Imagery-Focused Therapy for Visual Hallucinations: A Case Series.

INTRODUCTION: Visual hallucinations (VH) are more common than previously thought and are linked to higher levels of distress and disability in people with a psychotic illness. Despite this, scant attention has been given to VHs in the clinical literature, and the few therapy case series of cognitive behavioural therapy (CBT) published to date have not demonstrated reliable change. In other areas of clinical research, problematic mental imagery has been found to be more strongly related to negative affect in psychological disorders than negative linguistic thinking, and imagery focused techniques have commonly been found to improve the outcomes in CBT trials. Given VHs have many similarities with visual mental imagery and many of the distressing beliefs associated with VHs targeted in CBT are maintained by accompanying mental imagery (i.e., imaging a hallucinated figure attacking them), it seems plausible that an imagery-focused approach to treating VHs may be most effective. METHODS: The current study is a multiple baseline case series (N = 11) of a 10-session imagery-focused therapy for VH in a transdiagnostic sample. RESULTS: The study had good attendance and feedback, no adverse events and only one [seemly unrelated] drop-out, suggesting good feasibility, safety and acceptability. The majority of clients reported reduction on both full-scale measures (administered at 3 baselines, midtherapy, posttherapy and 3-month follow-up) and weekly measures of VH severity and distress, ranging from medium to large effect sizes. CONCLUSIONS: The case series suggests that an imagery-focused approach to treating VHs may be beneficial, with a recommendation for more rigorous clinical trials to follow.

Guiding Ethical Decisions in Cochlear Implantation for the Hearing Impaired with Comorbid Psychosis.

AbstractCochlear implants can restore hearing in people with severe hearing loss and have a significant impact on communication, social integration, self-esteem, and quality of life. However, whether and how much clinical benefit is derived from cochlear implants varies significantly by patient and is influenced by the etiology and extent of hearing loss, medical comorbidities, and preexisting behavioral and psychosocial issues. In patients with underlying psychosis, concerns have been raised that the introduction of auditory stimuli could trigger hallucinations, worsen existing delusions, or exacerbate erratic behavior. This concern has made psychosis a relative contraindication to cochlear implant surgery. This is problematic because there is a lack of data describing this phenomenon and because the psychosocial benefits derived from improvement in auditory function may be a critical intervention for treating psychosis in some patients. The objective of this report is to provide an ethical framework for guiding clinical decision-making on cochlear implant surgery in the hearing impaired with psychosis.

Impairment of olfactory identification ability in ultra-high risk for psychosis and drug-naïve first episode psychosis.

OBJECTIVE: Patients with psychotic diseases have been reported to exhibit abnormalities in their olfactory discrimination. These alterations have also been identified in people at high genetic or clinical risk for psychosis, suggesting olfactory discrimination dysfunction may be a potential risk factor for developing psychosis. Thus, the purpose of our study is to explore the difference in olfactory discrimination ability in the prosal stage and early stage of psychosis and to explore the potential risk factor of developed psychosis. METHODS: We compared olfactory identification and cognitive function in 89 ultra-high-risk (UHR) individuals, 103 individuals with Drug-naïve first-episode schizophrenia (FES), 81 genetic high-risk (GHR) individuals, and 97 healthy controls (HC). Additionally, we compared olfactory identification and cognitive function between two groups; UHR individuals who later transitioned to psychosis (UHR-T; n = 33) and those who did not transition (UHR-NT; n = 42)). Furthermore, we analyzed the correlations between olfactory discrimination ability and cognitive function and symptoms and compared the olfactory function between men and women. RESULTS: Patients with first-episode schizophrenia (FES) and those at ultra-high risk (UHR) for psychosis exhibited more significant deficits in olfactory identification than healthy controls (HC), while no differences in olfactory identification dysfunction were observed between the genetic high risk (GHR) and HC groups. Notably, individuals in the UHR group who later developed psyhchosis displayed a steeper marked decline in their baseline olfactory identification ability than that of those in the UHR group who did not develop psychosis. Cognitive dysfunction is widely observed in both the FES and UHR groups, with a distinct correlation identified between olfactory discrimination function and cognitive performance. Finally, overall, women exhibit significantly superior olfactory function than men. CONCLUSION: In conclusion, these findings suggest that impairment of olfactory identification exists in the early stage of psychosis. Olfactory identification dysfunction may therefore be a potential marker of predicting the transition to schizophrenia.

Exploring Psychosis in Neurodegenerative Dementia: Connecting Symptoms to Neurobiology.

