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Schizophrenia Research Oct 2020Long chain polyunsaturated fatty acid (PUFA) levels have been implicated in the pathology of psychotic disorders. We investigated the relationship between childhood PUFA...
BACKGROUND
Long chain polyunsaturated fatty acid (PUFA) levels have been implicated in the pathology of psychotic disorders. We investigated the relationship between childhood PUFA levels and later psychotic experiences (PE's) in a large birth cohort.
METHODS
Plasma levels of Ω-3 and Ω-6 fatty acids (FA's) were assayed at ages 7 and 16 years. PE's were assessed at ages 12 and 18 years using a semi-structured interview. Primary outcome was any PE's at 18 years; sensitivity analyses examined incident PE's between ages 12 and 18 years, persistent PE's (at 12 and 18) and psychotic disorder at 18 years. Genetic instruments for Ω-3 and Ω-6 were derived and used in a multivariable Mendelian Randomization analysis.
RESULTS
Higher levels of Ω-6 FA's AA, OA and AdA at age 7 years were weakly associated with a reduced risk for PE's at 18 years, however, effect sizes were small and attenuated after adjusting for confounders (strongest evidence for OA; adjusted OR, 0.842; 95% CI, 0.711, 0.998; p, 0.048). Total Ω-6 levels at age 16 years were associated with an increased odds of psychotic disorder at age 18 years. However, there was no association between Ω-6/Ω-3 ratio and psychosis outcomes, nor with genetic instruments of total Ω-3 or Ω-6 levels.
CONCLUSIONS
There is no strong evidence that total plasma Ω-3 FA levels or Ω-6/Ω-3 ratios in childhood and mid-adolescence are associated with increased risk for PE's or psychotic disorder, but very marginal evidence that alterations in the Ω-6 pathway at developmental time points might influence risk.
Topics: Adolescent; Child; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Humans; Psychotic Disorders
PubMed: 33067055
DOI: 10.1016/j.schres.2020.09.018 -
Journal of Geriatric Psychiatry and... Nov 2023Approximately 15% of older adults may experience psychotic phenomena. Primary psychiatric disorders that manifest with psychosis (delusions, hallucinations, and... (Review)
Review
Approximately 15% of older adults may experience psychotic phenomena. Primary psychiatric disorders that manifest with psychosis (delusions, hallucinations, and disorganized thought or behavior) account for less than half. Up to 60% of late-life psychotic symptoms are due to systemic medical or neurological conditions, particularly neurodegenerative diseases. A thorough medical workup including laboratory tests, additional procedures if indicated, and neuroimaging studies is recommended. This narrative review summarizes current evidence regarding the epidemiology and phenomenology of psychotic symptoms encountered as part of the neurodegenerative disease continuum (including prodromal and manifest stages). Prodromes are constellations of symptoms that precede the onset of overt neurodegenerative syndromes. Prodromal psychotic features, particularly delusions, have been associated with an increased likelihood of receiving a neurodegenerative disease diagnosis within several years. Prompt prodrome recognition is crucial for early intervention. The management of psychosis associated with neurodegenerative diseases includes behavioral and somatic strategies, although evidence is scarce and mostly limited to case reports, case series, or expert consensus guidelines, with few randomized controlled trials. The complexity of psychotic manifestations warrants management by interprofessional teams that provide coordinated, integrated care.
Topics: Humans; Aged; Neurodegenerative Diseases; Psychotic Disorders; Hallucinations; Neuroimaging
PubMed: 36941085
DOI: 10.1177/08919887231164357 -
Schizophrenia Bulletin Mar 2017The presence of depression in schizophrenia has been a challenge to the Kraepelinian dichotomy, with various attempts to save the fundamental distinction including... (Review)
Review
The presence of depression in schizophrenia has been a challenge to the Kraepelinian dichotomy, with various attempts to save the fundamental distinction including evoking and refining diagnoses such as schizoaffective disorder. But the tectonic plates are shifting. Here we put forward a summary of recent evidence regarding the prevalence, importance, possible aetiological pathways and treatment challenges that recognizing depression in schizophrenia bring. Taken together we propose that depression is more than comorbidity and that increased effective therapeutic attention to mood symptoms will be needed to improve outcomes and to support prevention.
Topics: Comorbidity; Depressive Disorder; Humans; Psychotic Disorders; Schizophrenia
PubMed: 27421793
DOI: 10.1093/schbul/sbw097 -
Cyberpsychology, Behavior and Social... Apr 2023Meta-analyses have found that social cognition training (SCT) has large effects on the emotion recognition ability of people with a psychotic disorder. Virtual reality...
