Schizophrenia Spectrum Psychosis Research Articles

Is the Association Between Parents’ Mental Illness and Child Psychopathology Mediated via Home Environment and Caregiver’s Psychosocial Functioning? A Mediation Analysis of the Danish High Risk and Resilience Study—VIA7, a Population-Based Cohort Study

Abstract We aimed to investigate to which degree the home environment and/or primary caregivers’ level of functioning mediate the association between parental mental illness (eg, schizophrenia) and child psychopathology. We used data from the nationwide Danish High Risk and Resilience Study—VIA7. The study sample comprised 522 seven-year-old children. The main outcome was the child psychopathology, assessed with the Child Behavior Checklist (CBCL). The exposure variable had 3 categories: children at familial high risk of schizophrenia spectrum psychosis (FHR-SZ), bipolar disorder (FHR-BP), and population-based controls. Mediators were quality of the Home Observation for Measurement of the Environment (HOME) and primary caregiver’s Personal and Social Performance Scale (primary caregiver functioning). Primary caregiver’s IQ and polygenic risk scores (PRS) for the educational attainment of the children were considered as covariates. We found a significant indirect adjusted effect of FHR status vs controls on CBCL total scores (FHR-SZ = 5.34, 95% confidence interval [CI]: 3.50–7.47 and FHR-BP = 4.54, 95% CI: 2.65–6.68), through primary caregiver functioning and HOME. Both mediators combined explained 53% and 64% variation of the total effects of FHR-SZ and FHR-BP, respectively. Adjusting for the PRS in the mediation models only resulted in minor changes in the FHR effects on the CBCL. We conclude that the HOME and the primary caregiver functioning are important mediating factors for child psychopathology, especially in children born with familial risk for severe mental illness. This knowledge may represent a window of opportunity for the development of preventive strategies (eg, intervention to improve primary caregiver functioning and home environment).

Fusiform gyrus volume reduction associated with impaired facial expressed emotion recognition and emotional intensity recognition in patients with schizophrenia spectrum psychosis

Impaired social cue perception such as emotional recognition is a prominent feature in patients with schizophrenia, adversely affecting psychosocial outcomes and worsening clinical manifestations of the disease. However, few structural neuroimaging studies have investigated both facial emotion recognition and emotion intensity recognition in schizophrenia. Ninety patients with schizophrenia spectrum psychosis and fifty healthy controls underwent structural magnetic resonance imaging. The gray matter volumes of emotion recognition areas such as the bilateral caudal anterior cingulate cortex, rostral anterior cingulate cortex, fusiform gyrus, insula, amygdala, and hippocampus, were compared between patients and controls. Emotional recognition levels and symptom severities were examined. Group analysis showed that the gray matter volumes of the patients were significantly smaller in left hippocampus and fusiform gyrus compared with healthy controls. A correlation analysis revealed that larger left fusiform gyrus volume was associated with better facial emotion recognition and emotional intensity recognition in patients with schizophrenia spectrum psychosis. Additionally, left fusiform gyrus volumes showed a significant negative correlation with the negative symptom scores at baseline. These findings suggest that gray matter abnormalities in the left fusiform gyrus are associated with impaired social emotion recognition and severity of negative symptoms at baseline in patients with schizophrenia spectrum psychosis.

Behind the opaque curtain: A 20-year longitudinal study of dissociative and first-rank symptoms in schizophrenia-spectrum psychoses, other psychoses and non-psychotic disorders

BackgroundDepersonalization and derealization are currently considered diagnostically distinct from first-rank symptoms (FRS) seen in schizophrenia-spectrum psychoses. Nevertheless, the lived experiences of these symptoms can be very similar phenomenologically. AimsTo investigate the interrelationships between depersonalization, derealization and FRS in individuals with different types of psychotic and non-psychotic diagnoses. MethodsThe Chicago Follow-up Study was a prospective longitudinal research program designed to study psychopathology and recovery in psychiatric disorders consisting of 555 participants, who were recruited at index hospitalization and studied over six follow-up timepoints at approximately 2, 4.5, 7.5, 10, 15, and 20 years later. The primary clinical indices were depersonalization, derealization and Schneiderian FRS that were measured at index hospitalization and at each subsequent follow-up. Results62.8% of participants had at least four follow-ups. There were significant differences in the course and chronicity of depersonalization, derealization and first-rank symptoms across the three diagnostic groups. For the whole sample, derealization was significantly associated with FRS at 2-, 4.5- and 7.5-year follow-up timepoints whereas depersonalization was related to FRS from 10-year follow-up to 20-year follow-up. In participants with schizophrenia, overall depersonalization was more often associated with passivity phenomena whereas derealization was more often associated with overall delusions. There was also a significant effect of time on the associations between depersonalization, derealization and FRS across follow-ups. ConclusionsDepersonalization and derealization should be viewed as transdiagnostic phenomena that are associated with FRS psychopathology along a continuum, although they are more closely associated with schizophrenia-spectrum psychoses.

