On the Optimal Diagnosis and the Evolving Role of Pimavanserin in Parkinson's Disease Psychosis.

Parkinson's disease (PD) is associated with the development of psychosis (PDP), including hallucinations and delusions, in more than half of the patient population. Optimal PD management must therefore involve considerations about both motor and non-motor symptoms. Often, clinicians fail to diagnosis psychosis in patients with PD and, when it is recognized, treat it suboptimally, despite the availability of multiple interventions. In this paper, we provide a summary of the current guidelines and clinical evidence for treating PDP with antipsychotics. We also provide recommendations for diagnosis and follow-up. Finally, an updated treatment algorithm for PDP that incorporates the use of pimavanserin, the only US FDA-approved drug for the treatment of PDP, was developed by extrapolating from a limited evidence base to bridge to clinical practice using expert opinion and experience. Because pimavanserin is only approved for the treatment of PDP in the US, in other parts of the world other recommendations and algorithms must be considered.

A case report of a patient with Turner syndrome who develops catatonia secondary to psychotic symptoms.

RATIONALE: Turner syndrome (TS) is a genetic disorder associated with partial or complete monosomy X abnormalities; some patients may have a higher risk of psychiatric symptoms. Catatonia is associated with a wide range of life-threatening complications with complex pathogenesis; However, It very rare for patients with TS to develop psychotic symptoms and eventually progress to catatonia. This case report describes the diagnostic and therapeutic course of catatonia-associated TS. PATIENT CONCERNS: In this study, we report the case of a patient with TS who initially developed sudden hallucinations, delusions, and emotional instability, followed by catatonia. DIAGNOSES: The patient was diagnosed with: unspecified catatonia; TS. INTERVENTIONS: Treatment included administering a combination of esazolam injections and olanzapine tablets, placing a gastric tube and urinary catheter, and providing nutritional support. OUTCOMES: After treatment, the patient's hallucinations, delusions, and catatonia disappeared, with no residual sequelae, and social functioning returned to normal. LESSONS: For patients with TS who present with psychotic symptoms and catatonia, a comprehensive evaluation is necessary, and treatment with antipsychotics and benzodiazepines is effective.

Juvenile neuropsychiatric systemic lupus erythematosus: A specific clinical phenotype and proposal of a probability score.

OBJECTIVE: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic auto-immune disease involving several organs. Neuropsychiatric (NP) SLE (NPSLE) is frequent in j-SLE and associated with increased morbidity/mortality. Although NPSLE classification criteria exist, attributing NP features to j-SLE remains a major challenge. The study objective is to thoroughly describe j-NPSLE patients and assist in their diagnosis. METHODS: This is a 4-year retrospective monocentric study of j-SLE patients. NP events were attributed to j-SLE using standardised diagnostic criteria and multidisciplinary paediatric clinical expertise. Clinical features, brain magnetic resonance imaging (MRI)s and samples analysis including cerebrospinal fluid were assessed. A risk of j-NPSLE score was developed based on multivariable logistic regression analysis. RESULTS: Of 39 patients included, 44% were identified as having j-NPSLE. J-NPSLE diagnosis was established at the onset of j-SLE in 59% of patients. In addition to frequent kidney involvement (76%) and chilblains (65%), all j-NPSLE patients displayed psychiatric features: cognitive symptoms (82%), hallucinations (76%), depressed mood (35%), acute confused state (18%) and catatonia (12%). Neurological involvement was often mild and nonspecific, with headache (53%) in about half of the patients. The main features reported on brain MRI were nonspecific T2/FLAIR white matter hyperintensities (65%), and cerebral atrophy (88%). Upon immunosuppressive treatment, clinical improvement of NP features was observed in all j-NPSLE patients. The score developed to attribute j-NPSLE probability, guide further investigations and appropriate treatments is based on hallucinations, memory, sleep and renal involvement (Sensitivity: 0.95 Specificity: 0.85). Cerebrospinal fluid (CSF) neopterin assessment increases the score sensitivity and specificity. CONCLUSION: Physicians should carefully and systematically assess the presence of NP features at diagnosis and early stages of j-SLE. For j-NPSLE patients with predominant psychiatric features, a multidisciplinary collaboration, including psychiatrists, is essential for the diagnosis, management and follow-up.