Meta-analyses have found that social cognition training (SCT) has large effects on the emotion recognition ability of people with a psychotic disorder. Virtual reality (VR) could be a promising tool for delivering SCT. Presently, it is unknown how improvements in emotion recognition develop during (VR-)SCT, which factors impact improvement, and how improvements in VR relate to improvement outside VR. Data were extracted from task logs from a pilot study and randomized controlled trials on VR-SCT ( = 55). Using mixed-effects generalized linear models, we examined the: (a) effect of treatment session (1-5) on VR accuracy and VR response time for correct answers; (b) main effects and moderation of participant and treatment characteristics on VR accuracy; and (c) the association between baseline performance on the Ekman 60 Faces task and accuracy in VR, and the interaction of Ekman 60 Faces change scores (i.e., post-treatment - baseline) with treatment session. Accounting for the task difficulty level and the type of presented emotion, participants became more accurate at the VR task ( = 0.20, < 0.001) and faster ( = -0.10, < 0.001) at providing correct answers as treatment sessions progressed. Overall emotion recognition accuracy in VR decreased with age ( = -0.34, = 0.009); however, no significant interactions between any of the moderator variables and treatment session were found. An association between baseline Ekman 60 Faces and VR accuracy was found ( = 0.04, = 0.006), but no significant interaction between difference scores and treatment session. Emotion recognition accuracy improved during VR-SCT, but improvements in VR may not generalize to non-VR tasks and daily life.
Topics: Humans; Pilot Projects; Psychotic Disorders; Emotions; Reaction Time; Virtual Reality; Randomized Controlled Trials as Topic
PubMed: 37071641
DOI: 10.1089/cyber.2022.0228 -
Neuropsychopharmacology : Official... Oct 2020There have been few studies performed to examine the pathophysiological differences between different types of psychosis, such as between delusional disorder (DD) and...
The role of dopamine dysregulation and evidence for the transdiagnostic nature of elevated dopamine synthesis in psychosis: a positron emission tomography (PET) study comparing schizophrenia, delusional disorder, and other psychotic disorders.
There have been few studies performed to examine the pathophysiological differences between different types of psychosis, such as between delusional disorder (DD) and schizophrenia (SZ). Notably, despite the different clinical characteristics of DD and schizophrenia (SZ), antipsychotics are deemed equally effective pharmaceutical treatments for both conditions. In this context, dopamine dysregulation may be transdiagnostic of the pathophysiology of psychotic disorders such as DD and SZ. In this study, an examination is made of the dopamine synthesis capacity (DSC) of patients with SZ, DD, other psychotic disorders, and the DSC of healthy subjects. Fifty-four subjects were recruited to the study, comprising 35 subjects with first-episode psychosis (11 DD, 12 SZ, 12 other psychotic disorders) and 19 healthy controls. All received an F-DOPA positron emission tomography (PET)/magnetic resonance (MR) scan to measure DSC (K value) within 1 month of starting antipsychotic treatment. Clinical assessments were also made, which included Positive and Negative Syndrome Scale (PANSS) measurements. The mean K was significantly greater in the caudate region of subjects in the DD group (ES = 0.83, corrected p = 0.048), the SZ group (ES = 1.40, corrected p = 0.003) and the other psychotic disorder group (ES = 1.34, corrected p = 0.0045), compared to that of the control group. These data indicate that DD, SZ, and other psychotic disorders have similar dysregulated mechanisms of dopamine synthesis, which supports the utility of abnormal dopamine synthesis in transdiagnoses of these psychotic conditions.
Topics: Antipsychotic Agents; Dopamine; Humans; Positron-Emission Tomography; Psychotic Disorders; Schizophrenia, Paranoid
PubMed: 32612207
DOI: 10.1038/s41386-020-0740-x -
Schizophrenia Bulletin Oct 2019Characterizing the link between childhood trauma and adult neurocognitive function in psychosis is crucial for improving the fields understanding of how early... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Characterizing the link between childhood trauma and adult neurocognitive function in psychosis is crucial for improving the fields understanding of how early environmental risk factors impact the presentation of the disorder. To date, the literature has been inconsistent: meta-analytic synthesis is lacking, and it is unclear whether specific cognitive functions are affected.
METHODS
A meta-analysis was performed on a total of 3315 subjects with a psychotic disorder. The links between childhood trauma, overall neurocognitive function, and four cognitive subdomains (working memory, executive function, verbal/visual memory, and attention/processing speed) were examined. Relevant sample characteristics and methodological moderators were tested. The strength of the association between trauma and overall neurocognition in individuals with psychotic disorders was also compared to that of healthy controls.