The following commentary discusses a review by Cressot et al. entitled: 'Psychosis in Neurodegenerative Dementias: A Systematic Comparative Review'. The authors describe the epidemiology and phenomenology of psychosis across neurodegenerative dementias. Dementia with Lewy bodies had the highest reported prevalence of psychosis at 74% followed by Alzheimer's disease, 54% and frontotemporal degeneration, 42%. Detailed characterization of psychosis shows differences in the types of hallucinations and delusions by dementia type. These findings suggest that different types of dementia related pathology are associated with high rates of psychosis with more specific symptom profiles than previously appreciated. Understanding the differences and variety of psychotic experiences across dementia types may have diagnostic and therapeutic implications for treating hallucinations and delusions in populations suffering from neurodegenerative diseases.

Repetitive transcranial magnetic stimulation can improve negative symptoms and/or neurocognitive impairments in the first psychosis episode: A randomized controlled trial.

OBJECTIVE: Negative symptoms and neurocognitive impairments in psychosis correlate with their severity. Currently, there is no satisfactory treatment. We aimed to evaluate and compare the effects of repetitive transcranial magnetic stimulation(rTMS) on negative symptoms and neurocognitive impairments in patients in first-episode of psychosis(FEP) in a randomized controlled trial(RCT). METHOD: This is a single-site RCT of 85 patients with FEP. Patients were randomized to receive a 4-week course of active(n = 45) or sham rTMS(n = 40). Factor analysis was applied to a cross-sectional dataset of 744 FEP patients who completed negative symptom evaluation and neurocognitive battery tests. Two independent dimensions were generated and used for the K-means cluster analysis to produce sub-clusters. rTMS of 1-Hz was delivered to the right orbitofrontal(OFC) cortex. RESULTS: Two distinct dimensional factors of neurocognitive functions(factor-1) and negative symptoms(factor-2), and three clusters with distinctive features were generated. Significant improvements in factor-1 and factor-2 were observed after 4-weeks of rTMS treatment in both the active and sham rTMS groups. The repeated-measures analysis of variance revealed a significant effect of time×group(F = 5.594, p = 0.021, η2 = 0.073) on factor-2, but no effect of time×group on factor-1. Only improvements in negative symptoms were significantly different between the active and sham rTMS groups(p = 0.028). Patients in cluster-3 characterized by extensive negative symptoms, showed greater improvement in the active rTMS group than in the sham rTMS group. CONCLUSIONS: The 1-Hz right OFC cortex rTMS is more effective in reducing negative symptoms than neurocognitive impairments. It is especially effective in patients with dominantly negative symptoms in FEP.

[Functional hypercortisolism in mental disorder - association with psychopathological manifestations and course of the disease]. / Funktsional'nyi giperkortitsizm pri psikhicheskom rasstroistve ­ assotsiatsiya s psikhopatologicheskimi proyavleniyami i techeniem zabolevaniya.

The article presents a case of a long-term mental disorder in a 35-year-old woman with a persistent laboratory-confirmed increase in cortisol levels, without clinical manifestations of hypercortisolism. The first signs of mental illness appeared at the age of 14; over the past 8 years, the disease has been continuous and manifests itself in the form of a predominantly depressive state with increasing severity and complication of symptoms. Throughout all the years of the disease, active psychopharmacotherapy was carried out, combinations of antidepressants with antipsychotics and mood stabilizers were used, but no pronounced effect was achieved. Inpatient treatment in the clinic of the Mental Health Research Center for 5 months using several methods of enhancing antidepressant therapy had a good therapeutic effect and made it possible to achieve complete remission of the disease. There was a normalization of laboratory parameters of cortisol along with a decrease in the severity of pathopsychological symptoms, which indicates the genesis of hypercortisolism secondary to mental illness and its functional nature. It is assumed that hypercortisolism in this patient contributed to the formation of atypical clinical symptoms and resistance to antidepressant therapy. The discussion substantiates the need to consult a psychiatrist in case of persistent hypercortisolism in the absence of clinical manifestations of Cushing's syndrome. The detection of persistent hypercortisolism in patients with depression determines the advisability of active therapy using several tactics to enhance the effect of antidepressants.

Safety Profile of Pimavanserin Therapy in Elderly Patients with Neurodegenerative Disease-Related Neuropsychiatric Symptoms: A Phase 3B Study.

