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Duration of psychosis and outcome in first-episode schizophrenia. American Journal of Psychiatry, 149(9), 1183-1188
Abstract
This study was undertaken to assess the potential effect of duration of untreated illness on outcome in a group of first-episode schizophrenic patients.
Seventy patients with schizophrenia diagnosed according to the Research Diagnostic Criteria entered the study and were followed for up to 3 years. All patients received standardized treatment and uniform assessments both during the acute phase of their illness and throughout the follow-up period. Outcome was measured in terms of time to remission of acute psychotic symptoms as well as degree of symptom remission.
The mean duration of psychotic symptoms before initial treatment was 52 weeks, preceded by a substantial prepsychotic period. According to survival analysis, duration of illness before treatment was found to be significantly associated with time to remission as well as with level of remission. The effect of duration of illness on outcome remained significant when diagnosis and gender variables, themselves associated with outcome, were controlled in a regression analysis. Duration of illness was not correlated with age at onset, mode of onset, premorbid adjustment, or severity of illness at entry into the study.
Duration of psychosis before treatment may be an important predictor of outcome in first-episode schizophrenia. Acute psychotic symptoms could reflect an active morbid process which, if not ameliorated by neuroleptic drug treatment, may result in lasting morbidity. Further implications of these findings are discussed.
... Given the typical onset of illness, many adolescents with a diagnosis of schizophrenia may be experiencing their first episode and have never received antipsychotic medication. Not receiving antipsychotic medication for an extended period after diagnosis of psychosis has been associated with structural changes in the brain and relatively poor clinical outcomes [22][23][24][25][26][27]. Several studies have examined the efficacy of different antipsychotics among first-episode and treatment-naïve (TN) adult patients [28][29][30][31][32][33][34][35]. ...
... Currently, regulatory approval of lurasidone in the United States for adolescents with schizophrenia is limited to doses of 40-80 mg/ day. However, the results of a recent analysis [67] of young adults (ages [18][19][20][21][22][23][24][25] with schizophrenia reported that use of higher doses (120-160 mg/day) is associated with a notable increase in effect size. For example, the effect size of lurasidone 80 mg/day (vs. ...
... A second potential implication of the current findings is that TN adolescent patients appear to respond especially well to early treatment intervention with lurasidone, while not receiving early treatment may result in a relatively poor clinical outcome that may include a greater degree of brain structural changes [22][23][24][25]. Shortening the duration of untreated psychosis by earlier antipsychotic intervention is likely to improve outcomes in youth with earlyonset schizophrenia [70,71]. ...
Background
To evaluate the efficacy of short-term lurasidone in antipsychotic treatment-naïve (TN) adolescents with schizophrenia versus those treated previously (TP) with antipsychotics.
Methods
Patients aged 13–17 with schizophrenia, and a Positive and Negative Symptom Scale (PANSS) score ≥ 70 and < 120, were randomized to 6 weeks of double-blind treatment with lurasidone (40 or 80 mg/day) or placebo. In a post-hoc, pooled-dose analysis, efficacy was evaluated for TN (criteria: never received antipsychotic treatment) versus TP at the time of the study. Treatment response criteria: ≥20% reduction in PANSS total score.
Results
Altogether, 57 TN and 269 TP patients enrolled in the 6-week DB study. Mean endpoint change in PANSS total score was significantly greater for lurasidone versus placebo in both the TN group (−25.0 vs. -14.4; p < 0.02; effect size = 0.75), and in the TP group (−17.3 vs. -10.0; p < 0.001; effect size = 0.45); and responder rates were higher for lurasidone versus placebo in both the TN group 84.6% versus 38.9%; number needed to treat [NNT] = 3 and in the TP group (60% vs. 42%; NNT = 6). Rates of treatment-emergent adverse events, and mean changes in body weight and metabolic parameters were similar for the TN and TP groups.
Conclusions
In a 6-week, placebo-controlled trial, lurasidone demonstrated significant efficacy in adolescents with schizophrenia regardless of previous antipsychotic therapy status; however, the effect size was notably larger in the TN patient group. In both the TN and TP groups, minimal effects were noted on weight, metabolic parameters, or prolactin.
... This prolonged antipsychotic exposure may confound efforts to elicit associations between predictor variables and treatment response. Also, if some forms of schizophrenia involve a neurodegenerative process (1)(2)(3)(4)(5)(6), treatment response may change over the course of the illness. If this is the case, studies of treatment response during the initial, middle, and later stages of the illness are needed. ...
... We have been engaged in a study of patients with first-episode schizophrenia and schizoaffective disorder since 1986; patients in the study have extensive baseline assessments and are treated according to a standardized medication algorithm and followed for at least 5 years. In previous communications (4,7,8), we presented findings on treatment response for patients who initially entered the study. This communication presents the findings on acute treatment response for the entire final study group of 118 patients; data for the entire group on baseline extrapyramidal symptoms (9) and tardive dyskinesia (10) have been previously reported. ...
... There is evidence showing that the early stages of schizophrenia are essential for the formation and prediction of disease course and outcome (7). First-episode schizophrenia (FES) is the stage at which individual first presents symptoms that are consistent with those of schizophrenia and formally receives a clear diagnosis of schizophrenia after professional evaluation. ...
... Consensus diagnosis of FES was reached based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis criterion (43). Exclusion criteria included history of substance dependence, (12,43) 23.48 ± 6.01 (14,43) 21.50 ± 5.10 (12,36) 23.68 ± 4.04 (18,43) 24.14 ± 4.77 (18,43) 23.11 ± 2.84 (18,29) Duration of education (years) 12.32 ± 3.18 (6,20) 12.74 ± 3.35 (6,20) 11.95 ± 3.02 (7,18) 13.85 ± 2.81 (8.5, 20) 13.70 ± 3.01 (8.5, 20) 14.07 ± 2.52 (10,18) Age of onset ( 48.10 ± 9.12 (31,67) other diseases of the central nervous system, or unstable medical conditions. In order to eliminate the confounding effect of neuroleptic medication, all FES patients were antipsychoticnaïve. ...
Background: Previous first-episode schizophrenia (FES) studies have reported abnormalities in the volume and mid-sagittal size of the corpus callosum (CC), but findings have been inconsistent. Besides, the CC shape has rarely been analyzed in FES. Therefore, in this study, we investigated FES-related CC shape abnormalities using 198 participants [92 FES patients and 106 healthy controls (HCs)].
Methods: We conducted statistical shape analysis of the mid-sagittal CC curve in a large deformation diffeomorphic metric mapping framework. The CC was divided into the genu, body, and splenium (gCC, bCC, and sCC) to target the key CC sub-regions affected by the FES pathology. Gender effects have been investigated.
Results: There were significant area differences between FES and HC in the entire CC and gCC but not in bCC nor sCC. In terms of the localized shape morphometrics, significant region-specific shape inward-deformations were detected in the superior portion of gCC and the anterosuperior portion of bCC in FES. These global area and local shape morphometric abnormalities were restricted to female FES but not male FES.
Conclusions: gCC was significantly affected in the neuropathology of FES and this finding was specific to female FES. This study suggests that gCC may be a key sub-region that is vulnerable to the neuropathology of FES, specifically in female patients. The morphometrics of gCC may serve as novel and efficient biomarkers for screening female FES patients.
... In medicine, the term prodrome, derived from the Greek prodromo § (meaning forerunner), denotes a constellation of symptoms that is present prior to the emergence of the characteristic symptoms of a disease. Applied to schizophrenia, the initial prodrome has been defined as a period of prepsychotic disturbance ranging from the onset of the first noticeable features to the onset of frank psychotic phenomena, particularly delusions and hallucinations (e.g., Loebel et al., 1992;Yung & McGorry, 1996a). The dating of the prodromal and the psychotic onset may be assessed by the patient himself or by a significant other, although these judgments do not necessarily lead to the establishment of the same time points or interval. ...