A phenomenological comparison of auditory hallucinations between borderline personality disorder and schizophrenia: A systematic review.

OBJECTIVE: Borderline personality disorder (BPD) with auditory hallucinations (AHs) may inadvertently be misdiagnosed with a primary psychotic disorder, such as schizophrenia (SZ). This misidentification can lead to challenges in providing effective psychological treatment. This review therefore aims to identify the phenomenological characteristics of AHs in BPD in comparison to SZ, as well as psychological interventions that explicitly target AHs in BPD. METHODS: A systematic review was conducted to summarise the existing evidence base regarding the phenomenological similarities and differences of AHs in BPD and SZ, along with the identification of psychological interventions for AHs in BPD. RESULTS: Eighteen studies were eligible for inclusion. Compared to the SZ group, BPD clients were characterised by more persistent and repetitive AHs, significantly more voice-related distress and appraisals of omnipotence, and an earlier age of onset of AHs. The BPD group also reported more severe depression and anxiety, a higher incidence of childhood trauma, and more negative self-schema. Cognitive Behaviour Therapy Coping Strategy Enhancement (CBT-CSE) might be a promising intervention to reduce AH-related distress in BPD, although further studies are required to determine its effectiveness. CONCLUSION: In order to prevent misdiagnosis of AHs in BPD, the DSM-5 may need to acknowledge the broader and more frequent occurrence of psychosis symptoms in BPD clients. Such clarification may enhance diagnostic practices and facilitate more timely access to treatment. There is also a need to develop and trial psychological interventions that explicitly target AHs in BPD.

Parkinson disease psychosis: from phenomenology to neurobiological mechanisms.

Parkinson disease (PD) psychosis (PDP) is a spectrum of illusions, hallucinations and delusions that are associated with PD throughout its disease course. Psychotic phenomena can manifest from the earliest stages of PD and might follow a continuum from minor hallucinations to structured hallucinations and delusions. Initially, PDP was considered to be a complication associated with dopaminergic drug use. However, subsequent research has provided evidence that PDP arises from the progression of brain alterations caused by PD itself, coupled with the use of dopaminergic drugs. The combined dysfunction of attentional control systems, sensory processing, limbic structures, the default mode network and thalamocortical connections provides a conceptual framework to explain how new incoming stimuli are incorrectly categorized, and how aberrant hierarchical predictive processing can produce false percepts that intrude into the stream of consciousness. The past decade has seen the publication of new data on the phenomenology and neurobiological basis of PDP from the initial stages of the disease, as well as the neurotransmitter systems involved in PDP initiation and progression. In this Review, we discuss the latest clinical, neuroimaging and neurochemical evidence that could aid early identification of psychotic phenomena in PD and inform the discovery of new therapeutic targets and strategies.

Facilitation of sensorimotor temporal recalibration mechanisms by cerebellar tDCS in patients with schizophrenia spectrum disorders and healthy individuals.

Core symptoms in patients with schizophrenia spectrum disorders (SSD), like hallucinations or ego-disturbances, have been associated with a failure of internal forward models to predict the sensory outcomes of self-generated actions. Importantly, forward model predictions must also be able to flexibly recalibrate to changing environmental conditions, for example to account for additional delays between action and outcome. We investigated whether transcranial direct current stimulation (tDCS) can be used to improve these sensorimotor temporal recalibration mechanisms in patients and healthy individuals. While receiving tDCS on the cerebellum, temporo-parietal junction, supplementary motor area, or sham stimulation, patients with SSD and healthy control participants were repeatedly exposed to delays between actively or passively elicited button presses and auditory outcomes. Effects of this procedure on temporal perception were assessed with a delay detection task. Similar recalibration outcomes and faciliatory effects of cerebellar tDCS on recalibration were observed in SSD and healthy individuals. Our findings indicate that sensorimotor recalibration mechanisms may be preserved in SSD and highlight the importance of the cerebellum in both patients and healthy individuals for this process. They further suggest that cerebellar tDCS could be a promising tool for addressing deficits in action-outcome monitoring and related adaptive sensorimotor processes in SSD.

Hallucinations in patients with obstructive sleep apnea-hypopnea syndrome: report of 3 cases.