Background: Pimavanserin, a 5-HT2A receptor inverse agonist/antagonist, is the only medication approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Further expanding knowledge of the safety profile of pimavanserin in PDP and neurodegenerative diseases (NDD) such as Alzheimer's disease is of great interest for informing its use in patients with PDP (with or without dementia), given this population is highly sensitive to adverse effects following antipsychotic use. Objective: This trial evaluated the effects of pimavanserin compared to placebo in frail older adults and elderly patients with neuropsychiatric symptoms related to NDD, such as hallucinations and delusions, to better understand the safety of pimavanserin in this population. Methods: This was a phase 3b, 8-week treatment (study duration of up to 16 weeks), multicenter, randomized, double-blind, placebo-controlled, two-arm parallel-group trial (NCT03575052). The primary endpoint was safety and tolerability, measured by treatment-emergent adverse events (TEAEs). Secondary safety endpoints were change from baseline in motor and cognitive function; exploratory endpoints included suicidality, sleep quality, and neuropsychiatric symptoms. Results: Incidences of TEAEs were similar between treatment groups; 29.8% reported ≥1 TEAE (pimavanserin: 30.4%; placebo: 29.3%), and 1.8% reported serious TEAEs (pimavanserin: 2.0%; placebo: 1.5%). Pimavanserin did not impact motor- or cognitive-related function. Conclusions: Pimavanserin was well tolerated and not associated with motor or cognitive impairment. Together, these findings highlight the manageable and generally favorable safety profile of pimavanserin in patients with NDD, contributing to our knowledge on the safety of pimavanserin as it generalizes to patients with PDP.

Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity.

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. We report the first in-depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). We also explore correlations between psychotic symptoms and posterior fossa abnormalities. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms; ratings demonstrated select sex differences but no domain-wise correlations with IQ. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in psychosis-risk.

Towards a scalable approach to assess speech organization across the psychosis-spectrum -online assessment in conjunction with automated transcription and extraction of speech measures.

Automatically extracted measures of speech constitute a promising marker of psychosis as disorganized speech is associated with psychotic symptoms and predictive of psychosis-onset. The potential of speech markers is, however, hampered by (i) lengthy assessments in laboratory settings and (ii) manual transcriptions. We investigated whether a short, scalable data collection (online) and processing (automated transcription) procedure would provide data of sufficient quality to extract previously validated speech measures. To evaluate the fit of our approach for purpose, we assessed speech in relation to psychotic-like experiences in the general population. Participants completed an 8-minute-long speech task online. Sample 1 included measures of psychometric schizotypy and delusional ideation (N = 446). Sample 2 included a low and high psychometric schizotypy group (N = 144). Recordings were transcribed both automatically and manually, and connectivity, semantic, and syntactic speech measures were extracted for both types of transcripts. 73%/86% participants in sample 1/2 completed the experiment. Nineteen out of 25 speech measures were strongly (r > 0.7) and significantly correlated between automated and manual transcripts in both samples. Amongst the 14 connectivity measures, 11 showed a significant relationship with delusional ideation. For the semantic and syntactic measures, On Topic score and the Frequency of personal pronouns were negatively correlated with both schizotypy and delusional ideation. Combined with demographic information, the speech markers could explain 11-14% of the variation of delusional ideation and schizotypy in Sample 1 and could discriminate between high-low schizotypy with high accuracy (0.72-0.70, AUC = 0.78-0.79) in Sample 2. The moderate to high retention rate, strong correlation of speech measures across manual and automated transcripts and sensitivity to psychotic-like experiences provides initial evidence that online collected speech in combination with automatic transcription is a feasible approach to increase accessibility and scalability of speech-based assessment of psychosis.

Self-assessment scale of auditory verbal hallucinations (SAVH): A novel tool for patients with schizophrenia.

BACKGROUND: A scale for self-assessment of auditory verbal hallucinations (SAVH) was developed for patients, and this study aimed to validate the scale by investigating its psychometric properties. METHODS: Forty one patients with schizophrenia or schizoaffective disorders (DSM-5) self-assessed their hallucinations using nine SAVH questions. Each question was scored from 0 to 5, indicating the severity of the symptoms. Patients were also evaluated with the Brief Psychiatric Rating Scale (BPRS), Auditory Hallucination Rating Scale (AHRS), and Birchwood Insight Scale (BIS). The psychometric properties of the SAVH were assessed by the face, internal consistency, construct, convergent and discriminant validities. RESULTS: SAVH scores were used to examine the psychometric properties. Cronbach's α and Guttman's Lambda-6 were 0.67 and 0.73 respectively. Significant correlations were observed between SAVH and AHRS total scores, as well as BPRS hallucinatory behavior subscores. No significant correlations were found between total SAVH scores and (i) levels of insight or (ii) negative BPRS subscores. Factor analysis on SAVH revealed three factors accounting for 59.3 % of the variance. Most patients found the questions clear, appropriate, and of adequate length. CONCLUSIONS: SAVH demonstrated good psychometric properties, suggesting its utility in assessing auditory verbal hallucinations (AVH). This self-assessment could be valuable in evaluating AVH treatment efficacy, monitoring AVH, and empowering patients.

