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.

Traumatic experiences and cognitive profiles of schizophrenia cases influenced by the BDNF Val66met polymorphism.

The association of early trauma exposure with current cognition was examined in a research series of 56 schizophrenia cases with respect to the BDNF Val66Met polymorphism (rs6265, Val66Val, Val66Met, Met66Met), as met allele carriers have reduced neurotrophic activity. The Perceptual Organization Index had a significant negative correlation with trauma exposures only in met carriers, including early physical abuse, general trauma after age 18 years, and physical abuse. Within the Val66Val subgroup, there were no significant correlations between WAIS indices and traumatic experiences.

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.

Factor Structure of the Positive and Negative Syndrome Scale (PANSS) Differs by Sex.

Although the Positive and Negative Syndrome Scale (PANSS) is widely used in clinical research, factor analytic studies of the scale have been inconsistent and questions remain about the underlying factor structure of schizophrenia symptoms. The purpose of this study was to examine whether the factor structure of the PANSS differs in men and women with schizophrenia. Principal components analysis (PCA) with equamax rotation was used to examine the factor structure of the PANSS separately in 124 males and 74 females with schizophrenia-related psychoses. In males, a four-factor structure was identified: 1) Negative, 2) Cognitive, 3) Positive, and 4) Hostility. In females, a four-factor structure also emerged: 1) Negative, 2) Cognitive, 3) Positive, and 4) Depression. The most notable difference between the male and female PCAs was the presence of a depression factor in the females and a hostility factor in males. These results support sex differences in the factor structure of schizophrenia symptoms, which has important implications for clinical research.

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.

Cognitive impairment, behavioral impairment, depression, and wish to die in an ALS cohort.

OBJECTIVE: To evaluate relationships among cognitive, behavioral, and psychiatric/psychosocial measures assessed in a multicenter cohort of patients with amyotrophic lateral sclerosis (ALS). METHODS: Recently diagnosed patients with definite or probable ALS diagnosis were administered 7 standardized psychiatric/psychosocial measures, including the Patient Health Questionnaire for diagnosis of depression and elicitation of wish to die. The Cognitive Behavioral Screen was used to classify both cognitive and behavioral impairment (emotional-interpersonal function). An ALS version of the Frontal Behavioral Inventory and Mini-Mental State Examination were also administered. RESULTS: Of 247 patients included, 79 patients (32%) had neither cognitive nor behavioral impairment, 100 (40%) had cognitive impairment, 23 (9%) had behavioral impairment, and 45 (18%) had comorbid cognitive and behavioral decline. Cognitive impairment, when present, was in the mild range for 90% and severe for 10%. Thirty-one patients (12%) had a major or minor depressive disorder (DSM-IV criteria). Cognitive impairment was unrelated to all psychiatric/psychosocial measures. In contrast, patients with behavioral impairment reported more depressive symptoms, greater hopelessness, negative mood, and more negative feedback from spouse or caregiver. A wish to die was unrelated to either cognitive or behavioral impairment. CONCLUSIONS: While we found no association between cognitive impairment and depression or any measure of distress, behavioral impairment was strongly associated with depressive symptoms and diagnoses although seldom addressed by clinicians. Thoughts about ending life were unrelated to either cognitive or behavioral changes, a finding useful to consider in the context of policy debate about physician-assisted death.

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.

Prefrontal neuronal integrity predicts symptoms and cognition in schizophrenia and is sensitive to genetic heterogeneity.

Schizophrenia is a genetically complex syndrome with substantial inter-subject variability in multiple domains. Person-specific measures to resolve its heterogeneity could focus on the variability in prefrontal integrity, which this study indexed as relative rostralization within the anterior cingulate cortex (ACC). Twenty-two schizophrenia cases and 11 controls underwent rigorous diagnostic procedures, symptom assessments (PANSS, Deficit Syndrome Scale) and intelligence testing. All underwent multivoxel MRSI at 3T to measure concentrations of the neuronal-specific biomarker N-acetylaspartate (NAA) in all of the voxels of the ACC. The concentrations of NAA were separately calculated and then compared across the rostral and caudal subregions to generate a rostralization ratio, which was examined with respect to the study measures and to which cases carried a missense coding polymorphism in PTPRG, SCL39A13, TGM5, NTRK1 or ARMS/KIDINS220. Rostralization significantly differed between cases and controls (χ(2)=18.40, p<.0001). In cases, it predicted verbal intelligence (r=.469, p=.043) and trait negative symptoms (diminished emotional range (r=-.624, p=.010); curbed interests, r=-.558, p=.025). Rostralization was similar to controls for missense coding variants in TGM5 and was significantly greater than controls for the PTPRG variant carrier. This is the first study examining the utility of MRS metrics in describing pathological features at both group and person-specific levels. Rostralization predicted core illness features and differed based on which signaling genes were disrupted. While future studies in larger populations are needed, ACC rostralization appears to be a promising measure to reduce the heterogeneity of schizophrenia for genetic research and selecting cases for treatment studies.

Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort.

OBJECTIVES: To characterize the prevalence of cognitive and behavioral symptoms using a cognitive/behavioral screening battery in a large prospective multicenter study of amyotrophic lateral sclerosis (ALS). METHODS: Two hundred seventy-four patients with ALS completed 2 validated cognitive screening tests and 2 validated behavioral interviews with accompanying caregivers. We examined the associations between cognitive and behavioral performance, demographic and clinical data, and C9orf72 mutation data. RESULTS: Based on the ALS Cognitive Behavioral Screen cognitive score, 6.5% of the sample scored below the cutoff score for frontotemporal lobar dementia, 54.2% scored in a range consistent with ALS with mild cognitive impairment, and 39.2% scored in the normal range. The ALS Cognitive Behavioral Screen behavioral subscale identified 16.5% of the sample scoring below the dementia cutoff score, with an additional 14.1% scoring in the ALS behavioral impairment range, and 69.4% scoring in the normal range. CONCLUSIONS: This investigation revealed high levels of cognitive and behavioral impairment in patients with ALS within 18 months of symptom onset, comparable to prior investigations. This investigation illustrates the successful use and scientific value of adding a cognitive-behavioral screening tool in studies of motor neuron diseases, to provide neurologists with an efficient method to measure these common deficits and to understand how they relate to key clinical variables, when extensive neuropsychological examinations are unavailable. These tools, developed specifically for patients with motor impairment, may be particularly useful in patient populations with multiple sclerosis and Parkinson disease, who are known to have comorbid cognitive decline.

Hypo-metabolism of the rostral anterior cingulate cortex associated with working memory impairment in 18 cases of schizophrenia.

Working memory (Work-Mem), the capacity to hold and manipulate information, activates the anterior cingulate cortex (ACC), especially its caudal subregion. Impaired Work-Mem and structural and functional abnormalities of the ACC are reported in schizophrenia. This study aims to elucidate the pathogenesis of Work-Mem dysfunction in schizophrenia by comparing metabolite concentrations across ACC subregions. This retrospective study of 18 schizophrenia cases and 10 matched controls used proton magnetic resonance spectroscopic imaging ((1)H-MRSI, TR/TE = 1800/35 ms, 0.5 cm(3) spatial resolution) to test whether the Work-Mem Index of the Wechsler Adult Intelligence Scale, third edition is associated with differences in the rostral to caudal ACC ratios of N-acetylaspartate (NAA) and creatine (Cr). Higher caudal:rostral ACC Cr (but not NAA) concentrations were associated with decreased Work-Mem Index in cases (r = -0.6, p = 0.02), with a similar trend in controls (r = -0.56, p = 0.10), although caudal:rostral ACC Cr correlated with NAA in cases and controls (r = 0.67 and 0.62, p < 0.05 for both). NAA and Cr ratios did not correlate with myo-inositol, excluding gliosis as the underlying process. Subjects' sex and age had no effects on these relationships. The findings suggest that rostral ACC energy hypo-metabolism, possibly arising from neurodevelopmental processes, is associated with working memory impairment in schizophrenia. Changes in the rostral (not the expected caudal) subregion underscore the interconnections between the ACC subregions and may offer laboratory markers for treatment trials, etiology studies, and perhaps even enhanced identification of prodromal "at risk" subjects.

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.

Opinions of Japanese and American ALS caregivers regarding tracheostomy with invasive ventilation (TIV).

Our objective was to learn more about possible factors contributing to the higher rates of tracheostomy with invasive ventilation (TIV) for ALS patients in Japan compared with the United States by eliciting attitudes of caregivers of ALS patients in both countries. One hundred and fifty-four American caregivers from five, geographically-distributed ALS clinics and 66 Japanese caregivers from six sites in Japan completed questionnaires regarding TIV. Results showed that 33% of American caregivers were in favor of TIV for their family member compared to 53% of Japanese caregivers; 44% of American and 37% of Japanese caregivers were undecided; and 22% of American and 10% of Japanese caregivers were opposed (p <.01). Within patient-caregiver dyads, agreement in the American sample was fair, while the Japanese dyads showed poor agreement. Maintaining quality of life and patients reaching a milestone were the most common reasons for favoring TIV in the American and Japanese samples, respectively. Reasons for opposing TIV did not significantly differ. Findings suggest that caregiver preferences may influence actual choices for ALS patients. More frequent endorsement of TIV by Japanese vs. American caregivers is consistent with higher rates of TIV among Japanese patients. The results reflect the importance of caregivers' opinions in patient care.

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.