Chronic Psychosis Research Articles

Schizophrenia spectrum disorders: does the non-psychotic schizophrenia exist?

Current understanding of schizophrenia comes from Kraepelin’s dementia praecox doctrine, a disease that combined Kalbaum’s catatonia, Hecker’s hebephrenia and chronic delusional psychoses and later renamed to schizophrenia thanks to Bleuler. Since the beginning of the XX century, the systematics of schizophrenia has undergone a serious evolution and narrowing of diagnostic boundaries, which is reflected in various revisions of the ICD and editions of the DSM. Currently, the existence of non-psychotic forms of schizophrenia, mainly manifested by negative symptoms, is being questioned. In addition, the need for diagnostic differentiation of schizophrenia from autism spectrum disorder, which have only external similarities, but require fundamentally different therapeutic interventions, is emphasized.

Chronic Psychosis in a Patient with Usher Syndrome

Abstract Usher syndrome refers to a group of inherited disorders characterized by visual and auditory impairment. The risk of psychosis in Usher syndrome is higher than that in the general population and is difficult to approach and treat in light of sensory impairment. We present a case of a male with continuous psychotic symptoms for 20 years, in the setting of undiagnosed progressively deteriorating visual and auditory function, with details of treatment given. Possible underlying mechanisms of psychosis in such cases are discussed in brief.

Prosopagnosie et syndrome de Capgras : deux syndromes en miroir ?

First described in the 19th century in patients with brain lesions, prosopagnosia was named in 1947 by Joachim Bodamer (1910–1985), a German neuropsychiatrist. The term refers to the inability to recognise a familiar face, a rarely isolated symptom. Prosopagnosia is thought to result from brain lesions, predominantly at the ventral right temporo-occipital junction. There are more common cases of developmental prosopagnosia, where no lesion has been identified. Capgras syndrome (CS), described by Joseph Capgras (1873–1950), a psychiatrist, consists of the persistent belief that a close relative, identified, has been replaced by a look-alike. SC, considered a delusional disorder of identification or familiarity, has been described in chronic psychoses, mainly schizophrenia. It is also reported in the course of neurodegenerative diseases (mainly Alzheimer's disease, Lewy body dementia, Parkinson's dementia). Lesion-based forms have recently been described. Prosopagnosia and SC were initially thought to result from mirror-image lesions involving a single factor, one affecting an overt ventral circuit for face recognition (in the case of prosopagnosia), the other a covert dorsal circuit involved in emotional and vegetative responses (in the case of CS). Lesion network mapping has been used in both lesion-related conditions and suggests a more complex figure. Lesions causing prosopagnosia were correlated with one of the main regions associated with face recognition, the right fusiform face area, and anticorrelated with left frontal regions possibly involved in visual attentional control. In lesional forms of CS or other delusional misidentification syndromes, there was a correlation with left retrosplenial cortex, an area associated with familiarity processing, and a correlation with right frontal regions associated with belief evaluation. This finding supports the intervention of two factors in CS, one generating the impaired familiarity associated with perception and the other the genesis and persistence of a delusional idea. The debate on the mechanisms of CS is not settled, especially as it is limited to its lesional forms, but studies using lesion network mapping already mark a more general paradigm shift, with attention shifting from lesions (clinico-anatomical method) to circuit dysfunction.

All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis.

