Persistent Psychotic Symptoms Research Articles

3-Methoxy-Phencyclidine Induced Psychotic Disorder: A Literature Review and an 18F-FDG PET/CT Case Report.

New Psychoactive Substances (NPS) are modifying the drug scenario worldwide and have become a public health concern because of their toxicological profiles and their harmful physical/psychological effects. 3-Methoxy-Phencyclidine (3-MeO-PCP), a non-competitive antagonist of glutamate N-methyl-D-aspartate (NMDA) receptors, belongs to the phencyclidine-like subfamily of arylcyclohexylamines and has gained attention for its toxic, sometimes fatal, effects. Despite several cases of intoxication and death reported in the literature, little is known about substance-induced psychotic disorders (SIP) and potential cognitive impairment following 3-MeO-PCP intake. This literature review aimed to summarize available evidence about 3-MeO-PCP mechanisms of action and physical and psychotropic effects and to spread preliminary findings about persistent psychotic symptoms and impaired cognitive functioning. Additionally, the case of an SIP is reported in a 29-year-old man with small oral intakes of 3-MeO-PCP over two weeks until a high dose ingestion. Psychometric and neuropsychological assessment and brain [18F]-fluorodeoxyglucose positron emission tomography integrated with computed tomography were used to support clinical description. Identifying and addressing the characteristic clinical features and neural substrates of NPS-induced psychoses might help clinicians with a more precise differentiation from other psychotic disorders. Although further studies are required, phenotyping the cognitive profile of NPS users might provide targets for tailored therapeutic approaches.

The effect of lithium on clozapine-induced neutropenia reduction in refractory schizoaffective disorder

Resistant schizoaffective disorder has persistent psychotic symptoms and intermittent mood swings. A satisfying method for treating these patients is the use of the antipsychotic drug clozapine, but its use is limited due to significant side effects such as leukopenia and neutropenia. Lithium carbonate is another psychiatric drug that reduces these side effects. We hypothesized that lithium, along with clozapine, in addition to controlling side effects, could have a dual effect on mood episodes in schizoaffective disorder, and used it in a chronic case. The patient was a 48-year-old man with a 20-year history of the disease. Therefore, the use of lithium along with clozapine is recommended in refractory schizoaffective patients.

Klassieke psychedelica: veiligheid, neveneffecten en medicatie-interacties

Classic psychedelics: safety, side effects and medication interactions Given the growing scientific and social interest in the use of classic psychedelics for psychiatric disorders, physicians are increasingly confronted with patients resorting to these drugs. To this date, treatment with classic psychedelics within a medical framework is non-existent. Patients could seek such a treatment themselves by means of a retreat under the guidance of (non-)professionals in a non-official health facility in countries where the use of these substances is legalised. They could also go ‘underground’ in countries where these substances are illegal. It is important that physicians have an open conversation with their patients in order to adequately inform them and make a risk assessment. In this article, the safety, side effects and drug interactions of classic psychedelics are reported. Classic psychedelics are non-addictive and have a low toxicity. Their use under controlled conditions reduces the risk of serious unwanted effects, such as persistent psychotic symptoms, disabling flashback phenomena or increased suicidality. Under uncontrolled conditions and in the absence of psychological support, these risks are, however, real and thus the use of these drugs to treat psychological symptoms should be strongly discouraged. Interactions with other drugs are possible. This risk should be assessed individually for each patient, depending on the medication and type of psychedelic.

The Development of Psychosis in Patients with Substance Use Disorder and Its Association with Cavum Septum Pellucidum and Adhesio Interthalamica.

It is known that there is a relationship between psychotic disorders and the presence of cerebral midline defects, such as the cavum septum pellucidum and the absence of adhesio interthalamica. This study aims to investigate whether these defects in people with alcohol/substance use disorders are associated with the occurrence and persistence of psychotic symptoms. The files of the patients who were hospitalized in an addiction inpatient unit were retrospectively scanned. The presence of cavum septum pellucidum and the absence of adhesio interthalamica were determined by evaluation of the magnetic resonance imaging findings. The presence of psychotic symptoms at admission and the persistence of psychotic symptoms after 2 weeks of detoxification treatment were used as dependent variables in different logistic regression models. The presence of cavum septum pellucidum and the absence of adhesio interthalamica were included in 2 separate models as independent variables. The results of the regression analyses showed no significant relationship with respect to cavum septum pellucidum. However, the analyses revealed that the absence of adhesio interthalamica increases the risk of the persistence of psychotic symptoms. Our findings suggest that the absence of adhesio interthalamica can be considered a structural risk factor for the development of psychosis in people receiving treatment for substance use.

