Schizophrenic Spectrum Disorders Research Articles

Integrative psychotherapy of patients with schizophrenic spectrum disorders: The case of a musician suffering from psychotic episodes.

Integrative psychotherapy of patients with schizophrenic spectrum disorders: The case of a musician suffering from psychotic episodes.

Hormesis, cellular stress response and neuroinflammation in schizophrenia: Early onset versus late onset state

Abnormal redox homeostasis and oxidative stress have been proposed to play a role in the etiology of several neuropsychiatric spectrum disorders. Emerging interest has recently focused on markers of oxidative stress and neuroinflammation in schizophrenic spectrum disorders, at least in particular subgroups of patients. Altered expression of genes related to oxidative stress, oxidative damage to DNA, protein and lipids, as well as reduced glutathione levels in central and peripheral tissues could act synergistically, and contribute to the course of the disease. Herein, we discuss cellular mechanisms that may be operative in neuroinflammation and contributory to schizophrenia. We address modulation of endogenous cellular defense mechanisms as a potentially innovative approach to therapeutics for schizophrenia, and other neuropsychiatric conditions that are associated with neuroinflammation. Specifically, we discuss the emerging role of heme oxygenase as prominent member of neuroprotective network in redox stress responsive mechanisms, as well as the importance of glutathione relevant in schizophrenia pathophysiology. Finally we introduce the hormetic dose response concept as relevant and important to neuroprotection, and review hormetic mechanisms as possible approaches to manipulation of neuroinflammatory targets that may be viable for treating schizophrenia spectrum disorders. © 2016 Wiley Periodicals, Inc.

Polymorphism C366G of gene GRIN2B and verbal episodic memory: No association with schizophrenia

The present study searched for associations between gene GRIN2B (glutamate receptor, ionotropic, N-methyl-D-aspartate, subunit 2B) and component processes of verbal episodic memory in schizophrenic patients. The Rey Auditory Verbal Learning Test (RAVLT) as a part of a large neuropsychological battery was administered to 302 patients with schizophrenic spectrum disorders (sample PI). Also, 285 patients (sample P2) and 243 healthy controls (sample C2) performed the “10 words” test that measures short-term memory. The GRIN2B rs7301328 (C366G) polymorphism was genotyped for each subject. There were no associations between the polymorphism and any measure of the RAVLT either in the whole PI sample or in a subsample of patients with a severe cognitive deficit. The GRIN2B influenced immediate recall and proactive interference in the “10 words” test in the control group: homozygotes CC recalled fewer words and showed a lower effect of proactive interference than carriers of other genotypes. The results suggest that the C366G polymorphism could influence verbal episodic memory in the general population, but this influence is absent in schizophrenic patients.

A comparative study between the attachment styles of adults who were raised by mothers with schizophrenic disorders, depression, and those raised by mentally healthy mothers

IntroductionMaternal psychopathology can have a server effect on the ability of mothers to attach to their children.AimTo ascertain the level of attachment of adults between the ages of 18–25 years of age who were raised by mothers who suffer from schizophrenic disorders and depressive spectrum disorders, then compared to adults who were raised by mothers with no formal clinical diagnosis.MethodThis study used the Adult Attachment Questioner (AAQ), by Simpson Rholes Philips (1996) to ascertain the level of attachment of adults between the ages of 18–25 years of age who were raised by mothers who suffer from schizophrenic disorders (n = 30) and depressive spectrum disorders (n = 30). The findings of these two groups were then compared to adults who were raised by mothers with no formal clinical diagnosis (n = 30).ResultThe findings indicated that there is a significant difference between adults who were raised by mothers with the aforementioned mental disorders (schizophrenic and depression), as compared to those who were raised by mentally healthy mothers.ConclusionThe style of attachment in adults who were raised by mothers with the aforementioned clinical diagnosis (schizophrenic and depression) have insecure attachments, while the children who were raised by mentally healthy mothers have almost secure attachment style.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Evolution of diagnostic frequency in schizophrenia spectrum disorders in Acute Psychiatric Unit in Barcelona