Lateralized evoked responses in parietal cortex demonstrate visual short-term memory deficits in first-episode schizophrenia

Working memory dysfunction may be central to neurocognitive deficits in schizophrenia. Maintenance of visual information in working memory, or visual short-term memory (vSTM), is linked to general cognitive dysfunction and predicts functional outcome. Lateralized change-detection tasks afford investigation of the contralateral delay activity (CDA), a useful tool for investigating vSTM dysfunction. Previous work suggests “hyperfocusing” of attention in schizophrenia, such that CDA is increased when a single item is maintained in vSTM but reduced for multiple items. If observed early in the disease, vSTM dysfunction may be a key feature of schizophrenia or target for intervention. We investigated CDA during lateralized vSTM of one versus three items using sensor-level electroencephalography and source-level magnetoencephalography in 26 individuals at their first episode of schizophrenia-spectrum psychosis (FESz) and 26 matched healthy controls. FESz were unable to modulate CDA with increased memory load – high-load CDA was reduced and low-load CDA was increased compared to controls. Further, sources of CDA in posterior parietal cortex were reduced in FESz and indices of working memory were correlated with neurocognitive deficits and symptom severity. These results support working memory maintenance dysfunction as a central and early component to the disorder. Targeted intervention focusing on vSTM deficits may be warranted to alleviate downstream effects of this disability.

Naturalistic follow-up study of rehospitalization rates and assigned disability status of patients with first-episode schizophrenia spectrum psychosis in South East Latvia: preliminary results

Background Patients with first-episode schizophrenia spectrum psychosis (FEP) are at risk of not visiting an out-patient psychiatrist and are assigned disability status within a short period after diagnosis. Objective The aim of this study was to conduct a naturalistic follow-up of FEP patients to explore their use of mental healthcare services and the rate of assigned disability status after FEP. Methods This was the first study in Latvia to include all consecutive patients with FEP admitted to the largest regional hospital in South East Latvia, Daugavpils Psychoneurological Hospital (DPNH). Patients received standard treatment in a real-world environment. The mean follow-up time was 33 months (Min = 20 months, Max = 40 months). Results From the 94 consecutive FEP patients admitted to DPNH (1 January 2016 to 31 December 2017), 68 participated and provided informed consent to be followed up. During the first 12 months after discharge from the acute psychiatric ward, 23% (n = 14) never visited a psychiatrist, and 6.5% (n = 4) had a single visit to get prescription for medication. Furthermore, 36.1% (n = 22) had a rehospitalization during the first 12 months. At the end of follow-up period, 34.4% (n = 21) of patients were assigned disability status within a median time of 8 months (IQR 4.5‒20.0). Conclusion Approximately, one-third of patients did not continue treatment as out-patients after FEP. One-third of FEP patients were assigned disability status. We suggest that Latvia needs improved treatment options for FEP patients, such as early intervention.

Mismatch Negativity and Impaired Social Functioning in Long-Term and in First Episode Schizophrenia Spectrum Psychosis.

Mismatch negativity (MMN) is elicited by infrequent physical parameter sound changes. MMN to pitch-deviants (pMMN) and duration-deviants (dMMN) are severely reduced in long-term schizophrenia (Sz). Although symptom factors (positive, negative, cognitive) are inconsistently associated with MMN amplitude in Sz, several studies have shown smaller dMMN is associated with impaired social functioning in Sz. MMN is less reduced at the first psychotic episode in the schizophrenia spectrum (FESz). Meta-analyses demonstrate that pMMN is not reduced, while dMMN is moderately impaired. Correlations of pMMN and dMMN with symptom factors in FESz are also equivocal. Associations with social functioning have not been reported. FESz and matched controls (n = 40/group), and Sz and matched controls (n = 50/group) were assessed for baseline and current cognitive functioning, symptoms, and social functioning, and pMMN and dMMN were recorded. Sz showed reductions in pMMN (p = 0.001) and dMMN (p = 0.006) amplitude. By contrast, pMMN (p = 0.27) and dMMN (p = 0.84) were not reduced in FESz. However, FESz showed associations between both MMNs and negative symptoms and social functioning. More impaired MMNs in FESz were associated with increased negative symptoms and impaired social functioning, both current and in the year prior to the emergence of psychosis. These data suggest that the extent of pathological process occurring before first psychosis as reflected in compromised social behavior prior to first break and reduced interpersonal communication and increased alogia at first break is indexed by pMMN and dMMN, putative biomarkers of disease progression sensitive to functional impairment.