Late life onset of persistent psychosis and incident dementia: risk stratification by baseline cognitive status

AbstractBackgroundMild Behavioral Impairment (MBI) is a validated neurobehavioral syndrome characterized by later life emergent and persistent neuropsychiatric symptoms (NPS) as an at‐risk state for incident cognitive decline and dementia. Psychosis is one of the five domains of MBI, although dementia risk with MBI‐psychosis is not well quantified. Here, we assessed the longitudinal association of MBI‐psychosis with incident dementia in dementia‐free participants.MethodData were obtained from the National Alzheimer Coordinating Centre (NACC). Participants with neurodevelopmental, neurological and/or psychiatric disorders were excluded. Participants with normal cognition (NC) or mild cognitive impairment (MCI) at baseline were included. MBI‐psychosis status was defined based on persistence of Neuropsychiatric Inventory Questionnaire delusions and hallucinations symtoms across two consecutive visits. Kaplan‐Meier curves of ten‐year dementia‐free survival probability were generated for MBI‐psychosis versus those with no NPS prior to dementia diagnosis. Cox proportional hazard models were implemented to assess the risk of dementia, adjusted for age, sex, education, race, APOE e4 status, and clinical cognitive diagnosis. Interaction terms were included for relevant demographic variables. Secondary analyses were implemented to compare the risk associated with MBI‐psychosis to MBI without psychosis.ResultThe final sample consisted of 3,446 participants with no NPS (age = 73.1±9.6; 63% female; 13.2% MCI), and 58 with MBI‐psychosis (age = 74.9±9.9; 55.2% female; 69% MCI). MBI‐psychosis was associated with lower chance of dementia‐free survival over ten years and 3.36 times greater risk for dementia compared to no NPS (CI:2.19‐5.15, p<0.001). Moderation analysis revealed that in NC, those with MBI‐psychosis were at 8.15 times greater risk of dementia than those with no NPS (CI:2.57‐25.88, p<0.001). In MCI, the MBI‐psychosis‐associated dementia risk was 3.08 times greater (CI:1.95‐4.85, p<0.001). In the secondary analysis comparing MBI‐psychosis to MBI without psychosis (n = 2068), MBI‐psychosis was associated with 2.29 times greater risk of dementia (CI: 1.52‐3.4, p<0.001).ConclusionAlthough psychosis is an infrequently endorsed MBI domain, when present, it is associated with substantial risk for dementia. This risk differs between cognitive strata and is significantly greater when MBI‐psychosis emerges in NC versus MCI. The emergence of persistent psychotic symptoms in later life should be flagged for clinical attention, and a dementia assessment considered.

The clinical profile and outcome of patients receiving continuation electroconvulsive therapy (C-ECT): A retrospective study.

There is a lack of data on the use of continuation electroconvulsive therapy (C-ECT) from India. This study aimed to evaluate the clinical profile and outcome of patients receiving C-ECT. The ECT register was used to identify patients receiving C-ECT (ECT after completion of an acute course, to maintain remission or prevent relapse) from 2011 to July 2022. Socio-demographic, clinical, and treatment outcome details were extracted from their treatment records. A total of 72 C-ECT courses were identified that were used in 60 patients. Out of all the patients receiving ECT, only 3.25% of patients receive C-ECT. The majority of the patients were male (60%). The mean age of the patients at the time of starting ECT was around 39 years. The most common diagnosis was schizophrenia (73.3%), followed by recurrent depressive disorder (21.6%). The most common indication was persistent psychotic symptoms poorly responding to multiple antipsychotic trials of 3.09 (SD: 1.39), including clozapine. These patients received a mean of 22.58 (SD: 8.05; range: 10 to 46) ECTs, with 10.0 (SD: 4.83) ECTs for the management of the acute phase of illness and 12.57 (SD: 6.20) ECTs as part of continuation treatment. The majority (61.1%) of the patients received four (once weekly) C-ECTs in the first month, followed by three more in the next month. However, 16 patients received weekly ECTs during the second month too, as symptoms worsened with the lowering of frequencies. Twelve patients received more than one C-ECT course. The majority of the patients maintained the improvement gained during the acute phase or showed further improvement with C-ECT along with ongoing pharmacotherapy as rated on appropriate scales. The Clinical Global Impressions-Severity (CGI-S) difference before and after C-ECTs was 2.94 (SD: 0.88). C-ECT is considered in only in a small proportion of patients. However, when used, it is effective in maintaining the benefits gained during the acute course of ECT and preventing relapse.

