Resting-state alterations in emotion salience and default-mode network connectivity in atypical trajectories of psychotic-like experiences.

Social cognition is commonly altered in people with psychosis. Two main brain networks have been implicated: the default-mode network (DMN), which is associated with socio-cognitive processing, and the salience network (SN) associated with socio-affective processing. Disturbances to the resting-state functional connectivity of these networks have been identified in schizophrenia and high-risk individuals, but there have been no studies in adolescents displaying distinct trajectories of subclinical psychotic-like experiences (PLEs). To address this, the present study measured SN and DMN resting-state connectivity in a unique longitudinally followed sample of youth (n = 92) presenting with typical and atypical 4-year PLE trajectories. Compared to the typically developing low PLE control group, the atypical increasing PLE trajectory displayed reduced connectivity between the SN and DMN, increased connectivity between left and right insula, and widespread dysconnectivity from the insula and amygdala. These alterations are similar to those reported in schizophrenia and clinical high-risk samples, suggesting that early detection may be useful for mapping the developmental trajectories of psychotic disorders.

Cross-cultural differences through subjective cognition: illustration in translatology with the SSTIC-E in the UAE.

The development of appropriate and valid multicultural and multilingual instruments research is necessary due to a growing multicultural and multilingual society in the 21st century. We explored the use of a cognitive scale related to subjective complaints, focusing on the first step: a cross-cultural and semantic validation. This study presents the translation and cross-validation process of the "Subjective Scale to Investigate Cognition in Schizophrenia" (SSTICS) for the United Arab Emirates (UAE) region via different languages used in Dubaï/Abu Dhabi. This scale measures cognitive complaints and has been validated with psychosis and used in 20 clinical trials worldwide. It evaluates areas of the illness related to self-awareness focusing on memory dysfunction and deficits of attention, language, and praxis. We described the method of cross-cultural validation, with back-translation, semantic steps, and societal contexts. The use of the Subjective Scale to Investigate Cognition in Emirates (SSTIC-E) was explored with different samples of UAE Arabic-speaking subjects. First, a pilot sample mean SSTICS total score was 16.5 (SD:16.9); (p < 0.001). The SSTIC-E was then administered to 126 patients and 84 healthy control participants. The healthy group has a lower mean score of 22.55 (SD = 12.04) vs. 34.06 (SD = 15.19). The method was extended to nine other languages, namely, Pakistani/Urdu, Hindi, Marathi, Lithuanian, Serbian, German, Romanian, Sinhala, and Russian. The scales are provided in the article. The overall aim of the translation process should be to stay close to the original version of the instrument so that it is meaningful and easily understood by the target language population. However, for construct validity, some items must be adapted at the time of translation to ensure that the questioned cognitive domain is respected. For example, cooking, an executive function, does not have the same occurrence for an Emirati male, or remembering a prime minister's name, semantic memory, requires an electoral system to appoint the leader of a country. Translation methods and processes present many challenges but applying relevant and creative strategies to reduce errors is essential to achieve semantic validation. This study aims to measure personally experienced knowledge or attitudes; such language effects can be a thorny problem.

Prevalence and risk factors for metabolic syndrome in schizophrenia, schizoaffective, and bipolar disorder.

BACKGROUND: Metabolic Syndrome (MetS) is a risk for developing cardiovascular diseases and its prevalence is especially high in psychiatric patients. To date, there is limited data from the United Arab Emirates (UAE) on the prevalence of MetS. Therefore, we aimed to investigate its prevalence and possible risk factors in a large sample of psychiatric patients in the UAE. METHODS: A cross-sectional study was conducted at Al-Ain Hospital, in Al-Ain City, UAE. We collected demographic and clinical data on patients diagnosed with schizophrenia, schizoaffective, and bipolar affective disorder in the period between January 2017 and December 2020. This included their secondary diagnosis (psychiatric or medical), vital signs (heart rate, systolic and diastolic blood pressure, Body Mass Index [BMI]), metabolic parameters (fasting blood glucose, cholesterol, triglycerides, low-density lipoprotein, high-density lipoproteins), and prescribed medications. We used the American Association of Clinical Endocrinology (AACE) criteria to diagnose MetS. RESULTS: We included 889 subjects and of these, 79.8% (N = 709) had a BMI ≥25 kg/m2 and 9.8% (N = 87) had no abnormal metabolic parameters. Overall, 28.1% (N = 250) had MetS with no statistical difference between the three groups. Fasting blood glucose levels and abnormally elevated triglycerides were significant predictors for MetS. CONCLUSION: Our study found that around one in three patients had MetS irrespective of the three diagnoses. Some variables were significant predictors for MetS. Our findings were consistent with other studies and warrant the need for regular screening and management of abnormal metabolic parameters.

