed pregnant women.

BACKGROUND: The randomized controlled trial in which both the patient and the treating clinician are kept blinded to the treatment is the "gold standard" for treatment research assignment. However, in psychotherapy research, evaluations can only be single blind; thus, such studies are inherently more limited. METHODS: A 12-week, bilingual, parallel-design, controlled clinical treatment trial compared interpersonal psychotherapy for antepartum depression (IPT-P) with a parenting education program (PEP) provided to a control group. An outpatient sample of 142 women who met DSM-IV criteria for major depressive disorder was randomly assigned to IPT-P or PEP between September 2005 and May 2011. Only 110 cases were assessed at baseline and had at least 1 other treatment week of paired ratings by a therapist and a blinded independent evaluator (IE). The 17-item Hamilton Depression Rating Scale and the Clinical Global Impressions Scale were administered weekly by a therapist and every 4 weeks by a blinded IE. We examined cross-informant agreement on ratings of mood and global improvement and severity. RESULTS: Nonblinded therapists consistently rated the IPT-P treatment group as more improved than the PEP control group throughout treatment, whereas the ratings by the blinded IE were significantly higher than the therapist ratings, indicating less improvement in the IPT-P group compared with the control group. The ratings suggest that rater bias may have caused the therapist raters to perceive subjects as more improved because of the expectation that IPT-P would be more effective than the PEP control condition. CONCLUSION: Ratings in psychotherapy research must be made by anonymous participation in treatment and an independent clinical evaluator who is blind to all therapy.

Telomere length, family history, and paternal age in schizophrenia.

Leukocyte telomere length (LTL) is longer in association with advanced paternal age, but this association has not been examined along with family history (FH) in schizophrenia. LTL was measured by PCR and compared across cases and controls as part of a study to examine the characteristics of paternal age related schizophrenia. The 53 schizophrenia cases had similar mean LTL as 20 controls, although cases were significantly older than controls and overwhelmingly smoked cigarettes. Multivariate analyses showed that a FH of schizophrenia was associated with longer LTL in both male and female cases. Later paternal age was also related to longer LTL in male cases, but with shorter LTL in female cases. Male cases with older fathers and a FH had the longest LTL. The genetic architecture associated with a familial risk for schizophrenia may include pathways that lengthen LTL. Paternal aging conferred an additional increase in LTL lengthening in male cases, but reduced LTL in female cases. The gender difference in LTL for paternal aging is consistent with the severe illness features reported for female cases with older fathers and could implicate epigenetic alterations in the paternal X chromosomal region with advanced paternal age in association with the risk for schizophrenia.

ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

Increased breastfeeding rates in black women after a treatment intervention.

There has been a considerable increase in rates of breastfeeding in the United States. Despite these trends, black women continue to fall below medical recommendations. Impoverished and poorly educated women also have a comparatively lower rate of breastfeeding. Provider encouragement and supportive interventions increase breastfeeding initiation among women of all backgrounds. The data presented come from a three-site randomized controlled bilingual depression treatment trial from 2005 to 2011 that examined the comparative effectiveness of interpersonal psychotherapy and a parenting education program. Breastfeeding education and support were provided for the majority of participants in each intervention. Breastfeeding status was queried at postpartum week 4. We found higher rates of breastfeeding in black women compared with those reported in national surveys. The black breastfeeding rate did not significantly differ from that of white or Hispanic women. American-born black women were just as likely to breastfeed as American-born white women, both at significantly greater rates than American-born Hispanic women. We also found no differences in breastfeeding rate in poorly educated and impoverished women. These data must be seen against the backdrop of a significant intervention to treat depression. Because breastfeeding interventions have been shown to increase breastfeeding rates, the support provided in our study likely increased rates in groups that lag behind.

In vivo 7 Tesla imaging of the dentate granule cell layer in schizophrenia.

PURPOSE: The hippocampus is central to the pathophysiology of schizophrenia. Histology shows abnormalities in the dentate granule cell layer (DGCL), but its small size (~100 µm thickness) has precluded in vivo human studies. We used ultra high field magnetic resonance imaging (MRI) to compare DGCL morphology of schizophrenic patients to matched controls. METHOD: Bilateral hippocampi of 16 schizophrenia patients (10 male) 40.7 ± 10.6 years old (mean ± standard deviation) were imaged at 7 Tesla MRI with heavily T2*-weighted gradient-echo sequence at 232 µm in-plane resolution (0.08 µL image voxels). Fifteen matched controls (8 male, 35.6 ± 9.4 years old) and one ex vivo post mortem hippocampus (that also underwent histopathology) were scanned with same protocol. Three blinded neuroradiologists rated each DGCL on a qualitative scale of 1 to 6 (from "not discernible" to "easily visible, appearing dark gray or black") and mean left and right DGCL scores were compared using a non-parametric Mann-Whitney test. RESULTS: MRI identification of the DGCL was validated with histopathology. Mean right and left DGCL ratings in patients (3.2 ± 1.0 and 3.5 ± 1.2) were not statistically different from those of controls (3.9 ± 1.1 and 3.8 ± 0.8), but patients had a trend for lower right DGCL score (p = 0.07), which was significantly associated with patient diagnosis (p = 0.05). The optimal 48% sensitivity and 80% specificity for schizophrenia were achieved with a DGCL rating of ≤2. CONCLUSION: Decreased contrast in the right DGCL in schizophrenia was predictive of schizophrenia diagnosis. Better utility of this metric as a schizophrenia biomarker may be achieved in future studies of patients with homogeneous disease subtypes and progression rates.