... In contrast, the establishment of the end of the prodrome, and thus of the beginning of the first psychotic episode, is less problematic (Beiser, Erickson, Fleming, & Iacono, 1993), notwithstanding the currently held belief (see Claridge, 1985Claridge, , 1994Johns & Van Os, 2001;Van Os, 2003) that psychotic symptoms, although also characterized by some qualitative change, occur on a continuum with normal experiences. According to Loebel et al. (1992) and Beiser et al. (1993), the prodromal period in schizophrenia lasts around 2 years on average, whereas Häfner and collaborators in their very detailed and innovative "Age, Beginning, and Course" (ABC) study of schizophrenia (e.g., Häfner & Maurer, 1996;Maurer & Häfner, 1997) report a mean duration of 5 years. In some cases, prodromes of even 11 years or more have been reported Møller & Husby, 2000). ...
In this article a literature-based model (the Schizotypic Syndrome Questionnaire [SSQ] model) is presented that gives a description of the temporal unfolding of the schizophrenic prodrome. As a guiding principle for the selection of the symptoms in the model, the hypothesis was held that the main prodromal features determine each other in terms of cause and effect. Furthermore, the developmental pathways between the symptoms were not allowed to be in conflict with the usual observation that negative symptoms precede psychotic-like ones nor-at least in broad outline-with J.P. Docherty, D.P. van Kammen, S.G. Siris, and S.R. Marder's (1978) description of the various onset stages in the development of a schizophrenic psychosis. For the definitive version of the SSQ model, 12 symptoms were selected (e.g., affective flattening, suspicion, and delusional thinking). After specifying the paths to be estimated, the model was examined in two randomly drawn samples from a total community-based sample of 771 normal subjects and in the total sample itself, in each case resulting in adequate fit values. Moreover, all postulated pathways were found to be significantly different from zero. The use of a normal sample was based on the continuum hypothesis. Given the present-day discussions concerning the tenability of the schizophrenia concept, the model's implications with respect to that issue are particularly emphasized. Furthermore, the concept of the schizophrenia prodrome itself is critically discussed. © 2005 Wiley Periodicals, Inc. J Clin Psychol 61: 909-938, 2005.
... The prodromal stage of schizophrenia was first conceptualized in 1911 by Bleuler and was defined as the preliminary signs and symptoms of an illness that does not fulfill the characteristic criteria of the disease [5]. It was defined by Loebel et al. as the time interval from the onset of unusual behavioral symptoms to the onset of psychotic symptoms [8]. ...
... The prodromal stage of psychosis can be detected at an early stage through the regular followup of high-risk patients to prevent or delay the onset of psychotic disorders. Early management of psychosis leads to better function preservation and, therefore, better long-term outcomes [8][9]. ...
Psychosis is a syndrome characterized by features of reality distortion such as delusions and hallucinations. It may occur as a primary mental disorder or secondary to a medical or neurological illness or substance abuse. Several genetic, environmental, and protective risk factors have been identified and require further study. Neurobiological damage at the onset of schizophrenia is the most active and destructive. Therefore, it is important to detect the prodromal phase of psychosis so that interventions can be started early and the onset of psychosis delayed. Herein, we review the relevant epidemiological data on psychosis, particularly in Saudi Arabia. In addition, the risk and protective factors of psychosis will be discussed.
Recent findings have shown that psychosis development is affected by genetic and environmental factors. Psychotic disorders are considered a cause of disability and are, therefore, a substantial economic burden. Consequently, it is important to try and detect the psychosis in its prodromal stage, where intervention may slow its progression and improve general wellbeing. Several tools have been identified to screen for the prodrome of psychosis, one of which is the prodromal questionnaire-brief version. This has been shown to be a promising tool that can be self-administered by the patient in contrast to long interview-based tools, which are time-consuming and require a physician to perform. Despite the limited evidence in the literature, there have been significant improvements in the outcomes of patients with psychosis when treated in the prodromal period.
In summary, this article provides psychiatrists and researchers with an overview of psychosis, its risk factors, the prodromal stage of psychosis, tools to detect the prodromal phase, and potential treatments during this phase.
... 52,55,56 This is further hindered by challenges in determining when symptoms commenced due to the common delay between symptom onset and contact with psychiatric services, particularly in the era in which these studies were conducted. [85][86][87] Moreover, subgroups of patients that display "impaired LI" often exhibit poorer learning in the non-pre-exposed condition, 53,54,63,[88][89][90] rendering results attributable to general learning deficits. The absence of empirical justifications for the crude and variable distinctions between subgroups, and the common necessity for idiosyncratic parsing of data to achieve "statistically significant" results, 91 risks overfitting models to data, casting doubt on the reliability of these results. ...
Background
The Salience Hypothesis posits that aberrations in the assignment of salience culminate in hallucinations and unusual beliefs, the ‘positive symptoms’ of schizophrenia. Evidence for this comes from studies on latent inhibition, referring to the phenomenon that prior exposure to a stimulus impedes learning about the relationship between that stimulus and an outcome.
Design
This paper reviewed all published studies examining the relationship between latent inhibition and both schizophrenia and schizotypy.
Results
Contemporary literature suggests that latent inhibition is attenuated in both people with schizophrenia and those loading highly on measures of schizotypy, the multidimensional derivative of schizophrenia. This suggests that these individuals assign greater salience to stimuli than healthy controls and people scoring low on measures of schizotypy, respectively. However, several confounds limit these conclusions. Studies on people with schizophrenia are limited by the confounding effects of psychotropic medications, idiosyncratic parsing of samples, variation in dependent variables and lack of statistical power. Moreover, latent inhibition paradigms are limited by the confounding effects of learned irrelevance, conditioned inhibition, negative priming and novel pop-out effects.
Conclusions
This review concludes with the recommendation that researchers develop novel paradigms that overcome these limitations to evaluate the predictions of the Salience Hypothesis.
... another Australian innovation, Lithium [3], the FEP paradigm ("a stitch in time…") changed how we conceptualize and practice psychiatry. Key concepts such as the duration of untreated psychosis [4], prodromal symptoms [5], and ultra-high risk mental state [6] became well embedded within our lexicon. The International Early Psychosis Association was established in the early 1990s, and Early Intervention in Psychiatry journal was published in the late 2000s [1]. ...
First episode psychosis remains one of the most critical research areas in psychiatry. Much progress has been made, but more progress is required to translate the ideas and promises into reality. In this Editorial, we provide the context and invite contributions for our BMC Psychiatry Collection on First Episode Psychosis.
... The prodromal phase has an average duration of between 1 and 5 years and is often associated with high psychosocial Frontiers in Psychology 02 frontiersin.org impairment and disability (Loebel et al., 1992;Beiser et al., 1993;Häfner et al., 1993). Prodromal states are characterized by non-specific symptoms of different nature, including restlessness, concentration, social and cognitive difficulties, fear, low self-esteem, social withdrawal, poor school or work performance, worsening quality of life, anxiety, sleep disorders, personality, and mood changes, and attenuated psychotic symptoms (Yung et al., 2007). ...
Introduction
Several studies have identified ultra-high-risk criteria that may characterize an at-risk mental state and predict the transition of psychotic evolution. Personality traits may play a crucial role in this process.
Aims
The current study aims to: (a) explore the evolution of an initial diagnosis over 12 months; (b) assess differences in social and occupational functioning; (c) identify common (trans-diagnostic) personality traits of psychotic risk.
Methods
The sample includes 97 (44 males and 53 females) young adults. They completed an assessment that consists of socio-demographic data, the Social and Occupational Functioning Scale, the Early Recognition Inventory-retrospective assessment onset of schizophrenia, and the Personality Inventory for DSM-5 (PID-5). According to the tests’ assessment, the sample was divided into three different groups: Ultra-High Risk (UHR), At-Risk, and Not at risk. One year after the first evaluation, psychiatrists administered the QuickSCID-5 to verify the diagnostic trajectories of the sample.