There is no statistical difference between schizophrenia, schizoaffective disorder, and bipolar disorder with regards to the prevalence of metabolic syndrome.Fasting blood glucose levels and abnormally elevated triglycerides were significant predictors of metabolic syndrome.Screening of metabolic parameters is important as well as the careful tailoring of the choice of antipsychotics.

Metabolic syndrome and its relation to antipsychotic polypharmacy in schizophrenia, schizoaffective and bipolar disorders.

The risk of metabolic syndrome (MetS) has been attributed to antipsychotic use in psychiatric patients. To date, there is limited data on the relationship between antipsychotic polypharmacy and MetS in patients with schizophrenia, schizoaffective disorder and bipolar disorder. Therefore, we aimed to investigate the rate of MetS in patients with these disorders receiving antipsychotic monotherapy and polypharmacy. We conducted a cross-sectional study on patients seen between January 2017 and December 2020, collecting data on the class, type, route of administration and number of antipsychotics received. We used the American Association of Clinical Endocrinology criteria to diagnose MetS. We included 833 subjects of whom 573 (68.8%) received antipsychotic monotherapy and 260 (31.2%) received polypharmacy. Overall, 28.6% ( N  = 238) had MetS with no statistical difference between the two groups. Diastolic blood pressure and receiving olanzapine were significant predictors for developing MetS. In conclusion, our study found no significant difference in the rate of MetS between antipsychotic monotherapy and polypharmacy. A number of variables were significant predictors for MetS. Our findings were consistent with other studies and warrant the need for careful choice of antipsychotics and regular screening and management of abnormal metabolic parameters.

Treatment with psychostimulants and atomoxetine in people with psychotic disorders: reassessing the risk of clinical deterioration in a real-world setting.

BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine. AIMS: To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before. METHOD: This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year. RESULTS: Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24-0.54; P < 0.0001). CONCLUSIONS: These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.

Evaluating real-world effectiveness of accelerated transcranial magnetic stimulation for treatment-resistant depression in a tertiary referral center based in Quebec, Canada.

OBJECTIVE: To assess the effectiveness of accelerated transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD) in a tertiary referral center in Quebec, Canada, focusing on a real-world clinical setting. METHODS: We reviewed the data of 247 TRD patients treated between January 2012 and May 2022 who received accelerated TMS. Participants were adults diagnosed with unipolar or bipolar depression, resistant to at least two antidepressant trials, and assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Significant symptom reduction was found in the completer sample (N = 147), with 46.3 % of patients meeting post-treatment response criteria and 36.1 % achieving remission. Baseline severity of depression, age, and the number of antidepressant trials were key predictors of treatment outcomes. Patients who did not complete treatment had generally more severe depressive and anxious symptoms and greater treatment resistance. No significant differences in response rates were observed across different TMS coils. CONCLUSION: The study demonstrated the effectiveness and tolerability of accelerated TMS for TRD in a real-world clinical setting.

The Utility of CYP2D6 and CYP2C19 Variants to Guide Pharmacological Treatment in Complex Unipolar Major Depression: A Pilot Longitudinal Study.

Major depression is a frequent condition which variably responds to treatment. In view of its high prevalence, the presence of treatment resistance in major depression significantly impacts on quality of life. Tailoring pharmacological treatment based on genetic polymorphisms is a current trend to personalizing pharmacological treatment in patients with major depressive disorders. Current guidelines for the use of genetic tests in major depression issued by the Clinical Pharmacogenomics Implementation Consortium (CPIC) are based on CYP2D6 and CYP2C19 polymorphisms which constitute the strongest evidence for pharmacogenomic guided treatment. There is evidence of increased clinical response to pharmacological treatment in major depression although largely in non-treatment resistant patients from Western countries. In this study, well characterised participants (N = 15) with complex, largely treatment resistant unipolar major depression were investigated, and clinical improvement was measured at baseline and at week-8 after the pharmacogenomics-guided treatment with the Montgomery Åsberg Depression Rating Scale (MÅDRS). Results suggested a statistically significant improvement (p = 0.01) of 16% at endpoint in the whole group and a larger effect in case of changes in medication regime (28%, p = 0.004). This small but appreciable effect can be understood in the context of the level of treatment resistance in the group. To our knowledge, this is the first study from the Middle East demonstrating the feasibility of this approach in the treatment of complex major depressive disorders.

