Stages Of Psychotic Disorders Research Articles

The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction.

Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. This paper reviews the literature relevant to the underlying neurobiology of psychosis. The dopamine hypothesis has been a major influence in the study of the neurochemistry of psychosis and in development of antipsychotic drugs. However, it became clear early on that other factors must be involved in the dysfunction involved in psychosis. In the current review, it is reported how several of these factors, namely dysregulation of neurotransmitters [dopamine, serotonin, glutamate, and γ-aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, and oligodendrocytes), the hypothalamic-pituitary-adrenal axis, the gut microbiome, oxidative stress, and mitochondrial dysfunction contribute to psychosis and interact with one another. Research on psychosis has increased knowledge of the complexity of psychotic disorders. Potential new pharmacotherapies, including combinations of drugs (with pre- and probiotics in some cases) affecting several of the factors mentioned above, have been suggested. Similarly, several putative biomarkers, particularly those related to the immune system, have been proposed. Future research on both pharmacotherapy and biomarkers will require better-designed studies conducted on an all stages of psychotic disorders and must consider confounders such as sex differences and comorbidity.

Personality functioning and self-disorders in individuals at ultra-high risk for psychosis, with first-episode psychosis and with borderline personality disorder.

Assessment of personality functioning in different stages of psychotic disorders could provide valuable information on psychopathology, course of illness and treatment planning, but empirical data are sparse. To investigate personality functioning and sense of self in individuals at ultra-high risk (UHR) for psychosis and with first-episode psychosis (FEP) in comparison with a clinical control group of individuals with borderline personality disorder (BPD) and healthy controls. In a cross-sectional design, we investigated personality functioning (Structured Interview of Personality Organization, STIPO; Level of Personality Functioning Scale, LPFS) and disturbances of the basic self (Examination of Anomalous Self-Experience, EASE) in 107 participants, comprising 24 individuals at UHR, 29 individuals with FEP, 27 individuals with BPD and 27 healthy controls. The UHR, FEP and BPD groups had moderate to severe deficits in personality organisation (STIPO) compared with the healthy control group. Self-functioning with its subdomain (facet) 'self-direction' (LPFS) was significantly worse in participants with manifest psychosis (FEP) compared with those at-risk for psychosis (UHR). The FEP group showed significantly worse overall personality functioning than the UHR group and significantly higher levels of self-disturbance (EASE) than the BPD group, with the UHR group lying between these diagnostic groups. Hierarchical cluster analysis based on the seven STIPO domains yielded three clusters differing in level of personality functioning and self-disturbances. Our data demonstrate that psychotic disorders are associated with impaired personality functioning and self-disturbances. Assessment of personality functioning can inform treatment planning for patients at different stages of psychotic disorder.

Sleep-dependent memory consolidation in schizophrenia: A systematic review and meta-analysis

Sleep disturbances and cognitive impairment are both persistent and common features of schizophrenia. Accumulating evidence indicates that sleep-dependent memory consolidation might be impaired in patients with schizophrenia compared to healthy controls. The current systematic review was performed in accordance with PRISMA guidelines. A random-effects model was used to calculate effect sizes (Hedge's g). In the quantitative review, three separate meta-analyses were conducted for procedural memory in healthy controls, schizophrenia, and comparison between healthy controls and schizophrenia. Additionally, separate meta-analyses were conducted for the studies using finger tapping motor sequence task, as it is the most commonly used task. The current systematic review included 14 studies including 304 patients with schizophrenia and 209 healthy controls. The random-effects model analyses for sleep-dependent procedural memory consolidation resulted in a small effect size in schizophrenia (g=0.26), a large effect size in healthy controls (g=0.98), a moderate effect size in healthy controls vs schizophrenia (g=0.64). For the studies using finger tapping motor sequence task, meta-analyses resulted in a small effect size in schizophrenia (g=0.19), a large effect size in healthy controls (g=1.07), a moderate effect size in healthy controls vs schizophrenia (g=0.70). In the qualitative review, there was also impaired sleep-dependent declarative memory consolidation in schizophrenia compared to healthy controls. Current findings support that sleep improves memory consolidation in healthy adults, but there is a deficit in sleep-dependent memory consolidation in people with schizophrenia. Future studies investigating sleep-dependent consolidation of different memory subtypes with polysomnography in different stages of psychotic disorders are needed.

Large-Scale Thalamocortical Triple Network Dysconnectivities in Patients With First-Episode Psychosis and Individuals at Risk for Psychosis.