Results
Overall, the most prevalent category diagnoses were anxiety/depression, personality disorders, and psychosis. Specifically, the most common diagnosis in the UHR group was psychosis. Moreover, in the UHR group, the social and occupational functioning score was the lowest. In terms of differences in PID-5 personality traits, the At-risk and UHR groups scored highest in detachment and disinhibition. No statistically significant differences were found between the groups for negative affectivity, antagonism, and psychoticism traits.
Conclusion
Results obtained by the current study should be considered an attempt to better understand the diagnostic trajectories and trans-diagnostic personality traits in a group of young help-seekers, specifically in UHR. Findings highlight both the importance of diagnosis and personality traits evaluation to customize a specific intervention based on the level of psychotic risk. Clinical suggestions are reported.
... The criteria for recovery from schizophrenia have, thus, been revised to the sustained [i.e., longer than 2 years (45, 46)] remission of symptoms, social functioning (47), productivity, independent functioning, and optimism about the outcome from schizophrenia (46, 48,49). Many clinical studies have found that, according to these criteria, recovery from schizophrenia does occur (50)(51)(52)(53)(54)(55). However, the recovery of self is a difficult question in the context of schizophrenia. ...
Objective
Identity recovery in people diagnosed with schizophrenia who have committed homicide poses several difficulties. Premorbid mental illnesses, the experience of psychosis, and the absence of cohesive ego functions may result in the inability to integrate the homicidal act into self-identity. Problems with integration increase the risk of recidivism and further mental problems. The aim of the present research was to explore how homicidal people diagnosed with schizophrenia make sense of their actions, and how they identify with the homicide.
Method
Six semi-structured interviews were conducted at a long-term psychiatric home with people who had committed homicide and who had been diagnosed with schizophrenia. The interviews were transcribed verbatim and analysed using interpretative phenomenological analysis (IPA), an idiographic method rooted in phenomenologist traditions that focuses on how participants experience and make sense of events in their lives, and how those events affect their identity and sense of self.
Results
Three personal experiential themes were established as a result of the analysis: (1) homicide and responsibility; (2) homicide and self; and (3) control over threats to self and self-evaluation. (1) Homicide was often reported to have been committed in a non-conscious, delusional state that may have led to the loss of self-determination. (2) Our interviewees struggled to integrate their acts into their identities. They distanced themselves from the crime or held multiple, parallel interpretations of the act. (3) Recovering patients experienced the constant threat of entering into a delusional reality and losing control. The importance of control was central to their self-evaluation. The patients appeared to distance themselves from the homicidal act and to regard their delusional selves as a threat to their lives.
Conclusion
Therapy aimed at bolstering self-control, supporting the integration of the fragmented self, and raising awareness of the connections between delusional reality and standard, intersubjective reality may be helpful in reducing the instability of the self. Therapy aimed at processing complex grief and loss of family is also needed.
... Los estudios de seguimiento a personas desde el primer episodio de psicosis en la década de los ochenta comenzaron a mostrar que, en la mayoría de los casos, los pacientes con esquizofrenia alcanzaban una "meseta" en cuanto a su psicopatología y no necesariamente tenían un curso deteriorante (10)(11)(12). Por otro lado, el tratamiento con antipsicóticos comenzó a mostrar mayor efectividad y el impacto negativo de la duración prolongada de la psicosis no tratada se transformó en foco de una posible intervención temprana para la psicosis (13)(14)(15)(16). En este escenario más www.webapal.org ...
Studies in Brazil and Chile have shown that around 19 people per 100,000 inhabitants will have a first psychotic episode each year. Evidence has shown that intervening early in schizophrenia spectrum disorders is effective and cost-effective. However, in Latin America, first episode units are notoriously rare. The implementation of these services is an urgent need in our region that will require the joint work of multiple inter-institutional actors. In this review we address the need to implement early intervention programs in psychosis in Latin America, its characteristics, its advantages, its challenges and its limitations.
... Studies reported that brief attenuated psychotic symptoms appear in the "Late at-risk of psychosis state" 7,[12][13][14] . However, since most of symptoms are non-specific, high-risk individuals remain difficult to detect, and the disease might go unnoticed for a period estimated at 1-2 years, even after the onset of diagnosable symptoms 3,5,7,12,15,16 . ...
For patients at high-risk for developing schizophrenia, a delayed diagnosis could be affected, among many reasons, by their patterns of healthcare use. This study aims to describe and generate a typology of patients’ care trajectories (CTs) in the 2 years preceding a first diagnosis of schizophrenia, over a medico-administrative database of 3712 adults with a first diagnosis between April 2014 and March 2015 in Quebec, Canada. This study applied a multidimensional approach of State Sequence Analysis, considering together sequences of patients’ diagnoses, care settings and care providers. Five types of distinct CTs have emerged from this data-driven analysis: The type 1, shared by 77.6% of patients, predominantly younger men, shows that this group sought little healthcare, among which 17.5% had no healthcare contact for mental disorders. These individuals might benefit from improved promotion and prevention of mental healthcare at the community level. The types 2, 3 and 4, with higher occurrence of mental disorder diagnoses, represent together 19.5% of the study cohort, mostly middle-aged and women. These CTs, although displaying roughly similar profiles of mental disorders, revealed very dissimilar sequences and levels of care providers encounters, primary and specialized care use, and hospitalizations. Surprisingly, patients of these CTs had few consultations with general practitioners. An increased attentiveness for middle-aged patients and women with high healthcare use for mental disorders could help to reduce delayed diagnosis of schizophrenia. This calls for further consideration of healthcare services for severe mental illness beyond those offered to young adults.
... This indicates that female gender may be considered as a risk factor for delayed access to care. Loebel et al (1992) found that male gender was associated with longer DUP. Our study found no significant difference between genders. ...
Over the past few decades there has been a growing interest in first-episode psychosis (FEP), help-seeking behaviour and pathways to care. Treating psychotic disorders in their earliest stages has become a key focus for research and clinical care (Yung & McGorry, 2007). FEP studies show that the average time between onset of symptoms and first effective treatment is often 1 year or more (McGlashan, 1987). This long duration of untreated psychosis (DUP) is undesirable. Early treatment helps minimise the risk of the serious consequences of untreated psychosis, in terms of changes in mental state and behaviour (Larsen et al, 1998; Wyatt et al, 1998) and can reduce suffering (Ho et al, 2003). Some early results suggested that an 'early intervention in psychosis' (EIP) service is more cost-effective than generic services (Mihalopoulos et al, 1999).
... Thus, the prevention of second episodes should be an important focus given the potential harm to the patient and family, as well as the high cost they can represent for society ( Bernardo and Mezquida, 2012 ;Bernardo et al., 2017, Bernardo et al., 2021. To prevent this worsening, the first-episode population represents a key opportunity to study the clinical variables and functional outcomes of psychotic disorders and to prevent potential relapses ( Wyatt, 1991 ;Loebel et al., 1992 ;Andreasen et al., 2013 ). Thus, identifying biomarkers for second relapses might allow for early diagnosis, more accurate prognosis and individualised interventions. ...