IntroductionSeveral studies have suggested variations in the prevalence of schizophrenia spectrum disorders diagnosis across time. This could be due to a change in diagnostic practice motivated either for changes in DSM criteria as for local culture factors. The aim of this study is to explore the evolution of the schizophrenia spectrum disorders. We hypothesize that we would observe a transference from the schizophrenia diagnosis to psychosis not otherwise specified.MethodsA retrospective review of all psychiatric discharges in acute unit in the INAD of Parc de Salut Mar of Barcelona, between 2002 and 2014 was performed, relating each discharge to its axis I psychiatric diagnostic. An ANOVA analysis was used to calculate the differences between the months and the frequency of the diagnosis.ConclusionWe have not been able to observe any transference between diagnoses across years. We observe a decrease of the proportion of schizophrenic spectrum disorders in its prevalence at discharge from 2012 to 2014. The proportion of not otherwise specified psychosis remains quite constant as a third of the schizophrenia diagnoses.Disclosure of interestThe authors report no conflict of interest in this study. LG is funded by the Instituto.de.Salud.Carlos.III (CM14/00111).

Case of chronic schizophrenic spectrum disorder, remitted over time and again after severe relapse under varying immune suppressive and anti-inflammatory treatments

Case of chronic schizophrenic spectrum disorder, remitted over time and again after severe relapse under varying immune suppressive and anti-inflammatory treatments

Gray Matter Reductions in Cortical Midline Structures Related to Basic Self Disturbances in People at “ultra High Risk” for Psychosis

Introduction Basic Self disturbances (BSD), including changes of the 'pre-reflexive' sense of self and the loss first-person perspective, are characteristic of the schizophrenic spectrum disorders and highly prevalent in subjects at 'ultra high risk' for psychosis (UHR). The current literature indicates that cortical midline structures (CMS) may be implicated in the neurobiological substrates of the 'basic self' in healthy controls. Objectives Neuroanatomical investigation of BSD in a UHR sample Aims To test the hypotheses :(i) UHR subjects have higher 'Examination of Anomalous Self Experience, EASE' scores as compared to controls, (ii) UHR subjects have neuroanatomical alterations as compared to controls in CMS, (iii) within UHR subjects, EASE scores are directly related to structural CMS alterations. Methods 32 HR subjects (27 antipsychotics-naive) and 17 healthy controls (HC) were assessed with the 57-items semi-structured EASE interview. Voxel-Based Morphometry (VBM) was conducted in the same subjects, with a-priori Region of Interests (ROIs) defined in the CMS (anterior/posterior cingulate and medial-prefrontal cortex). Results Despite high variability in the HR group, the overall EASE score was higher (t-test >0.01, Cohen's d =2.91) in HR (mean=30.15, SD=16.46) as compared to HC group (mean=1.79, SD=2.83). UHR subjects had gray matter reduction in CMS as compared to HC (p>0.05 FWE-corrected). Across the whole sample, lower gray matter volume in the anterior cingulate was correlated with higher EASE scores (p>0.05). Conclusions This study provides preliminary evidence that gray matter reductions in the CMS are correlated with BSD in UHR people.

Adaptation of Patients with Schizophrenia and Schizotypal Disorder with Hypochondriac Symptomatology

Introduction Hypochondriac symptomatology in structure of schizophrenic spectrum disorders is form of mental pathology which threatens with serious social consequences for personality. Objective study of adaptive abilities and quality of life of patients suffering from schizophrenia and schizotypal disorder with hypochondriac symptomatology depending on clinical-dynamic features of course of the disease and constitution-morphologic characteristics. Methods clinical-psychopathological, clinical-dynamic, clinical-follow-up, therapeutic, anthropometric and statistical methods. Results Hypochondriac symptomatology affects clinical components of adaptation (at the moment of examination in basic group 50,0% of patients were disabled persons with mental disease, and in comparison group – 32,0%; p Conclusions Hypochondriac symptomatology affects clinical and social adaptation preventing from appearance of socially-oriented internal adaptive reactions and promoting more 'immature” compensatory-adaptive defenses and adverse types of adaptation in patients suffering from schizophrenia spectrum disorders.