Influence of cannabis use on incidence of psychosis in people at clinical high risk.

Evidence for case-control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome. Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale. During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome. These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder.

A longitudinal study of late-life psychosis and incident dementia and the potential effects of race and cognition

Later-life psychotic symptoms are meaningful and are associated with adverse outcomes. Psychosis is an important domain in mild behavioural impairment (MBI), a syndrome that incorporates later-life emergent and persistent neuropsychiatric symptoms (NPS) in dementia-free individuals into dementia prognostication. However, MBI-psychosis-associated risk and its interaction with race has not been well quantified. Here we determined risk of incident dementia in dementia-free participants with MBI-psychosis and effect modification by race as an important factor in assessing the risk of psychosis. Data for participants with normal cognition (NC) or mild cognitive impairment (MCI) from the National Alzheimer Coordinating Centre were used. Participants with neurodevelopmental, neurological and/or longstanding psychiatric disorders were excluded. MBI-psychosis was defined by persistence of delusions and hallucinations across two consecutive visits. Kaplan–Meier curves of ten-year dementia-free survival were generated for MBI-psychosis versus no NPS before dementia diagnosis. Cox proportional hazard models were implemented to assess relative incidence rates, adjusted for cognitive status, age, sex, education, race and APOE-ε4 status. Interaction terms were included for relevant demographic variables. Similar secondary analyses utilized MBI-no-psychosis as reference. The sample consisted of 3,704 no-NPS (age = 72.8 ± 9.9; 62.7% female; 13.4% MCI) and 66 MBI-psychosis (age = 75.2 ± 9.8; 53% female; 72.7% MCI) participants. For MBI-psychosis, in reference to no NPS, the hazard ratio (HR) for incident dementia was 3.76 (CI: 2.53–5.58, p < 0.001), while for conventionally captured psychosis, the HR was 1.92 (CI: 1.58–2.33, p < 0.001). Interaction analyses revealed that in NC, those with MBI-psychosis had a 9.96-fold greater incidence of dementia than those with no NPS (CI: 3.65–27.22, p < 0.001). In MCI, the MBI-psychosis-associated dementia incidence was 3.38-fold greater than no-NPS (CI: 2.22–5.15, p < 0.001). Furthermore, MBI-psychosis-associated dementia incidence in Black participants was 7.44-fold greater than no NPS (CI: 3.54–15.65, p < 0.001), while in white participants, it was 3.18-fold greater (CI: 1.94–5.2, p < 0.001). In a secondary analysis, compared with MBI-no-psychosis (n = 2,260), MBI-psychosis had a 2.47-fold greater incidence of dementia (CI: 1.69–3.59, p < 0.001). Although psychosis is an infrequently endorsed MBI domain, when present it is associated with substantial risk for dementia. HRs differed between cognitive strata, and these differences were significantly greater when MBI-psychosis emerged in NC as opposed to MCI, emphasizing the importance of cognitive assessment at the time of symptom emergence. In addition, the relationship between MBI-psychosis and incident dementia was stronger in Black participants than in white participants. The emergence of persistent psychotic symptoms in older adults is clinically meaningful, and MBI-psychosis identifies a high-risk group for precision medicine approaches to dementia prevention. In this analysis, authors examined the potential interaction of later-life emergent and persistent psychotic symptoms with race and cognition on incident dementia, finding that participants with mild behavioural impairment (MBI) psychosis were at greater risk for incident dementia than those who had no neuropsychiatric symptoms (NPS). Moreover, the risk of incident dementia for Black participants with MBI-psychosis was elevated.

