Search

Negative symptoms reflect one of the most debilitating aspects of one of the most debilitating diseases known to humankind. As yet, our treatments for negative symptoms are palliative at best and our understanding of their causes is relatively superficial. To address this, we are developing objective ambulatory tools for digitally phenotyping their severity which can be used outside the confines of the traditional clinical and research settings. The present study evaluated the feasibility, reliability and validity of ambulatory vocal acoustic and facial emotion expression analysis. Videos were provided by 25 patients with schizophrenia or schizoaffective disorder and 27 nonpsychiatric controls using inexpensive, non-invasive ambulatory recording methods. Controls provided 411 video recordings, and patients provided 377 video recordings; an average of 15.22 and 14.50 per participant per group respectively. The vast majority (over 80%) of these videos were usable for analysis. An empirically-supported, limited-feature vocal (7 features) and facial (3 features) set was examined. Within participants, these features varied considerably over time, but showed moderate to good test-retest reliability in many cases once contextual factors (e.g., activity involved in at the time of testing) were accounted for. Vocal and facial features showed statistically significant convergence with a “gold standard” negative symptom measure. Ambulatory vocal/facial features were more strongly associated with engagement in social or work activities in patients than negative symptom ratings. These data support the use of ambulatory vocal/facial analytic technologies for digital phenotyping of these negative symptoms.

Background Some studies have suggested that antipsychotic-naive patients with nonaffective psychosis (NAP) have glucose intolerance. Aims To conduct a systematic review and meta-analysis of fasting glucose (FG), two hour values in the oral glucose tolerance test (2HG), fasting insulin concentration (INS), and insulin resistance (IR). Method We identified possibly relevant studies, then selected studies, following usual guidelines, with two authors reviewing the manuscripts. We required studies to include subjects with nonaffective psychosis and control subjects. Results There were 911 patients and 870 control subjects in the analysis of FG; their average ages were respectively 28.7 and 29.5 years. Significant differences were found for all four variables, with effect size estimates ranging from 0.21 to 0.58. Conclusions As a group, at the time of first clinical contact for psychosis, people with NAP have a slight increase in FG, which most of them maintain in the normal range despite a small increase in IR by secreting additional INS. When faced with a physiological challenge such as a glucose tolerance test or antipsychotics, they are no longer able to maintain a normal glucose concentration.

article i nfo Objective: The use of dopaminergic antagonist antipsychotics is associated with hyperprolactinemia, but some studieshavefoundincreasedprolactinconcentrationsinantipsychotic-naivepatientswithschizophreniaandre- lated disorders. We conducted a systematic review and meta-analysis of studies of prolactin in antipsychotic- naive patient with these disorders (PRISMA No. CRD42015016337). Data sources: PubMed (Medline), PsycInfo, and Web of Science were searched for articles from 1950 to the pres- ent in English. Study selection: Seven studies of males (N = 141 for patients, N = 191 for control subjects) and five studies of females (N = 67 and N = 116) met criteria for inclusion: data on blood prolactin concentrations for both control subjectsandantipsychotic-naivepatients with schizophreniaor a relateddisorder,with dataavailable separately for males and females. Data extraction: Data was extracted from the papers by one author and independently verified by a second. Results: The mean effect size for males was 1.02 (95% CI, 0.77, 1.26; p b 0.001) and 0.43 for females (95% CI 0.11, 0.76; p b 0.01). Meta-regression analyses for age, smoking, body mass index (BMI), year of publication, and cor- tisol were not significant. Funnel plots did not suggest the presence of a publication bias. Conclusions: Our meta-analyses found significantly increased prolactin levels in both male and female antipsychotic-naive patients with schizophrenia and related disorders. The small number of studies and limited matchingfor potentiallyconfounding variables insome of thestudies were limitationsof this analysis. Prolonged hyperprolactinemia may lead to sexual dysfunction and osteoporosis, and some antipsychotics cause additional elevation of prolactin concentrations. © 2016 Elsevier B.V. All rights reserved.

