Emergence Of Psychotic Symptoms Research Articles

Elucidating the role of Early Maladaptive Schemas for psychotic symptomatology

Although cognitive accounts postulate negative self-concepts as a causal factor in the emergence of psychotic symptoms, little is known about the role of specific self-schemas for psychotic symptomatology. Building on a differentiated and treatment-informed schema model, we aimed to elucidate the role of Early Maladaptive Schemas (EMS) for psychotic symptomatology, particularly their specificity to patients with psychosis and their association with positive versus negative symptoms. We assessed EMS with the Young Schema Questionnaire in patients with psychosis (n=81), patients with depression (n=28) as well as healthy participants (n=60). In the psychosis sample symptoms were rated using the Positive and Negative Syndrome Scale. In comparison to healthy participants, patients with either psychosis or depression showed a higher overall number and intensity of EMS whereas the psychosis and the depression sample did not significantly differ. The overall number and intensity of EMS were significantly associated with positive but not with negative symptoms. Contrary to previous findings, patients with psychosis and patients with depression did not differ in the EMS subscale Mistrust/Abuse. The results suggest that EMS are particularly relevant to positive symptoms. Our findings imply that addressing maladaptive schemas in patients with psychosis by making use of the schema-concept holds potential.

Prolonged duration of untreated psychosis: a problem that needs addressing.

The duration of untreated psychosis (DUP) refers to the period of time between the emergence of psychotic symptoms and the initiation of appropriate clinical treatment. Prolonged DUP is associated with a range of adverse consequences, including more severe illness course, cognitive deficits and poor functioning. Problems with recognition of illness and in seeking help contribute to DUP, but another major cause of prolonged DUP is delays within secondary mental health services. In an attempt to reduce these delays, National Health Service England and the Department of Health have set new targets to improve access to early intervention services which will come into effect in April 2016. Given this background, we aimed to examine the DUP and pathways to care of new patients entering an early intervention service. We also examined whether they were receiving National Institute for Health and Care Excellence (NICE) concordant treatment. This will enable us to establish a baseline so that the impact of the new targets can be determined and to assess the degree of change that will be required to implement these. De-identified electronic records of 165 patients accepted into the service over a 12-month period were analysed. Median DUP was 6 months. There was a median of 2 contacts prior to service entry. Community Mental Health Teams were the largest source of referrals. The majority of patients had a DUP exceeding the international target of 3 months. The findings appear to support previous evidence that this may be partially attributable to significant delays within the mental health care system.

Self-recovery in schizophrenia: Insight from autobiographical narratives of patients

The self or identity is often seriously challenged by the emergence of psychotic symptoms. A first reason for that is most likely due to the traumatic experience caused by the sudden emergence of hallucinations or persecutory ideas that challenge both the representation of oneself and that of the world and others. A second reason is linked to the social consequences of having a mental illness and of being assigned with the label of “mentally ill or disabled person”. A third relates to the patients’ cognitive impairment that alters their ability to take distance from these self-challenging events, to give a meaning to these experiences and to build coherent narratives of their life that integrate a great variety of personal experiences such as turning points or unpleasant events. For these reasons, recovering from a severe mental illness is a process through which the self evolves by integrating the lessons of past personal events, building new representations of oneself and looking to new directions for future projects. Excerpts of patients’ narratives collected in experimental setting will be presented in order to illustrate how indexes of recovery can be measured in self-narratives and how they help identifying the steps of self-recovery that have been identified in qualitative research on patients with schizophrenia .

A review of neuroimaging studies of young relatives of individuals with schizophrenia: A developmental perspective from schizotaxia to schizophrenia