A Complicated Case: Presenting Neuropsychiatric Symptoms After COVID Infection

IntroductionThe COVID-19 pandemic has affected millions of people worldwide. Among a large number of deaths, COVID-19 has caused significant health-related sequelae involving many systems of the body. Some results include increased anxiety, depression, insomnia, and other distress symptoms. Additionally, there are reports of sudden onset of psychosis in patients with no psychiatric history following COVID-19.ObjectivesEmphasizing the importance of Covid 19 causing many psychiatric diseases, although its etiology is not yet known.MethodsReport of a clinical caseResultsWe report a 68-year-old previously healthy woman with no personal or family history of mental illness who was hospitalized due to COVID-19 and then started to have psychiatric complaints. She had complaints such as refusal to speak, eat and drink, fear of death which started after her discharge from the hospital due to COVID-19.On 14.07.2021, she applied to the psychiatry outpatient clinic of our hospital for the first time. In addition to the existing complaints, we have considered the preliminary diagnoses of dementia and psychotic depression due to the increasing fear of being alone, going out alone, confusion in the interim periods, and thoughts that someone will harm her and her family. We consulted the neurology clinic and she was admitted to the neurology service with a preliminary diagnosis of encephalitis. During her hospitalization, the patient’s EEG and MRI were taken, LP was performed, and no pathology was detected in the examinations. Her current psychiatric treatment (escitalopram 10mg/d, medazepam 2mg/d, and olanzapine 2,5mg/d) continued throughout her hospitalization in the neurology service, but her complaints did not change. She was fed formula with an NG tube, IV hydration was provided, and a urinary catheter was inserted.After ruling out neurological disease on 12.08.2021, the patient was admitted to our psychiatry service with a prediagnosis of catatonic-psychotic depression. Electroconvulsive therapy was planned because the visual hallucinations and persecutory delusions persisted. Total of 7 sessions of ECT were received. The patient’s oral intake started with the current treatment, and her fluent speech began. Olanzapine dose was increased to 7.5mg/d, and escitalopram dose was increased to 20mg/d due to persistent depressive and psychotic symptoms. The patient was discharged on 02.09.2021 with the current treatment. Her complaints had improved before she was discharged.Conclusions COVID-19 remains an emerging disease with unknown psychological sequelae. Caution should be exercised regarding psychiatric symptoms and associated risks in patients with a recent diagnosis of COVID-19. Cytokine storm may also be involved in the etiology, in addition to many psychological factors such as fear of illness, uncertainty, and isolation. Potential risk factors and underlying biological mechanisms should be investigated.Disclosure of InterestNone Declared

Het maligne neurolepticasyndroom kan zich presenteren zonder koorts

Neuroleptic malignant syndrome can present without fever Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic adverse reaction to antipsychotic drugs. A fast recognition of NMS is vital to prevent a fatal outcome. In this article, the case of a 15-year-old boy with psychosis presenting with motor symptoms like tremor and akathisia while on olanzapine is discussed. Due to persistent psychotic symptoms and motoric side effects under olanzapine, the therapy was switched to aripiprazole. This switch resulted in a dramatic worsening of the symptoms and a sudden decrease in global functioning. Psychosis with catatonia was diagnosed and lorazepam was started, with a moderate effect. After several days, lower back pain, chest pain, excessive sweating and rigidity emerged. A blood sample showed extremely high serum creatine kinases. The catatonic state had evolved to NMS during the switch to antipsychotics. The absence of hyperthermia delayed the diagnosis because of the misleading idea that NMS is always associated with an increased body temperature.

A two-year follow-up study on the first manic episode due to mood-incongruent psychosis.

Mood-incongruent psychosis during bipolar disorder has been associated with poor outcomes. However, it remains unknown whether this is secondary to persistent affective or psychotic symptoms or both. Sixty-eight patients with bipolar disorder between the ages of 16 and 45 were recruited during their first psychiatric hospitalization for mania. These patients were evaluated using structured and semi-structured clinical interview then followed longitudinally. Outcomes during the first twenty-four months of follow-up were compared between patients with mood-incongruent psychosis and those without (i.e., patients with mood-congruent psychosis or no psychosis) during the index manic episode. Specifically, ratings of the percent of weeks during follow-up with the duration of mood incongruent psychotic symptom, any psychotic symptom, affective syndromes, and scores of global outcomes were compared. Comparing the 24-month follow-up results between the two groups, patients with mood incongruent psychotic symptoms had a lower global functional rating scale, efficacy index, while the duration of mood incongruent psychotic symptom, any psychotic symptom, and complete affective symptom showed statistically significant differences between the two groups. There were also statistically significant differences between the two groups in the duration of mood stabilizers, and antidepressants use, typical antipsychotics, and atypical antipsychotics. Partial correlation analysis reveals the scores of the global assessment of functioning scale (GAF) after 24 months showed a significant negative correlation with the length of time of incongruent psychotic symptoms. Still, the correlation was intermediate (correlation coefficients less than 0.5，r2 =-0.471, P<0.001). Mood-incongruent psychosis that occurs during the first manic episode appears to predict an increased likelihood of persistent psychotic symptoms during the subsequent twenty-four months. This persistence of psychosis is associated with a worse overall course of illness than patients without mood-incongruent psychosis. These results apply to a relatively short outcome period, and the sample size is relatively small.