The Brief Negative Symptom Scale (BNSS) grew out of a recommendation by the NIMH-sponsored Consensus Development Conference on Negative Symptoms that a scale based on contemporary concepts be developed. We assessed sensitivity to change of the BNSS in a trial of MIN-101, which showed efficacy for negative symptoms (PANSS pentagonal model) at daily doses of 32 and 64mg/day. Using mixed-effects model for repeated measures, we examined change in BNSS total score and in the BNSS factors of anhedonia/avolition/asociality (AAA), and expressivity (EXP). Compared to placebo, the 64mg group (N=83) showed a significant decrease in BNSS total score (effect size d [ES] 0.56, p

Objective As a group, people with schizophrenia have a number of subtle anatomical abnormalities as well as physiological abnormalities that precede antipsychotic treatment. Some studies have also found shorter birth length or shorter adult height in people with schizophrenia compared to control subjects. We performed a systematic review and meta-analysis of studies of birth length and adult height in schizophrenia, following PRISMA guidelines (Prospero Registration # CRD42016043718). Data sources We searched the PsycInfo, Web of Science, and PubMed databases for articles published 1947–2016. Study selection Articles were included if they had data for patients diagnosed with schizophrenia and a matched control group of subjects without a psychotic disorder; both groups were measured for birth length and/or adult height (18 years or older); and the paper was published in English. Data extraction One author extracted the data, which was verified by the other. Results For adult height, six studies with 1,122 patients and 250,200 control subjects were included in analyses. There were six birth length studies, which included 984 patients and 976,296 controls. The patients did not differ from comparison subjects in birth length (effect size estimate = − 0.03; CI: − 0.09, 0.03), but adults were slightly shorter than comparison subjects (− 0.15; − 0.24, − 0.06). In meta-regression of adult studies, the variables of first episode versus clinical sample, and population registry versus non-registry were not significant. Matching for several important variables was usually lacking in these studies. Conclusions While there appears to be no difference in birth length between people with schizophrenia and comparison subjects, the former may be slighter shorter in adult life. The cause of such a discrepancy, if confirmed, is not clear, and lack of matching on potentially confounding variables undermines confidence in any conclusion.

Several lines of evidence suggest schizophrenia is a segmental progeria, that is, some but not all aspects of accelerated aging may be present. However, the evidence has not been consistent. Problems with matching and confounding may account for some of these discrepancies. Given the etiopathophysiological heterogeneity of schizophrenia, it is possible that only a specific pathophysiological group within schizophrenia is associated with progeroid features, while others are not, or that one group is associated with a particular segment of aging features, while other progeroid features are found in another pathophysiological subgroup. In the aging research field, significant progress has been made in identifying the molecular pathways that confer aging: epigenetic changes, inflammation, proteostasis, adult stem cell function, metabolic changes, and adaptation to stress, and macromolecular damage. In addition to replication and clarification of existing kinds of evidence, examining these aging pathways would improve our understanding of progeria in schizophrenia.

In a multicenter study involving 217 subjects of European ancestry [106 patients with schizophrenia and 111 healthy subjects], we tested the hypothesis that the catechol- O -methyl transferase (COMT) Val 158 Met and/or the brain-derived neurotrophic factor (BDNF) C 270 T gene polymorphisms are associated with schizophrenia. The COMT and BDNF genotype and their allele distribution did not differ between patients with schizophrenia and healthy comparison subjects. These results do not support the hypothesis that the COMT Val 158 Met or BDNF C 270 T gene polymorphisms are associated with liability to schizophrenia.

