Prazosin use in a patient with rare Neurobeachin gene deletion shows improvement in paranoid behavior: a case report.

BACKGROUND: Disruption of the Neurobeachin gene is a rare genetic mutation that has been implicated in the development of autism and enhanced long-term potentiation of the hippocampal CA1 region, causing a heightened conditioned fear response and impaired fear extinction. Prazosin, an alpha-1 receptor antagonist, has been used in patients with posttraumatic stress disorder to mitigate the increased alpha-1 activity involved in fear and startle responses. Here we report a case of a patient with a rare Neurobeachin gene deletion, who demonstrated marked and sustained improvement in paranoid behavior within days of prazosin initiation. CASE PRESENTATION: The patient is a 27-year-old White male with autism spectrum disorder, obsessive-compulsive disorder, and schizophrenia, with a chromosome 13q12 deletion including deletion of the Neurobeachin gene, who presented to the emergency department due to worsening functional status and profound weight loss as a result of only eating prepackaged foods. He had not showered or changed clothes in several months prior to presentation. He was hospitalized in the inpatient psychiatric unit for 2 months before prazosin was initiated. During that time, he demonstrated paranoia as evidenced by heightened sensitivity to doors opening, guarded interactions, and limited communication with providers and other patients. He also exhibited poor grooming habits, with aversion to showering, shaving, and changing clothes. Since initiating prazosin, he has demonstrated a brighter affect, initiates and maintains conversations, showers and changes clothes on a regular basis, and eats a variety of foods. At the time of this report, the patient was discharged to live in an apartment with a caregiver after a 7-month inpatient hospitalization. CONCLUSIONS: Low-dose prazosin shows rapid and sustained improvement in paranoid behavior in a patient with a rare Neurobeachin gene deletion. Prazosin has a relatively favorable side effect profile with once-daily dosing and low cost. Prazosin may provide clinical improvement in patients with Neurobeachin gene deletions due to its theoretical attenuation in fear response through alpha-1 antagonism.

Neuropsychiatric manifestations in adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is an uncommon inflammatory condition characterised by a triad of fevers, arthralgias and a salmon-coloured rash. It is also strongly associated with high ferritin levels, whose role in its pathogenesis is not entirely clear. Central nervous system (CNS) manifestations are exceedingly rare in this disease, accounting for only a handful of reported cases. Herein, we describe a case of a 63-year-old woman who developed new-onset psychiatric symptoms in the months preceding her diagnosis. 2 months after her diagnosis, she experienced an exacerbation of psychiatric symptoms followed by new-onset seizures in conjunction with an acute lung infection. In addition, we discuss two other previously reported cases of AOSD patients with psychiatric symptoms as their initial presentation.

Pylons ablaze: Examining the role of 5G COVID-19 conspiracy beliefs and support for violence.

Amid increased acts of violence against telecommunication engineers and property, this pre-registered study (N = 601 Britons) investigated the association between beliefs in 5G COVID-19 conspiracy theories and the justification and willingness to use violence. Findings revealed that belief in 5G COVID-19 conspiracy theories was positively correlated with state anger, which in turn, was associated with a greater justification of real-life and hypothetical violence in response to an alleged link between 5G mobile technology and COVID-19, alongside a greater intent to engage in similar behaviours in the future. Moreover, these associations were strongest for those highest in paranoia. Furthermore, we show that these patterns are not specific to 5G conspiratorial beliefs: General conspiracy mentality was positively associated with justification and willingness for general violence, an effect mediated by heightened state anger, especially for those most paranoid in the case of justification of violence. Such research provides novel evidence on why and when conspiracy beliefs may justify the use of violence.

Proposed symptom-based model of the origins of schizophrenia.

Schizophrenia is considered a severe mental illness and effects an estimated 1% of the world population. The evidence suggests that incidence rate has been and will continue to be stable over time. Here we adopt a symptomatology-focused evolutionary informed approach to discuss the possible biological adaptations of various presentations of schizophrenia. It is our contention that rather than thinking about schizophrenia as a single disorder, or even a spectrum of disorders, marked by social maladaptation and personal subjective distress, that an evolutionary interpretation based on adaptive nature of individual, or small clusters of, symptoms could prove to be more useful in better understanding the pathophysiology of schizophrenia and its relationship with other psychiatric diagnoses.