Changes in corticostriatal connectivity and striatal tissue iron associated with efficacy of clozapine for treatment‑resistantschizophrenia.

RationaleThough numerous studies demonstrate the superiority of clozapine (CLZ) for treatment of persistent psychotic symptoms that are characteristic of treatment-refractory schizophrenia (TRS), what remains unknown are the neural and molecular mechanisms underlying CLZ’s efficacy. Recent work implicates increased corticostriatal functional connectivity as a marker of response to non-CLZ, dopamine (DA) D2-receptor blocking antipsychotic drugs. However, it is undetermined whether this connectivity finding also relates to CLZ’s unique efficacy, or if response to CLZ is associated with changes in striatal DA functioning.ObjectiveIn a cohort of 22 individuals with TRS, we examined response to CLZ in relation to the following: (1) change in corticostriatal functional connectivity; and (2) change in a magnetic resonance-based measure of striatal tissue iron (R2’), which demonstrates utility as a proxy measure for elements of DA functioning.MethodsParticipants underwent scanning while starting CLZ and after 12 weeks of CLZ treatment. We used both cortical and striatal regions of interest to examine changes in corticostriatal interactions and striatal R2’ in relation to CLZ response (% reduction of psychotic symptoms).ResultsWe first found that response to CLZ was associated with an increase in corticostriatal connectivity between the dorsal caudate and regions of the frontoparietal network (P < 0.05, corrected). Secondly, we observed no significant changes in striatal R2’ across CLZ treatment.ConclusionOverall, these results indicate that changes in corticostriatal networks without gross shifts in striatal DA functioning underlies CLZ response. Our results provide novel mechanistic insight into response to CLZ treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00213-022-06138-0.

Role of Religion and Spirituality in Managing Residual Schizophrenia: Article Review

Background: Residual Schizophrenia is a chronic condition of schizophrenia characterized by a history of leastwise one psychotic episode with more prominent negative symptoms. Schizophrenic patients who have persistent psychotic symptoms and patients with residual schizophrenia should receive adequate pharmacotherapy, and may consider additional cognitive therapy, as it has been shown to help reduce relapse rates, reduce psychotic symptoms, and improve or stabilize the patient's mental state. Objective: To determine the role of religion and spirituality in the management of patients with residual schizophrenia.Methods: The design of this research is a literature review or library review, which is a systematic, direct, and reproducible research method by identifying, evaluating, and synthesizing published research.Result: Patients with a higher level of religion or spirituality or their strong personal belief system are more likely to use positive appraisal to deal with their illness or problem which includes giving positive meaning to the situation and being optimistic. Conclusion: The presence of religion and spirituality help the coping mechanisms of residual Schizophrenia patients which also improves patient management, accelerate the healing process, and increases QOL of patients. Keywords: Spirituality, Religion, Residual Schizophrenia.

Medication Adherence and its Association with Subjective Well Being among Persons with Schizophrenia: A Descriptive Trial from Assam

Medicationnon-adherence has been associated with persistence of psychotic symptoms, relapse, and hospitalisation inpatientswithschizophrenia. Adherenceto antipsychotic drug treatment is a key issue for nurses and treatment team members caring forpatientswho typically are on chronic, progressive disease course. The study was conducted at LGB Regional Institute of Mental Health, Tezpur, Assam to assess the medication adherence and its association with subjective well-being. Descriptive research design was opted for the present study with 85 samples selected by using convenience sampling technique. Semi-structured interview technique was used to collect the data. Descriptive and inferential statistics were used to analyse the obtained data. Results showed that 34.1 percent patients were not adherent to medication. Significant association was found between the Subjective well-being and Medication Adherence at 0.05 level of significance. Significant association was also found between the medication adherence and Inadequate Mental Mastery Factor (Factor 8) of Subjective well-being at 0.02 level of significance.