Screening of substance use may prove useful to prevent readmission after the first episode of psychosis. The aim of the present study was to evaluate the influence of drug use on readmission risk in a first-episode psychosis sample, and to determine whether the cannabis/cocaine subscale of the Dartmouth Assessment of Lifestyle Inventory (DALI) is a better predictive instrument than urinary analysis.After admission, first-episode psychotic patients were interviewed for substance use and assessed with the DALI scale. They also underwent blood and urine sampling. Time to readmission was studied as a dependent outcome. The Kaplan-Meier estimator was applied to estimate the survival curves for bivariate analysis. The Cox proportional hazards model for multivariate analysis was assessed in order to control for potential confounders. ROC curve and validity parameters were used to assess validity to detect readmission.Fifty-eight patients were included. The DALI cannabis/cocaine subscale and urinalysis were associated with increased readmission risk in survival curves, mainly the first five years of follow-up. After controlling for potential confounding variables for readmission, only the DALI cannabis/cocaine subscale remained as a significant risk factor. In terms of validity, the DALI cannabis/cocaine subscale was more sensitive than urinalysis. Alcohol assessments were not related to readmission.The findings demonstrated that a quick screening self-report scale for cannabis/cocaine use disorders is superior to urinary analysis for predicting readmission. Future research should consider longitudinal assessments of brief validated screening tests in order to evaluate their benefits in preventing early readmission in first-episode psychosis.

The current study examined the psychometric properties of the Brief Negative Symptom Scale (BNSS), a next-generation rating instrument developed in response to the NIMH sponsored consensus development conference on negative symptoms. Participants included 100 individuals with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who completed a clinical interview designed to assess negative, positive, disorganized, and general psychiatric symptoms, as well as functional outcome. A battery of anhedonia questionnaires and neuropsychological tests were also administered. Results indicated that the BNSS has excellent internal consistency and temporal stability, as well as good convergent and discriminant validity in its relationships with other symptom rating scales, functional outcome, self-reported anhedonia, and neuropsychological test scores. Given its brevity (13-items, 15-minute interview) and good psychometric characteristics, the BNSS can be considered a promising new instrument for use in clinical trials.

Objective To examine the structural integrity of the dorsolateral prefrontal-basal ganglia–thalamocortical circuit in people with the deficit form of schizophrenia. Method A three-dimensional structural MRI sequence was used to conduct morphometric assessments of cortical and subcortical regions in deficit and nondeficit outpatients with schizophrenia and healthy controls. Results The superior prefrontal and superior and middle temporal gyral gray matter volumes were significantly smaller in the deficit versus the nondeficit group and normal control groups. There were no significant group differences in examined subcortical structures. Conclusion People with deficit schizophrenia are characterized by selective reductions in the prefrontal and temporal cortex.

Numerous studies indicate that social dysfunction is associated with negative symptoms of schizophrenia during the chronic phase of illness. However, it is unclear whether social abnormalities exist during the premorbid phase in people who later develop schizophrenia with prominent negative symptoms, or whether social functioning becomes progressively worse in these individuals from childhood to late adolescence. The current study examined differences in academic and social premorbid functioning in people with schizophrenia meeting criteria for deficit (i.e., primary and enduring negative symptoms) (DS: n = 74) and non-deficit forms of schizophrenia (ND: n = 271). Premorbid social and academic functioning was assessed for childhood, early adolescence, and late adolescence developmental periods on the Premorbid Adjustment Scale (PAS). Results indicated that both DS and ND participants showed deterioration in social and academic functioning from childhood to late adolescence. However, while ND schizophrenia demonstrated greater deterioration of academic compared to social premorbid functioning from childhood to late adolescence, the DS group exhibited comparable deterioration across both premorbid domains, with more severe social deterioration than the ND group. Findings suggest that people with DS show poorer social premorbid adjustment than those with ND as early as childhood, and are particularly susceptible to accelerated deterioration as the onset of schizophrenia becomes imminent. Thus, poor premorbid social adjustment and significant social deterioration from childhood to adolescence may be a hallmark feature of people who later go on to develop prominent negative symptoms and a unique marker for the DS subtype of schizophrenia.