Paranoid Ideation Without Psychosis Is Associated With Depression, Anxiety, and Suicide Attempts in General Population.

This study aimed to characterize the association between paranoid ideation without psychosis (PIP) and suicide attempts in a general population. A total of 12,532 adults were randomly selected as the study sample through one-person-per-household method. Subjects completed a face-to-face interview. Among 12,532 subjects, 471 (3.76%) met criteria for the PIP group. The PIP group was younger with more divorced/widowed/separated and lower income than the non-PIP group. The PIP group showed more than fivefold higher lifetime suicide attempt (LSA) rates and ninefold multiple attempt rates than the non-PIP group. Among PIP symptoms, "spouse was being unfaithful" showed the strongest association with LSA (adjusted odds ratio [AOR], 4.49; 95% confidence interval, 2.95-6.85). Major depressive disorder (MDD) in combination with PIP was associated with a higher risk of LSA (AOR, 15.39; 95% confidence interval, 9.63-24.59) compared with subjects without MDD or PIP. In conclusion, PIP, especially "doubting spouse," was significantly associated with LSA. PIP in combination with comorbid MDD showed higher risk of LSA than subjects without PIP or MDD.

Rural birth/upbringing and childhood adversities are associated with psychotic experiences in university students in China.

BACKGROUND: Urbanicity has been reported to associate with an increased risk of psychotic experiences (PEs) in developed countries but less is known about the situation in developing countries. The present study aimed to investigate the effects of birth/upbringing place and other environmental factors on PEs in Chinese university students. METHODS: A computer-assisted cross-sectional survey was conducted on 4620 second-year undergraduates, using a stratified cluster sampling. Birth places and residential mobility before 16 years old were recorded. PEs were measured using the subscales of psychoticism and paranoid ideation in the Symptom Checklist-90-R (SCL-90-R). Six questions extracted from the childhood section of the World Mental Health Composite International Diagnostic Interview (WMH-CIDI) were used to assess childhood trauma. RESULTS: Generalized ordered logit model of multiple regression analysis revealed that participants with rural birth/upbringing (e.g. rural upbringing, on graded factor score of psychoticism and paranoid ideation [GFSPPI], 0 versus 1 & 2, odds ratio [OR] 1.409, 95% CI 1.219-1.628, p < 0.00001; 0 & 1 versus 2, OR 1.584, 95% CI 1.179-2.128, p < 0.00001) and those who reported childhood trauma (e.g. on GFSPPI, 0 versus 1 & 2, OR 1.737, 95% CI 1.498-2.014, p < 0.00001; 0 & 1 versus 2, OR 1.618, 95% CI 1.224-2.140, p < 0.00001) were apt to present more severe PEs. While upbringing places and childhood trauma affected both the presence and the severity of PEs, gender affected the presence or absence of PEs only (e.g. females, on GFSPPI, 0 versus 1 & 2, OR 1.887, 95% CI 1.631-2.183, p < 0.00001; 0 & 1 versus 2, OR 0.927, 95% CI 0.702-1.223, p = 0.593). Besides, the number of risk factors was associated with the severity of PEs in the cumulative odds logistic regression analysis (e.g. 3 risk factors versus 0 risk factor, on GFSPPI, OR 4.126, 95% CI 3.075-5.537, p < 0.00001). CONCLUSIONS: Female, rural birth/upbringing and childhood trauma are risk factors of PEs in university students in China. The discrepancy in the findings between developed countries and China has important implications for urbanicity as a risk factor for PEs.

Adolescent Paranoia: Prevalence, Structure, and Causal Mechanisms.