Neurotrophins have been proposed to be involved in biological mechanisms which might underlie different clinical outcomes in schizophrenia. The aims of the present study were to examine the BDNF/NGF plasma levels in a cohort of first-episode schizophrenia (FES) patients in remission as potential biological predictors of relapse; to study the associations between these neurotrophins and the symptomatology severity through different stages after a FES in two independent cohorts. 2EPs-Cohort: 69 first-episode in clinical remission were included. BDNF/NGF plasma levels and symptom severity were measured at enrollment and at 3-year or at the time of the second episode/relapse. FLAMM-PEPs-Cohort: 65 first-episodes were also included. BDNF/NGF and symptom severity were obtained at enrollment and 2-year follow-up. Symptomatology was assessed with the Marder-PANSS-Factor scores. Plasma neurotrophins did not differ significantly over time and neither BDNF/NGF were predictors of relapse. Besides, in remission stages, baseline BDNF levels showed significant correlations with both positive and negative symptoms (p<0.05); NGF, with negative symptomatology (p<0.01). Similarly, in the FLAMM-PEPs-Cohort, baseline BDNF/NGF levels showed significant correlations with negative symptoms (and not positive symptomatology) at follow-up (p<0.05). In both cohorts, lower levels correlated with higher symptom severity. Findings did not support a role for BDNF/NGF plasma levels as biomarkers of relapse in FES patients. Nevertheless, baseline BDNF/NGF may lead to be considered potentially useful biomarkers of long-term severity in schizophrenia and of the underlying illness traits, specially of negative symptomatology severity. More longitudinal studies in FES samples and adding a control group are warranted to replicate these findings.
... Adapted from Ciompi et al (Ciompi, 1980) and Shepherd et al (Shepherd et al., 1989) A prodromal phase consisting of a more subtle decline in cognitive and social functioning commonly precedes the first psychotic episode and can begin years before the onset of frank psychotic symptoms (Compton, 2004). A duration of untreated psychosis (DUP) may also precede the first clinical diagnosis of FEP (McGlashan, 1999), whose length is associated with time to symptom remission (Loebel et al., 1992), response to antipsychotics (Karson et al., 2016), symptom severity, and functional outcomes (Marshall et al., 2005). Meta-analytic evidence suggests that the length of DUP could explain between 2-13% of the variance of outcome in schizophrenia (Penttila et al., 2014). ...
My thesis considers the theme of comorbidity between cardiometabolic disorders and schizophrenia by focussing on three key aspects: the nature of association between cardiometabolic disorders and schizophrenia; the potential for common underlying biological mechanisms for the comorbidity; and the prediction of cardiometabolic risk in young adults with psychosis. On the nature of association between cardiometabolic disorders and schizophrenia, using longitudinal repeat measure data from a large birth cohort, I found that disruption to glucose-insulin homeostasis through childhood/adolescence is associated with increased risk of psychosis in early-adulthood; may not be fully explained by common sociodemographic and lifestyle factors; and may be specific to it. On the mechanisms of association between cardiometabolic disorders and schizophrenia, I used a range of genetic and observational epidemiological methods to examine whether inflammation and shared genetic liability may be common underlying biological mechanisms for the comorbidity. Using birth cohort data, I show that genetic risk for type 2 diabetes is associated with psychosis-risk in adulthood, and vice versa. I also show that genetic risk for type 2 diabetes may influence psychosis risk by increasing systemic inflammation. Using summary data from large genome-wide association studies (GWAS), I show a thread of evidence for shared genetic overlap between schizophrenia, cardiometabolic and inflammatory traits. Finally, using Mendelian randomization, I show evidence supporting that inflammation may be a common cause for insulin resistance and schizophrenia. On the prediction of cardiometabolic risk in young adults with psychosis, I performed a systematic review of cardiometabolic risk prediction algorithms and explored their predictive performance in a sample of young people at risk of developing psychosis. In doing so, I show that none are likely to be suitable for this population. Then, using patient data, I developed and externally validated the Psychosis Metabolic Risk Calculator (PsyMetRiC), the first cardiometabolic risk prediction algorithm specifically tailored for young people with psychosis. Together, my work suggests that cardiometabolic disorders and schizophrenia share aetiologic mechanisms, namely inflammation and shared genetic liability. I have shown that it is possible to accurately predict cardiometabolic risk in young people with psychosis using a tool tailored for the population. Such tools can in future become valuable resources for clinicians to reduce the risk of long-term cardiometabolic morbidity and mortality in people with schizophrenia.
... Akhirakhir ini penelitian di bidang ini lebih banyak difokuskan pada gangguan psikotik tahap awal (early psychosis) atau psikosis episode pertama (first episode psychosis). Ini disebabkan kemungkinan tingkat kesembuhan psikosis awal ini (Cullberg et al., 2002;Gitlin et al. 2001;Edwards et al., 1998;Loebel et al.,1992) Pemahaman empatik terhadap pengalaman subjektif penderita psikotik juga mulai banyak di kaji. Misalnya, Lucas (1999) menyebut pengalaman mereka sebagai 'extra ordinary '. ...
... We also conducted a series of sensitivity analyses to test the robustness of our findings. For example, although the average psychosis prodrome is approximately 2 years (Loebel et al., 1992), we observe a relatively small attenuation of estimates in the 5-year lagged models, making it unlikely reverse causation explains the associations we observe. ...
Background
We aimed to examine the temporal relationships between traumatic events (TE), post-traumatic stress disorder (PTSD) and non-affective psychotic disorders (NAPD).
Methods
A prospective cohort study of 1 965 214 individuals born in Sweden between 1971 and 1990 examining the independent effects of interpersonal and non-interpersonal TE on incidence of PTSD and NAPD using data from linked register data (Psychiatry-Sweden). Mediation analyses tested the hypothesis that PTSD lies on a causal pathway between interpersonal trauma and NAPD.
Results
Increasing doses of interpersonal and non-interpersonal TE were independently associated with increased risk of NAPD [linear-trend incidence rate ratios (IRR) adjusted = 2.17 [95% confidence interval (CI) 2.02–2.33] and IRR adjusted = 1.27 (95% CI 1.23–1.31), respectively]. These attenuated to a relatively small degree in 5-year time-lagged models. A similar pattern of results was observed for PTSD [linear-trend IRR adjusted = 3.43 (95% CI 3.21–3.66) and IRR adjusted = 1.45 (95% CI 1.39–1.50)]. PTSD was associated with increased risk of NAPD [IRR adjusted = 8.06 (95% CI 7.23–8.99)], which was substantially attenuated in 5-year time-lagged analyses [IRR adjusted = 4.62 (95% CI 3.65–5.87)]. There was little evidence that PTSD diagnosis mediated the relationship between interpersonal TE and NAPD [IRR adjusted = 0.92 (percentile CI 0.80–1.07)].
Conclusion
Despite the limitations to causal inference inherent in observational designs, the large effect-sizes observed between trauma, PTSD and NAPD in this study, consistent across sensitivity analyses, suggest that trauma may be a component cause of psychotic disorders. However, PTSD diagnosis might not be a good proxy for the likely complex psychological mechanisms mediating this association.
... The importance of early recognition of psychotic disorders has been underscored by studies suggesting a possible association between duration of untreated psychosis and eventual outcome [24,25]. Due to the relative rarity of DD, general practitioners are not experienced in recognizing these disorders, but the development of screening tools will help. ...
The World Health Organization (WHO) developed a 7-year Mental Health Action Plan in 2013, which recommends integration of health and social care services into community-based settings, implementation of strategies for health promotion and prevention of illness, and support of research. In this review, we highlight partial hospitalization programs (PHPs) for delusional disorder (DD), with a special focus on the health and psychosocial needs of women. We suggest that PHPs are, in many ways, ideal settings for carrying out WHO recommendations. PHPs are multidisciplinary and consequently are able to provide a wide range of flexible program offerings. Programming in PHPs is able to address, with proven efficacy, individual needs, such as those presented by women at the various stages of their reproductive life. PHPs are a community bridge between hospital and outpatient services and can quickly adapt to specific needs as affected by gender, but also by age and cultural origins. They are ideal settings for professional training and for conducting clinical research. PHPs operate on the principle of shared decision making, and thus more readily than many other treatment sites, engage difficult-to-treat patients, such as those with DD, by successfully establishing long-term relationships of trust.
... It is a proven fact that environmental factors may potentially interact with biological risk factors to mediate the timing of onset, course, and severity of the disorder in this subgroup of the population. A family history of psychosis was seen in 21.3%, similar to that of other studies [11,15,17]. Our study also observed that family history of psychiatric illness in first, second, and third-degree relative were 28%, 26.7%, and 1.3% respectively. ...