In an effort to identify the developing abnormalities preceding psychosis, Dr. Ming T. Tsuang and colleagues at Harvard expanded Meehl's concept of "schizotaxia," and examined brain structure and function in families affected by schizophrenia (SZ). Here, we systematically review genetic (familial) high-risk (HR) studies of SZ using magnetic resonance imaging (MRI), examine how findings inform models of SZ etiology, and suggest directions for future research. Neuroimaging studies of youth at HR for SZ through the age of 30 were identified through a MEDLINE (PubMed) search. There is substantial evidence of gray matter volume abnormalities in youth at HR compared to controls, with an accelerated volume reduction over time in association with symptoms and cognitive deficits. In structural neuroimaging studies, prefrontal cortex (PFC) alterations were the most consistently reported finding in HR. There was also consistent evidence of smaller hippocampal volume. In functional studies, hyperactivity of the right PFC during performance of diverse tasks with common executive demands was consistently reported. The only longitudinal fMRI study to date revealed increasing left middle temporal activity in association with the emergence of psychotic symptoms. There was preliminary evidence of cerebellar and default mode network alterations in association with symptoms. Brain abnormalities in structure, function and neurochemistry are observed in the premorbid period in youth at HR for SZ. Future research should focus on the genetic and environmental contributions to these alterations, determine how early they emerge, and determine whether they can be partially or fully remediated by innovative treatments.

Altered Striatal Functional Connectivity in Subjects With an At-Risk Mental State for Psychosis

Recent functional imaging work in individuals experiencing an at-risk mental state (ARMS) for psychosis has implicated dorsal striatal abnormalities in the emergence of psychotic symptoms, contrasting with earlier findings implicating the ventral striatum. Our aims here were to characterize putative dorsal and ventral striatal circuit-level abnormalities in ARMS individuals using resting-state functional magnetic resonance imaging (fMRI) and to investigate their relationship to positive psychotic symptoms. Resting-state fMRI was acquired in 74 ARMS subjects and 35 matched healthy controls. An established method for mapping ventral and dorsal striatal functional connectivity was used to examine corticostriatal functional integrity. Positive psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental State and the Positive and Negative Syndrome Scale. Compared with healthy controls, ARMS subjects showed reductions in functional connectivity between the dorsal caudate and right dorsolateral prefrontal cortex, left rostral medial prefrontal cortex, and thalamus, and between the dorsal putamen and left thalamic and lenticular nuclei. ARMS subjects also showed increased functional connectivity between the ventral putamen and the insula, frontal operculum, and superior temporal gyrus bilaterally. No differences in ventral striatal (ie, nucleus accumbens) functional connectivity were found. Altered functional connectivity in corticostriatal circuits were significantly correlated with positive psychotic symptoms. Together, these results suggest that risk for psychosis is mediated by a complex interplay of alterations in both dorsal and ventral corticostriatal systems.

The Second Revision of the Dopamine Theory of Schizophrenia: Implications for Treatment and Drug Development

In this edition of Biological Psychiatry, Egerton et al. (1) from the Institute of Psychiatry at King’s College in London published the results of an imaging study measuring dopamine (DA) synthesis capacity in subjects presenting potentially prodromal symptoms of schizophrenia. Subjects fulfilled clinical criteria associated with a 20% to 40% risk of presenting a psychotic episode within 1 to 3 years (2), a condition labeled as ultra-high risk (UHR). Compared with matched control subjects, striatal DA synthesis capacity (measured with positron emission tomography as the uptake of [F]DOPA) was increased in UHR subjects. Analysis of striatal functional subdivisions showed that the [F] DOPA uptake was increased in the associative striatum (AST) and not in the ventral striatum (VST). This outcome confirms an earlier result from the same group in a smaller cohort (3) and suggests that abnormalities of DA function in the AST precede the emergence of psychotic symptoms in UHR subjects. The authors should be complimented for having submitted their initial findings to the rigor of replication in an independent cohort. As pointed out by the authors, replication of a clinical finding by the same investigators does carry less weight than independent replication. Nonetheless, replication studies are extremely important and might not be given enough attention and credit in the field. Given that the recruitment criteria, clinical evaluation, and imaging technique were maintained between the two studies, the data can be pooled, and this combined analysis will be especially important for the follow-up studies. Based on the UHR criteria, it is anticipated that 20% to 40% of these subjects will present a psychotic episode within 2 years and that this episode might be the first psychotic manifestation of a chronic psychotic disorder such as schizophrenia. In the follow-up of the first cohort, the authors observed that increased [F]DOPA uptake at baseline was associated with higher risk of psychotic transition within 3 years. It will be very important to ascertain if the prognostic value of elevated [F]DOPA uptake in the AST is replicated in this larger cohort. This result provides an important contribution to a large body of imaging work performed over the last decade that generated a remarkably consistent picture of alteration of DA function in schizophrenia [reviewed in (4,5)]. Using either [F]DOPA uptake or competition studies between endogenous DA and DA D2 receptor ligands, several groups have documented that schizophrenia is associated with increases in striatal presynaptic DA function, at least during the period of psychotic exacerbation, and that this increase is associated with the severity and acuity of psychotic symptoms. This DA dysregulation does not appear to be a