RESULTS
Among individuals with psychotic disorders, there was a significant association between overall cognition and childhood trauma, r = -.055; 95% CI = -0.09, -0.02, P = .002. There was also a modest, negative relationship between childhood trauma and working memory, r = -.091; 95% CI = -0.15, -0.03, P = .002. Moderators did not have a significant effect on these analyses. Further, the association between childhood trauma and neurocognition was significantly stronger in healthy controls compared to patients with a psychotic disorder.
CONCLUSION
A small negative association was found between overall cognition and childhood trauma in individuals with psychotic disorders. Results suggest the association is less strong for individuals with a psychotic disorder compared to healthy populations. Findings are informative for prominent etiological models of psychosis.
Topics: Adult Survivors of Child Adverse Events; Adverse Childhood Experiences; Attention; Cognition; Cognitive Dysfunction; Executive Function; Humans; Memory; Memory, Short-Term; Mental Status and Dementia Tests; Psychotic Disorders
PubMed: 30376115
DOI: 10.1093/schbul/sby150 -
Brain and Behavior Jun 2018Working Memory and Task-Switching are essential components of cognitive control, which underlies many symptoms evident across multiple neuropsychiatric disorders,... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Working Memory and Task-Switching are essential components of cognitive control, which underlies many symptoms evident across multiple neuropsychiatric disorders, including psychotic and mood disorders. Vulnerability to these disorders has a substantial genetic component, suggesting that clinically unaffected first-degree relatives may carry some vulnerability-related traits. Converging evidence from animal and human studies demonstrates that dopamine transmission, striatal and frontal brain regions, and attention and switching behaviors are essential components of a multilevel circuit involved in salience, and disruptions in that circuit may lead to features of psychosis. Yet, it is possible that unaffected relatives may also possess characteristics that protect against development of illness. We hypothesized that reduced switch cost in a cued task-switching task, may be a behavioral expression of this "resilience" phenotype that will be observable in unaffected relatives.
METHODS
We tested a large community sample (n = 536) via the web, to assess different subcomponents of cognitive control, including task-switching and working memory, as well as risk-taking, among individuals who report having an affected relative with a psychotic or mood disorder.
RESULTS
Healthy individuals with suspected genetic risk due to a self-reported familial history of a psychotic disorder demonstrated better task-switching performance compared to healthy people without a psychiatrically ill relative and those with a relative with a mood disorder. This result was specific to illness status and task domain, in that individuals with a personal history of depression or anxiety did not show improved task-switching performance, and this improvement was selective to task-switching and not seen in other putative cognitive control domains (working memory or risk taking).
CONCLUSIONS
Although this study has limitations and independent replication is needed, these preliminary findings suggest a potential avenue for understanding susceptibility to these disorders by highlighting possible protective as well as vulnerability-related aspects of risk phenotypes.
Topics: Adult; Attention; Female; Frontal Lobe; Humans; Male; Memory, Short-Term; Neuropsychological Tests; Phenotype; Psychotic Disorders; Reaction Time; Resilience, Psychological; Risk Factors; Self Report; Spatial Memory; Young Adult
PubMed: 30106252
DOI: 10.1002/brb3.988 -
Harvard Review of Psychiatry 2016After participating in this activity, learners should be better able to: (Review)
Review
LEARNING OBJECTIVES
After participating in this activity, learners should be better able to:
ABSTRACT
The psychosis prodrome, or period of clinical and functional decline leading up to acute psychosis, offers a unique opportunity for identifying mechanisms of psychosis onset and for testing early-intervention strategies. We summarize major findings and emerging directions in prodromal research and provide recommendations for clinicians working with individuals suspected to be at high risk for psychosis. The past two decades of research have led to three major advances. First, tools and criteria have been developed that can reliably identify imminent risk for a psychotic disorder. Second, longitudinal clinical and psychobiological data from large multisite studies are strengthening individual risk assessment and offering insights into potential mechanisms of illness onset. Third, psychosocial and pharmacological interventions are demonstrating promise for delaying or preventing the onset of psychosis in help-seeking, high-risk individuals. The dynamic psychobiological processes implicated in both risk and onset of psychosis, including altered gene expression, cognitive dysfunction, inflammation, gray and white matter brain changes, and vulnerability-stress interactions suggest a wide range of potential treatment targets and strategies. The expansion of resources devoted to early intervention and prodromal research worldwide raises hope for investigating them. Future directions include identifying psychosis-specific risk and resilience factors in children, adolescents, and non-help-seeking community samples, improving study designs to test hypothesized mechanisms of change, and intervening with strategies that, in order to improve functional outcomes, better engage youth, address their environmental contexts, and focus on evidence-based neurodevelopmental targets. Prospective research on putatively prodromal samples has the potential to substantially reshape our understanding of mental illness and our efforts to combat it.