Background Previous studies have found increased prolactin concentrations in antipsychotic-naive patients with schizophrenia. However, the roles of other hormones, and of potentially confounding variables such as gender and smoking, have not been considered. Methods Blood from newly diagnosed, antipsychotic-naive patients with nonaffective psychosis (13 women and 20 men) and matched controls (12 women and 21 men) was assayed for prolactin, as well as three other hormones that impact prolactin concentrations: thyrotropin-stimulating hormone (TSH), ghrelin, and cortisol. Results Patients had significantly higher prolactin concentrations: female patients had a mean [SD] of 37.1 ng/mL [24.9] vs. 13.5 ng/mL [7.2] for female control subjects (p = .001), while male patients had a mean of 15.3 ng/mL [9.5] vs. 7.6 ng/mL [2.2] for male control subjects (p = .006). Patients and control subjects did not differ on concentrations of TSH, ghrelin, or cortisol. The group differences could not be attributed to differences in age, gender, smoking, body mass index, ethnicity, or the socioeconomic status of the family of origin. Conclusions Increased prolactin concentrations in antipsychotic-naive patients do not appear to be due to important confounding variables, or to the effects of elevated TSH, ghrelin, or cortisol.

Advanced paternal age (APA) is a risk factor for nonaffective psychosis (NAP) in the offspring, although the mechanism(s) of this association are not clear. The aim of this study was to examine whether later childbearing can be explained by parental schizophrenia, and in doing so, further evaluate the "de novo mutation" hypothesis for the association between APA and NAP.Using binary logistic regression, the association between APA and parental history of schizophrenia in the offspring, considering maternal and paternal history separately, was examined in 1) all persons with NAP born in Finland between 1950 and 1969 (Finnish NAP Cohort, n = 13,712), and 2) members of the Northern Finland 1966 Birth Cohort (NFBC 1966, n = 10,224), a general population birth cohort.In the Finnish NAP Cohort, having a mother with schizophrenia was associated with APA (Odds Ratio [OR] for linear trend = 1.20, 95% confidence interval 1.12-1.29, p0.01). In the NFBC 1966 sample, having a mother with schizophrenia was associated with APA at the trend level (OR = 1.14, 0.99-1.31, p = 0.07). By contrast, there was no association between having a father with schizophrenia and APA.In both a general population cohort and a birth cohort of subjects with nonaffective psychosis, APA was associated with maternal, but not paternal, schizophrenia. These findings suggest that increased genetic risk from the mother may explain the association between APA and nonaffective psychosis, and argue against the "de novo mutation" hypothesis.

Patients with schizophrenia who have primary, enduring negative symptoms, or the deficit syndrome, have poorer psychosocial functioning but lesser clinical distress compared with nondeficit patients. Poor awareness of impairment in patients with deficit schizophrenia may contribute to this seeming contradiction. We hypothesized that poor insight would be present early in the course of illness in deficit patients, and that those with deficit features would have greater impairment in insight than those without deficit features. One-hundred one first-episode patients with nonaffective psychotic disorders were categorized into deficit ( n = 31) and nondeficit ( n = 70) groups. The deficit patients had significantly poorer insight than nondeficit patients when rated using a self-report questionnaire, and nearly significantly poorer insight rated by clinical researchers. Further, this effect remained for self-rated insight and reached statistical significance for researcher-rated insight after controlling for positive, negative, and general psychopathology symptoms. These results suggest that the treatment of deficit patients may be particularly complicated by poor insight.

Some studies suggest that schizophrenia is associated with an increased risk of diabetes independently of antipsychotic use. People with deficit schizophrenia, which is characterized by primary (or idiopathic), enduring negative symptoms, differ from those with nondeficit schizophrenia on course of illness, treatment response, risk factors, and biological correlates. We hypothesized that deficit and nondeficit subjects would also differ with regard to glucose tolerance. Newly diagnosed, antipsychotic-naïve subjects with nonaffective psychosis and matched control subjects were administered a 75 g oral glucose tolerance test (GTT). Two-hour glucose concentrations were significantly higher in the nondeficit patients (N=23; mean [SD] of 121.6 [42.0]) than in deficit (N=23; 100.2 [23.1]) and control subjects (N=59; 83.8 [21.9]); the deficit subjects also had significantly higher two-hour glucose concentrations than did the control subjects. These results provide further support that the deficit group has a distinctive etiopathophysiology.