Patients with schizophrenia receiving antipsychotic treatment present lower mortality rates than those who do not. However, the non-adherence rate is high, which can be partially addressed using long-acting injectable (LAI) antipsychotics. The impact of LAI treatments on all-cause mortality compared to oral antipsychotics remains unclear. To fill that gap, a random effects meta-analysis was conducted to analyze the odds ratio (OR) of all-cause, suicidal, and non-suicidal mortality among patients taking LAI antipsychotics compared to oral antipsychotics (PROSPERO:CRD42023391352). Individual and pooled LAI antipsychotics were analyzed against pooled oral antipsychotics. Sensitivity analyses were performed for study design, setting, and industry sponsorship. Meta-regressions were conducted for gender, age, antipsychotic dose, and race. Seventeen articles, total sample 12,042 patients (N = 5795 oral, N = 6247 LAI) were included. Lower risk of all-cause mortality for patients receiving LAI antipsychotics vs receiving oral antipsychotics was found (OR = 0.79; 95%CI = 0.66-0.95). Statistical significance was maintained when only studies comparing the same LAI and oral antipsychotic were included (OR = 0.79; 95%CI = 0.66-0.95; p = <0.01), as well as for non-suicidal mortality (OR = 0.77: 95%CI = 0.63-0.94; p = 0.01), but not for suicidal mortality (OR = 0.86; 95%CI = 0.59-1.26; p = 0.44). Mortality reduction was more pronounced for LAI antipsychotics in first-episode psychosis (FEP) (OR = 0.79; 95%CI = 0.66-0.96) compared to chronic psychosis. No individual LAI reported statistically significant differences against all pooled oral antipsychotics. LAI antipsychotics are associated with a lower risk of all-cause and non-suicidal mortality in individuals with schizophrenia compared to oral antipsychotics. Better adherence to the medication and health services may explain this difference. Whenever possible, the use of LAIs should be considered from the FEP.

Rethinking Mental Automatism: De Clérambault's Theory in the Age of Novel Psychoactive Drugs: Psychotropic Effects and Synthetic Psychosis.

The widespread use of novel psychoactive substances (NPSs)-defined as new narcotic or psychotropic agents not classified under the Single Convention on Narcotic Drugs of 1961 or the Convention on Psychotropic Substances of 1971-poses a significant challenge to contemporary mental health paradigms due to their impact on psychiatric disorders. This study revisits and expands upon the theory of mental automatism as proposed by Gaëtan Gatian de Clérambault, aiming to elucidate the psychopathological mechanisms underlying substance-induced psychoses (SIP) and their distinction from non-induced psychoses (schizophrenia and related disorders). Through a phenomenological and clinical investigation, we explore the relevance of mental automatism in the development of toxic psychoses, drawing upon the historical and contemporary literature. This research highlights the psychopathological distinctions between induced and non-induced psychoses and the transition mechanisms from acute to chronic psychosis states. De Clérambault's theory, supplemented by Janet, Jackson, and Bonhoeffer's contributions, provides a foundational framework for understanding the genesis of SIP. Our findings suggest that NPS consumption, particularly among adolescents and psychiatric patients, significantly correlates with increased risks of SIP, marked by a transition to chronicity influenced by biological lesions triggered by substance use. Furthermore, we propose a comprehensive framework for SIP, integrating mental automatism, psychopathological distinctions, and transition mechanisms. This framework aims to refine diagnostic criteria and therapeutic approaches, addressing gaps in clinical practice and research. The study underscores the need for a nuanced understanding of SIP, advocating for a paradigm shift in psychiatric assessment and treatment approaches to better address the complexities of substance-induced mental health disorders.

The New Horizon of Antipsychotics beyond the Classic Dopaminergic Hypothesis-The Case of the Xanomeline-Trospium Combination: A Systematic Review.

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer's disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected twenty-one sources referring to fourteen studies focused on KarXT, out of which only four have available results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data are needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