Anthropometry in antipsychotic-naïve first-episode psychosis patients: An exploratory approach to the role of environmental early life events in two independent samples.

BACKGROUND: Patients with schizophrenia exhibit a reduced life expectancy mainly due to medical-related pathologies which might have been initiated due to stressful events during fetal development. Indeed, intra-uterus growth patterns predict anthropometric measures in adulthood, describing risk factors for schizophrenia and metabolic disorders. We aim to evaluate anthropometric values in two cohorts of antipsychotic-naïve first-episode episode psychosis (FEP) and correlated them with surrogate markers of the fetal environment such as birth weight (BW) and season of birth. METHODS: BW, season of birth, and anthropometric values from 2 cohorts of FEP patients (Barcelona and Santander) were evaluated. In cohort B, 91 patients, and 110 controls while in cohort S, 644 and 235 were included respectively. RESULTS: Patients were shorter, slimmer, and with lower BMI compared with controls. In both cohorts, patients, and female patients born in winter displayed the shortest height. Regarding BW, height was significantly associated with the interaction of diagnosis and BW in the whole sample and the male subsample. CONCLUSIONS: Our results confirm reduced anthropometric features in FEP at onset while suggesting the influence of winter birth and BW, highlighting the role of early life events in the later outcome of FEP with sex differences.

Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer's Disease.

The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer's disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident cognitive impairment and is defined by the emergence of persistent NPSs among non-demented individuals in later life. These NPSs include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception and thought content, and social inappropriateness. Accumulating evidence has recently begun to shed more light on the genetic background of MBI, focusing on its potential association with genetic factors related to AD. The Apolipoprotein E (APOE) genotype and the MS4A locus have been associated with affective dysregulation, ZCWPW1 with social inappropriateness and psychosis, BIN1 and EPHA1 with psychosis, and NME8 with apathy. The association between MBI and polygenic risk scores (PRSs) in terms of AD dementia has been also explored. Potential implicated mechanisms include neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, and abnormal immune responses. In this review, we summarize and critically discuss the available evidence on the genetic background of MBI with an emphasis on AD, aiming to gain insights into the potential underlying neurobiological mechanisms, which till now remain largely unexplored. In addition, we propose future areas of research in this emerging field, with the aim to better understand the molecular pathophysiology of MBI and its genetic links with cognitive decline.

Prevalence and factors associated with psychosis among adults with epilepsy at a tertiary hospital in Uganda, cross-sectional study.

BACKGROUND: Psychotic disorders are prevalent among people with epilepsy compared to the general population. However, there is limited information regarding psychosis among people with epilepsy in Uganda. This study therefore determined the prevalence and associated factors of psychosis among adults with epilepsy attending Butabika National Referral Mental Hospital in Uganda. METHODS: This was a cross-sectional study involving adults with epilepsy. The diagnosis of psychosis was assessed using the Mini-International Neuropsychiatric Interview, module for Psychotic disorders. Logistic regression analysis identified factors associated with psychosis. RESULTS: Out of 250 participants, 6.8% had psychosis and 13.6% had depression. Psychosis was significantly associated with older age, greater perceived stigma and substance use. CONCLUSION: Psychosis affects nearly 7% of adults with epilepsy in Uganda especially among those who are older, with perceived stigma and substance use. Routine screening and early intervention to management of psychosis in PWE is highly recommended.

The relationship between substance use and self-reported aspects of social functioning in patients with a psychotic disorder.