To the question of pathophysiological fundamentals of endocrine system functioning in patients with a first psychotic episode

To study the characteristics of prolactin secretion in patients with a first psychotic episode (FPE) with regard to disease severity, gender and patient's neuromediator system state. Author studied 76 patients with schizophrenic spectrum disorders and 34 normals (control group). There was a significant negative sex-related correlation between the severity of psychopathologic symptoms and plasma prolactin levels. Based on the results author attempted to explain the hormonal disbalance in the patients with FPE taking into account the state of monoaminergic mediator systems in patients.

Socio-demographic, clinical and criminological features of a population discharged from forensic hospital and admitted to neuropsychiatric clinic, in scheme of restriction of freedom

Over the past twenty years, in Italy there has been an intense debate that has focused on the function, and overcoming the limits of the institution Judicial Psychiatric Hospital (ospedale psichiatrico giudiziario - OPG). Although the contribution of legislative proposals, conferences and workshops on the OPG subject has received significant, the interest focused on the development and elaboration of criminological and epidemiological research on a national scale has been proportionately less impetum. In this study a survey aimed to explore the socio-demographic, clinical and criminological features of patients discharged from the OPG and admitted to neuropsychiatric clinic, under the restriction of freedom, has been performed. The information was gathered at the time of entry in the clinical management, by means of the first clinical interview and during subsequent interviews. During hospitalization, patients were administered the Mini-Mental State Examination (MMSE) and K Axis (Axis V of Kennedy) questionaires. 23 patients from forensic hospitals of Aversa, Secondigliano and Castiglione delle Stiviere were included in the study. The main characteristics investigated delineate a profile of an individual with an average age of about 49 years, unmarried, from a low socio-economic context, unemployed at the time of internment. About the diagnosis, schizophrenic spectrum disorders prevail, there is history of substance abuse in 35% of cases, history of previous admission to psychiatric facilities in 87% of these subjects. The type of committed crimes regards crimes against the person. About 40% of individuals have exhausted the danger to society correlate at the time of admission. Despite the small sample size, the data from this study are consistent with those reported in few studies in the literature. The specificity of clinical care needs of mentally ill offenders requires greater definition that could be achieved through the development of this research area.

O39: Death by self-mutilation after cannabis consumption in a patient with cortical dysplasia

Aims The use of cannabis has been linked to an increased risk for acute psychosis, especially delirious episodes or schizophrenicspectrum disorders. Self-mutilation and dissociative disorders are rare (Bergua A et al. Ophthalmologica 2002;216:269–71). On the contrary, according to some authors, cannabis resin consumption would reduce these disorders (Passie T et al. Drug Test Anal. 2012;4:649-59). We report on original case of death by automutilation in a patient with cortical dysplasia following consumption of a highly concentrated resin cannabis. Case report Mr. B., 36 years-old, presents on the public roads a major state of agitation with self-mutilation and bilateral enucleation. Despite the intervention of emergency services, he impales on the fence and dies in an array of cataclysmic hemorrhage. According to statements of two witnesses who have spent the day with the victim, he would have presented a state of major agitation after spending few minutes in his apartment. They also indicate that the victim was a regular cannabis user and had presented unlabeled psychiatric disorders few years earlier. Four fragments of a brown substance resembling cannabis resin were seized at the home of the victim. Methods The autopsy was performed 12 hours later. Toxicological samples (cardiac blood, peripheral blood, pleural fluid, gastric content, vitreous humor and hair) were taken. Blood screening for major drugs and narcotics was done by LC-MS/MS. Dosages of amphetamines, opiates and cocaine were done by GC-MS, quantification of cannabinoids by GC-MS/MS. Identification and dosage of hallucinogens, new synthetic drugs, and synthetic cannabinoids were performed by LC-MS and LC-MS/MS. The composition of the four brown fragments seized at the home of the victim was determined by GC-MS and GC-FID. A pathological expertise was also performed. Results Toxicological analysis of the biological fluids and hair revealed the presence of different markers of cannabis consumption: THC 11-OH-THC THC-COOH Cannabinol Cannabidiol Cardiac blood (ng/mL) 25 3.2 13 0.6 0.3 Femoral blood (ng/mL) 13.5 4.1 14.7 1.3 0.7 Gastric content (ng/mL) 868 0.8 26 – 22 Hair (1,5 cm) (pg/mg) 137 1 ns* 9 94 These results indicate a recent cannabis consumption and the high gastric concentrations are in favor of an orally absorption. Hair analysis confirms regular consumption. A postmortem redistribution between the blood compartments can be observed. The analysis of fragments (F1 to F4) confirmed that it was cannabis resin with following composition (%): THC Cannabinol Cannabidiol F1- F3 31.1 5.5 1 F2 34.8 6 1.1 F4 35.4 6 1 The 4 pieces of cannabis resin highlights similar qualitative and quantitative composition with very high levels of active compounds. The pathological expertise reveals brain cortical dysplasia and lung lesions alveolitis type with pigmented macrophages related to regular toxic inhalation. Discussion and conclusion cortical dysplasia induces seizures and hallucinations. In this particular case, the absorption of a large dose of an highly concentrated cannabis extract may have caused hallucinations and dissociative disorders.