Aberrant thalamocortical connectivity and large-scale network interactions among the default mode network (DMN), salience network (SN), and executive control network (ECN) (ie, triple networks) have been regarded as critical in schizophrenia pathophysiology. Despite the importance of network properties and the role of the thalamus as an integrative hub, large-scale thalamocortical triple network functional connectivities (FCs) in different stages of the psychotic disorder have not yet been reported. Thirty-nine first-episode psychosis (FEP) patients, 75 individuals at clinical high risk (CHR) for psychosis, 46 unaffected relatives (URs) of schizophrenia patients with high genetic loading, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Modular community detection was used to identify cortical and thalamic resting-state networks, and thalamocortical network interactions were compared across the groups. Thalamic triple networks included higher-order thalamic nuclei. Thalamic SN-cortical ECN FC was greater in the FEP group than in the CHR, UR, and HC groups. Thalamic DMN-cortical DMN and thalamic SN-cortical DMN FCs were greater in FEP and CHR participants. Thalamic ECN-cortical DMN and thalamic ECN-cortical SN FCs were greater in FEP patients and URs. These results highlight critical modulatory functions of thalamic triple networks and the shared and distinct patterns of thalamocortical triple network dysconnectivities across different stages of psychotic disorders. The current study findings suggest that large-scale thalamocortical triple network dysconnectivities may be used as an integrative biomarker for extending our understanding of the psychosis pathophysiology and for targeting network-based neuromodulation therapeutics.

Obsessive-compulsive symptoms in psychotic disorders: pathogenesis and treatment

Comorbid disorders often occur in psychoses from the schizophrenia spectrum and are an additional burden for patients' quality of life, render treatment and rehabilitation prognosis more difficult and can also contribute to suicidal ideation. Specifically, obsessive-compulsive syndrome (OCS) and OC disorder (OCD) have been reported. What is known about the epidemiology and pathogenesis and which conclusions can be drawn regarding the diagnostics and treatment? This review evaluated current reports on comorbid OCS during different stages of psychotic disorders, starting with the at-risk mental state (ARMS) via the first manifestation and up to chronic courses. The focus was on pharmacological and psychotherapeutic consequences. Patients with ARMS suffer much more often from OCS than the general population. The prevalence is even higher in patients with afirst manifestation of psychosis. During the chronic courses ca. 30% of patients are affected by comorbid OCS and 12% fulfill the diagnostic criteria of aOCD. The pathogenesis can most likely be explained by agenetic disposition in the glutamatergic system, shared structural and functional abnormalities of cortical and subcortical structures, pharmacological influences and psychosocial stressors. Clozapine and other antipsychotics may induce or aggravate OCS in adose-dependent manner. In order to alleviate symptoms clozapine should be reduced to aminimally sufficient level. This can be attempted through combination, for example with dopaminergic antipsychotics. In general, serotonergic antidepressants can be added. Cognitive behavioral therapy should be offered to every patient with comorbid OCS. For future research multimodal longitudinal studies investigating the efficacy of interventions and aimed at the subjective level will be important.

Viewer and object mental rotation in young adults with psychotic disorders

Schizophrenia patients have difficulty with processing visuo-spatial information, which may explain their deficits with considering other people's point-of-view. Processing visuo-spatial information operates on egocentric and allocentric frames of reference. Here, we tested the ability of individuals at different stages of psychotic disorders, specifically ultra-high-risk for psychosis individuals, as well as first-episode psychosis, and chronic schizophrenia patients, to perform a viewer mental rotation task and an object mental rotation task. The two tasks were differentiated only by the instruction given. Healthy individuals and patients with a diagnosis of anxiety/depressive mood disorder served as non-patient and patient controls, respectively. The results show that first-episode psychosis and chronic schizophrenia patients, but not ultra-high-risk individuals, had more errors and longer response times with both mental rotation tasks than the two control groups. In addition, chronic schizophrenia patients had additional difficulty with the object rotation task. The difference in performance between groups and tasks remained significant even after controlling for age, IQ, and antipsychotic medication dose. The results indicate that patients with psychotic disorders have a deficit of mental spatial imagery that include both egocentric and allocentric representations. This deficit may explain the difficulty of these patients with perspective-taking, and inferring other people's point of view, thoughts or intentions which is at the core of the pathogenesis of schizophrenia.

Prediction of psychosis across protocols and risk cohorts using automated language analysis.