Hallucinations are false sensory perceptions that occur in the absence of an external stimulus. Three cases of hallucinations related to obstructive sleep apnea-hypopnea syndrome are reported, 2 of which improved with the initiation of continuous positive airway pressure therapy. So far there are no published reports in the literature that account for this relationship in the absence of primary or structural mental pathology. All 3 reported patients had visual hallucinations that were uncomfortable and frightening. Polysomnography showed moderate-to-severe obstructive sleep apnea-hypopnea syndrome with severe oxygen desaturation. Initiation of continuous positive airway pressure therapy achieved control of hallucinations in 2 patients during follow-up. Very little information is available on the coexistence of obstructive sleep apnea-hypopnea syndrome and hallucinations. Observational and experimental studies are required to clarify whether there is a causal relationship between the 2 pathologies as well as the therapeutic role that continuous positive airway pressure may have. CITATION: Venegas MA, Montoya JS. Hallucinations in patients with obstructive sleep apnea-hypopnea syndrome: report of 3 cases. J Clin Sleep Med. 2024;20(1):165-167.

Electrical stimulation induced self-related auditory hallucinations correlate with oscillatory power change in the default mode network.

Self-related information is crucial in our daily lives, which has led to the proposal that there is a specific brain mechanism for processing it. Neuroimaging studies have consistently demonstrated that the default mode network (DMN) is strongly associated with the representation and processing of self-related information. However, the precise relationship between DMN activity and self-related information, particularly in terms of neural oscillations, remains largely unknown. We electrically stimulated the superior temporal and fusiform areas, using stereo-electroencephalography to investigate neural oscillations associated with elicited self-related auditory hallucinations. Twenty-two instances of auditory hallucinations were recorded and categorized into self-related and other-related conditions. Comparing oscillatory power changes within the DMN between self-related and other-related auditory hallucinations, we discovered that self-related hallucinations are associated with significantly stronger positive power changes in both alpha and gamma bands compared to other-related hallucinations. To ensure the validity of our findings, we conducted controlled analyses for factors of familiarity and clarity, which revealed that the observed effects within the DMN remain independent of these factors. These results underscore the significance of the functional role of the DMN during the processing of self-related auditory hallucinations and shed light on the relationship between self-related perception and neural oscillatory activity.

A digital tool for self-assessment of auditory verbal hallucinations in schizophrenia.

Auditory verbal hallucinations (AVH) are experienced by approximately 70 % of patients with schizophrenia and are frequently associated with high levels of distress. Therefore, alleviating hallucinations is an important therapeutic challenge. However, for prescribing a personalized treatment adapted to the patient, an accurate and detailed assessment of AVH is necessary. Until now, there have been no self-evaluations; instead, only scales based on observer ratings have been used to assess AVH. Nevertheless, self-assessments may enhance patient symptom awareness and increase their insight and involvement in the treatment, promoting empowerment (Eisen et al., 2000). In this context, a mobile app called MIMO was devised in order to monitor AVHs assessed by the patients themselves. This app, including the Self-assessment of Auditory verbal Hallucinations (SAVH-https://sns-dollfus.com/), was devised as an ecological momentary assessment tool. The present study aimed to demonstrate the feasibility and acceptability of this app.

Executive control of language in schizophrenia patients with history of auditory verbal hallucinations: A neuropsychological and resting-state fMRI study.

BACKGROUND: As demonstrated by a plethora of studies, compromised executive functions (EF) and language are implicated in mechanisms of auditory verbal hallucinations (AVH), but the contribution of their interaction to AVH remains unclear. We hypothesized that schizophrenia patients with history of AVH (AVHh+) vs. without history of AVH (AVHh-) have a specific deficit of executive control of language and alterations in functional connectivity (FC) between the brain regions involved in EF and language, and these neuropsychological and neurophysiological traits are associated with each other. METHODS: To explore the executive control of language and its contribution to AVH, we used an integrative approach involving analysis of neuropsychological and resting-state fMRI data of 34 AVHh+, 16 AVHh-, and 40 healthy controls. We identified the neuropsychological and FC measures that differentiated between AVHh+, AVHh-, and HC, and tested the associations between them. RESULTS: AVHh+ were characterized by decreased category and phonological verbal fluency, utterance length, productivity in the planning tasks, and poorer retelling. AVHh+ had decreased FC between the left inferior frontal gyrus and the anterior cingulate cortex. Productivity in category verbal fluency was associated with the FC between these regions. CONCLUSIONS: Poor executive control of word retrieval and deficient programming of sentence and narrative related to more general deficits of planning may be the neuropsychological traits specific for AVHh+. A neurophysiological trait specific for AVHh+ may be a decreased FC between regions involved in language production and differentiation between alien- vs. self-generated speech and between language production vs. comprehension.

