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.

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.

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.

A prospective cohort study of neuropsychological test performance in ALS.

Our objective was to determine the prevalence and predictors of cognitive impairment in ALS, measure differences in survival among impaired and unimpaired patients, and assess changes in neuropsychological test performance over time. Fifty patients were enrolled in a prospective cohort study of neuropsychological performance. ANOVA and chi(2) tests assessed differences in clinical characteristics and neuropsychologic test results; general estimating equations assessed change in test performance; multiple regression determined which variables contributed to cognitive status; and Cox models compared survival. Thirty-six patients were categorized as cognitively normal, and 14 were impaired. Impaired patients were older at testing (p = 0.024), but no more likely to have bulbar signs. Predicators of impairment were symptom duration (p < 0.001), motor function (p < 0.001), and rate of ALS progression (p < 0.001). The Benton recognition (p < 0.001), Boston naming (p = 0.001), Wisconsin Card Sort (p = 0.001) and word generation (p = 0.001) tests contributed most strongly to cognitive status. Survival was worse in impaired patients (p = 0.027). Over time, only animal word generation declined (p = 0.016). In conclusion, 28% percent of patients were cognitively impaired. Older age and more severe ALS were associated with impairment. The strongest neuropsychological predictors of cognitive status were measures of executive, episodic memory and language function. Cognitively impaired patients had shorter survival time.

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.

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.

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.

Validity of a 'proxy' for the deficit syndrome derived from the Positive And Negative Syndrome Scale (PANSS).

Schizophrenia patients with the deficit syndrome (DS) may represent a homogeneous subgroup. To increase the practicability of diagnosing the DS, Kirkpatrick et al. [Kirkpatrick, B., Buchanan, RW., Breier, A. Carpenter, WT., 1993. Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Res. 47, 47-56.] proposed the use of a 'proxy' case identification tool using standardized symptom ratings instead of the Schedule for the Deficit Syndrome (SDS) which requires an independent clinical assessment. The Proxy for the Deficit Syndrome (PDS) is based on the extraction of symptoms that are essentially equivalent or overlap substantially with the restricted affect and diminished emotional range on the SDS. Kirkpatrick et al. [Kirkpatrick, B., Buchanan, RW., Breier, A. Carpenter, WT., 1993. Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Res. 47, 47-56.] reported good sensitivity and specificity in a comparison of SDS and PDS assessments among 100 chronic schizophrenia outpatients. The present investigation involves the comparison of the deficit syndrome as assessed by the "gold standard" Schedule for the Deficit Syndrome with the ratings of the same symptoms embodied in the "proxy instrument" the PANSS, within the same group of 156 inpatients. Forty-four patients were assessed by the SDS to have the deficit syndrome. Patients with and without the DS, as defined by the SDS, did not differ for age, education, age at illness onset and duration of illness. The two main 'proxy' measures PDS1 and PDS2 discriminated across the SDS groups. The direct dichotomous comparison of the actual SDS and the 'proxy' derived PDS groups demonstrated good specificity (78.6% and 79.5%) and moderate to very good sensitivity (61.4% and 86.4%) and there was a moderately low rate of false positive cases (21.4% and 20.5%). For the two main 'proxy' measures (PDS1 and PDS2) kappas were .38 and .59, representing poor to good agreement. In our sample of rigorously diagnosed schizophrenia inpatients, the use of a 'proxy' case identification tool for the deficit syndrome would appear to be a viable alternative in identifying a subgroup of schizophrenia patients with the deficit syndrome when the use of the actual SDS is not feasible. Further study is indicated before the PDS as extracted from the PANSS can be used in lieu of the SDS for identifying patients with this syndrome.

Physiological and behavioral effects of naloxone and lactate in normal volunteers with relevance to the pathophysiology of panic disorder.

This study investigates whether naloxone, an opioid receptor antagonist, could render normal controls, normally nonresponsive to panic inducing stimuli, sensitive to the physiological and behavioral effects of sodium lactate, a robust panicogen in panic disorder patients. Twelve normal controls received intravenous naloxone followed by sodium lactate. Four of these subjects underwent a separate infusion with naloxone followed by saline. Respiratory physiological symptoms were measured throughout. Clinical symptoms, assessed by the Acute Panic Inventory (API), an Anxiety Scale, and the Borg Breathlessness Scale, were recorded. Eight of the twelve subjects experienced strong physiological reactivity to naloxone-lactate manifested by significantly increased tidal volume. Concomitant increases in the API and Borg scales were demonstrated; however, fear or anxiety was not affected. The four subjects retested with naloxone followed by saline did not experience significant increases on any measure. These results provide preliminary evidence that endogenous opioid system function may be a key modulator of responsivity to sodium lactate. Dysregulation of the opioid system may potentially underlie critical aspects of panic disorder neurobiology, including respiratory abnormalities and suffocation sensitivity.