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Background:There is lack of data on use of Continuation Electro Convulsive Therapy (C-ECT) from India.Aim:This study aimed to evaluate the clinical profile and outcome of patients with severe mental illness receiving C-ECT.Method:ECT register was used to identify patients receiving C-ECT (ECT after completion of acute course, to maintain remission/ prevent relapse) during 2011 to 2021. Sociodemographic, clinical and outcome details were extracted from treatment records. Sixty C-ECT courses were identified, used in 49 patients.Results:Majority were male (58.3%), single (56.7%), unemployed (66.7%), belonged to Hindu religion (70%), middle socioeconomic status (91.7%) and urban background (66.7%). Mean age at starting of ECT was around 40 years. Commonest diagnosis was schizophrenia (75%) followed by recurrent depressive disorder (18.3%). Commonest indication was persistent psychotic symptoms despite multiple antipsychotic trials (3.33±1.37), including clozapine. They received a mean of 22.62±8.02 ECTs, of which 9.93±4.41 were acute phase and 12.68±6.52 were for continuation treatment. Majority (66.7%) of them received 4 C-ECTs in the first month, followed by 2 more in the next month. As symptoms worsened with lower frequencies, 16 patients received weekly ECTs during the second month too. CGI-severity scores decreased from 6.50±0.60 to 3.80±0.75 at the end of C-ECT course. Majority of them maintained improvement gained during acute phase or showed further improvement with C-ECT with ongoing pharmacotherapy as rated on appropriate scales.Conclusion:C-ECT is considered only in small proportion of patients but is effective in maintaining benefits gained during acute course of ECT and preventing relapse.

Fingertip advanced glycation end products and psychotic symptoms among adolescents

Case control studies have suggested that advanced glycation end products play a key role in the pathophysiology of chronic schizophrenia. However, the longitudinal association between advanced glycation end products and psychotic symptoms among drug-naïve adolescents remains unclear. This study examined whether advanced glycation end products could predict the trajectory of psychotic symptoms in drug-naive adolescents using data from prospective population-based biomarker subsample study of the Tokyo Teen Cohort. A total of 277 community-dwelling adolescents aged 13 years without antipsychotic medication were analyzed. Fingertip advanced glycation end products were measured in adolescents using noninvasive technology that can be used quickly. The trajectory of psychotic symptoms in a 12-month follow-up was assessed by experienced psychiatrists using a semi-structured interview. Of the 277 participants, 13 (4.7%) experienced persistent psychotic symptoms (psychotic symptoms at baseline and follow-up), 65 (23.5%) experienced transient psychotic symptoms (psychotic symptoms at baseline or follow-up), and 199 (71.8%) did not have psychotic symptoms. Multinomial logistic regression analysis adjusted for age and sex revealed that baseline fingertip advanced glycation end products might predict the risk of persistent psychotic symptoms (odds ratio = 1.68; 95% confidence interval, 1.05–2.69; P = 0.03). Altogether, fingertip advanced glycation end products potentially predicted the trajectory of psychotic symptoms among drug-naive adolescents, which indicated its involvement in the pathophysiology of early psychosis. Further studies are required to identify strategies to reduce adolescent advanced glycation end products, which may contribute to preventing the onset of psychosis.

Longitudinal symptomatic interactions in long-standing schizophrenia: a novel five-point analysis based on directed acyclic graphs.

Recent network models propose that mutual interaction between symptoms has an important bearing on the onset of schizophrenic disorder. In particular, cross-sectional studies suggest that affective symptoms may influence the emergence of psychotic symptoms. However, longitudinal analysis offers a more compelling test for causation: the European Schizophrenia Cohort (EuroSC) provides data suitable for this purpose. We predicted that the persistence of psychotic symptoms would be driven by the continuing presence of affective disturbance. EuroSC included 1208 patients randomly sampled from outpatient services in France, Germany and the UK. Initial measures of psychotic and affective symptoms were repeated four times at 6-month intervals, thereby furnishing five time-points. To examine interactions between symptoms both within and between time-slices, we adopted a novel technique for modelling longitudinal data in psychiatry. This was a form of Bayesian network analysis that involved learning dynamic directed acyclic graphs (DAGs). Our DAG analysis suggests that the main drivers of symptoms in this long-term sample were delusions and paranoid thinking. These led to affective disturbance, not vice versa as we initially predicted. The enduring relationship between symptoms was unaffected by whether patients were receiving first- or second-generation antipsychotic medication. In this cohort of people with chronic schizophrenia treated with medication, symptoms were essentially stable over long periods. However, affective symptoms appeared driven by the persistence of delusions and persecutory thinking, a finding not previously reported. Although our findings as ever remain hostage to unmeasured confounders, these enduring psychotic symptoms might nevertheless be appropriate candidates for directly targeted psychological interventions.