1143 – Clinical characteristics and cognitive functions of late-onset psychoses: a case-control study

Background Mental disorders are not uncommon in late life. The emergence of psychotic symptoms for the first time in later life poses a diagnostic challenge for clinicians assessing and treating elderly persons with mental illness. Objectives To determine the clinical characteristics and cognitive function impairments in elderly patients with late-onset psychosis compared with normal healthy control. Participants and methods A cross-sectional case-control study; 50 patients with late-onset non-schizophrenic psychoses compared to 50 normal, healthy volunteers matched for age, sex, and social standard. The case group was interviewed using the Structured Clinical Interview for DSM Axis-I diagnosis (SCID-I), the control group was chosen on basis of assessment using the General Health Questionnaire (GHQ). Both groups underwent a functional assessment of daily living using the following: (a) Activities of Daily Living scale (ADL), (b) Instrumental Activities of Daily Living (IADL), (c) Cambridge Mental Disorders of the Elderly Examination, section B (CAMCOG), and (d) the Wechsler Adult Intelligence Scale (WAIS) for cognitive assessment. Results No significant differences between both groups in sociodemographic variables, family, and medical histories, except occupational status, in case group they had significantly more professional and skilled jobs. They also showed significantly higher rates of diseases of the gastrointestinal, renal, and central nervous system. Moreover, they showed very high significant cognitive decline, as well as functional impairment in daily living activities compared with their healthy counterparts. Conclusion Patients with late-onset psychoses show more severe cognitive and functional impairments in their daily activities.This paves the way for future studies.

Differences in subcortical structures in young adolescents at familial risk for schizophrenia: A preliminary study

Schizophrenia has been associated with reduced volumes of subcortical structures on magnetic resonance imaging (MRI), but the relation of these reductions to familial risk for the disorder is unclear. We investigated the effect of familial risk for schizophrenia on regional subcortical volumes during adolescence, a period marked by steep maturational changes in brain structure and the emergence of psychotic symptoms. A group of 26 non-help-seeking, first-degree relatives of patients with schizophrenia and 43 matched healthy comparisons, between 9 and 18 years of age, underwent MRI scanning and were rated for the presence of prodromal symptoms. Five subcortical regions-of-interest were tested for group differences and group by age interactions, as well as correlations with low-level prodromal symptoms in the familial risk group. Relative to comparisons, familial risk subjects demonstrated greater positive volume–age relationships in hippocampus, putamen, and globus pallidus. These results suggest that relatives of individuals with schizophrenia exhibit structural abnormalities in the subcortex as early as pre-adolescence, which may reflect altered neurodevelopment of these regions.

Emergence of psychotic symptoms during Internet withdrawal

Emergence of psychotic symptoms during Internet withdrawal

Dopamine: A Marker of Psychosis and Final Common Driver of Schizophrenia Psychosis

Our attempt to understand schizophrenia in neurochemical terms began with the landmark studies of Carlsson and Lindqvist (1) in the 1960s. The results of these studies, based on the action of chlorpromazine, were strengthened by the binding studies carried out in both Seeman's (2) and Synder's (3) laboratories, which showed that antipsychotic potency was correlated with dopamine D2 receptor binding. The one major exception to this correlation is clozapine, which appears to be the most effective available drug for treating schizophrenia symptoms. The most recent version of the resulting dopamine hypothesis suggests that genetic, environmental, and developmental variables play major etiological roles in schizophrenia, but that striatal dopamine presynaptic overactivity remains the final trigger resulting in psychosis......