BACKGROUND: Adolescence can be a challenging time, characterized by self-consciousness, heightened regard for peer acceptance, and fear of rejection. Interpersonal concerns are amplified by unpredictable social interactions, both online and offline. This developmental and social context is potentially conducive to the emergence of paranoia. However, research on paranoia during adolescence is scarce. METHOD: Our aim was to examine the prevalence, structure, and probabilistic causal mechanisms of adolescent paranoia. A representative school cohort of 801 adolescents (11-15 y) completed measures of paranoia and a range of affective, cognitive, and social factors. A Bayesian approach with Directed Acyclic Graphs (DAGs) was used to assess the causal interactions with paranoia. RESULTS: Paranoid thoughts were very common, followed a continuous distribution, and were hierarchically structured. There was an overall paranoia factor, with sub-factors of social fears, physical threat fears, and conspiracy concerns. With all other variables controlled, DAG analysis identified paranoia had dependent relationships with negative affect, peer difficulties, bullying, and cognitive-affective responses to social media. The causal directions could not be fully determined, but it was more likely that negative affect contributed to paranoia and paranoia impacted peer relationships. Problematic social media use did not causally influence paranoia. CONCLUSIONS: There is a continuum of paranoia in adolescence and occasional suspicions are common at this age. Anxiety and depression are closely connected with paranoia and may causally contribute to its development. Paranoia may negatively impact adolescent peer relationships. The clinical significance of paranoia in adolescents accessing mental health services must now be established.

Psychosis, creativity and recovery: exploring the relationship in a patient.

Relation between mental illness and creativity is intricate. While many creative people show signs of mental illness, persons with severe mental illness occasionally have creative output beyond the ordinary. We are presenting a patient with psychotic illness whose creative potential took a positive turn during the illness phase and grew further following symptomatic improvement and helped in her recovery process. Observing the contrast related to creative productivity pre and post psychotic phase raises the probability of whether psychotic illness or process might enhance creative potential. The case additionally illustrates how creativity can be a useful method supporting recovery from severe mental illnesses.

Virtual-reality-based cognitive behavioural therapy versus waiting list control for paranoid ideation and social avoidance in patients with psychotic disorders: a single-blind randomised controlled trial.

BACKGROUND: Many patients with psychotic disorders have persistent paranoid ideation and avoid social situations because of suspiciousness and anxiety. We investigated the effects of virtual-reality-based cognitive behavioural therapy (VR-CBT) on paranoid thoughts and social participation. METHODS: In this randomised controlled trial at seven Dutch mental health centres, outpatients aged 18-65 years with a DSM-IV-diagnosed psychotic disorder and paranoid ideation in the past month were randomly assigned (1:1) via block randomisation to VR-CBT (in addition to treatment as usual) or the waiting list control group (treatment as usual). VR-CBT consisted of 16 individual therapy sessions (each 1 h long). Assessments were done at baseline, after treatment (ie, 3 months from baseline), and at a 6 month follow-up visit. The primary outcome was social participation, which we operationalised as the amount of time spent with other people, momentary paranoia, perceived social threat, and momentary anxiety. Analysis was by intention to treat. This trial was retrospectively registered with ISRCTN, number 12929657. FINDINGS: Between April 1, 2014, and Dec 31, 2015, 116 patients with a psychotic disorder were randomly assigned, 58 to the VR-CBT group and 58 to the waiting list control group. Compared with the control, VR-CBT did not significantly increase the amount of time spent with other people at the post-treatment assessment. Momentary paranoid ideation (b=-0·331 [95% CI -0·432 to -0·230], p<0·0001; effect size -1·49) and momentary anxiety (-0·288 [-0·438 to -0·1394]; p=0·0002; -0·75) were significantly reduced in the VR-CBT group compared with the control group at the post-treatment assessment, and these improvements were maintained at the follow-up assessment. Safety behaviour and social cognition problems were mediators of change in paranoid ideation. No adverse events were reported relating to the therapy or assessments. INTERPRETATION: Our results suggest that the addition of VR-CBT to standard treatment can reduce paranoid ideation and momentary anxiety in patients with a psychotic disorder. FUNDING: Fonds NutsOhra, Stichting tot Steun VCVGZ.

MDPV in forensic routine cases: Psychotic and aggressive behavior in relation to plasma concentrations.