Aim: The study aims to delineate the symptom profile of children and adolescents diagnosed with psychotic illnesses (F20-F29 as per ICD 10 diagnostic criteria). It also attempts to study the diagnostic break-up among psychotic subgroup. Methods and Material: A 3-year retrospective chart review of children and adolescents registered with child guidance clinic in a general hospital psychiatry setting, Chennai. The study uses a semi-structured proforma that attempts to evaluate socio-demographic details, clinical data about illness, symptom profile, diagnosis, comorbidity, and treatment plan. Results: The total number of records fulfilling the inclusion criteria was 75. Adolescent girls constituted around 52% of the total sample, and 48% were adolescent boys. The diagnostic subgroup that was predominant in our sample was acute polymorphic psychosis without symptoms of schizophrenia (30.7%) followed by unspecified nonorganic psychosis (26.7%) and schizophrenia (21.3%). The predominant symptoms cluster in our group was that of behavioural and perception symptoms with the least of catatonic and negative symptom clusters. Risperidone was the most commonly used antipsychotic in almost 80% of cases, as documented in clinical literature. 63 Conclusion: The study finding helps to delineate the myriad clusters of symptoms among early-onset psychotic illness. The varied symptom profile highlights the need to identify complex presentation at an early stage, need to screen and follow up on the course of nonspecific symptoms and to determine the treatment duration appropriately.
... It is a proven fact that environmental factors may potentially interact with biological risk factors to mediate the timing of onset, course, and severity of the disorder in this subgroup of the population. A family history of psychosis was seen in 21.3%, similar to that of other studies [11,15,17]. Our study also observed that family history of psychiatric illness in first, second, and third-degree relative were 28%, 26.7%, and 1.3% respectively. ...
... Although our length of DUP was consistent with that of other cohorts of first-episode psychoses, [80][81][82] it was still shorter than that reported in some other studies. [83][84][85] Given the variability in the definitions of DUP, 86 we urge caution when generalizing our observations to all studies of first-episode psychosis. It is also possible that some patients in the non-TR group could have been TR but were unable did not accept or tolerate clozapine; similarly, it is also possible that some individuals in the non-TR group could have developed TR if they were followed up over a longer time period of time. ...
Treatment resistance (TR) in patients with first-episode psychosis (FEP) is a major cause of disability and functional impairment, yet mechanisms underlying this severe disorder are poorly understood. As one view is that TR has neurodevelopmental roots, we investigated whether its emergence relates to disruptions in synchronized cortical mat-uration quantified using gyrification-based connectomes. Seventy patients with FEP evaluated at their first presentation to psychiatric services were followed up using clinical records for 4 years; of these, 17 (24.3%) met the definition of TR and 53 (75.7%) remained non-TR at 4 years. Structural MRI images were obtained within 5 weeks from first exposure to antipsychotics. Local gyrification indices were computed for 148 contiguous cortical regions using FreeSurfer; each subject's contribution to group-based structural covariance was quantified using a jack-knife procedure, providing a single deviation matrix for each subject. The latter was used to derive topological properties that were compared between TR and non-TR patients using a Functional Data Analysis approach. Compared to the non-TR patients, TR patients showed a significant reduction in small-worldness (Hedges's g = 2.09, P < .001) and a reduced clustering coefficient (Hedges's g = 1.07, P < .001) with increased length (Hedges's g = −2.17, P < .001), indicating a disruption in the organizing principles of cortical folding. The positive symptom burden was higher in patients with more pronounced small-worldness (r = .41, P = .001) across the entire sample. The trajectory of synchronized cortical development inferred from baseline MRI-based structural covariance highlights the possibility of identifying patients at high-risk of TR prospectively, based on individualized gyrification-based connectomes.
... [8] The age of onset of treatment-resistant schizophrenics is lower, the frequency of male patients is higher, the onset of symptoms is slower and less noisy, negative symptoms are more frequent, general symptom severity is higher, lateral and third ventricles are wider, basal growth hormone levels are higher. [9][10][11] Findings such as cortical shrinkage and lower catecholamine levels in cerebrospinal fluid have been reported in treatment-resistant patients. [12][13][14] Szeszko et al. [15] compared the brains that responded to antipsychotic treatment and did not respond (resistant schizophrenia), and found more cortical thinning in the prefrontal and occipital regions of the brains of those who did not respond to treatment. ...
... However, across the included studies, ethnicity was categorised crudely as black, white or Asian ethnicity. Although there is substantial evidence linking DUP to an increased frequency of relapse (Perkins et al. 2005;Loebel et al. 1992), and poorer social and work functioning (Perkins et al. 2005;Haas et al. 1998), our results did not support the importance of DUP in relation to employment and relationship status during first 9 years of illness. However, the significant variability in the definitions of DUP across the studies on first episode psychosis is noteworthy (Howes et al. 2021); thus, Page 17 / 43 ...
As employment and relationship status are important long-term outcomes in individuals with a diagnosis of first episode psychosis (FEP) disorders, there is a need to elucidate more accurately the extent of these social deficits in people with FEP. This in turn can aid treatment planning and policy development ultimately ensuring more complete and sustainable recoveries. We carried out a systematic review and meta-analysis of longitudinal studies in FEP reporting on employment and relationship status during the illness course. Random effects meta-analyses and meta-regression analyses were employed. Seventy-four studies were included with a sample totalling 15,272 (range = 20–1724) FEP cases with an average follow-up duration of 8.3 years (SD = 7.2). 32.5% (95%CI = 28.5–36.9) of people with a diagnosis of FEP disorders were employed and 21.3% (95%CI = 16.5–27.1) were in a relationship at the end of follow-up. Studies from high-income countries and Europe had a higher proportion of people in employment at the end of follow-up compared to middle-income nations and non-European countries. The inverse was found for relationship status. The proportion of people with a diagnosis of FEP in employment decreased significantly with longer follow-up. Living with family, being in a relationship at first contact and Black and White ethnicities were identified as significant moderators of these outcomes. These findings highlight marked functional recovery deficits for people with FEP, although cultural factors need to be considered. They support the need for interventions to improve employment opportunities, and social functioning, both in early psychosis and during the longitudinal illness course.
... The experience of the stigma by the caregivers is labelled as a courtesy/ associative stigma and affiliate stigma [14,15]. Due to stigma, the caregivers often conceal information about the mental illness in their closed ones or family members, may leave the patient alone or move away and socially withdraw from the patient [16][17][18]. ...
Stigma related to psychiatric illness not only impact the patients but also have adverse consequences on the caregivers. Stigma can lead to poor quality of life, social restriction, and psychological morbidity. Not much data is available on the stigma among the caregivers of patients with Obsessive–Compulsive Disorder (OCD). To evaluate the extent of stigma experienced by the caregivers of patients with OCD and its association with caregiver burden and coping. In a cross-sectional study, 53 caregivers of patients with OCD were evaluated on the Stigma Scale for Caregivers of People with Mental Illness (CPMI), Family Burden Interview (FBI) Schedule, and Family Coping Questionnaire (FCQ). The mean age of the caregivers was 45.9 years, with the number of years of formal education was 8.6 (SD: 5.4) years. Majority of the caregivers were male and married, were the spouse of the patient with a mean duration caregiving at the time of assessment being 122.6 months. In terms of stigma, the highest level of stigma was seen in the affective domain, followed by behavioural domain and least in the cognitive domain of CPMI. On FBI the highest level of burden was seen in the domain of disruption of routine family activities, followed by disruption of family interaction, disruption of family leisure activities, financial burden, the effect on the physical health of others, and effect on mental health others. On FCQ, Positive communication and resignation were the most commonly used coping mechanisms. The least commonly used coping strategy was the patient's social involvement. All the domains of CPMI had a significant positive association with a total objective score of FBI. In terms of coping, a higher level of stigma was associated with lower use of social involvement (all domains of stigma), coercion (cognitive domain and total stigma), and avoidance (all domains except for affective domain) as coping mechanisms. Lower use of positive communication was associated with higher stigma in the behavioural domain. Those with a high objective burden had a higher level of stigma on the cognitive and behaviour domain of the CPMI. Caregivers of patients with OCD experience a high level of stigma. A higher level of stigma is associated with the more use of maladaptive coping like avoidance and higher caregiver burden. Accordingly, it can be said that there is a need to focus on the caregivers of patients with OCD to improve the overall outcome of the patients.