431. Connectome-Based Predictive Modeling of Psychosis Symptoms in Early and Chronic Psychosis

431. Connectome-Based Predictive Modeling of Psychosis Symptoms in Early and Chronic Psychosis

Alcohol-Induced Psychosis: Beyond Korsakoff. Case report and Literature Review

IntroductionChronic consumption of alcohol has clear deleterious effects on the nervous system. Among its less-recognized consequences are subacute and chronic alcohol-induced psychotic disorders. Lasègue, Garnier, Magnan, and Michaux provided exhaustive clinical descriptions of different presentations of subacute alcoholic delusional disorder, while Kraepelin, Allamagny, and Neveu defined the characteristics of chronic alcoholic hallucinatory psychosis. Both conditions are characterized by the occurrence of hallucinations and vivid dream-like content in their delusions, along with potential emotional detachment from the symptoms. Presently, both conditions are categorized under the generic term ‘Alcohol-Induced Psychotic Disorder,’ with limited available scientific literature.ObjectivesOur goal is to bring attention to the existence of subacute and chronic alcohol-induced psychosis in individuals with long-term alcohol users.MethodsCase report using clinical records and a non-systematic literature review.ResultsA 63-year-old male, with a forty-year history of chronic alcoholism and no other prior mental health issues, was admitted in the emergency department. He conveyed vague delusional notions regarding his roommate and described vivid morning dreams in which he tried to communicate but couldn’t speak. This led him to believe his roommate harboured harmful intentions. Additionally, he mentioned that for the past two months, he had developed a telepathic connection with his sister and his deceased mother, with whom he felt he communicated without speaking. He described feeling strangement and anxiety concerning these experiences, which he firmly believed to be undeniably real. He reported being able to hear the voices of his mother and sister. He also described short-term memory problems dating back two years. He denied any other psychopathology and exhibited probable ideational and emotional impoverishment secondary to chronic alcohol consumption. Confirmation of the patient’s account was provided by his family members. The prescribed treatment included antipsychotic medication and a recommendation for alcohol abstinence.ConclusionsDescriptions of chronic and subacute alcohol-induced psychoses are found in early psychiatric textbooks but have been omitted from contemporary classifications. While their incidence is low among chronic alcohol users, they represent a severe clinical entity. These disorders are usually distinguished by the presence of delusions and vivid hallucinations characterized by dream-like content. This distinct symptomatology aids in the accurate differentiation from other psychotic disorders and clinicians should be aware of their existence.Disclosure of InterestNone Declared

Differential diagnosis in chronic psychosis: a case report

IntroductionA colombian woman aged 62, with previous diagnosis of paranoid schizophrenia. She retired from working 2 years ago, when she started taking care of her sick husband full-time.ObjectivesTo describe a chronic psychosis case and discuss the treatment options and differential diagnosis.MethodsWe used the face-to-face interviews during her last hospitalization and her electronic medical history.We also made a brief research about the effectiveness of risperidone depot in Pubmed.ResultsPsychiatric historyShe’s had 3 hospitalizations, all of them coincided with stressful vital situations. The first one occurred when she was dealing with a job issue. In the second one she was having an economic conflict with her husband. And the third one has coincided with worries about her retirement pension and her caregiver burden.Current episodeShe came to my hospital emergency department distressed because she thought her husband and her were victims of an international drug trafficking plot. She said a colombian drug cartel had sent 9 prostitutes to her village in order to steal from them, by pretending they were cleaning assistants, as a reprisal against her husband, who used to be a military in Colombia . She explained the nature of this event with great details. Also, she said the electric company was involved and they had tried to intoxicate her.The psychopathological exploration was altered with a correct speech in its form but incoherent in its content. She presented a highly structured delusional plot of prosecution. No major affective disorders were detected. She suffered from reactive insomnia and anxiety.EvolutionAt first, it was torpid, she felt perspicacious and angry about the admission. Later, as the antipsychotic started to work, the symptoms improved and she became calm and collaborative. She has never criticized the delusion plot, but it was encapsulated, and the affective resonance disappeared.We tried oral aripiprazole and paliperidone but retired both due to bad tolerance. Then we tried risperidone, with good tolerance and response, and started her current monthly treatment with Risperidone 100 mg depot.After one year, she has kept stable with no relapses and good adherence to the treatment.Differential diagnosisThe patient meets every diagnostic criteria of Delusional disorder (F22), as she has never experienced hallucinations and the functionality has not significantly decreased through the years. Also, she doesn’t meet the second criteria for Schizophrenia (F20).ConclusionsIt is important to explore the evolution of a psychotic disorder in order to differentiate between a schizophrenia and a delusional disorder, as the prognosis differs significantly.Using Risperidone monthly depot can be a good option for treating a psychotic disorder (Sampson et al. Cochrane Database Syst Rev 2016. 14;4(4)).Disclosure of InterestNone Declared

Tract-based analyses of white matter in schizophrenia, bipolar disorder, aging, and dementia using high spatial and directional resolution diffusion imaging: a pilot study.