Uncinate fasciculus white matter connectivity related to impaired social perception and cross-sectional and longitudinal symptoms in patients with schizophrenia spectrum psychosis

Dysfunctional social-emotional perception in patients with schizophrenia can result in adverse clinical symptoms and poorer long-term outcomes. The white matter tracts that interact among a number of brain regions have an important role to play. However, few neuroimaging studies focus on the effects of white matter connectivity on social-emotional perception in schizophrenia and its impact on patients’ clinical symptoms and long-term outcomes.Forty-one patients with schizophrenia spectrum psychosis and 42 healthy controls underwent structural magnetic resonance imaging. The white matter fractional anisotropy values of the emotion recognition areas, the bilateral anterior thalamic radiation, inferior longitudinal fasciculus, cingulum bundle, superior longitudinal fasciculus, and uncinate fasciculus were compared between patients with schizophrenia spectrum psychosis and healthy controls. Social-emotional perception levels and symptom severity at baseline and after 1 year were examined.A group analysis showed that white matter connectivity was significantly lower in the bilateral anterior thalamic radiation, cingulum bundle, right inferior longitudinal fasciculus, and uncinate fasciculus of patients with schizophrenia spectrum psychosis compared to the healthy controls. Contrastingly, a correlation analysis revealed that larger right uncinate fasciculus fractional anisotropy values were associated with lower social-emotional perception levels in patients with schizophrenia spectrum psychosis. Additionally, the white matter fractional anisotropy values of the right uncinate fasciculus showed a significant positive correlation with the severity of positive symptoms at baseline and with poor outcomes after 1 year.The findings of the present study suggest that impaired social-emotional perception in patients with schizophrenia spectrum psychosis is associated with larger white matter connectivity of the uncinate fasciculus, which is also associated with more severe symptoms at baseline and after 1-year. These results suggest that the uncinate fasciculus could affect the pathophysiology of schizophrenia.