... Numerous studies have reported any relation of DUI with gender. 18,19 Study from Hong Kong reported that males have a longer DUI than females. 20 In this current study female patients having longer median DUI values, though not statistically significant level. ...
... Some researchers believe DUP ends with initiation of treatment with antipsychotics, whereas some say it ends only with 'adequate treatment'. Defining 'adequate treatment' also poses further difficulties -For example, Loebel et al. 7 and Larsen et al. 8 defined 'adequate treatment' as 12 weeks and three weeks of antipsychotic treatment respectively. ...
... Previous studies suggest that low motivation and logistical, perceptual and cultural barriers hinder treatment engagement and subsequently limit successful implementation of family interventions like family psychoeducation. 13 [21][22][23][24][25][26][27][28][29][30][31] Logistical barriers include lack of financial resources, transportation problems and inadequate clinics operation hours. [32][33][34] Perceptual and cognitive barriers include lack of interest due to religious beliefs, substantial burden and perceived lack of benefit. ...
Introduction
Despite the proven effectiveness of coordinated specialty care (CSC) programmes for first episode psychosis in the USA, CSC programmes often have low levels of engagement in family psychoeducation, and engagement of racial and ethnic minority family members is even lower than that for non-Latino white family members. The goal of this study is to develop and evaluate a culturally informed FAmily Motivational Engagement Strategy (FAMES) and implementation toolkit for CSC providers.
Methods and analysis
This protocol describes a mixed methods, multi-phase study that blends intervention mapping and the Promoting Action on Research in Health Services framework to develop, modify and pilot-test FAMES and an accompanying implementation toolkit. Phase 1 will convene a Stakeholder Advisory Committee to inform modifications based on findings from phases 1 and 2. During phase 1, we will also recruit approximately 200 family members to complete an online survey to assess barriers and motivation to engage in treatment. Phase 2 we will recruit five family members into a 3-month trial of the modified FAMES and implementation toolkit. Results will guide the advisory committee in refining the intervention and implementation toolkit. Phase 3 will involve a 16-month non-randomised, stepped-wedge trial with 50 family members from five CSC programmes in community-based mental health clinics to examine the acceptability, feasibility and initial impact of FAMES and the implementation toolkit.
Ethics and dissemination
This study received Institutional Review Board approval from Washington State University, protocol #17 812–001. Results will be disseminated via peer review publications, presentations at national and international conferences, and to local community mental health agencies and committees.
Trial registration number
ClinicalTrials.gov Registry ( NCT04188366 ).
Aim
To review the baseline and clinical characteristics of patients referred to a New Zealand Early Psychosis Intervention (EPI) service across a 4-year timeframe.
Method
We compared two cohorts, and identified variables associated with being accepted or declined, and reasons for decline, by an EPI service between 2013 and 2017.
Results
There were 576 people with suspected psychosis referred to the EPI service for assessment: 300 (52%) were accepted, 221 (38%) declined and 55 (10%) were not processed. Reasons for being declined by EPI services were a long duration of psychosis (DUP, 48%) and no evidence of psychosis (47%). There were no significant differences between the accepted and declined group in Emergency Department presentations for self-harm or suicide attempts and acute admissions to a psychiatric inpatient unit over the 3-year follow-up period.
Conclusion
To optimise the identification of true positive cases, EPI services require clear entry criteria. Replicating this study in other EPI services with different entry criteria may provide evidence to develop a more uniform screening process. Improved outcomes may be enhanced by measuring effectiveness and liaising with other EPI services.
Neuropsychiatry research has generated a great deal of interest in non-invasive
studies of neurotransmitters such as glutamate. Direct in vivo evidence for
glutamatergic models of schizophrenia, a prevalent neuropsychiatric disorder, is
mostly unavailable in humans.
High field magnetic resonance spectroscopy at short echo times can noninvasively
measure in vivo levels of numerous human brain metabolites including
glutamate and its precursor glutamine.
The object of this thesis was to explore and implement short echo time proton
magnetic resonance spectroscopy (1H MRS) techniques optimized for the precise
and time efficient quantification of glutamate and glutamine in small regions
(1.5cc) of the human brain and to apply 1H MRS to the study of schizophrenia.
Technical developments concentrated on the implementation of ultra-short echo
time Stimulated Echo Acquisition Mode (STEAM) and multi-voxel STEAM. The
effect of these techniques on the quantification precision of detectable
metabolites was studied in phantoms and in vivo.
Applications to schizophrenia research concentrated on the study of nevertreated,
first episode patients and chronically ill patients compared to healthy volunteers. The progression of the disease was explored in a longitudinal study
of first-episode patients. The effect of the delay in treatment (duration of
untreated psychosis and duration of prodromal symptoms) on 1H MRS
metabolites was explored in first episode patients. The correlation of 1H MRS and
phosphorus MRS metabolite levels was explored in chronically ill patients.
The use of ultra-short echo time STEAM (TE=6ms) over short echo time STEAM
(TE=20ms) resulted in higher metabolite signal for most coupled metabolites,
however, this did not lead to an improved quantification precision in vivo except
for levels of glutamine and GABA. The use of multi-voxel STEAM reduces the
acquisition time of two regions of the brain by a factor of two without affecting
quantification accuracy and precision, but proper elimination of outer voxel
stimulated echoes is necessary. This thesis investigates previously unreported in
vivo implementation issues and quantification precision of ultra-short echo time
STEAM and multi-voxel STEAM, critical factors in the decision to implement
these optimized techniques in research protocols as opposed to routinely
available sequences.
Levels of glutamine were found to be higher than normal in the left anterior
cingulate of first episode patients with schizophrenia and lower than normal in
chronically ill patients. Levels of glutamine were higher than normal in the left
thalamus of both first episode and chronically ill patients. Thalamic levels of
glutamate plus glutamine decreased after 30 months of treatment compared to 10 months of treatment in first episode patients and reduced grey matter volumes
were detected in the hippocampus and dorsolateral prefrontal cortex.
Levels of glutamine in chronically ill patients correlated positively with
phosphoethanolamine levels in the anterior cingulate and levels of Nacetylaspartate
correlated negatively with levels of glycerophosphocholine in the
thalamus.
Levels of choline in never-treated, first episode patients correlated positively with
duration of untreated psychosis in both the anterior cingulate and thalamus.
Thalamic levels of NAA in the same patients correlated negatively with duration
of prodromal symptoms.
The clinical results have produced evidence consistent with glutamatergic
models of schizophrenia and supporting the existence of a progressive
component of the disease perhaps attributable to neurodegeneration. The clinical
studies were the first in the field to examine glutamate and glutamine in small
1.5cc voxels at high field strength (4.0 Tesla). If confirmed by other research
groups, these studies may influence the pharmacological approaches used in the
treatment of schizophrenia, possibly intervening earlier with neuroprotective
drugs and addressing the glutamatergic dysfunctions.