Reduced neural connectivity in the caudate anterior head predicts hallucination severity in schizophrenia.

BACKGROUND: Caudate functional abnormalities have been identified as one critical neural substrate underlying sensory gating impairments that lead to auditory phantom hallucinations in both patients with schizophrenia (SZ) and tinnitus, characterized by the perception of internally generated sounds in the absence of external environmental auditory stimuli. In this study, we tested the hypothesis as to whether functional connectivity abnormalities in distinct caudate subdivisions implicated in sensory gating and auditory phantom percepts in tinnitus, which are currently being localized for neuromodulation targeting using deep brain stimulation techniques, would be associated with auditory phantom hallucination severity in SZ. METHODS: Twenty five SZ and twenty eight demographically-matched healthy control (HC) participants, completed this fMRI resting-state study and clinical assessments. RESULTS: Between-group seed-to-voxel analyses revealed only one region, the caudate anterior head, which showed reduced functional connectivity with the thalamus that survived whole-brain multiple comparison corrections. Importantly, connectivity between the caudate anterior head with thalamus negatively correlated with hallucination severity. CONCLUSIONS: In the present study, we deliver the first evidence of caudate subdivision specificity for the neural pathophysiology underlying hallucinations in schizophrenia within a sensory gating framework that has been developed for auditory phantoms in patients with tinnitus. Our findings provide transdiagnostic convergent evidence for the role of the caudate in the gating of auditory phantom hallucinations, observed across patients with SZ and tinnitus by specifying the anterior caudate division is key to mediation of hallucinations, and creating a path towards personalized treatment approaches to arrest auditory phantom hallucinations from reaching perceptual awareness.

[Sleep paralysis during naptime as initial symptom of narcolepsy]. / Parálisis de sueño durante la siesta como síntoma inicial de narcolepsia.

INTRODUCTION: Narcolepsy is a disease of unknown etiology, with a very low prevalence (0.02-0.16% in adults, although it must be higher, given the underdiagnosis), characterized by the presence of excessive daytime sleepiness, hypnagogic and/or hypnopompic hallucinations, sleep paralysis and/or cataplexy (if present, we speak of type 1 narcolepsy and, if not, type 2 narcolepsy), whose average diagnostic delay is between 10 and 15 years. CASE REPORT: A 16-year-old male who consulted after visiting different specialists for presenting sleep paralysis during naps, which cause him fear and occasional objects falling from his hands (diagnosed as possible myoclonus). In the anamnesis we were surprised by the presence of sleep paralysis immediately after the start of the naps and, in the directed anamnesis, these sudden movements caused by emotions were compatible with cataplexies, so we performed a nocturnal polysomnographic study and a multiple sleep latency test. With evolution came hypnopompic hallucinations and fragmented nocturnal sleep, as well as occasional daytime sleepiness (thus completing the typical symptomatic tetrad of type 1 narcolepsy with cataplexy). CONCLUSION: Knowledge of this disease is important, considering it as a differential diagnosis in patients with episodes of intractable sleepiness, send these patients to expert doctors in sleep disorders and doing a good anamnesis, performing the necessary complementary tests for the diagnosis of this underdiagnosed disease for its correct management, which is decisive for improving the quality of life of these patients.