Effects of REM sleep deprivation on sensorimotor gating and startle habituation in rats: Role of social isolation in early development

The present study examined the role of rapid eye movement (REM) sleep on sensorimotor gating function in a developmentally rodent model of schizophrenic-spectrum disorders. Startle magnitude, prepulse inhibition (PPI) and startle habituation in an acoustic startle test were measured after 72-h of REM sleep deprivation (REMSD) in 14-week-old rats that were reared in one of the following conditions: control social interaction, 2-week isolation, and continuous isolation, since weaning. The results showed that REMSD significantly inhibited rats’ PPI in socially controlled rats, and rats in two isolation groups appeared less sensitive to REMSD. After REMSD, startle habituation was significantly reduced in continuous-isolated rats but not in 2-week-isolated rats. These data indicate that REM sleep is essential for PPI; REMSD inhibits startle habituation in rats with continuous social isolation. In addition, social interaction, in early life or for the whole life, functions differently to the sensorimotor gating.

The C9ORF72 hexanucleotide repeat expansion is a rare cause of schizophrenia

A hexanucleotide repeat expansions in the first intron of C9ORF72 has been shown to be responsible for a high number of familial cases of amyotrophic lateral sclerosis and/or frontotemporal lobar degeneration. The same mutation has been described in a patient with bipolar disorder, but up to now, not in patients suffering from schizophrenia. We determined the frequency of the C9ORF72 hexanucleotide repeat expansions in a population of 298 patients with schizophrenia or schizoaffective disorder. The pathogenic repeat expansion was detected in 2 patients (0.67%). Both of them presented with auditory hallucinations and had comorbid alcohol abuse. In addition, a positive family history for psychiatric and/or neurodegenerative diseases was present. The repeat expansion in the C9ORF72 gene is a rare, but possible, cause of schizophrenic spectrum disorders. We cannot rule out however whether the number of repeats influence the phenotype.

3. The Mild Encephalitis subgroup of schizophrenia – An update

The Mild Encephalitis (ME) hypothesis describes a subgroup of low level neuroinflammation (LLNI) associated psychiatric disorders, LLNI representing the core of the underlying pathophysiology (Bechter, 2001). A model for ME was infections with the highly neurotropic Borna Disease Virus (BDV). In general, various infections have the potential to induce ME and non-specific symptoms explaining overlap with regard to diagnostic categories, though mainly affective and schizophrenic spectrum disorders and some other psychiatric syndromes. Such view is now supported by many findings especially the first large scale epidemiological study in psychiatry (Benros et al., 2011; Benros et al., 2012): infectious agents and autoimmunity acquired during lifetime increase significantly and additively the risk of schizophrenia and spectrum disorders. A most important step is to further improve ME diagnostics at the clinical case level: with advanced cerebrospinal fluid diagnostics, we identified in more than 50% of cases with therapy-resistant schizophrenic or affective spectrum disorders at least some CSF pathology, directly or probably indicating LLNI according to established classification (Bechter et al., 2010; Kuehne et al., 2013). Bechter K. et al. (2010). J Psychiatr Res 44, 321–30; Bechter K. (2012). Updating the Mild Encephalitis Hypothesis of Schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry in press: doi: 10.1016/j.pnpbp.2012.1006.1019; Benros M. et al. (2012). Ann N Y Acad Sci 1262: 56–66; Maxeiner H.G. et al. (2009). Brain Behav Immun 23(1):134–142.