The rationale for early intervention in schizophrenia and related disorders

To examine the rationale and evidence supporting an early intervention approach in schizophrenia. A selective literature review was conducted. During the onset of schizophrenia, there is often a significant delay between the emergence of psychotic symptoms and the initiation of treatment. The average duration of untreated psychosis is around 1-2 years. During this period, brain function may continue to deteriorate and social networks can be irreversibly damaged. Studies have consistently linked longer duration of untreated psychosis with poorer outcomes and this relationship holds even after controlling for the potential confounding variable of premorbid functioning. In Norway, the early Treatment and Intervention in PSychosis study demonstrated that duration of untreated psychosis is amenable to intervention with the combination of educational campaigns and specialized early detection units substantially decreasing the period from onset of symptoms to treatment initiation. Furthermore, recent evidence from the randomized controlled OPUS and the Lambeth Early Onset trial studies have linked phase-specific early interventions to improved outcomes spanning symptoms, adherence to treatment, comorbid drug abuse, relapse and readmission. Some benefits persist after cessation of the intervention. Early intervention in schizophrenia is justified to reduce the negative personal and social impact of prolonged periods of untreated symptoms. Furthermore, phase-specific interventions are associated with improved outcomes, at least in the short term. Further research is needed to establish the optimum duration of such programmes.

Mentalization‐based psychodynamic psychotherapy for psychosis

This article discusses and illustrates the use of mentalization-based psychodynamic psychotherapy for disturbances of awareness of the self and others in patients with psychotic-spectrum disorders. The literature on impairments of mental processes involved in self-awareness and awareness of others occurring in psychotic illnesses and the relationship between childhood trauma and the emergence of psychotic symptoms is reviewed. A case illustrates how mentalization-based treatment can facilitate treatment engagement and be used to manage enactments in the psychotherapy with a patient with a psychotic disorder. Mentalization-based psychotherapy may offer a useful adjunct to antipsychotic medication and psychosocial evidence-based treatments in the care of individuals in the early phase of psychotic disorders.

Health consequences of illegal drug use

The aim of this article is to review recent research on the health consequences of illegal drug use and possible risk factors, with a particular focus on prospective evidence. Mortality studies have revealed qualitative and quantitative changes in causes of death among heroin and injecting drug users (IDUs), probably due to increasing exposure to harm reduction programs, the introduction of highly active antiretroviral therapy (HAART), the aging of drug users, and rising concurrent use of illegal drugs and prescription drugs. For morbidity, nonfatal overdose is still one of the most important concerns; likewise the higher prevalence of hepatitis C among non-IDUs and hepatitis A, B, C coinfection. Cannabis use has been consistently reported to be associated with the emergence of psychotic symptoms, yet that seems not to be the case for anxiety and depressive disorders. Use of 3,4 methylenedioxymethamphetamine (MDMA) has been linked with short-term negative effects on cognitive performance (i.e. visual memory). A series of longitudinal studies have shown enduring unfavorable effects of prenatal cocaine and marijuana exposure on children's physical, cognitive, and language development. Prospective evidence on illegal drug use in particular subpopulations may be needed to better understand health problems among users at different life stages and the possible long-term effects.

Lack of an inverse relationship between duration of untreated psychosis and cognitive function in first episode schizophrenia

This study assessed the relationship between duration of untreated psychosis (DUP) and cognitive measures in order to assess if longer DUP was associated with worse performance. One hundred two patients with first episode schizophrenia or schizoaffective disorder were assessed on cognitive measures of speed of processing, episodic memory, executive function, and visual spatial processing at baseline (when patients were drug naive and after 16 weeks of olanzapine or risperidone treatment), so that a change score could be derived. DUP was defined by the emergence of psychiatric symptoms and the emergence of psychotic symptoms. Data were analyzed correlationally, parametrically (after the group was divided into long and short DUP by median split), and by regression. We found that DUP for psychotic symptoms in this group of patients was long, with a median of 46 weeks. Neither correlational, parametric analyses in which DUP served as a class variable, nor multiple regression indicated that longer DUP was associated with worse cognition at baseline or smaller magnitude of improvement in cognition. Our results suggest that while early intervention may be critical for symptom amelioration by shortening DUP, early intervention for treatment of psychiatric symptoms may have little or no impact on cognitive function. Furthermore, assuming that cognition is a core symptom of schizophrenia, the notion that ongoing psychosis is somehow toxic for a variety of information processing domains appears questionable.