Background Some studies suggest that schizophrenia may be associated with an increased risk of diabetes, independently of antipsychotic medications and other confounding factors. Previous studies have also suggested that there is an increased prevalence of diabetes in the relatives of schizophrenia probands. Method First-degree siblings of schizophrenia probands ( N = 6) and control subjects ( N = 12) were administered a glucose tolerance test. Subjects were matched for gender, age, body mass index, neighborhood of residence, socio-economic status and smoking habits. Results The siblings of schizophrenia probands had a significantly increased two-hour mean glucose concentration compared to the control subjects (respective means [SD] were 100.5 mg/dL [27.7] vs. 78.0 [12.3]; p Conclusions Although confirmation with larger samples is needed, these results and other studies suggest that diabetes may share familial risk factors with schizophrenia.

Introduction We attempted to replicate two previous studies which found an increased risk of diabetes in the relatives of schizophrenia probands. Methods N = 34 patients with newly-diagnosed nonaffective psychosis and N = 52 non-psychiatric controls were interviewed for parental history of Type 2 diabetes. Results In a logistic regression model that included multiple potential confounders, psychosis was a significant predictor of Type 2 diabetes in either parent ( p Discussion We found an increased prevalence of Type 2 diabetes in the parents of nonaffective psychosis subjects. This association may be due to shared environmental or genetic risk factors, or both.

Objective: Although psychotic symptoms are central to the diagnostic criteria for schizophrenia, other neuropsychiatric syndromes as well as widespread anatomical and physiological abnormalities in the periphery are also common in the disorder. We decided to test the hypothesis that developmental abnormalities are present throughout the body by examining the oral cavity and in particular the teeth and dimensions of the palate of patients with schizophrenia. Method: Dental stone models (casts) were made from impressions of the teeth and palate in schizophrenia (N=28) and control (N=25) subjects. Blind to group membership, the palate height, palate width, and other features of each subject's cast were assessed by a dentist. Results: Patients with schizophrenia had significantly wider palates than control subjects; the palatal height did not differ between the two groups. The patients also had a high prevalence of several other anatomical abnormalities, few of which were present in the control subjects. Conclusions: This first blind, quantitative assessment of the palate and teeth of patients with schizophrenia revealed a wide palate and an increased prevalence of developmental abnormalities in the teeth. These findings are consistent with the emerging concept that schizophrenia is not so much a psychotic disorder as a developmental disorder in which psychosis is present, and in which there are a number of other abnormalities in the brain and the periphery. © 2007 Published by Elsevier B.V.

A three-syndrome categorization of schizophrenia has been recently proposed [Arndt, S., Alliger R.J., Andreasen, N.C., 1991. The distinction of positive and negative symptoms: the failure of a two-dimensional model. Br. J. Psychiatry 158, 317-322; Miller, D.D., Arndt, S., Andreasen, N.C., 1993. Alogia, attentional impairment, and inappropriate affect: their status in the dimensions of schizophrenia. Comp. Psychiatry 34, 221-226; Gur, R.E., Mozley, D., Resnick, S.M., Levick, S., Erwin, R., Saykin, A.J., Gur, R.C., 1991. Relations among clinical scales in schizophrenia. Am. J. Psychiatry 148, 472-478. Brown, K.W., White, T., 1992. Syndromes of chronic schizophrenia and some clinical correlates. Br. J. Psychiatry 161, pp. 317-322].Chronic, elderly, schizophrenia patients with deficit (N = 111), nondeficit with High reality distortion/Low conceptual disorganization (nondeficit-delusional) (N = 40) and nondeficit with Low reality distortion/High conceptual disorganization (nondeficit-disorganized) (N = 56) were followed-up for 6 years. Assessment included the Positive and Negative Syndrome Scale (PANSS), the Mini-mental Status Examination (MMSE) and the Alzheimer's Disease Assessment-Late Stage Cognitive and Non-Cognitive Subscale (ADAS-L Cog and ADAS-L Self care).At initial assessment, MMSE scores were significantly lower, while the ADAS-L Cog and Negative symptoms were significantly higher in the deficit and nondeficit-disorganized groups compared with the nondeficit-delusional group (all p values0.05). Positive symptoms were significantly lower in the deficit group than in both nondeficit syndrome groups (p0.05). On the ADAS-L Self Care scale the nondeficit-delusional group was the most impaired while the nondeficit-disorganized was the least impaired. There was a significant decline over time in MMSE scores in the deficit and the nondeficit-delusional groups (p0.01), but no change in the nondeficit-disorganized group. ADAS-L Cog and ADAS-L Self Care functions worsened over time in all three groups (p0.0001). Severity of negative symptoms was stable over time in deficit patients and in nondeficit-disorganized patients but worsened in nondeficit-delusional patients (p0.001). There was also a significant worsening of positive symptoms over time in deficit patients (p = 0.04).Deficit, nondeficit-delusional and nondeficit-disorganized patients with schizophrenia may represent distinct subgroups discriminated by different courses in negative and positive symptoms and cognitive status.