Language and speech are the primary source of data for psychiatrists to diagnose and treat mental disorders. In psychosis, the very structure of language can be disturbed, including semantic coherence (e.g., derailment and tangentiality) and syntactic complexity (e.g., concreteness). Subtle disturbances in language are evident in schizophrenia even prior to first psychosis onset, during prodromal stages. Using computer-based natural language processing analyses, we previously showed that, among English-speaking clinical (e.g., ultra) high-risk youths, baseline reduction in semantic coherence (the flow of meaning in speech) and in syntactic complexity could predict subsequent psychosis onset with high accuracy. Herein, we aimed to cross-validate these automated linguistic analytic methods in a second larger risk cohort, also English-speaking, and to discriminate speech in psychosis from normal speech. We identified an automated machine-learning speech classifier - comprising decreased semantic coherence, greater variance in that coherence, and reduced usage of possessive pronouns - that had an 83% accuracy in predicting psychosis onset (intra-protocol), a cross-validated accuracy of 79% of psychosis onset prediction in the original risk cohort (cross-protocol), and a 72% accuracy in discriminating the speech of recent-onset psychosis patients from that of healthy individuals. The classifier was highly correlated with previously identified manual linguistic predictors. Our findings support the utility and validity of automated natural language processing methods to characterize disturbances in semantics and syntax across stages of psychotic disorder. The next steps will be to apply these methods in larger risk cohorts to further test reproducibility, also in languages other than English, and identify sources of variability. This technology has the potential to improve prediction of psychosis outcome among at-risk youths and identify linguistic targets for remediation and preventive intervention. More broadly, automated linguistic analysis can be a powerful tool for diagnosis and treatment across neuropsychiatry.

The concept of basic symptoms: its scientific and clinical relevance.

The concept of basic symptoms: its scientific and clinical relevance.

Ethnic difference in medication adherence and compounding factors in treatment of early stages of psychotic disorders

Introduction Studies shown ethnic difference in illness-awareness, medication acceptance, difference in types and doses of medication prescribed in certain ethnic groups in treatment of psychosis. Objectives To study antipsychotic adherence patterns in ethnic groups and to study factors influencing. Aims To analyse any difference in the adherence patterns between ethnic groups and identify factors mediating any effects. Methods One hundred and twenty-seven consecutive patients presenting to early-intervention service in South-London included in naturalistic study. Sample binarised into Caucasian (white British, other white background, n =36, 28%) and combined Black and Minority Ethnic (BME, n =91, 72%) groups. Medication adherence studied using self and carer reports, looking for percentage of times taking medications, any gaps in treatment (atleast 1 month). Range of demographic and clinical parameters collected including use of substances and medications side-effects. Results Patients with treatment gap (atleast 1 month) had similar demographic and clinical characteristics with the rest, except the former were more likely to have reported extra-pyramidal (EPSE) (Pearson χ 2 =5.6, df=1, P =0.02), and to be BME rather than Caucasian (BME n =57, 64%, Caucasian n =16. 44%, Pearson χ 2 =4.5, df=1, P =0.05). These variables were further entered in stepped multivariate regression, only the effect of EPSE remained significant, with odds ratio 8, P =0.05. There was no difference in Chlorpromazine equivalent dose between ethnic groups (Caucasian mean-dose 156 mg, BME 138 mg, t =1.2, P =0.2). Also there was no significant difference in types of antipsychotics prescribed (χ 2 =4, P =0.1, df=2) between the ethnic groups. Conclusions Ethnic difference in antipsychotic adherence may also be influenced by sensitivity to certain side effects.

From ADHD to psychosis… executive functions and time

IntroductionCognitive impairment is present from the early stages of psychotic disorders. Alterations are found mainly in areas of attention, memory work and executive functions. During adolescence, ADHD patients often suffer from secondary disorders to lack of efficient procurement processes information by the poor development of executive functions.ObjectiveEvaluation of a patient whose diagnosis of ADD evolve to acute psychotic episode.MethodReview by clinical and psychometric tests developments in executive functions disorders.ResultsTwelve years old patient who comes to the hospital since 2012, was initially diagnosed with literacy difficulties and low academic performance, after MFF-20 speaks of Learning Disabilities. It presents lack of motivation, apathy, difficulty in scheduling and organization and adherence to schedules, so they diagnosed ADD. It is given treatment with methylphenidate and atomoxetine, presenting erratic path.After a year without treatment and the presence of a major stressful life event, at 17, has a first episode, consisting in mutiste attitude, phenomena of self-referenciality, experiences of control, enforcement and dissemination of ideas and auditory hallucination imperative type.ConclusionsThe presence of emocional dysregulation and alterations in the executive functions atribuyen to ADD, in this case, were premorbid symtomatology of a first psychotic episode. The presence of positive symptoms allows to clarify the diagnosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Prefrontal NAA and Glx Levels in Different Stages of Psychotic Disorders: a 3T 1H-MRS Study.