Analysis of the 5HT‐2A T102C receptor polymorphism and psychotic symptoms in Alzheimer's disease

Although the aetiology of psychotic symptoms in Alzheimer's disease (AD) is multi-factorial, alterations in serotonergic neurotransmission are often implicated. Polymorphisms of the serotonin receptor 5HT-2A are associated with hallucinatory symptoms and delusions in demented and non-demented cohorts. This study examined the role of the 5HT-2A T102C polymorphism in influencing psychotic symptoms in a large Northern Ireland AD population (n = 406, mean MMSE 13/30). Forty-eight percent of patients experienced delusional symptoms and 28% experienced hallucinations during the course of their dementia. No significant association was found either in frequency of genotype or allelic variation for either set of symptoms. Furthermore, the mean delusional and hallucinatory severity scores did not differ significantly among the three genotype groups. The lack of influence of the T102C polymorphism of the 5HT-2A receptor on the emergence of psychotic symptoms in AD contrasts with previous reports in other cohorts involving smaller numbers of subjects.

Persistent Auditory Hallucinations That Are Unresponsive to Antipsychotic Drugs

Persistent Auditory Hallucinations That Are Unresponsive to Antipsychotic Drugs

Association of Huntington's disease and schizophrenia-like psychosis in a Huntington's disease pedigree

BackgroundHuntington's disease (HD) is a dominantly inherited, neurodegenerative disorder due to expansion of a polymorphic trinucleotide repeat in the short arm of chromosome 4. Clinical manifestations consist of a triad of choreic movements, cognitive decline and psychiatric syndromes starting in the fourth to fifth decade. Psychiatric manifestations vary and may precede motor and cognitive changes. Personality changes and depression occur most commonly. Paranoid schizophrenia-like symptoms occur in 6% to 25% of cases.Case reportWe describe a 55 year-old woman with an 8 yearlong history of behavioural changes, multi-thematic delusions and auditory hallucinations. History and mental state examination were suggestive of paranoid schizophrenia. Neurological examination revealed discrete, involuntary movements affecting her arms and trunk. Genotyping detected an expanded allele (43 trinucleotide repeats). A three-generation-long family history of chorea and schizophrenia-like psychosis was found.ConclusionHD-families have been reported in which schizophrenia-like syndromes emerged in all or most HD-affected members long before they developed extra-pyramidal or cognitive changes. This has been attributed to more than mere coincidence. We hypothesise that in these families the HD gene is transmitted along with a low load of small-effect "psychosis genes" which, in the presence of the severe cognitive changes of HD, manifest as a schizophrenia-like phenotype. Further research is needed in order to clarify the links between genetic loading and the emergence of psychotic symptoms in Huntington's disease.

Clinical and genetic high-risk strategies in understanding vulnerability to psychosis

Neurodevelopmental processes active during the adolescent period have been hypothesized to participate in the deterioration in functioning associated with the onset of schizophrenia. A number of studies are now underway evaluating individuals in an ultra high-risk clinical state with neuroimaging assessments repeatedly over time, to determine whether particular neural changes predict an imminent onset of psychosis. However, the results of such studies will be difficult to interpret without reference to studies examining the distribution of these neural indicators in the non-clinically-affected first-degree relatives of patients with schizophrenia. Recent work deriving primarily from twin and family studies (i.e., genetic high-risk designs) indicates that some of the alterations in brain function and structure in schizophrenia are primarily genetically mediated and also appear in some of their unaffected first-degree relatives, while other alterations are present in individuals who manifest the illness phenotype but not in relatives at genetic risk. Whereas the primarily genetically mediated deficits shared by at-risk but non-symptomatic relatives are not likely to show differential change in the premorbid period, and may be necessary but clearly not sufficient for the development of psychotic symptoms, the deficits specific to patients who manifest the illness phenotype are good candidates for marking the neurobiological processes associated with the emergence of psychotic symptoms at the time of schizophrenia onset. Preliminary results from longitudinal studies of individuals ascertained initially in a prodromal (i.e., “clinical high-risk”) state appear to be interpretable within this framework.