The 2020 World Congress of Psychiatric Genetics: Schizophrenia highlights with an eye on sex differences

Persistent psychotic symptomatology might be present in a group of patients with borderline personality disorder (BPD) according to recent research findings.Investigate whether psychotic symptoms could be associated to greater cognitive and functional impairment in BPD patients.In this observational, cross-sectional study (PI14/01449 and PI17/01023), we investigated the incidence of persistent psychotic symptoms in BPD patients and its association with specific neurocognitive impairments. A sample of 120 patients with diagnosis of BPD according to DSM IV TR was studied.A substantial number of BPD patients (52, 43,3%) presented psychotic symptoms for a period longer than 6 months. Among BPD patients with psychotic symptoms, 25 (48%) presented hallucinations, 35 (67,3%) presented delusional thoughts and 8 patients (15%) presented both. BPD psychotic patients had greater global severity at the CGI than non-psychotic patients (p 0.02).Psychotic BPD patients had greater impairment in attention (Hedges g = −0.36, 95% CI = −0.72 to 0.00) and in the executive functions domain (Hedges g = −0.48, 95% CI = −0.84 to −0.12) including working memory and cognitive flexibility. There were no differences of neurocognitive performance between patients with hallucinations and patients with delusional thoughts.Persistent psychotic symptoms are present in one third of BPD patients and are probably associated with neurocognitive and social impairment. Thus, it is a priority to extensively investigate the nature of interactions between psychosis, BPD psychopathology and neurocognitive impairment, in order to better understand BPD phenotypes and to design adjusted treatment interventions.

A prospective multicenter assessor-blinded randomized controlled study to compare the efficacy of short versus long protocols of electroconvulsive therapy as an augmentation strategy to clozapine in patients with ultra-resistant schizophrenia (SURECT study)

BackgroundAlthough clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia, it leads to a poor or partial response in 40 to 70% of patients. Augmentation of clozapine with electroconvulsive therapy (ECT) is a highly effective and relatively safe treatment for these clozapine-resistant patients. However, parameters are not yet well specified, such as the optimal number of sessions, their frequency, and the relevance of maintenance ECT. Our objective is to compare the efficacy and tolerance between two protocols of combined ECT and clozapine treatment in patients with ultra-resistant schizophrenia (URS): a 6-month protocol (short protocol with 20 ECT sessions) and a 12-month protocol (long protocol with 40 ECT sessions).MethodsSixty-four patients with schizophrenia with persistent psychotic symptoms despite clozapine treatment will be enrolled in a prospective multicentric assessor-blinded randomized controlled trial. Patients will be randomly assigned to the short or the long protocol. The main outcome is the response rate assessed by the Positive and Negative Symptoms Scale (PANSS) 3 months after the end of the treatment in patients following the long protocol compared to those following the short protocol. The response was defined as a 30% reduction on the PANSS baseline. Clinical assessments (PANSS, BPRS, HAMD-21, YMRS, CGI, GAF, Modified Overt Aggression Scale (MOAS), and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS)) and plasma clozapine concentration will be performed at baseline and at 2, 4, 6, 9, 12, and 15 months. Neuropsychological measures (MMSE, RL/RI-16, Doors test, D2 Test of Attention, Copy of the Rey-Osterrieth complex figure) will be performed at baseline and at 6 and 15 months.DiscussionThe aims of this research are to optimize protocols of combined ECT with clozapine in patients with URS and to offer specific recommendations for these patients’ care.Trial registrationClinicalTrials.gov NCT03542903. Registered on May 31, 2018. Id RCB: 2017-A02657-46

A Legal Right to Clozapine Therapy for Incarcerated Individuals With Treatment-Resistant Schizophrenia.

People with serious mental illnesses increasingly are being treated in jails and prisons, and during incarceration are afforded a constitutional right to medical care. This right pertains to both general medical and mental illnesses and both acute and chronic conditions. However, incarcerated patients with treatment-resistant schizophrenia (TRS) often are not offered clozapine, the only medication for this debilitating illness approved by the U.S. Food and Drug Administration. In this column, the authors argue that incarcerated individuals with TRS have a statutory and constitutional right to treatment with clozapine.