T106. CHILDHOOD TRAUMA IS ASSOCIATED WITH THEORY OF MIND IMPAIRMENT IN SCHIZOPHRENIA-SPECTRUM PSYCHOSIS

BackgroundChildhood trauma (CT), a generic term encompassing experiences of severe abuse and neglect during childhood and adolescence, has been established as an important risk factor for the emergence of psychosis. Among the potential pathways involved in the CT-psychosis association, Theory of Mind (ToM) disruption holds a central position. ToM reflects the ability to attribute distinct mental states to oneself and other people, and correctly infer the beliefs, wishes, intentions and dispositions of others in order to predict their behavior and produce proper social responses. ToM is further elaborated in 1st order ToM (ToM1: the ability to understand that someone may hold a false belief about the state of the world) and 2nd order ToM (ToM2: the ability to understand that one person may hold a false belief about the belief of another person). Research shows that patients with schizophrenia-spectrum psychosis (SSP) exhibit marked deficits in ToM. CT may increase SSP risk by disrupting the emergence of normal ToM skills, thus inducing a vulnerability for cognitive errors, perceptual aberrations and impaired reality testing. Our study sought to explore the effect of CT on ToM performance in a group of SSP patients and a healthy control group (HC).MethodsWe compared 63 SSP patients to a healthy control group on measures of CT and ToM. CT (presence of parental antipathy, parental neglect, physical abuse, sexual abuse) was assessed with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q). ToM1 and ToM2 performance was measured with the Perception of Social Inference Test (PESIT). Chi-squared analysis was performed to compare CT rates between SSP patients and HCs. Mann-Whitney U tests were employed to detect differences in ToM between the two groups. Within each group, the impact of CT and polytraumatization (accumulation of different CT types) on ToM performance was examined.ResultsSSP patients displayed significantly higher CT rates (χ2 (1, N = 124) = 34.5, p < .001) and worse ToM performance (ToM1: U = 653,5, p < .001; ToM2: U = 435,5, p < .001) than HCs. SSP inpatients were 11.6 times more likely to have been exposed to severe CT than HCs. Within the SSP group, CT was associated with increased ToM2 deficits (U = 259, p = .020), while polytraumatization was negatively correlated to both ToM1 (rs = -.297, p = .020) and ToM2 (rs = -.341, p = .007) performance. Maternal antipathy (U = 207, p = .036) and neglect (U = 148, p = .017) were the CT subtypes associated with worse ToM2 performance. No similar effects were detected within the HC group.DiscussionOur finding of ToM deficits in SSP patients may indicate a bidirectional association, involving on the one hand a negative effect of psychotic illness on ToM skills, and on the other hand a vulnerability towards psychosis induced by severe, early disruptions in normal ToM acquisition. Worse ToM performance in SSP patients with cumulative CT may signify an additive or synergistic effect of CT and psychosis on ToM skills. The involvement of maternal antipathy and neglect in the aforementioned association highlights the pivotal role of the mother in the development of the child’s capacity to envision distinct mental states in self and others, a prerequisite for self-awareness and self-other individuation. The failure to detect similar effects in HCs may be attributed to the low frequency of CT in this group, potentially restricting the strength of this analysis. On the same matter, another explanation could be that CT by itself is not a sufficient condition for ToM impairment, and only becomes relevant when it acts in synergy with other harmful processes inherent in psychosis.

S242. BEFORE AND AFTER: PATHWAYS TO CARE AND AFTER DISCHARGE AT A NEWLY ESTABLISHED EARLY PSYCHOSIS INPATIENT UNIT

BackgroundThe duration from onset of psychotic symptoms to appropriate treatment also includes pathways to adequate care centers. Treatment delays within health care services might influence overall outcome of patients experiencing a first episode psychosis (FEP) negatively. In addition, subsequent postdischarge care is an essential part of maintaining treatment and therefore crucial for relapse prevention. This study aimed to examine pathways to specialized early intervention inpatient care and recommendations relating postdischarge care among patients with FEP at a newly established early psychosis inpatient unit within a general psychiatric service in a general hospital.MethodsData of all patients admitted to the early psychosis inpatient unit of the Clinical Division of Social Psychiatry of the Medical University of Vienna from 01.01.2016 to 31.03. 2017 were analysed. The unit was established in 2014. Diagnoses of FEP include first episode of schizophreniform, acute polymorphic, affective, organic or substance-related psychosis according to ICD-10.ResultsIn the given period a total of 127 patients were admitted, whereof 91 (= 71,7%) were diagnosed with a psychotic disorder at time of discharge. Among them 36 (= 39,6%) patients had a first episode psychosis, including 21 (58,3%) with schizophrenia spectrum psychosis, 10 (27,8%) with affective psychosis, 4 (11,1%) with substance-related psychosis and 1 (2,8%) with organic psychosis as main diagnosis at time of discharge. The mean age of FEP patients was 26.7 years (SD 10,4), with no significant differences concerning sex distribution (52,8% male, 47,2% female). For the majority of FEP patients, namely 23 (63,9%) referral was done through the acute psychiatric outpatient clinic. 4 (11,1%) patients were assigned by the specialized early psychosis outpatient clinic of the same department and 3 (8,3%) by mental health professionals in private practice. The other 5 (13,9%) FEP patients were transferred from either non-psychiatric or psychiatric inpatient units. The largest proportion of FEP patients (91,7%, n = 36) were discharged to secondary care, of those 16 (44,4%) to psychosocial outpatient services. 3 (8,3%) patients were assigned to day-care hospital.DiscussionOur results show that shortly after the establishment of an early psychosis inpatient unit within a general psychiatric service most referrals involved the acute psychiatric outpatient clinic. Hence, information on the availability and specialization was communicated adequately within the rest of the psychiatric staff. The comparatively low proportion of referrals from the early psychosis outpatient clinic might be related to the fact that it focusses on clinical high risk states, who might not be in need of inpatient treatment as much as FEP patients. To ensure pathways to specialized early psychosis care without delay raising awareness of early recognition within the psychiatric staff is required. Reported results concerning discharge recommendations imply that in most cases sufficient psychopathological stability for subsequent outpatient care was achieved. Furthermore, the high rate of referrals to secondary care might reflect the mental health service structure with specialized low threshold services in Vienna, Austria.