Schizophrenia and depression: Challenging the paradigm of two separate diseases—A controlled study of schizophrenia, depression and healthy controls

Background We studied descriptive and causal associations between schizophrenia, depressive symptoms and episodes of depression. Methods Untreated psychotic, depressive and negative symptoms were assessed retrospectively from onset until first admission using the IRAOS in a population-based sample of 232 first episodes of schizophrenia. A representative subsample of 130 patients, studied retrospectively until onset and followed up prospectively over 6 months after first admission, were compared with 130 age- and sex-matched healthy population controls and with 130 equally matched first admissions for unipolar depressive episodes. Results The lifetime prevalence of depressive mood (≥2 weeks) at first admission for schizophrenia was 83%. The most frequent initial symptom of schizophrenia was depressive mood, appearing more than 4 years before first admission and followed by negative symptoms and functional impairment. Showing considerable overlap in symptoms and functional impairment at their initial stages, schizophrenia and unipolar depression became clearly distinguishable with the emergence of psychotic symptoms. In the first psychotic episode 71% presented clinically relevant depressive symptoms, 23% fulfilled the ICD-10 criteria for a depressive episode. With remitting psychosis the prevalence of depression, too, decreased. The high frequency of depressive symptoms at the prepsychotic prodromal stage and their increase and decrease with the psychotic episode suggests that depression in schizophrenia might be expression of an early, mild stage of the same neurobiological process that causes psychosis. Conclusions The high prevalence of depression in the population and the diversity of its causes prompted us to speculate about a hierarchical model of preformed dimensional patterns of psychopathology.

Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions.

Both early (i.e., pre- and perinatal periods) and late (i.e., adolescent period) neurodevelopmental processes are thought to participate in the etiology and pathophysiology of schizophrenia. However, whether markers of these processes would be expected to predict an imminent onset of psychosis, as is hoped in the current generation of prodromal research programs, depends on whether their disruptions result from genetic factors shared by patients and some of their unaffected relatives, nongenetic factors specific to those who manifest the illness phenotype, or combinations of these sets of influences. Here we present recent work deriving primarily from high-risk and family-study (i.e., "genetic high-risk") designs, which provide a framework for investigating the neural changes that may occur proximally to the initial onset of psychosis. This work indicates that some of the alterations in brain function and structure in schizophrenia are primarily genetically mediated and also appear in some of patients' unaffected first degree relatives, while other alterations are present in individuals who manifest the illness phenotype but not in relatives at genetic risk (Cannon et al. 2002a, 2002c; Van Erp et al. 2002). Whereas the primarily genetically mediated deficits shared by at-risk but nonsymptomatic relatives are not likely to show differential change in the premorbid period and may be necessary but clearly not sufficient for the development of psychotic symptoms, the deficits specific to patients who manifest the illness phenotype are good candidates for marking the neurobiological processes associated with the emergence of psychotic symptoms at the time of schizophrenia onset. Preliminary results from longitudinal studies of individuals ascertained initially in a prodromal (i.e., "clinical high-risk") state appear to be interpretable within this framework. A number of questions arising from this line of inquiry need to be addressed in the current generation of prodromal research programs: To what extent do the neural systems affected by early and late neurodevelopmental influences overlap? Is there likely to be a schizophrenia-related disturbance in the processes associated with adolescent brain maturation, or are these maturational processes themselves intact, participating in psychosis onset only indirectly, by promoting a neurobiological context in which the early neurodevelopmental disturbances can be expressed in psychotic symptoms? What pattern of changes observable from in vivo imaging studies is consistent with a reduction in neuropil volume? We develop a framework for addressing these questions and evaluating their implications for understanding the roles of early and late neurodevelopmental influences in the etiology and pathophysiology of schizophrenia.