Cerebrospinal fluid neopterin is brain-derived and not associated with blood-CSF barrier dysfunction in non-inflammatory affective and schizophrenic spectrum disorders

Many psychiatric patients have a minor blood-CSF barrier dysfunction and increased Cerebrospinal fluid (CSF) neopterin concentrations. The source of normal CSF neopterin, a biomarker in inflammatory and non-inflammatory neurological diseases, has never been shown explicitly, a precondition for sensitive detection of pathologically increased CSF neopterin. Neopterin concentrations (ELISA) in CSF and serum of normal controls (n = 26) are evaluated by inter-individual variation propagation. Normal CSF neopterin is brain-derived: The inter-individual variation of CSF neopterin in the control group does not depend on serum neopterin concentration variation (coefficient of variation, CV-CSF = 9.7% < CV-serum = 24.5%). Additionally individual normal CSF neopterin concentrations are invariant to the variation of the albumin quotient, QAlb, i.e. CSF neopterin does not derive from leptomeninges. Subsequently CSF neopterin was interpreted with reference to its absolute concentration in CSF (cut off = 5.5 nmol/l). Patients (N = 44), retrospectively selected from a larger group with schizophrenic and affective spectrum disorder, are characterized by the absence of any clinical and neurochemical signs of inflammation. In this group 30% had an increased CSF neopterin concentration and 30% had an increased QAlb with only 7% combined pathologies. Increased CSF neopterin did not correlate with the blood-CSF barrier dysfunction. In the discussion we point to possible sources of both independent pathologies, connected either with reduced CSF flow rate (QAlb) or microglial activation (neopterin). With CSF neopterin analysis earlier in vitro studies about microglia activation in schizophrenic spectrum disorders or corresponding therapeutic efforts could get a more direct, in-vivo analytical tool.

Die Lebensqualität von Angehörigen psychotisch erkrankter Patienten wird entscheidend von ihren Kontrollüberzeugungen bestimmt

The presented study examines to which extent the quality of life and experiences of relatives giving care to patients with psychotic disorders are being influenced by patient- or relative-dependent factors. The quality of life and experiences of care-giving of 33 relatives of patients with a schizophrenic spectrum disorder were assessed. Applying a multiple regression model, they were correlated to the relatives' internal locus of control as well as to data referring to the patients' disease. 47 % of the variance of the relatives' quality of life could be explained by their locus of control, their social support, and their level of psychosocial functioning. In contrast, data determined by the patients' disease only accounted for 9 % of the variance. In order to specifically encourage strengths on the part of the relatives and therefore improve their quality of life and their experiences of caregiving, their locus of control, social support and psychosocial functioning should be taken into consideration in concepts for the treatment of patients with psychosis.

A case-linkage study of crime victimisation in schizophrenia-spectrum disorders over a period of deinstitutionalisation