Schizotypy has become an increasingly important construct for elaborating psychotic disorders that vary along the schizophrenic spectrum. However, different schizotypy inventories vary in conceptual approach and measurement. In addition, commonly used schizotypy scales have been seen as qualitatively different from screening instruments for prodromal schizophrenia like the Prodromal Questionnaire-16 (PQ-16). Our study investigated the psychometric properties of three schizotypy questionnaires (the Schizotypal Personality Questionnaire-Brief, Oxford-Liverpool Inventory of Feelings and Experiences, and the Multidimensional Schizotypy Scale) as well as the PQ-16 in a cohort of 383 non-clinical subjects. We initially evaluated their factor structure using Principal Component Analysis (PCA) and used Confirmatory Factor Analysis (CFA) to test a newly proposed composition of factors. PCA results support a three-factor structure of schizotypy that accounts for 71 % of the total variance, but also shows cross-loadings of some schizotypy subscales. CFA of the newly composed schizotypy factors (together with an added neuroticism factor) shows good fit. Analyses including the PQ-16 indicate considerable overlap with measures of trait schizotypy, suggesting that the PQ-16 might not be quantitatively or qualitatively different from schizotypy measurements. Taken together, results indicate that there is good support for a three-factor structure of schizotypy but also that different schizotypy measurements grasp facets of schizotypy differently. This points towards the need for an integrative approach for assessing the construct of schizotypy.
Decades of research show that psychosocial treatments are effective for psychosis, yet they remain unimplemented as the American healthcare system relies primarily on pharmacological solutions instead. This book reviews the history and current state of research to provide a more nuanced understanding of the evidence for and barriers to psychosocial care for psychosis. It addresses a wide range of mental health research and multi-professional practice domains from historical, personal, societal, professional, and systems perspectives. The varied perspectives presented illustrate factors that limit support for recovery in SMI and psychosis as well as real hope for recovering the US mental healthcare system. With contributions of experts by training and by experience, this book represents an essential resource for students, practitioners and researchers.
Background
Hippocampal abnormalities are among the most consistent findings in schizophrenia. Numerous studies have reported deficits in hippocampal volume, function, and connectivity in the chronic stage of illness. While hippocampal volume and function deficits are also present in the early stage of illness, there is mixed evidence of both higher and lower functional connectivity. Here, we use graph theory to test the hypothesis that hippocampal network connectivity is broadly lowered in early psychosis and progressively worsens over two years.
Methods
We examined longitudinal resting-state functional connectivity in 140 participants (68 individuals in the early stage of psychosis, 72 demographically similar healthy control individuals). We used an anatomically-driven approach to quantify hippocampal network connectivity at two levels: 1) a core hippocampal-medial temporal lobe cortex (MTLC) network; and 2) an extended hippocampal-cortical network. Group and time effects were tested in a linear mixed effects model.
Results
Early psychosis patients showed elevated functional connectivity in the core hippocampal-MTLC network, but contrary to our hypothesis, did not show alterations within the broader hippocampal-cortical network. Hippocampal-MTLC network hyperconnectivity normalized longitudinally and predicted improvement in positive symptoms, but was not associated with increasing illness duration.
Conclusions
These results show abnormally elevated functional connectivity in a core hippocampal-MTLC network in early psychosis, suggesting selectively increased hippocampal signaling within a localized cortical circuit may be a marker of the early stage of psychosis. Hippocampal-MTLC hyperconnectivity could have prognostic and therapeutic implications.
Rationale
At present, the research on the prevention of schizophrenia is still in its infancy. Pyrroloquinoline quinone (PQQ) has potential to treat psychological and neurological diseases including schizophrenia. However, the preventive effect of PQQ on schizophrenia remains unclear.
Objectives
In this study, we aimed to examine the preventive effect of supplementation of dietary PQQ from pregnancy or after birth on dizocilpine (MK-801)-induced schizophrenia-like behaviors in mice.
Results
Supplementation of dietary PQQ from pregnancy could effectively prevent MK-801-induced weight gain decrease, hyperlocomotion, stereotypical behavior, ataxia, exploratory activity decrease, social interaction disorder, memory deficit, and depression in mice. Supplementation of dietary PQQ after birth could effectively prevent MK-801-induced weight gain decrease, stereotypical behavior, ataxia, and memory deficit in mice. Female mice responded to a greater degree than males in preventing MK-801-induced weight gain decrease in both forms of PQQ supplementation. For mice that began PQQ supplementation after birth, females performed better than males in preventing MK-801-induced ataxia, memory deficit, and depression. For mice that began PQQ supplementation from pregnancy, males performed better than females in preventing MK-801-induced memory deficit. In vitro experiments indicated that PQQ supplementation in the earlier stage of life contributed to the growth of neurons and the development of neurites.
Conclusions
Our current study suggested that PQQ supplementation from pregnancy or postpartum could prevent some schizophrenia-like behaviors induced by MK-801 in mice. Our work supported the potential usage of dietary supplement of PQQ in preventing or alleviating symptoms associated with schizophrenia.
Decades of research show that psychosocial treatments are effective for psychosis, yet they remain unimplemented as the American healthcare system relies primarily on pharmacological solutions instead. This book reviews the history and current state of research to provide a more nuanced understanding of the evidence for and barriers to psychosocial care for psychosis. It addresses a wide range of mental health research and multi-professional practice domains from historical, personal, societal, professional, and systems perspectives. The varied perspectives presented illustrate factors that limit support for recovery in SMI and psychosis as well as real hope for recovering the US mental healthcare system. With contributions of experts by training and by experience, this book represents an essential resource for students, practitioners and researchers.
Background
There is a relative lack of long-term, prospective data evaluating the safety and effectiveness of treatment in early-onset adolescent patients with schizophrenia who are treatment-naïve. The aim of this post-hoc analysis was to examine the long-term safety and effectiveness of lurasidone in adolescents with schizophrenia who were antipsychotic treatment-naïve (TN; at the time of enrolment in the initial study) compared to adolescents treated previously (TP) with an antipsychotic.
Methods
Patients aged 13–17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible-dose (20–80 mg/day) lurasidone study.
Results
The long-term analysis sample consisted of 50 TN and 221 TP patients, of whom 40% and 43%, respectively, discontinued prematurely. The three most common adverse events for TN and TP patients, respectively, were headache (26.0%, 23.5%); schizophrenia (14.0%, 12.2%), dizziness (16.0%, 4.1%), and nausea (16.0%, 11.8%). At endpoint, mean increase in weight was similar to expected weight gain based on growth charts for both TN (+4.5 kg vs. + 5.7 kg) and TP (+4.6 kg vs. + 6.6 kg) patients. Minimal changes were observed for each group in metabolic parameters and prolactin. Mean improvement was consistently greater in the TN vs. TP group (-19.2 vs. −15.9; effect size of 0.33) for between-group change in PANSS total score at Week 104.
Conclusions
In both TN and TP adolescents with schizophrenia, long-term treatment with lurasidone was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin, with generally small differences noted in rates of reported AEs. Continued improvement in symptoms of schizophrenia was evident for both the TN and TP groups. These data indicate that lurasidone is a safe and efficacious treatment option for treatment-naïve youth with schizophrenia, who are generally most sensitive to antipsychotic adverse effects.
Background
Mental illness exposes persons to stigma and this stigma also affects family caregivers of persons with mental illness. The objective of the study was to assess the prevalence of perceived stigma and associated factors among primary caregivers of children and adolescents with mental illness, Addis Ababa, Ethiopia.
Methods
A cross-sectional study design and systematic random sampling technique were used to recruit 408 participants at St. Paul’s Hospital Millennium Medical College and Yekatit-12 Hospital Medical College, Addis Ababa, Ethiopia. We collected the data by face-to-face interview. Devaluation of Consumer Families Scale was used to measure perceived stigma. Patient Health Questionnaire-9 and Oslo-3 social support scale were the instruments used to assess the factors. Coded variables were entered into Epidata V.3.1 and exported to SPSS V.21 for analysis. Binary logistic regression was used for analysis.