S102. DIAGNOSTIC CHALLENGES AT TIME OF INPATIENT ADMISSION: DIAGNOSTIC SHIFTS IN PATIENTS WITH FIRST EPISODE PSYCHOSIS

BackgroundFirst episode psychoses (FEP) may present with diffuse symptoms and a broad range of clinical phenotypes, leading to difficulties in the early detection of the different pluripotent trajectories and consequently to instability of the diagnoses. The aim of this study was to assess the stability of diagnoses at time of admission compared to discharge in patients with FEP at a newly established early psychosis inpatient unit within a general psychiatric service in a general hospital.MethodsCharts of all patients admitted to the early psychosis inpatient unit of the Clinical Division of Social Psychiatry of the Medical University of Vienna between 01.01.2016 and 31.03.2017 were reviewed. FEP was defined as a first presentation of affective, schizophreniform, acute polymorphic, organic or substance-related psychosis according to ICD-10.Results127 patients were admitted during the said period, among whom 92 (72,4%) were diagnosed with a psychotic disorder at time of admission. 39,1% (n=36) of those had a FEP, whereof 58,3% (n=21) were diagnosed with schizophrenia spectrum psychosis, 27,8% (n=10) with affective psychosis, 11,1% (n=4) with substance-related psychosis and 2,8% (n=1) with organic psychosis as main diagnosis at time of discharge. In 50% (n=18) of FEP patients, diagnosis at time of admission was not maintained. 54,2% (n=13) of FEP patients who were admitted with a schizophrenia spectrum diagnosis had a shift in diagnosis at time of discharge, whereof 46,2% (n=6) were adjusted to another diagnosis of the same spectrum and 53,8% (n=7) to a diagnosis of either affective spectrum, substance-related psychosis or organic psychosis. 100% (n=2) of those with a persistent delusional disorder had a different diagnosis at discharge, as well as 56,3% (n=9=) of those admitted with a diagnosis of acute and transient psychotic disorders. Changes in the admission diagnoses of affective psychosis were necessary in 44,4% (n=4), whereof one half was adjusted to another diagnosis of the same spectrum and the other half to a diagnosis of the schizophrenia spectrum.DiscussionThe diagnostic instability in this study underlines the concept of the highly dynamic and changeable nature of psychopathology in the early stages and the pluripotent trajectories of psychosis. Furthermore, inadequate information available for specific diagnosis at time of admission as well as diagnostic uncertainty at the onset of psychosis could be implicated in the described diagnostic instability. The broad range of clinical phenotypes of early psychosis and the limitations of current diagnostic risk and identification approaches for the assessment of first episode psychosis indicate psychopathology conformed to a more dimensional rather than categorical model, as well as the need of a more dynamic model of prediction, such as the clinical staging model.

M145. ALTERED SUBCORTICAL EMOTIONAL SALIENCE PROCESSING AND A ‘JUMPING TO CONCLUSIONS’ BIAS IN PARKINSON’S PATIENTS WITH PSYCHOTIC SYMPTOMS

BackgroundCurrent research does not provide a clear explanation for why some patients with Parkinson’s Disease (PD) develop psychotic symptoms. In schizophrenia research the ‘aberrant salience hypothesis’ of psychosis has been influential in explaining the development of psychotic symptoms. The theory proposes that dopaminergic dysregulation leads to inappropriate attribution of salience to otherwise irrelevant or non-informative stimuli, facilitating the formation of hallucinations and delusions, by providing irrational explanations. However, this theory has received very limited attention in the context of PD-psychosis.MethodsIn the study, we investigated salience processing in 14 PD-patients with psychotic symptoms, 23 PD-patients without psychotic symptoms and 19 healthy controls. All patients received dopaminergic medication. There was no difference in the medication dose between the two patient groups. We examined emotional salience using a visual oddball fMRI paradigm that has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow (arterial spin labelling fMRI). Furthermore, a subgroup of the two patient groups complete a behavioural ‘jumping to conclusions’ task.ResultsWe found significant differences in brain responses to emotional salience between the two patient groups. PD-patients with psychotic symptoms revealed enhanced brain responses in the striatum, the hippocampus and the amygdala compared to patients without psychotic symptoms. PD-patients with psychotic symptoms showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores. Furthermore, our data provide first indications for dysfunctional top-down processes, measured in a ‘jumping to conclusions’ bias.DiscussionOur study suggests that enhanced signalling in the striatum, hippocampus and amygdala together with deficient top-down cognitive regulations is associated with the development of psychotic symptoms in PD, similarly to that proposed in the ‘aberrant salience hypothesis’ of psychosis in schizophrenia.