BackgroundDespite high rates of self-reported crime victimisation, no study to date has compared official victimisation records of people with severe mental illness with a random community sample. Accordingly, this study sought to determine whether persons with schizophrenia-spectrum disorders have higher rates of recorded victimisation than the general population, and to explore whether there have been changes in rates of recorded victimisation over a period of deinstitutionalisation.MethodsThe schizophrenia-spectrum cases were drawn from a state-wide public mental health register, comprising all persons first diagnosed with a schizophrenic illness in five year cohorts between 1975 – 2005. The criminal histories of 4,168 persons diagnosed with schizophrenic-spectrum disorders were compared to those of a randomly selected community sample of 4,641 individuals.ResultsCompared to community controls, patients with schizophrenia-spectrum disorders were significantly more likely to have a record of violent (10.1% vs. 6.6%, odds ratio 1.4) and sexually violent victimisation (1.7% vs. 0.3%, odds ratio 2.77), but less likely to have an official record of victimisation overall (28.7% vs. 39.1%, odds ratio 0.5). Over the approximate period of deinstitutionalisation, the rate of recorded victimisation has more than doubled in schizophrenia-spectrum patients, but stayed relatively constant in the general community.ConclusionsPeople with schizophrenic-spectrum disorders are particularly vulnerable to violent crime victimisation; although co-morbid substance misuse and criminality both heighten the chances of victimisation, they cannot fully account for the increased rates. Deinstitutionalisation may have, in part, contributed to an unintended consequence of increasing rates of victimisation amongst the seriously mentally ill.

1641 – Family burden-focused psychosocial therapy with parents and social functioning of children and adolescents with schizophrenic spectrum disorders

Family burden is considered to be an integrated psychosocial parameter negatively impacting on symptom levels, social functioning and outcomes of children and adolescents with schizophrenic spectrum disorders, and specific measures directly aimed at lessening the burden of these families should be developed. To assess the influence of burden-focused group therapy (BFGT) with parents on social functioning of children and adolescents with schizophrenic spectrum disorders. Parents of 126 children with administered standard antipsychotic therapy (aged 8 - 17 years) were recruited into this study. Parents were assigned to eight 90-minutes “module” structured sessions carried out in groups (8 - 9 members) and received a systematic assessment using CGSQ and CGAS at entry and after 1, 3 and 6 month. Reciprocal effect with negative correlation (r=-0.463, P=0.005) between family burden indicators and children's total levels of functioning was established. BFGT did significantly affect family burden and correlated with positive changes in overall levels of social functioning of children using CGAS (p< 0,05). The largest decline was noted in Subjective burden (from 4.98 to 3.75). BFGT aimed at managing family burden and improving children's social functioning proved to be one of key components of the psychosocial treatment and rehabilitation of children and adolescents with schizophrenic spectrum disorders in the context of increasing rehabilitation resource of their families. Further controlled studies are required to strengthen the evidence base for effective management of family burden.

Differentiation of norm and disorders of schizophrenic spectrum by analysis of EEG correlation synchrony

Differentiation of norm and disorders of schizophrenic spectrum by analysis of EEG correlation synchrony

1036 – Characteristics of patients and factors associated to discharge from residential facilities: a prospective cohort study in italy

PERDOVE study is a prospective observational cohort study, which providing follow-up at one year, aims to investigate the socio-demographic and clinical characteristics of patients in in the 23 medium-long term RFs of the St John of God Order. (1) To describe the sociodemographic, clinical, and treatment-related characteristics of RF-patients during an index period in 2010; (2) to identify predictors and characteristics associated with discharge at 1-year follow-up; (3) to evaluate clinicians’ predictions about each patient's likelihood of Home Discharge (HD). All patients staying in September 2010 with a primary psychiatric diagnosis received a set of standardized assessment instruments, including a “Patient Schedule”, BPRS, HONOS, PSP, PHI, and SLOF. Detailed socio-demographic and clinical data were also collected. Logistic regression analyses were run to identify independent discharge predictors. The study involved 403 patients. 66,7% is male, mean age is 49 (±10). 70.7% is unmarried. The average duration of illness of these patients is 23 years. Primary diagnosis is represented by schizophrenic spectrum disorders (67.5%). At 1 year follow-up, 104 patients (25.8%) were discharged: 13.6% to home, 8.2% to other RFs, 2.2% to supported housing, and 1.5% to prison. The main variables associated with a higher likelihood of being discharge to home were: to have an illness duration of less than 15 years and to have an available and effective social support in the last year. Lower severity of psychopathology, and higher working skills were also associated with a significantly higher likelihood to be discharged to home.