The new psychoactive substance 3,4-methylenedioxypyrovalerone (MDPV) belongs to the group of synthetic cathinones and is purchased mainly as "research chemical" or "bath salt" on the illegal drug market, also in South Bavaria. MDPV was detected in blood and urine samples from 2010 on in 50 authentic routine cases in a forensic setting. Plasma concentrations in 46 cases with available blood specimens ranged from approximately 1.0 to 301µg/L (median 23.7; mean 47.9µg/L), detected by a fully validated LC-MS/MS method. Subjects aged between 16 and 54 years (median 36; mean 35 years) and reflected experienced chronic drug users. Accused offences were mainly violent crimes such as bodily harm, robberies, homicides and acts of resistance. A lot of subjects showed highly aggressive and violent behavior with endangerment of self and others and/or psychotic symptoms as confusion, hallucinations or paranoia. The risk for such behavior rises with MDPV plasma concentrations above as low as 30µg/L, whereby a time interval of 1.5h on average between incident and/or observation of impairment and blood sampling has to be taken into account. Comprehensive toxicological analysis proved poly-drug use in almost all cases including opiates/opioids, benzodiazepines and other sedatives, antidepressants and other stimulants, also other new psychoactive substances. Alcohol was detected only in three cases. Co-consumed benzodiazepines seem not be able to completely prevent psychotic effects despite their use as first-line treatment for patients with synthetic cathinone poisonings. The study demonstrates that relatively low plasma concentrations of MDPV could be associated with mental impairment which is relevant in the assessment of forensic cases.

Interpersonal sensitivity in those at clinical high risk for psychosis mediates the association between childhood bullying victimisation and paranoid ideation: A virtual reality study.

BACKGROUND: Experience of bullying victimisation in childhood and heightened interpersonal sensitivity have been independently linked to the clinical high risk for psychosis. AIM: To examine the potential mediating effect of interpersonal sensitivity in explaining the link between childhood bullying victimisation and real-time paranoid ideation in adult participants at clinical high risk for psychosis. METHOD: In a cross-sectional study data were collected for 64 individuals at clinical high risk for psychosis. Measures included history of bullying victimisation, interpersonal sensitivity and state paranoid ideation following exposure to a social virtual reality environment. The virtual reality scenario was a London Underground journey. RESULTS: Path analysis indicated that interpersonal sensitivity fully explained the significant association between severe bullying victimisation in childhood and paranoid ideation in the clinical-high risk group. Based on AIC criteria the best model selected was the full mediation model: severe bullying→interpersonal sensitivity→state paranoid ideation. The results suggest that severity of bullying is more important than frequency of bullying in explaining state paranoid ideation. CONCLUSIONS: The significant role played by interpersonal sensitivity in the association between being bullied in childhood and paranoid ideation in the clinical high risk group suggests that this could become a target for intervention.

[Terrorism, youth, ideals and paranoia]. / Terrorisme, jeunesse, idéaux et paranoïa.

Adolescence is a period of initiation during which individuals learn to free themselves from the hold of their impulses. Fanaticism prevents this process: the subject regresses into a paranoid-type sectarian and murderous way of functioning. The fanaticism of the adolescent could thereby be related to a distorted spiritual search for his or her purpose.

Personality traits in patients with myotonic dystrophy type 2.

Myotonic dystrophy type 2 (DM2) is a multisystem disorder that affects many organs and systems, including the brain. The objective is to analyze personality patterns in myotonic dystrophy type 2 (DM2) compared to DM1 control group. The study comprised 27 consecutive genetically confirmed DM2 patients and control group of 44 DM1 patients. Personality traits were assessed with the Millon Multiaxial Clinical Inventory III (MMCI III). In DM2 group there were no scale with pathological scores, although compulsive and paranoid traits were the most prominent. DM2 patients had lower scores compared to DM1 patients in almost all scales. Pathological scores on clinical symptom scales were not observed, although anxiety scale almost approached this value. Patients with higher compulsive score had higher level of education (rho = +0.53, p < 0.01). On the other hand, higher paranoid score correlated with younger age at onset (rho = -0.34, p < 0.01) and lower educational level (rho = -0.26, p < 0.05). Our results did not show significant personality impairments in patients with DM2. However, following personality traits were predominant: compulsive (in patients with higher education) and paranoid (in patients with lower education and earlier age at onset). The most common clinical symptoms were anxiety and somatization.