TITLE: Parálisis de sueño durante la siesta como síntoma inicial de narcolepsia.Introducción. La narcolepsia es una enfermedad de etiología desconocida, de prevalencia muy baja (el 0,02-0,16% en adultos, aunque debe ser mayor, dado el infradiagnóstico), caracterizada por la presencia de somnolencia diurna excesiva, alucinaciones hipnagógicas y/o hipnopómpicas, parálisis de sueño y/o cataplejía (si está presente, se habla de narcolepsia de tipo 1 y, si no, de narcolepsia de tipo 2), cuya media de retraso diagnóstico se sitúa entre los 10 y los 15 años. Caso clínico. Varón de 16 años que consulta tras visitar a distintos especialistas por presentar parálisis de sueño durante las siestas, que le producen miedo y ocasional caída de objetos de las manos (diagnosticadas como posibles mioclonías). En la anamnesis nos sorprendió la presencia de parálisis de sueño inmediatamente tras el inicio de las siestas y, en la anamnesis dirigida, esos movimientos bruscos provocados por emociones eran compatibles con cataplejías, por lo que realizamos un estudio polisomnográfico nocturno y un test de latencias múltiples del sueño. Con la evolución aparecieron alucinaciones hipnopómpicas y sueño fragmentado nocturno, así como ocasional somnolencia diurna (se completó así la tétrada sintomatológica típica de la narcolepsia con cataplejía de tipo 1). Conclusión. Es importante el conocimiento de esta enfermedad, plantearla como diagnóstico diferencial en pacientes con episodios de somnolencia incoercible, realizar la derivación a consultas especializadas en trastornos de sueño y una buena anamnesis dirigida, e indicar las pruebas complementarias necesarias para el diagnóstico de esta enfermedad infradiagnosticada para su correcto manejo, tan determinante para la mejora de la calidad de vida de estos pacientes.

The moderating effect of cognitive impairment on the relationship between inner speech and auditory verbal hallucinations among chronic patients with schizophrenia.

BACKGROUND: Even though there is an increasing amount of evidence from behavioral and neuroimaging studies to suggest that pathological inner speech plays a role in the emergence of auditory verbal hallucinations (AVH), studies investigating the mechanisms underlying this relationship are rather scarce. Examining moderators might inform the development of new treatment options for AVH. We sought to extend the existing knowledge by testing the moderating role of cognitive impairment in the association between inner speech and hallucinations in a sample of Lebanese patients with schizophrenia. METHODS: A cross-sectional study was conducted from May till August 2022, enrolling 189 chronic patients. RESULTS: Moderation analysis revealed that, after controlling for delusions, the interaction of experiencing voices of other people in inner speech by cognitive performance was significantly associated with AVH. In people having low (Beta = 0.69; t = 5.048; p < .001) and moderate (Beta = 0.45; t = 4.096; p < .001) cognitive performance, the presence of voices of other people in inner speech was significantly associated with more hallucinations. This association was not significant in patients with high cognitive function (Beta = 0.21; t = 1.417; p = .158). CONCLUSION: This preliminarily study suggests that interventions aiming at improving cognitive performance may also have a beneficial effect in reducing hallucinations in schizophrenia.

Decreased insight, but not self-stigma or belief about medicine, is associated with greater severity of delusions in a sample of long-stay patients with schizophrenia: a cross-sectional study.

BACKGROUND: There are, to date, limited and inconsistent findings concerning the relationship between insight and psychotic symptoms, despite some evidence in favor of the clinical and therapeutic relevance of the insight construct. We aimed to add to the pool of the available data in this area, by examining the correlations between the severity of insight and positive psychotic symptoms (delusions and auditory hallucinations), while accounting for self-stigma and attitudes towards medication, in a sample of long-stay inpatients with schizophrenia. METHODS: A cross-sectional study was conducted at the Psychiatric Hospital of the Cross, between July and October 2021. A total of 82 patients diagnosed with schizophrenia (aged 55.55 ± 10.21 years, 54.9% males) were enrolled. The semi-structured psychotic symptom rating scales, the Birchwood Insight Scale, the Belief About Medicine Questionnaire, and the Internalized Stigma of Mental Illness were used. RESULTS: The mean duration of illness in years was 30.15 ± 11.73, and the mean duration of hospitalization in years was 17.56 ± 9.24. Sixteen out of the 82 patients (19.5%) were considered as having poor insight. Bivariate analyses showed that higher chlorpromazine equivalent dose was significantly associated with more delusions, whereas higher insight was significantly associated with lower delusions. Multivariable analyses revealed that Higher chlorpromazine equivalent dose (Beta = 0.004) was significantly associated with more delusions, whereas higher insight (Beta = - 0.89) was significantly associated with less delusions. No significant associations were found between insight, self-stigma and hallucinations. CONCLUSION: Our results imply that more impaired insight is associated with greater severity of delusions, above and beyond the effects of self-stigma and medication doses. These findings are valuable to aid clinicians and researchers improve their understanding of the relationship insight-psychotic symptoms, and could help personalize prevention and early intervention strategies in schizophrenia.