Structural brain connectivity abnormalities have been associated with several psychiatric disorders. Schizophrenia (SCZ) is a chronic disabling disorder associated with accelerated aging and increased risk of dementia, though brain findings in the disorder have rarely been directly compared to those that occur with aging. We used an automated approach to reconstruct key white matter tracts and assessed tract integrity in five participant groups. We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n =28), bipolar disorder (BPD, n =21), and SCZ (n =22) participants aged 18-30, and healthy elderly (ELD, n =15) and dementia (DEM, n =9) participants. Volume, fractional (FA), radial diffusivity (RD) and axial diffusivity (AD) of seven key white matter tracts (anterior thalamic radiation, ATR; dorsal and ventral cingulum bundle, CBD and CBV; corticospinal tract, CST; and the three superior longitudinal fasciculi: SLF-1, SLF-2 and SLF-3) were analyzed with TRACULA. Group comparisons in tract metrics were performed using multivariate and univariate analyses. Clinical relationships of tract metrics with recent and chronic symptoms were assessed in SCZ and BPD participants. A MANOVA showed group differences in FA (λ=0.5; p=0.0002) and RD (λ=0.35; p<0.0001) across the seven tracts, but no significant differences in tract AD and volume. Post-hoc analyses indicated lower tract FA and higher RD in ELD and DEM groups compared to CON, BPD and SCZ groups. Lower FA and higher RD in SCZ compared to CON did not meet statistical significance. In SCZ participants, a significant negative correlation was found between chronic psychosis severity and FA in the SLF-1 (r= -0.45; p=0.035), SLF-2 (r= -0.49; p=0.02) and SLF-3 (r= -0.44; p=0.042). Our results indicate impaired white matter tract integrity in elderly populations consistent with myelin damage. Impaired tract integrity in SCZ is most prominent in patients with advanced illness.

Prevalence of spontaneous movement disorders (dyskinesia, parkinsonism, akathisia and dystonia) in never-treated patients with chronic and first-episode psychosis: a systematic review and meta-analysis

BackgroundThe aim of this systematic review and meta-analysis is to evaluate and compare the prevalence rates of spontaneous movement disorders (SMDs), including dyskinesia, parkinsonism, akathisia and dystonia, in antipsychotic-naïve individuals...

Clinical systematics of chronic delusional psychoses in schizophrenia and schizophrenia-spectrum pathology

To develop a systematics of chronic delusional psychoses in schizophrenia and pathology of the schizophrenic spectrum that takes into account psychopathological structure (the mechanism of delusional formation) and the trajectories of the disease course (the ratio of negative/positive dimensions). The study sample was recruited from the large Moscow psychiatric hospital in 2019-2024 and included 126 patients (94 male, 32 female, mean age 36.5±12.1 years) hospitalized with ICD-10 diagnosis of paranoid schizophrenia (F20.00) or delusional disorder (F22). A clinical-psychopathological method was used. The study identifies three variants of paranoid domains, the typology of which takes into account both the psychopathological structure and the trajectories of their development, which determine the dominance of predominantly negative or positive symptoms throughout the disease: 1) psychosis with delusional interpretations and predominant orientation of symptoms towards the negative pole of the schizophrenia psychopathology (n=37, 29.4%); 2) psychosis with hallucinatory delusions and predominant direction of symptoms towards the positive pole of the schizophrenia psychopathology (n=50, 39.7%); and 3) «combined» hallucinatory-delusional psychosis with a simultaneous orientation of symptoms to the negative/positive poles of the schizophrenia psychopathology (n=39, 30.9%). Detailed phenomenological characteristics of each of the three presented variants are given. The developed three-component taxonomy confirms, on the model of chronic delusional psychoses appearing in schizophrenia and the pathology of the schizophrenia spectrum, the concept of simultaneous representation of two relatively independent domains determined by neurobiological processes in the schizophrenia psychopathology positive and negative disorders.