Pitch and Duration Mismatch Negativity and Heschl's Gyrus Volume in First-Episode Schizophrenia-Spectrum Individuals.

Background. The mismatch negativity (MMN) brainwave indexes novelty detection. MMN to infrequent pitch (pMMN) and duration (dMMN) deviants is reduced in long-term schizophrenia. Although not reduced at first psychosis, pMMN is inversely associated with left hemisphere Heschl's gyrus (HG) gray matter volume within 1 year of first hospitalization for schizophrenia-spectrum psychosis, consistent with pathology of left primary auditory cortex early in disease course. We examined whether the relationship was present earlier, at first psychiatric contact for psychosis, and whether the same structural-functional association was apparent for dMMN. Method. Twenty-seven first-episode schizophrenia-spectrum (FESz) and 27 matched healthy comparison (HC) individuals were compared. EEG-derived pMMN and dMMN were measured by subtracting the standard tone waveform (80%) from the pitch- and duration-deviant waveforms (10% each). HG volumes were calculated from T1-weighted structural magnetic resonance imaging using Freesurfer. Results. In FESz, pMMN amplitudes at Fz were inversely associated with left HG (but not right) gray matter volumes, and dMMN amplitudes were associated significantly with left HG volumes and at trend-level with right HG. There were no structural-functional associations in HC. Conclusions. pMMN and dMMN index gray matter reduction in left hemisphere auditory cortex early in psychosis, with dMMN also marginally indexing right HG volumes. This suggest conjoint functional and structural pathology that affects the automatic detection of novelty with varying degrees of penetrance prior to psychosis. These brainwaves are sensitive biomarkers of pathology early in the psychotic disease course, and may serve as biomarkers of disease progression and as therapeutic outcome measures.

Psychosis in Parkinson's disease and parkinsonism in antipsychotic-naive schizophrenia spectrum psychosis: clinical, nosological and pathobiological challenges.

Following the formulation of operational criteria for the diagnosis of psychosis in Parkinson’s disease, a neurodegenerative disorder, the past decade has seen increasing interest in such nonmotor psychopathology that appears to be independent of dopaminergic therapy. Similarly, there has been a resurgence of interest in motor aspects of the neurodevelopmental disorder of schizophrenia, including spontaneous parkinsonism that appears to be independent of antipsychotic treatment. This review first addresses the clinical and nosological challenges of these superficially paradoxical insights and then considers pathobiological challenges. It proposes that diverse modes of disturbance to one or more element(s) in a cortical-striatal-thalamocortical neuronal network, whether neurodegenerative or neurodevelopmental, can result in movement disorder, psychosis or both. It then proposes that time- and site-dependent dysfunction in such a neuronal network may be a generic substrate for the emergence of psychosis not only in Parkinson’s disease and schizophrenia-spectrum disorders but also in other neuropsychiatric disorders in which psychosis, and sometimes movement disorders, can be encountered; these include substance abuse, cerebrovascular disease, cerebral trauma, cerebral neoplasia, epilepsy, Huntington’s disease, frontotemporal dementia, Alzheimer’s disease and multiple sclerosis.

Developmental Genes and Regulatory Proteins, Domains of Cognitive Impairment in Schizophrenia Spectrum Psychosis and Implications for Antipsychotic Drug Discovery: The Example of Dysbindin-1 Isoforms and Beyond.