Head to Toe Psychiatry: The Lady Who Limped in front of a Psychiatrist.

Physical examination is a core component of any assessment done by a physician. Despite that, a physical examination is not always a top priority in many patients with psychiatric illnesses. We present the case of a woman with a prior diagnosis of a delusional disorder with overinvested religious beliefs. The patient had been stable on treatment for many years and only recently presented with a physical complaint, and manifestation assumed to be due to the nature of her psychiatric illness and, hence, overlooked by many physicians before being examined by her last psychiatrist. This resulted in a significant mobility problem for the patient. The patient showed partial insight, linking her pain to a "message from God." Despite the delusional context, the psychiatrist was allowed to examine her feet and discovered significant neglect and poor foot hygiene. This case emphasizes the importance of conducting thorough physical examinations in psychiatric settings. Moreover, it presents an example of situations preventing psychiatric patients from being examined despite displaying obvious physical signs.

Can Cotard Syndrome Be Induced?: Illustration With a Rare Case of Potential Organ Transplant.

ABSTRACT: Cotard syndrome is a rare condition characterized by delusions ranging from a belief that one has lost organs to insisting that one has lost one's soul or is dead. This is the report a case of a 45-year-old man who was comatose after an attempted suicide. This was initially diagnosed as brain death and use of his organs for transplantation was actively considered. However, he awakened days later with new-onset Cotard syndrome. It remains difficult to know the link, unconscious or conscious, between this patient's delusions and the fleeting intention of doctors who intended to transplant his organs. This is the first description of a coincidence between delusional denial of an organ and the potential medico-surgical act of having an organ removed. This case is an opportunity to revisit the philosophical concepts of negation and nihilism. A multidisciplinary reflection is needed to give meaning to other clinical presentations.

Impact of early use of long-acting injectable antipsychotics on functional outcome in first episode psychosis: a 3-year longitudinal study.

OBJECTIVES: To describe, in a naturalistic setting, the impact of the early use of LAI-AP on functional outcomes of early psychosis patients as compared to oral antipsychotics (OAP). METHODS: Longitudinal prospective 3-year naturalistic study of all consecutive admissions (n = 416) to two Early intervention services (EIS) for psychosis comparing baseline characteristics and the evolution of global functioning, occupation (work and studies), and living arrangements autonomy according to the route of administration of the antipsychotic medication. The cohort was divided into four groups: LAI-AP first (started on LAI-AP and later received OAP), OAP first, LAI-AP only, and OAP only. RESULTS: Global assessment of functioning (GAF) improved in all groups, but our mixed-effect model did not show any significant association between the route of administration and the GAF outcome. The LAI-AP only group was significantly less likely to have extreme residential instability at 3 years than the other groups despite its highest proportion of homeless youth and their poor prognostic factors at baseline. CONCLUSIONS: Our naturalistic study suggests a significant protective effect of LAI-AP on extreme residential instability for the most vulnerable patients, but no impact of the first AP administration route on other functional outcomes was observed at 3 years of follow-up. Key pointsLong-acting injectable antipsychotics seem promising to avoid extreme residential instability in early psychosis.Global assessment of functioning (GAF) improved in all groups.There was no significant association between the first route of administration and global functionning.

Effectiveness of pharmacogenomic tests including CYP2D6 and CYP2C19 genomic variants for guiding the treatment of depressive disorders: Systematic review and meta-analysis of randomised controlled trials.