Olfaction and cognition in schizophrenia: sex matters.

Cognitive and olfactory deficits occur in schizophrenia, but little is known whether sex modifies these deficits. We examined the relationship between olfaction and cognition in 55 schizophrenia patients and 32 healthy controls. Patients and controls demonstrated significant differences performing cognitive tasks. In patients, sex modified all relationships of odor identification to cognition. Female patients showed significantly stronger trends than male patients correlating better smell identification with higher scores on intelligence, memory, and attention, whereas their correlations of odor identification with executive functioning contradicted those of male patients. Odor acuity significantly correlated with several cognitive measures, especially in male patients, in whom better acuity was generally associated with better cognition. Female patients again differed significantly from males; odor acuity correlations with cognitive measures were weaker, or contradicted, those of male patients. These findings indicate significant sex differences in olfactory processing in schizophrenia. Combining the sexes in research analyses may obscure important differences.

Olfactory acuity is associated with mood and function in a pilot study of stable bipolar disorder patients.

OBJECTIVES: Olfactory dysfunction is described in several neuropsychiatric disorders but there is little research on olfactory processing in bipolar disorder. METHODS: We assessed odor detection threshold (sensitivity) and smell identification test scores, along with symptoms, cognition, and social function in 20 DSM-IV bipolar disorder patients and 44 control subjects. RESULTS: The patient and control groups had similar demographic measures, intelligence, and mean olfaction scores, but significantly differed in social domains, including adjustment, function, and anxiety. Odor detection sensitivity showed significantly opposite correlations for the depressive and manic mood domains in bipolar disorder (r to z = 2.83, p = 0.005). Depressive symptoms were related to increased sensitivity (the ability to detect odors at a lower concentration) and mania symptoms were related to decreased sensitivity for odor detection. Increased sensitivity for odor detection also predicted significantly better employment (r = -0.642, p = 0.024), whereas less sensitivity was associated with social avoidance (r = 0.702, p =0.024) and social fear (r = 0.610, p = 0.046). CONCLUSIONS: Diminished odor detection sensitivity predicted mania and social avoidance, whereas more sensitive odor detection predicted more depressive symptoms but better employment functioning in bipolar disorder patients. Odor acuity may be an illness state marker of mood syndromes in bipolar disorder. Alternatively, differences in odor acuity may identify heterogeneous subgroups within the bipolar spectrum. Longitudinal assessments in a large, sex-stratified sample are needed to understand the implications of odor sensitivity in patients with bipolar disorder.

Long-term outcome for the surgical treatment of infective endocarditis with a focus on intravenous drug users.

BACKGROUND: We reviewed our experience with surgical procedures for infective endocarditis (IE) in order to evaluate modern outcomes and objectively examine our institutional preferences, including the use of bioprostheses in intravenous drug users (IVDUs) regardless of age and prompt surgical intervention in patients with either septic cerebral emboli or active infection. METHODS: Review of medical records was conducted from February 1999 to November 2010. The Social Security Death Index was used to determine death from any cause in the postoperative period. Hospital records were used to identify infectious complications, recurrent endocarditis, and reoperation. RESULTS: Sixty-four patients were identified as IVDUs and 133 patients as non-IVDUs. Survival at 30 days, 1 year, 5 years, and 10 years for IVDUs and non-IVDUs was 91.2% versus 93.6%, 77.5% versus 83.0%, 46.7% versus 71.1%, and 41.1% versus 52.0%, respectively. Cox regression analysis identified intravenous drug use as an independent risk factor for diminished survival (p=0.03), although not for reoperation (p=0.95) despite 95.3% of IVDUs receiving bioprostheses versus 73.7% of non-IVDUs (p=0.0002, Fisher's exact test). Forty-three patients were identified as having preoperative septic cerebral emboli; none had a perioperative hemorrhagic event. Active infection approached significance as an independent risk factor for the composite end point of recurrent IE and perioperative infection (odds ratio 2.8; 95% confidence interval, 0.777 to 10.9; p=0.12, Fisher's exact test). CONCLUSIONS: Bioprostheses are reasonable for IVDUs undergoing valve replacement for IE regardless of age. Prompt surgical intervention in the setting of septic cerebral emboli is justified; in the setting of active infection it is less clear.