BACKGROUND: In patients with a psychotic disorder, rates of substance use (tobacco, cannabis, and alcohol) are higher compared to the general population. However, little is known about associations between substance use and self-reported aspects of social functioning in patients with a psychotic disorder. METHODS: In this cross-sectional study of 281 community-dwelling patients with a psychotic disorder, linear regression models were used to assess associations between substance use (tobacco, cannabis, or alcohol) and self-reported aspects of social functioning (perceived social support, stigmatization, social participation, or loneliness) adjusting for confounders (age, gender, and severity of psychopathology). RESULTS: Compared to nonsmokers, both intermediate and heavy smokers reported lower scores on loneliness (E = -0.580, SE = 0.258, p = 0.025 and E = -0.547, SE = 0,272, p = 0.046, respectively). Daily cannabis users reported less social participation deficits than non-cannabis users (E = -0.348, SE = 0.145, p = 0.017). Problematic alcohol use was associated with more perceived social support compared to non-alcohol use (E = 3.152, SE = 1.102, p = 0.005). Polysubstance users reported less loneliness compared to no users (E = -0.569, SE = 0.287, p = 0.049). CONCLUSIONS: Substance use in patients with psychosis is associated with more favorable scores on various self-reported aspects of social functioning.

Neurophysiological treatment effects of mesdopetam, pimavanserin and clozapine in a rodent model of Parkinson's disease psychosis.

Psychosis in Parkinson's disease is a common phenomenon associated with poor outcomes. To clarify the pathophysiology of this condition and the mechanisms of antipsychotic treatments, we have here characterized the neurophysiological brain states induced by clozapine, pimavanserin, and the novel prospective antipsychotic mesdopetam in a rodent model of Parkinson's disease psychosis, based on chronic dopaminergic denervation by 6-OHDA lesions, levodopa priming, and the acute administration of an NMDA antagonist. Parallel recordings of local field potentials from eleven cortical and sub-cortical regions revealed shared neurophysiological treatment effects for the three compounds, despite their different pharmacological profiles, involving reversal of features associated with the psychotomimetic state, such as a reduction of aberrant high-frequency oscillations in prefrontal structures together with a decrease of abnormal synchronization between different brain regions. Other drug-induced neurophysiological features were more specific to each treatment, affecting network oscillation frequencies and entropy, pointing to discrete differences in mechanisms of action. These findings indicate that neurophysiological characterization of brain states is particularly informative when evaluating therapeutic mechanisms in conditions involving symptoms that are difficult to assess in rodents such as psychosis, and that mesdopetam should be further explored as a potential novel antipsychotic treatment option for Parkinson psychosis.

Epilepsy and psychosis.

Psychotic disorders are eight times more frequent in epilepsy than in the general population. The various clinical syndromes are classified according to their chronology of onset in relation to epileptic seizures: ictal psychoses (during epileptic discharge), post-ictal psychoses (PIP, after a seizure), interictal psychoses (IIP, with no chronological link) and those related to complete seizure control. Antiepileptic drugs can cause psychotic disorders in all these situations. Post-ictal psychoses (PIP) are affective psychoses that occur after a lucid interval lasting 12 to 120hours following a cluster of seizures. They last an average of 10days, with an abrupt beginning and end. PIP are directly linked to epileptic seizures, and disappear when the epilepsy is controlled. Interictal psychoses are schizophrenias. The management of psychotic disorders in epilepsy is neuropsychiatric, and requires close collaboration between epileptologists and psychiatrists. Antipsychotics can be prescribed in persons with epilepsy. Even today, psychotic disorders in epilepsy are poorly understood, under-diagnosed and under-treated.

Moral learning and positive schizotypy: Social cognitive mechanisms in psychosis- proneness.

BACKGROUND: Delusional thoughts such as paranoia and conspiratorial thinking reflect beliefs in others' intentions to do harm. Given the integral role of harm evaluation in moral cognition, a better understanding of how psychosis-prone individuals process others' moral characters may provide insights into social cognitive mechanisms of these types of delusions. METHODS: An online sample of 293 participants was drawn from the general population, using Amazon Mechanical Turk. Participants performed a moral inference task, where they predicted and judged the binary choices of two fictitious agents ("good" or "bad") to impose harm under different levels of financial incentives. An investment game involving the same agents then examined participants' trust behavior. Psychosis-proneness was measured with the Multidimensional Schizotypy Scale Brief Edition. RESULTS: A set of multiple regressions showed that positive schizotypy was associated with a lower yet more confident pre-experimental expectation of the agent's moral character, lower prediction accuracy of the agent's harm preferences, less belief revision, and undifferentiated perception of the good and bad agents' characters. Positive schizotypy was also related to higher expectations for reciprocity in the investment game, regardless of agent characters. CONCLUSION: Our findings suggest that inflexible beliefs associated with psychosis-proneness extend beyond negative prior expectations, also reflecting difficulties in moral learning. The resulting undifferentiated moral impressions might contribute to undue suspicion of benevolent individuals and increased gullibility to malicious ones, potentially further strengthening conspiratorial beliefs.