Major depressive disorders are prevalent conditions with limited treatment response and remission. Pharmacogenomics tests including CYP2D6 and CYP2C19 genomic variants provide the most reliable actionable approach to guide choice and dosing of antidepressants in major depression to improve outcomes. We carried out a meta-analysis and meta-regression analyses of randomised controlled trials evaluating pharmacogenomic tests with CYP2D6 and CYP2C19 polymorphisms in major depression. A systematic review was conducted according to PRISMA and Cochrane guidelines to search several electronic databases. Logarithmically transformed odds ratios (OR) and confidence intervals (CI) for improvement, response and remission were calculated. A random-effects meta-analysis and meta-regression analyses were subsequently carried out. Twelve randomised controlled trials were included. Pharmacogenomic tests in the treatment of depression were more effective than treatment as usual for improvement (OR:1.63, CI: 1.19-2.24), response (OR: 1.46; CI: 1.16-1.85) and remission (OR: 1.85; CI: 1.23-2.76) with no evidence of publication bias. Remission was less favourable in recent studies. The results are promising but cautious use of pharmacogenomics in major depression is advisable. PROSPERO registration ID: CRD42021261143.

Frequency of illness anxiety (hypochondriasis) by proxy encountered by doctors in parents towards their children.

BACKGROUND: Illness anxiety disorder is a condition of having a persistent fear of having a serious or life-threatening illness despite few or no symptoms. Current classification systems assume that illness anxiety is experienced relative to one's own health, and not towards others ("by proxy"), yet it has been observed to occur in parents towards their children. This study was designed to survey doctors about how commonly they encounter illness anxiety by proxy (IAP). METHODS: We conducted a qualitative survey of 149 physicians who work with children (pediatricians, psychiatrists, and general practitioners) from the United Arab Emirates (UAE) and Egypt. The survey was administered via email and a paper-based form. In the UAE, 108 physicians were emailed the survey; 55 (50.1%) responded. For the email survey we used items from the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). An additional 100 physicians were surveyed in person; 94 (94%) responded. RESULTS: Nearly all respondents (98.7%) reported having encountered IAP in parents. Of these, 51 (34.2%) reported frequently encountering these types of health anxieties, and 50 (33.6%) reported that the parents' concern that their child had a serious disease persisted despite reassurance and appropriate medical evaluation. Seventy-eight (52.3%) respondents reported that exaggeration of actual existing symptoms was the most common reason for parents' fears; 72 (48.3%) reported that the concerned parent was more likely to be the mother; and 36 (24.2%) reported that most parents were not 100% certain of their own beliefs. CONCLUSIONS: IAP is frequently encountered by pediatricians, psychiatrists, and general practitioners. Practitioners who work with children and their parents need to be aware of this phenomenon to provide appropriate support and treatment. More research is needed to screen for the extent and severity of this phenomenon.

A functional neuroimaging study of self-other processing alterations in atypical developmental trajectories of psychotic-like experiences.

Self-disturbances constitute a hallmark of psychosis, but it remains unclear whether these alterations are present in at-risk populations, and therefore their role in the development of psychosis has yet to be confirmed. The present study addressed this question by measuring neural correlates of self-other processing in youth belonging to three developmental trajectories of psychotic experiences. Eighty-six youths were recruited from a longitudinal cohort of over 3800 adolescents based on their trajectories of Psychotic-Like Experiences from 12 to 16 years of age. Participants underwent neuroimaging at 17 years of age (mean). A functional neuroimaging task evaluating self- and other-related trait judgments was used to measure whole-brain activation and connectivity. Youth who showed an increasing trajectory displayed hypoactivation of the dorsomedial prefrontal cortex and hypoconnectivity with the cerebellum. By contrast, youth who showed a decreasing trajectory displayed decreased activation of the superior temporal gyrus, the inferior frontal gyrus, and the middle occipital gyrus. These findings suggest that the increasing trajectory is associated with alterations that might erode distinctions between self and other, influencing the emergence of symptoms such as hallucinations. The decreasing trajectory, in comparison, was associated with hypoactivations in areas influencing attention and basic information processing more generally. These alterations might affect the trajectories' susceptibilities to positive vs. negative symptoms, respectively.

Neural alterations of emotion processing in atypical trajectories of psychotic-like experiences.