Topics: Biomedical Research; Brain; Humans; Meta-Analysis as Topic; Practice Guidelines as Topic; Protective Factors; Psychotic Disorders; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors
PubMed: 26954594
DOI: 10.1097/HRP.0000000000000109 -
Translational Psychiatry Nov 2020Cognitive impairments are considered core features in schizophrenia and other psychotic disorders. Cognitive impairments are, to a lesser degree, also documented in...
Polygenic scores for schizophrenia and general cognitive ability: associations with six cognitive domains, premorbid intelligence, and cognitive composite score in individuals with a psychotic disorder and in healthy controls.
Cognitive impairments are considered core features in schizophrenia and other psychotic disorders. Cognitive impairments are, to a lesser degree, also documented in healthy first-degree relatives. Although recent studies have shown (negative) genetic correlations between schizophrenia and general cognitive ability, the association between polygenic risk for schizophrenia and individual cognitive phenotypes remains unclear. We here investigated the association between a polygenic score for schizophrenia (SCZ) and six well-defined cognitive domains, in addition to a composite measure of cognitive ability and a measure of premorbid intellectual ability in 731 participants with a psychotic disorder and 851 healthy controls. We also investigated the association between a PGS for general cognitive ability (COG) and the same cognitive domains in the same sample. We found no significant associations between the SCZ and any cognitive phenotypes, in either patients with a psychotic disorder or healthy controls. For COG we observed stronger associations with cognitive phenotypes in healthy controls than in participants with psychotic disorders. In healthy controls, the association between COG (at the p value threshold of ≥0.01) and working memory remained significant after Bonferroni correction (β = 0.12, p = 8.6 × 10). Altogether, the lack of associations between SCZ and COG with cognitive performance in participants with psychotic disorders suggests that either environmental factors or unassessed genetic factors play a role in the development of cognitive impairments in psychotic disorders. Working memory should be further studied as an important cognitive phenotype.
Topics: Cognition; Humans; Intelligence; Neuropsychological Tests; Psychotic Disorders; Schizophrenia
PubMed: 33257657
DOI: 10.1038/s41398-020-01094-9 -
Scientific Reports Mar 2021In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are...
In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are based on symptomatic descriptions since no unambiguous biomarkers are known to date. However, when underlying causes of psychotic symptoms, like inflammation, ischemia, or tumor affecting the neural tissue can be identified, a different classification is used ("psychotic disorder with delusions due to known physiological condition" (ICD-10: F06.2) or psychosis caused by medical factors (DSM5)). While CSF analysis still is considered optional in current diagnostic guidelines for psychotic disorders, CSF biomarkers could help to identify known physiological conditions. In this retrospective, partly descriptive analysis of 144 patients with psychotic symptoms and available CSF data, we analyzed CSF examinations' significance to differentiate patients with specific etiological factors (F06.2) from patients with schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F2). In 40.3% of all patients, at least one CSF parameter was out of the reference range. Abnormal CSF-findings were found significantly more often in patients diagnosed with F06.2 (88.2%) as compared to patients diagnosed with F2 (23.8%, p < 0.00001). A total of 17 cases were identified as probably caused by specific etiological factors (F06.2), of which ten cases fulfilled the criteria for a probable autoimmune psychosis linked to the following autoantibodies: amphiphysin, CASPR2, CV2, LGl1, NMDA, zic4, and titin. Two cases presented with anti-thyroid tissue autoantibodies. In four cases, further probable causal factors were identified: COVID-19, a frontal intracranial tumor, multiple sclerosis (n = 2), and neurosyphilis. Twenty-one cases remained with "no reliable diagnostic classification". Age at onset of psychotic symptoms differed between patients diagnosed with F2 and F06.2 (p = 0.014), with the latter group being older (median: 44 vs. 28 years). Various CSF parameters were analyzed in an exploratory analysis, identifying pleocytosis and oligoclonal bands (OCBs) as discriminators (F06.2 vs. F2) with a high specificity of > 96% each. No group differences were found for gender, characteristics of psychotic symptoms, substance dependency, or family history. This study emphasizes the great importance of a detailed diagnostic workup in diagnosing psychotic disorders, including CSF analysis, to detect possible underlying pathologies and improve treatment decisions.
Topics: Adolescent; Adult; Age of Onset; Aged; Autoimmune Diseases of the Nervous System; Biomarkers; COVID-19; Cerebrospinal Fluid Proteins; Child; Child, Preschool; Humans; Middle Aged; Psychotic Disorders; Retrospective Studies; Schizophrenia; Young Adult
PubMed: 33785807
DOI: 10.1038/s41598-021-86170-w