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.

Lipid monitoring in patients with schizophrenia prescribed second-generation antipsychotics.

OBJECTIVES: Treatment with second-generation antipsychotic (SGA) medications has been linked with increased rates of the metabolic syndrome (i.e., dyslipidemia, obesity, and hyperglycemia). Several sets of published recommendations now provide clinicians with guidelines for monitoring metabolic parameters in individuals with schizophrenia treated with SGAs. However, few data are available regarding actual metabolic monitoring practices in this patient population. The objectives of the study were to determine baseline lipid monitoring rates for individuals with schizophrenia prescribed SGAs during the period prior to the publication of monitoring guidelines and to determine whether individuals with abnormal lipid levels received follow-up monitoring sooner than individuals with normal levels. METHOD: Lipid monitoring rates for 408 individuals with schizophrenia who were prescribed SGAs from October 1999 to October 2003 were examined using administrative data from a Veterans Affairs facility. Survival analysis was used to examine time to follow-up lipid measurement and to compare time to follow-up measure for individuals with normal initial lipid levels versus those with elevated initial lipid levels. RESULTS: Eighty-five percent of individuals had at least 1 measurement for total cholesterol or triglycerides in a 4-year period. Abnormal initial measurements predicted significantly earlier follow-up monitoring (p < .005 for total cholesterol, p < .05 for triglycerides, p < .001 for low-density lipoprotein cholesterol). However, median time to follow-up measure was 304 days (approximately 10 months) for individuals with elevated total cholesterol levels, which is too long for optimal clinical follow-up. CONCLUSION: Program managers and clinicians should assess adequacy of monitoring and support quality improvement initiatives in this area.

The factorial structure of the schedule for the deficit syndrome in schizophrenia.

Deficit schizophrenia (DS) is considered a distinct subtype within the diagnosis of schizophrenia. While the common assumption is that DS represents a single, cohesive domain of psychopathology, the factorial structure of DS has not been investigated. We assessed 52 individuals with DSM-IV diagnoses of schizophrenia with DS. A principal component analysis (PCA) was conducted on the symptoms of the Schedule for the Deficit Syndrome. The PCA resulted in 2 distinct factors explaining 73.8% of the variance. Factor 1 (avolition) is made up of symptoms of curbing of interests, diminished sense of purpose, and diminished social drive. Factor 2 (emotional expression) is made up of symptoms of restricted affect, diminished emotional range, and poverty of speech. The results indicate that DS is best characterized by these 2 factors. The great majority of participants (86%) displayed DS symptoms from both factors. On average, participants had 4.19 (S.D. = 1.39) symptoms that were primary, enduring, and at least moderate in severity. The mean severity of symptoms was 2.25 (S.D. = 1.06). We discuss possible links between the obtained factors and putative neurobiological mechanisms, as well as directions for future research.

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.

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.

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.

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.

Odor identification, eye tracking and deficit syndrome schizophrenia.

BACKGROUND: Deficit syndrome (DS) schizophrenia patients have smooth pursuit eye movement (SPEM) dysfunction. We examined if they also had smell identification deficits, since social affiliation is related to olfaction in other mammals. METHODS: Sixty-seven patients had DS assessments: 31 patients had SPEM and 50 had Smell Identification Test (SIT) assessments, and 14 patients had both measurements. RESULTS: DS patients had worse SPEM and SIT performance than the non-DS patients. Areas under the receiver-operator characteristic (ROC) curves for SIT and SPEM were both fairly accurate in identifying the DS. The odds ratio (OR) for the DS for impaired versus normal SPEM was 6.21 (95% confidence interval [CI]: 1.21, 32.25) and for microsmia versus normosmia was 10.4 (95% CI: 1.23, 88.18). Further analyses showed that the association of SIT with both SPEM and the DS could account for the SPEM-DS association. CONCLUSIONS: We found a strong association between the DS and SIT scores suggesting that the neural substrates of olfaction may be related to social affiliation in humans, as they are in other mammals. These data further support the notion that the DS defines a homogeneous subgroup of schizophrenia patients and further suggest that dysfunction in the neural circuitry of olfaction may contribute to its pathophysiology.