Free water imaging of the cholinergic system in dementia with Lewy bodies and Alzheimer's disease.

INTRODUCTION: Degeneration of cortical cholinergic projections from the nucleus basalis of Meynert (NBM) is characteristic of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), whereas involvement of cholinergic projections from the pedunculopontine nucleus (PPN) to the thalamus is less clear. METHODS: We studied both cholinergic projection systems using a free water-corrected diffusion tensor imaging (DTI) model in the following cases: 46 AD, 48 DLB, 35 mild cognitive impairment (MCI) with AD, 38 MCI with Lewy bodies, and 71 controls. RESULTS: Free water in the NBM-cortical pathway was increased in both dementia and MCI groups compared to controls and associated with cognition. Free water along the PPN-thalamus tract was increased only in DLB and related to visual hallucinations. Results were largely replicated in an independent cohort. DISCUSSION: While NBM-cortical projections degenerate early in AD and DLB, the thalamic cholinergic input from the PPN appears to be more selectively affected in DLB and might associate with visual hallucinations. HIGHLIGHTS: Free water in the NBM-cortical cholinergic pathways is increased in AD and DLB. NBM-cortical pathway integrity is related to overall cognitive performance. Free water in the PPN-thalamus cholinergic pathway is only increased in DLB, not AD. PPN-thalamus pathway integrity might be related to visual hallucinations in DLB.

[Narcolepsy Type 1 With Comorbid Schizophrenia: A Case Report].

We present the case of an 18-year-old male patient who had narcolepsy type 1 and comorbid schizophrenia. The patient's first symptom was mainly excessive daytime sleepiness, which was followed by psychotic symptoms, including hallucinations, delusions, and abnormal speech and behaviors. After admission to the hospital, the patient underwent a number of ancillary tests. Multiple sleep latency test (MSLT) showed that the mean sleep latency was 2 min and the hypocretin-1 was found to be 90.56 pg/mL. The patient was diagnosed with: 1) schizophrenia; 2) narcolepsy. After receiving antipsychotic drugs and behavioral therapy, the patient's hallucinations and abnormal speech and behaviors disappeared, and delusions and excessive daytime sleepiness decreased significantly. The symptoms and manifestations of narcolepsy type 1 overlaps with those of schizophrenia, which may lead to misdiagnosis and underdiagnosis in clinical practice. The case is presented with a view to providing a reference for the clinical diagnosis and treatment of narcolepsy type 1 with comorbid schizophrenia.

Discrimination of auditory verbal hallucination in schizophrenia based on EEG brain networks.

Auditory verbal hallucinations (AVH) are a core positive symptom of schizophrenia and are regarded as a consequence of the functional breakdown in the related sensory process. Yet, the potential mechanism of AVH is still lacking. In the present study, we explored the difference between AVHs (n = 23) and non-AVHs (n = 19) in schizophrenia and healthy controls (n = 29) by using multidimensional electroencephalograms data during an auditory oddball task. Compared to healthy controls, both AVH and non-AVH groups showed reduced P300 amplitudes. Additionally, the results from brain networks analysis revealed that AVH patients showed reduced left frontal to posterior parietal/temporal connectivity compared to non-AVH patients. Moreover, using the fused network properties of both delta and theta bands as features for in-depth learning made it possible to identify the AVH from non-AVH patients at an accuracy of 80.95%. The left frontal-parietal/temporal networks seen in the auditory oddball paradigm might be underlying biomarkers of AVH in schizophrenia. This study demonstrated for the first time the functional breakdown of the auditory processing pathway in the AVH patients, leading to a better understanding of the atypical brain network of the AVH patients.

Associations among psychosis, mood, anxiety, and posttraumatic stress symptoms: A network analysis.