Result
A total of 408 participants were interviewed, with a response rate of 96.5%. The magnitude of perceived stigma was 38.5% with 95% CI (33.6-43.1). Majority (68.6%) of the respondents were female. In the multivariate logistic regression, being mother (AOR = 2.8, 95% CI: 1.59, 4.91), absence of other caregiver (AOR = 2.0, 95% CI: 1.15, 3.49), poor social support (AOR = 3.9, 95% CI: 1.59, 6.13), and symptoms of depression (AOR = 2.9, 95% CI: 1.88, 3.65) were factors significantly associated with perceived stigma.
Conclusion
The prevalence of perceived stigma among primary caregivers of children and adolescents with mental illness was high. Being mother, absence of other caregiver, poor social support, and symptoms of depression were factors significantly associated with perceived stigma.
Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.
This chapter reviews common presentations of psychosis in transitional age youth (TAY) with a focus on schizophrenia spectrum disorders. Diagnostic approaches and assessment tools are outlined in addition to the clinical course and outcomes unique to this population. Evidence-based treatment of first-episode psychosis (FEP) is highlighted with an emphasis on coordinated specialty care (CSC) programs that utilize team-oriented recovery-based principles and a shared decision-making philosophy. Special consideration is given to the importance of using a developmental approach while engaging with transitional age youth with early psychosis and their families.
The common occurrence of trauma-related mental illnesses in transitional age youth (TAY) deserves special focus both in terms of context and treatment options. This chapter will discuss the prevalence and consequences of trauma in TAY, which can range from brief acute reactions to chronic disabling conditions. Considerations for psychotherapeutic and pharmacological interventions for this age group will be discussed. Treatments generally involve psychotherapy, and there are a number of evidence-based ones to choose from, though most originated for use with adolescents or adults. Further research is needed to determine adaptability for TAY. Pharmacologic options can support patients through symptom targeting and remission, particularly in combination with psychotherapy. Finally, special considerations and challenges in trauma intervention with this age group will be discussed.
Contemporary young adults differ from those of previous generations in their heavy engagement with screen media, including increasingly sophisticated video gaming and social media. This change in lifestyle has significant implications for their mental health and its treatment, for good and ill. Young adults typically prioritize screen media habits, thus displacing risky behavior such as recreational drug and alcohol use, sexual intercourse, and violence. Yet this also displaces healthy habits including adequate sleep, reading books, and in-person socializing. Some young adults develop an impairing but treatable behavioral addiction to gaming and other screen media, although names and definitions regarding the phenomenon vary greatly. Digital media behaviors interact with depression, anxiety, ADHD, and autism spectrum disorders in distinct manners which must be assessed and addressed in treatment. Psychiatrists should incorporate aspects of digital media habits and experiences into their assessments and formulations of young adult patients, adapting practice to the highly digitized lives of this generation.
This book was originally published in 2004 and concerns developmental neurobiology. In the decade preceding publication, developmental neurobiology made important strides towards elucidating the pathophysiology of psychiatric disorders. Nowhere has this link between basic science and clinical insights become clearer than in the field of schizophrenia research. Each contributor to this volume provides a fresh overview of the relevant research, including directions for further investigation. The book begins with a section on advances in developmental neurobiology. This is followed by sections on etiological and pathophysiological developments, and models that integrate this knowledge. The final section addresses the clinical insights that emerge from the developmental models. This book will be valuable to researchers in psychiatry and neurobiology, students in psychology, and all mental health practitioners.
Resumen
La identificación y el tratamiento tempranos de la esquizofrenia pueden aliviar los síntomas, retrasar el comienzo y mejorar la evolución de la psicosis. Así, la detección de individuos en situación de riesgo durante la fase prodrómica es una tarea importante. Los enfoques universales para la detección selectiva de la población general o los sujetos sanos en situación de riesgo no han resultado posibles hasta la fecha. Sin embargo, se han desarrollado criterios clínicos para detectar individuos en situación de riesgo ultra-elevado para entornos especializados, llevándose a la práctica en estudios de intervención. Este artículo examina la justificación racional para la detección e intervención tempranas de la psicosis, junto con una revisión de algunos estudios actuales. Éstos llevan a cabo la prevención utilizando estrategias de intervención psicológica, farmacológica o de ambos tipos y han demostrado resultados prometedores en individuos con riesgo alto. La Red Alemana de Investigación sobre Esquizofrenia (GRNS) está realizando dos estudios multicéntricos de intervención temprana; uno con intervención psicológica temprana en sujetos que manifiestan síntomas prodrómicos tempranos, aplicando el segundo ensayo tratamiento clínico e intervención farmacológica temprana en sujetos que experimentan síntomas prodrómicos tardíos (sujetos de riesgo alto). A pesar de los resultados prometedores, el tamaño de muestra de muchos de los estudios actuales es pequeño, con un periodo breve de duración del estudio. Los beneficios completos de la detección e intervención tempranas se deberían revelar después que se hayan realizado estudios más grandes y largos.
Resumen
Los padres, especialmente las madres, tienen un papel crítico en la iniciación del tratamiento psiquiátrico de su hijo con primer episodio de esquizofrenia. El conocimiento de las actitudes de las madres hacia la enfermedad de su hijo antes del tratamiento psiquiátrico y hacia el comienzo del tratamiento es esencial para el desarrollo de intervenciones para reducir la duración de la psicosis no tratada (DPNT). En el presente estudio, se entrevistó a las madres (n = 61) de pacientes ingresados consecutivamente con trastornos esquizofré-nicos de comienzo reciente sobre sus opiniones acerca de la naturaleza de los síntomas la primera vez que se presentaron síntomas psicóticos en su hijo y las opiniones sobre la razón principal para el tratamiento psiquiátrico; su percepción de los problemas en la iniciación del tratamiento psiquiátrico y las propuestas que pudieran tener para iniciar el tratamiento en un momento anterior en el tiempo. Alrede-dor del 57% de las madres no pensaba que su hijo tenía una psicosis cuando los síntomas psicóticos se presentaron por primera vez. La mayona de las madres que pensaron inmediatamente que su hijo sufría de un trastorno psicótico suponían que este trastorno lo causaba el uso de drogas callejeras. Alrededor de un tercio de las madres (el 32,8%) pensaba que la resistencia de los pacientes a reconocer que necesitaban ayuda era el obstáculo principal en la iniciación del tratamiento psiquiátrico. Más de la mitad de las madres percibía factores relacionados con la provisión de asistencia profesional como problemas en la iniciación del tratamiento psiquiátrico. Dada la resistencia de los pacientes a aceptar el tratamiento, estos problemas complican más su iniciación. Las madres ponen de relieve que un enfoque más activo por los profesionales sanitarios podría reducir la demora del tratamiento.
Resumen
El objetivo de este estudio naturalista fue investigar la influencia posible del período sin tratamiento (PST) del trastorno depresivo mayor (TDM) sobre la evolución a largo plazo de la enfermedad. Ciento trece pacientes con TDM recurrente, según los criterios del DSMIV- TR, seguidos durante 5 años, se seleccionaron y entrevistaron, y se revisaron sus historias clínicas. El PST se definió como el intervalo entre el inicio del primer episodio depresivo y el primer tratamiento antidepresivo. La muestra se dividió en dos grupos según el PST: un grupo con un PST ≤ 12 meses (n = 75) y otro con un PST > 12 meses (n=38). Las principales variables demográficas y de evolución clínica de los dos grupos se compararon usando el test de la t de Student o de χ ² . Los pacientes con un PST más prolongado eran más jóvenes en el inicio (t=2,8, p=0,006) y la duración de la enfermedad fue mayor (t=3,20, p=0,002) que en los pacientes con un PST más corto. Además, el número total de episodios depresivos que ocurrieron antes del primer tratamiento antidepresivo fue mayor en el grupo con PST más prolongado (t=-2,223, p < 0,03). Aunque están limitadas por la naturaleza retrospectiva del estudio, estas conclusiones preliminaries podrían indicar que un PST más prolongado puede influir negativamente en la evolución del TDM. Son necesarios estudios prospectivos de mayor tamaño para investigar con más profundidad el papel del PST en el TDM.
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