Psychotic-like experiences and happiness in the English general population.

BACKGROUND: Psychotic-like experiences (PLEs) have been associated with a variety of adverse outcomes but how they affect happiness in individuals with PLE is unknown. Thus, the aim of the study was to assess the association between PLEs and happiness, and the factors that may influence this association. METHODS: Nationally representative data from the 2007 Adult Psychiatric Morbidity Survey including adults aged ≥ 16 years was analyzed. The Psychosis Screening Questionnaire was used to assess past 12-month PLE. Individuals who endorsed at least one of the following were considered to have any PLE: thought control, paranoia, strange experiences, auditory hallucinations. Happiness (3-point scale) was assessed with a validated question with higher scores indicating lower levels of happiness. The association between PLE and happiness was assessed by multivariable ordinal logistic regression. Mediation analysis was also performed. RESULTS: Among the 7363 individuals included in the analysis, the prevalence of any PLE increased with decreasing levels of happiness [very happy (2.3%), fairly happy (5.4%), not too happy (14.9%)]. This was also shown in the multivariable analysis adjusted for sociodemographic factors and stressful life events (from very happy to not too happy: OR = 2.41; 95%CI = 1.86-3.12). Mediation analysis showed that anxiety disorders explained the largest proportion of the association (38.8%) followed by depressive episode (28.5%), insomnia (21.9%), disability (16.5%), pain (12.5%), social support (10.0%), and physical health conditions (6.0%). LIMITATIONS: The cross-sectional design limits causal inference. CONCLUSION: Interventions to identify and address conditions that may have a negative impact on happiness in individuals with PLE may be important to improve their well-being.

A latent genetic subtype of major depression identified by whole-exome genotyping data in a Mexican-American cohort.

Identifying data-driven subtypes of major depressive disorder (MDD) is an important topic of psychiatric research. Currently, MDD subtypes are based on clinically defined depression symptom patterns. Although a few data-driven attempts have been made to identify more homogenous subgroups within MDD, other studies have not focused on using human genetic data for MDD subtyping. Here we used a computational strategy to identify MDD subtypes based on single-nucleotide polymorphism genotyping data from MDD cases and controls using Hamming distance and cluster analysis. We examined a cohort of Mexican-American participants from Los Angeles, including MDD patients (n=203) and healthy controls (n=196). The results in cluster trees indicate that a significant latent subtype exists in the Mexican-American MDD group. The individuals in this hidden subtype have increased common genetic substrates related to major depression and they also have more anxiety and less middle insomnia, depersonalization and derealisation, and paranoid symptoms. Advances in this line of research to validate this strategy in other patient groups of different ethnicities will have the potential to eventually be translated to clinical practice, with the tantalising possibility that in the future it may be possible to refine MDD diagnosis based on genetic data.

Do paranoid delusions exist on a continuum with subclinical paranoia? A multi-method taxometric study.

BACKGROUND: There is widespread interest in whether psychosis exists on a continuum with healthy functioning. Previous research has implied that paranoia, a common symptom of psychosis, exists on a continuum but this has not been investigated using samples including both patients and non-patients and up-to-date taxometric methods. AIM: To assess the latent structure of paranoia in a diverse sample using taxometric methods. METHOD: We obtained data from 2836 participants, including the general population as well as at-risk mental state and psychotic patients using the P-scale of the Paranoia and Deservedness Scale. Data were analysed using three taxometric procedures, MAMBAC, MAXEIG and L-MODE (Ruscio, 2016), and two sets of paranoia indicators (subscales and selected items from the P scale), including and excluding the patient groups. RESULTS: Eleven of the twelve analyses supported a dimensional model. Using the full sample and subscales as indicators, the MAMBAC analysis was ambiguous. Overall, the findings converged on a dimensional latent structure. CONCLUSIONS: A dimensional latent structure of paranoia implies that the processes involved in sub-clinical paranoia may be similar to those in clinical paranoia.