Objective: Serious depression is a common and important complication of schizophrenia. In a prospective, population-based study, we tested the hypothesis that suspiciousness increases the risk for the later development of depression in schizophrenia. Method: Data came from the Epidemiological Catchment Area (ECA) study. Baseline clinical and demographic features were used to predict the onset of new episodes of depression at 1 year follow-up. As ECA diagnoses were based on lay interviews, which may have low sensitivity compared with clinical diagnoses, two overlapping groups of putative schizophrenia patients were defined. Results: Suspiciousness was associated with an increased risk of new episodes of depression in both patient groups, after accounting for demographic variables. There was no association between an increased risk of depression and either disorganization or hallucinations and delusions. Conclusions: Suspiciousness appears to be a specific risk factor for depression in psychotic groups. Interventions that decrease suspiciousness, or mitigate its isolating effects, might decrease the risk of serious depression and suicide.

Winter birth has been shown to increase the risk of schizophrenia in adult life. It has been hypothesized that this effect is due to seasonal variation in infectious diseases, including influenza, as exposure to influenza during mid gestation also increases the risk of schizophrenia. However, in many areas there is little variation in temperature during the year, although rainfall may vary greatly. We tested the hypothesis that, in a tropical region with wet and dry seasons, schizophrenia births would be related to rainfall. The data came from the city of Mossoro in north-eastern Brazil. In this area there is no meaningful variation in temperature, but there is a rainy season with little precipitation during the rest of the year. In this region, the prevalence of influenza parallels that of rainfall. There was a significant relationship between rainfall and the number of schizophrenia births three months later. In contrast, there was no significant relationship between rainfall and general population births three months later. The relationship of birth to rainfall, rather than winter birth, may be associated with risk of schizophrenia in tropical regions; exposure to influenza during gestation may be the basis for such a relationship.

Patients with schizophrenia in the Suffolk County Mental Health Project were categorized into groups with (n = 32) and without (n = 52) the deficit syndrome, using a case identification method based on the Brief Psychiatric Rating Scale. The deficit group had a lower level of function at both index admission and 24-month follow-up; these differences could not be attributed to group differences in demographic variables, chronicity of illness, or a greater severity of psychosis in the deficit syndrome group. The number of patients categorized as deficit was greater at 24 months (34%) than at 6 months (25%).

Drug abuse is common in schizophrenia. Previous studies suggested patients with the deficit syndrome have a lower risk of drug abuse than do patients without deficit features. We distinguished deficit and nondeficit groups in the DSM-IV Field Trial dataset, and compared the two groups relative to current and lifetime (worst ever) severity of alcohol, cannabis, and other drugs of abuse. Deficit syndrome patients had a lower severity of current use of alcohol and other drugs, but the two groups did not differ significantly relative to cannabis use. Deficit patients also had less severe lifetime use of all three classes of drugs. These findings could not be attributed to differences between the deficit and nondeficit groups in demographics, severity of psychotic symptoms, chronicity of illness, or the quality of information available for the two groups. Deficit categorization and drug abuse were independently associated with poor level of function. Negative symptoms broadly defined were weaker predictors of drug abuse than was the deficit/nondeficit categorization. These findings further support the validity of the deficit syndrome of schizophrenia. Within schizophrenia, groups with relatively high or low risk for substance abuse can be identified.