H-Magnetic Resonance Spectroscopy (1H-MRS) can offer insights in various neuropathologies by measuring metabolite levels in the brain. In the current study we investigated the levels of glutamate + glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate + glutamic acid (NAA + NAAG; neuronal viability) in the prefrontal cortex of patients with a psychotic disorder and people at Ultra High Risk (UHR) for psychosis. A 1H-MRS spectrum was acquired in 31 patients with a recent onset psychotic disorder and 60 with a chronic state, 16 UHR patients and 36 healthy controls. Absolute metabolite levels were calculated using LCModel with a reference water peak. Groups were compared while taking into account age and partial volume effects. Moreover, we investigated associations with positive and negative symptoms, duration of illness, and antipsychotic treatment in patients. The most notable finding is that chronicity of schizophrenia was related to decreased levels of Glx and NAA. On the other hand, although on an exploratory note, UHR showed increased levels of prefrontal Glx and NAA levels with increasing age. Our results may indicate an initial Glx and NAA increase and subsequent decrease during illness progression that may be related to the neurotoxic effects of glutamate.

Childhood adversity and social functioning in psychosis: Exploring clinical and cognitive mediators

Childhood adversity may increase risk of impaired social functioning across the continuum of psychosis. However, the pathways by which adversity dictates functional outcome remain underexplored. This study investigated the association between childhood adversity and social functioning, and the clinical and cognitive mediators of this relationship. Fifty-four clinical (20 chronic, 20 first episode, 14 at ultra-high risk) and 120 non-clinical participants completed standardised questionnaires, semi-structured interviews and tests of theory of mind ability. The authors used multiple group structural equation modelling to fit mediation models allowing for differential relationships between the clinical and non-clinical samples. When examining each pathway separately, depression, paranoia and anxious attachment mediated the effect of childhood adversity on social functioning. In a combined model, depression was the only significant mediating variable with greater adversity predicting lower mood across groups. Childhood adversity did not significantly predict theory of mind ability in any of the models. This is the first study to indicate that childhood adversity acts on social functioning by increasing levels of depression, suggesting a common mechanism across the spectrum of psychosis. Clinical interventions should target low mood in order to improve social functioning at all stages of psychotic disorder.

Medication Adherence Patterns and Influencing Factors in the Early Stages of Psychotic Disorders

Introduction Medication adherence is a matter of relevance for early treatment of psychotic disorder. Objectives To understand pattern of medication adherence in this population and factors influencing. Aims To understand the antipsychotic adherence pattern in early stages of psychotic disorder and to identify factors that influence. Methods Natural observation study of 136 patients of first-episode psychosis presenting to Early intervention service in multicultural South London. Data derived from case notes and interviews using standard rating scales for first 18 months. Results Only 39% of patients (n=50) were 100% time adherent with antipsychotic medication in the first month (rest were 83%). Patients using illicit substances were less likely 100% adherent (Pearson χ2= 13.1, df=1,p=0.001). Caucasian patients were more likely to be fully adherent in the first month than Ethnic minority patients (Pearson χ2= 7.5, df=1, p=0.009). During the follow-up period about 57% patients had weeks of not taking antipsychotic, mostly after recovery from first episode. Ethnicity (Pearson χ2=4.5, df=1, p=0.05) and experience of extrapyramidal side-effect (Pearson χ2= 5.6, df=1, p=0.02) were associated with this gap. Involvement of a carer in treatment was associated with better (100%) adherence during follow-up (Pearson χ2= 4.9, df=1,p=0.03). Conclusions Interventions in early stages of psychosis should focus on therapies involving carers/ families and giving attention to illicit substances use and delivered in way relevant to the local ethnic population. Also antipsychotics chosen carefully, using a lower dose and actively looking for emergence of side-effects.

The Italian guidelines for early intervention in schizophrenia: development and conclusions

The effectiveness of early intervention in schizophrenia is still under discussion. The guidelines described in the present paper were aimed at contributing to the current debate by providing Italian practitioners, families, patients and health managers with evidence-based information on early intervention. They also examined the diagnostic tools that are currently available for assessing different stages of psychotic disorders. A multidisciplinary panel of experts (the Guidelines Development Group) used a set of key-questions to develop an explicit search strategy to conduct a systematic review of the literature published from January 2000 to June 2006. Trained personnel then selected papers from those yielded by the literature search. The Guidelines Development Group's final recommendations were scaled according to the Italian National Guidelines System grading system. The evidence available up to the time of the literature search does not allow for recommendation of early intervention targeting prodromal or at-risk patients to prevent progression from the prodromal phase to acute, full-blown psychosis, nor to improve prognosis. Conversely, identification and timely treatment of first-episode psychotic patients through specific early intervention programmes are highly recommended. The Italian Guidelines on early intervention in schizophrenia are based on a comprehensive assessment of an updated, large-scale body of literature. They draw specific, evidence-based conclusions to assist clinicians and stakeholders in the planning and implementation of appropriate intervention programmes. Further research is needed to ascertain the effectiveness of early intervention in delaying or preventing the conversion to psychosis and improving prognosis in prodromal or at-risk patients. Further investigation is also required for first-episode and critical period patients.