Alongside positive and negative symptomatology, deficits in working memory, attention, selective learning processes, and executive function have been widely documented in schizophrenia spectrum psychosis. These cognitive abnormalities are strongly associated with impairment across multiple function domains and are generally treatment-resistant. The DTNBP1 (dystrobrevin-binding protein-1) gene, encoding dysbindin, is considered a risk factor for schizophrenia and is associated with variation in cognitive function in both clinical and nonclinical samples. Downregulation of DTNBP1 expression in dorsolateral prefrontal cortex and hippocampal formation of patients with schizophrenia has been suggested to serve as a primary pathophysiological process. Described as a “hub,” dysbindin is an important regulatory protein that is linked with multiple complexes in the brain and is involved in a wide variety of functions implicated in neurodevelopment and neuroplasticity. The expression pattern of the various dysbindin isoforms (-1A, -1B, -1C) changes depending upon stage of brain development, tissue areas and subcellular localizations, and can involve interaction with different protein partners. We review evidence describing how sequence variation in DTNBP1 isoforms has been differentially associated with schizophrenia-associated symptoms. We discuss results linking these isoform proteins, and their interacting molecular partners, with cognitive dysfunction in schizophrenia, including evidence from drosophila through to genetic mouse models of dysbindin function. Finally, we discuss preclinical evidence investigating the antipsychotic potential of molecules that influence dysbindin expression and functionality. These studies, and other recent work that has extended this approach to other developmental regulators, may facilitate identification of novel molecular pathways leading to improved antipsychotic treatments.

Altered subcortical emotional salience processing differentiates Parkinson's patients with and without psychotic symptoms.

Current research does not provide a clear explanation for why some patients with Parkinson's Disease (PD) develop psychotic symptoms. The 'aberrant salience hypothesis' of psychosis has been influential and proposes that dopaminergic dysregulation leads to inappropriate attribution of salience to irrelevant/non-informative stimuli, facilitating the formation of hallucinations and delusions. The aim of this study is to investigate whether non-motivational salience is altered in PD patients and possibly linked to the development of psychotic symptoms. We investigated salience processing in 14 PD patients with psychotic symptoms, 23 PD patients without psychotic symptoms and 19 healthy controls. All patients were on dopaminergic medication for their PD. We examined emotional salience using a visual oddball fMRI paradigm that has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow as assessed with arterial spin labelling fMRI. We found significant differences between patient groups in brain responses to emotional salience. PD patients with psychotic symptoms had enhanced brain responses in the striatum, dopaminergic midbrain, hippocampus and amygdala compared to patients without psychotic symptoms. PD patients with psychotic symptoms showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores. Our study suggests that enhanced signalling in the striatum, dopaminergic midbrain, the hippocampus and amygdala is associated with the development of psychotic symptoms in PD, in line with that proposed in the 'aberrant salience hypothesis' of psychosis in schizophrenia.

Implementing the Latvian Early Intervention Program (LAT-EIP) for Patients With Schizophrenia Spectrum First-Episode Psychosis: Study Protocol.

Background: Patients with first-episode psychosis are mainly young people in the active phase of their social and professional lives, and psychosis is a serious disruption of normal life with high risk of disability. Integrated biopsychosocial early intervention treatment is crucial for patients with first-time psychosis episode. The purpose of this trial is to adapt the first early intervention program for patients with first-time non-affective psychosis in Latvia, and to investigate whether it is possible to integrate this kind of treatment approach in the frame of existing services and whether it provides better outcomes for patients than existing services. Design/Methods: The study has a nonrandomized controlled design in a real-life environment. Participants are all consecutive patients presenting in the psychiatric emergency room with first-time non-affective schizophrenia spectrum psychosis episode (ICD criteria F23, F20) from a catchment area of 262,541 inhabitants, with urban and rural regions. The Latvian Early Intervention Program is a 6-month program developed from existing treatment guidelines and recommendations and adapted to a low-resource environment, integrated in an existing outpatient unit. This study aimed to test the hypothesis that the patients who received intervention have milder symptoms, higher functioning, and better adherence to outpatient treatment. The study primary aims are: 1) to establish and examine in practice the adapted early intervention for patients with first schizophrenia spectrum psychosis; 2) compare clinical and functional outcomes (including occupation, housing, and social relationships) between intervention treatment and standard treatment; and 3) compare the number of rehospitalizations, adherence to outpatient treatment, and assigned disability. Secondary aims are: 1) to compare full recovery status in both treatment groups at 12 months follow-up and 2) to develop recommendations for establishing early intervention programs in limited resource settings. Discussion/Conclusions: Across the world, there is wide inequality in the availably and accessibility to early intervention treatment. This study will increase our knowledge in early intervention treatment approach and outcomes for patients with schizophrenia spectrum first psychosis episode in real-life working clinical practices. We hope to provide theoretical and practical aspects to develop strategies for early intervention service implementation in limited resource mental healthcare settings.