The aim of this study was to investigate the neural bases of facial emotion processing before the onset of clinical psychotic symptoms in youth belonging to well-defined developmental trajectories of psychotic-like experiences (PLEs). A unique sample of 86 youths was recruited from a population-based sample of over 3800 adolescents who had been followed from 13 to 17 years of age. Three groups were identified based on validated developmental trajectories: a control trajectory with low and decreasing PLEs, and two atypical trajectories with moderate to elevated baseline PLEs that subsequently decreased or increased. All had functional magnetic resonance imaging data collected during a facial emotion processing task. Functional activation and connectivity data were analyzed for different contrasts. The increasing PLE trajectory displayed more positive psychotic symptoms while the decreasing trajectory exhibited more negative symptoms relative to the control group. During face processing, both atypical trajectories displayed decreased activations of the right inferior frontal gyrus (IFG), while the increasing trajectory displayed a negative signal in the precentral gyrus. The increasing PLE trajectory also displayed impaired connectivity between the amygdala, ventromedial prefrontal cortex, and cerebellum, and between the IFG, precuneus, and temporal regions, while the decreasing trajectory exhibited reduced connectivity between the amygdala and visual regions during emotion processing. Both atypical PLE trajectories displayed alterations in brain regions involved in attention salience. While the increasing trajectory with more positive symptoms exhibited dysconnectivity in areas that influence emotion salience and face perception, the decreasing trajectory with more negative symptoms had impairments in visual information integration areas. These group-specific features might account for the differential symptom expression.

Multidimensional analysis of adult patients' care trajectories before a first diagnosis of schizophrenia.

For patients at high-risk for developing schizophrenia, a delayed diagnosis could be affected, among many reasons, by their patterns of healthcare use. This study aims to describe and generate a typology of patients' care trajectories (CTs) in the 2 years preceding a first diagnosis of schizophrenia, over a medico-administrative database of 3712 adults with a first diagnosis between April 2014 and March 2015 in Quebec, Canada. This study applied a multidimensional approach of State Sequence Analysis, considering together sequences of patients' diagnoses, care settings and care providers. Five types of distinct CTs have emerged from this data-driven analysis: The type 1, shared by 77.6% of patients, predominantly younger men, shows that this group sought little healthcare, among which 17.5% had no healthcare contact for mental disorders. These individuals might benefit from improved promotion and prevention of mental healthcare at the community level. The types 2, 3 and 4, with higher occurrence of mental disorder diagnoses, represent together 19.5% of the study cohort, mostly middle-aged and women. These CTs, although displaying roughly similar profiles of mental disorders, revealed very dissimilar sequences and levels of care providers encounters, primary and specialized care use, and hospitalizations. Surprisingly, patients of these CTs had few consultations with general practitioners. An increased attentiveness for middle-aged patients and women with high healthcare use for mental disorders could help to reduce delayed diagnosis of schizophrenia. This calls for further consideration of healthcare services for severe mental illness beyond those offered to young adults.

Cannabidiol effects on cognition in individuals with cocaine use disorder: Exploratory results from a randomized controlled trial.

BACKGROUND: Cocaine use disorder (CUD) is associated with various cognitive deficits that impede patients' functionality, prognosis and therapeutic outcomes. New pharmacological treatments for CUD that could improve cognition are needed. OBJECTIVE: To explore whether cannabidiol (CBD) is superior to placebo to improve cognitive functioning in individuals with CUD. METHODS: We conducted an exploratory analysis of a single site, randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in reducing craving, cocaine use and relapse in individuals with CUD. Seventy-eight individuals diagnosed with CUD were randomized to receive either CBD (800 mg) or placebo for 92 days. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess inhibition (Stop Signal Task; SST), risky decision making (Cambridge Gambling Task; CGT) and visual memory (Pattern Recognition Memory; PRM). This assessment was made on day 1, day 7 and at week 6. We controlled for sex, severity of dependence and baseline cognitive scores in our generalized estimating equation models. RESULTS: Both groups performed similarly on the PRM (correct answers: p = 0.080), SST (stop signal reaction time: p = 0.644) and CGT (quality of decision making: p = 0.994; deliberation time: p = 0.507; delay aversion: p = 0.968; risk taking: p = 0.914) tests. CONCLUSIONS: We found no evidence for 800 mg of CBD to be more efficacious than placebo for improving cognitive outcomes. Clinical trials evaluating pharmacological treatments for CUD should continue to be a research priority.