The associations among psychotic experiences (i.e., hallucinations and delusions), trauma exposure, and posttraumatic stress symptoms are complex and multidirectional. Using network analysis to understand how psychotic experiences and symptoms of posttraumatic stress disorder (PTSD) relate to one another may identify new interventional targets to treat comorbidity and its underlying pathological processes. This study aimed to use network analysis to examine the associations among psychotic experiences; negative symptoms of psychosis; and symptoms of PTSD, anxiety, and depression. In this population-based cohort study, 4,472 participants (36.7% male) were assessed for psychotic experiences, negative symptoms of psychosis, PTSD, anxiety, and depression at age 23 (M = 23.86 years, SD = 0.520) or 24 years (M = 24.03, SD = 0.848). Associations among symptoms were assessed via network analysis. Exploratory graph analysis identified three clusters of densely connected symptoms within the overall network: psychotic experiences; PTSD symptoms; and depressive and anxiety symptoms and negative symptoms of psychosis. Psychotic experiences had the strongest associations with other symptoms in the network, and symptoms of anxiety played a key role in bridging psychotic experiences, symptoms of PTSD, and depressive symptoms. Consistent with the stress reactivity and affective models for psychotic experiences, the results suggest that symptoms of anxiety and emotional distress (e.g., hyperarousal, panic) may have a key role in the development and maintenance of psychotic experiences and symptoms of PTSD. Targeting these symptoms may ameliorate symptom burden transdiagnostically.

Exploring the association between lifetime traumatic experiences and positive psychotic symptoms in a group of long-stay patients with schizophrenia: the mediating effect of depression, anxiety, and distress.

BACKGROUND: Positive psychotic symptoms of schizophrenia are generally characterized by hallucinations and delusions. We propose to assess the relationship between total composite trauma and positive psychotic symptoms, along with the mediation effect of cognition, fear of COVID-19, insomnia, anxiety, distress, and depression of Lebanese patients with schizophrenia. METHODS: A cross-sectional study was carried out, between June and July 2021, by deriving data from 155 long-stay in-patients diagnosed with schizophrenia. RESULTS: Depression, anxiety, and distress but not cognitive impairment, insomnia, and fear of COVID-19) mediated the association between lifetime traumatic experiences and positive psychotic symptoms. Higher traumatic experiences were associated with greater depression, anxiety, and distress, indicating a significant positive total effect on positive psychotic scores. Moreover, higher depression, anxiety, and distress were significantly associated with higher positive psychotic symptoms. CONCLUSION: Our results contribute to the existing knowledge by suggesting other possible intervention paths through mediating factors. Interventions that improve anxiety, depression, and distress severity may be effective in reducing positive psychotic symptoms among patients with schizophrenia having experienced lifetime trauma.

Impact of low-frequency repetitive transcranial magnetic stimulation on functional network connectivity in schizophrenia patients with auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has shown potential in the treatment of AVH. However, the underlying neural mechanismof rTMS in the treatment of AVH remains largely unknown. In this study, we used a static and dynamic functional network connectivity approach to investigate the connectivity changes among the brain functional networks in schizophrenia patients with AVH receiving 1 Hz rTMS treatment. The static functional network connectivity (sFNC) analysis revealed that patients at baseline had significantly decreased connectivity between the default mode network (DMN) and language network (LAN), and within the executive control network (ECN) as well as within the auditory network (AUD) compared to controls. However, the abnormal network connectivity patterns were normalized or restored after rTMS treatment in patients, instead of increased connectivity between the ECN and LAN, as well as within the AUD. Moreover, the dynamic functional network connectivity (dFNC) analysis showed that the patients at baseline spent more time in this state that was characterized by strongly negative connectivity between the ENC and AUD, as well as within the AUD relative to controls. While after rTMS treatment, the patients showed a higher occurrence rate in this state that was characterized by strongly positive connectivity among the LAN, DMN, and ENC, as well as within the ECN. In addition, the altered static and dynamic connectivity properties were associated with reduced severity of clinical symptoms. Both sFNC and dFNC analyses provided complementary information and suggested that low-frequency rTMS treatment could induce intrinsic functional network alternations and contribute to improvements in clinical symptoms in patients with AVH.