Non-negative Matrix Factorization Reveals Resting-State Cortical Alpha Network Abnormalities in the First-Episode Schizophrenia Spectrum

BackgroundLittle is known about neural oscillatory dynamics in first-episode psychosis. Pathophysiology of functional connectivity can be measured through network activity of alpha oscillations, reflecting long-range communication between distal brain regions. MethodsResting magnetoencephalographic activity was collected from 31 individuals with first-episode schizophrenia spectrum psychosis and 22 healthy control individuals. Activity was projected to the realistic cortical surface, based on structural magnetic resonance imaging. The first principal component of activity in 40 Brodmann areas per hemisphere was Hilbert transformed within the alpha range. Non-negative matrix factorization was applied to single-trial alpha phase-locking values from all subjects to determine alpha networks. Within networks, energy and entropy were compared. ResultsFour cortical alpha networks were pathological in individuals with first-episode schizophrenia spectrum psychosis. The networks involved the bilateral anterior and posterior cingulate; left auditory, medial temporal, and cingulate cortex; right inferior frontal gyrus and widespread areas; and right posterior parietal cortex and widespread areas. Energy and entropy were associated with the Positive and Negative Syndrome Scale total and thought disorder factors for the first three networks. In addition, the left posterior temporal network was associated with positive and negative factors, and the right inferior frontal network was associated with the positive factor. ConclusionsMachine learning network analysis of resting alpha-band neural activity identified several aberrant networks in individuals with first-episode schizophrenia spectrum psychosis, including the left temporal, right inferior frontal, right posterior parietal, and bilateral cingulate cortices. Abnormal long-range alpha communication is evident at the first presentation for psychosis and may provide clues about mechanisms of dysconnectivity in psychosis and novel targets for noninvasive brain stimulation.

Preventing Suicide Begins With Regular Assessments

Preventing Suicide Begins With Regular Assessments

The role of attachment anxiety in the relationship between childhood trauma and schizophrenia-spectrum psychosis

Childhood trauma (CT) is a comprehensive concept encompassing experiences of sexual, physical, and emotional abuse, and neglect during childhood and adolescence. Patients with schizophrenia-spectrum psychosis (SSP) display higher rates of CT than healthy controls. Among the potential mediators of this association, insecure attachment has gained attention and empirical validation. The present study aimed to extend existing knowledge on this field by exploring the role of the two attachment dimensions, attachment anxiety and attachment avoidance, in the CT-SSP association. A clinical sample of 63 SSP inpatients was compared to a healthy control group on CT and attachment style measures. Correlations between CT, attachment dimensions and psychopathology were sought. Mediation analyses were also performed to examine whether attachment anxiety and/or attachment avoidance mediated the CT-SSP association. Patients displayed higher rates of CT and insecure attachment than controls. Attachment anxiety and severity of Mother Antipathy were linked to severity of hallucinations. Attachment anxiety was recognized as the sole mediator of the CT-SSP association. Our findings suggest that individuals with severe CT and increased attachment anxiety represent a risk population warranting early clinical attention, regular monitoring and tailored therapeutic interventions aimed at reducing the psychological impact of trauma.

From Computation to the First-Person: Auditory-Verbal Hallucinations and Delusions of Thought Interference in Schizophrenia-Spectrum Psychoses.

Schizophrenia-spectrum psychoses are highly complex and heterogeneous disorders that necessitate multiple lines of scientific inquiry and levels of explanation. In recent years, both computational and phenomenological approaches to the understanding of mental illness have received much interest, and significant progress has been made in both fields. However, there has been relatively little progress bridging investigations in these seemingly disparate fields. In this conceptual review and collaborative project from the 4th Meeting of the International Consortium on Hallucination Research, we aim to facilitate the beginning of such dialogue between fields and put forward the argument that computational psychiatry and phenomenology can in fact inform each other, rather than being viewed as isolated or even incompatible approaches. We begin with an overview of phenomenological observations on the interrelationships between auditory-verbal hallucinations (AVH) and delusional thoughts in general, before moving on to review several theoretical frameworks and empirical findings in the computational modeling of AVH. We then relate the computational models to the phenomenological accounts, with a special focus on AVH and delusions that involve the senses of agency and ownership of thought (delusions of thought interference). Finally, we offer some tentative directions for future research, emphasizing the importance of a mutual understanding between separate lines of inquiry.