Linking enlarged choroid plexus with plasma analyte and structural phenotypes in clinical high risk for psychosis: A multisite neuroimaging study

BackgroundChoroid plexus (ChP) enlargement exists in first-episode and chronic psychosis, but whether enlargement occurs before psychosis onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to clinical, neuroanatomical, and plasma analytes. MethodsClinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. 509 participants (169 controls, 340 CHR) were recruited. Conversion status was determined after 2-years of follow-up, with 36 psychosis converters. The lateral ventricle ChP was manually segmented from baseline scans. A subsample of 31 controls and 53 CHR had plasma analyte and neuroimaging data. ResultsCompared to controls, CHR (d = 0.23, p = 0.017) and non-converters (d = 0.22, p = 0.03) demonstrated higher ChP volumes, but not in converters. In CHR, greater ChP volume correlated with lower cortical (r = -0.22, p < 0.001), subcortical gray matter (r = -0.21, p < 0.001), and total white matter volume (r = -0.28,p < 0.001), as well as larger lateral ventricle volume (r = 0.63,p < 0.001). Greater ChP volume correlated with makers functionally associated with the lateral ventricle ChP in CHR [CCL1 (r = -0.30, p = 0.035), ICAM1 (r = 0.33, p = 0.02)], converters [IL1β (r = 0.66, p = 0.004)], and non-converters [BMP6 (r = -0.96, p < 0.001), CALB1 (r = -0.98, p < 0.001), ICAM1 (r = 0.80, p = 0.003), SELE (r = 0.59, p = 0.026), SHBG (r = 0.99, p < 0.001), TNFRSF10C (r = 0.78, p = 0.001)]. ConclusionsCHR and non-converters demonstrated significantly larger ChP volumes compared to controls. Enlarged ChP was associated with neuroanatomical alterations and analyte markers functionally associated with the ChP. These findings suggest that the ChP may be a key an important biomarker in CHR.

The role of scoliosis on the comorbidity and demographics of neurofibromatosis type 1 patients: A retrospective analysis of the National Inpatient Sample database.

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome in the United States, affecting every 1 in 3000 individuals. NF1 occurs due to non-functional mutations in the NF1 gene, which expresses neurofibromin, a protein involved in tumour suppression. As a result, NF1 typically presents with non-cancerous neoplasm masses called neurofibromas across the body. Out of all NF1 abnormalities, the most common skeletal abnormality seen in around 10%-30% of NF1 patients is scoliosis, an improver curvature of the spine. However, there is a lack of research on the effects of scoliosis on demographics and morbidities of NF1 patients. We performed a national analysis to investigate the complex relationship between NF1 and scoliosis on patients' demographics and comorbidities. We conducted a retrospective cross-sectional analysis of the 2017 US National Inpatient Sample database using univariable Chi-square analysis and multivariable binary logistic regression analysis to determine the interplay of NF1 and scoliosis on patients' demographics and comorbidities. Our query resulted in 4635 total NF1 patients, of which 475 (10.25%) had scoliosis and 4160 (89.75%) did not. Demographic analysis showed that NF1 patients with scoliosis were typically younger, female and white compared to NF1 patients without scoliosis. Comorbidity analysis showed that NF1 patients with scoliosis were more likely to develop malignant brain neoplasms, epilepsy, hydrocephalus, pigmentation disorders, hypothyroidism, diabetes with chronic complications and coagulopathy disorders. NF1 patients with scoliosis were less likely to develop congestive heart failure, pulmonary circulation disease, peripheral vascular disease, paralysis, chronic pulmonary disease, lymphoma and psychosis. NF1 patients with scoliosis were predominantly younger, female, white patients. The presence of scoliosis in NF1 patients increases the risks for certain brain neoplasms and disorders but serves a protective effect against some pulmonary and cardiac complications.

Risk Factors of Emergency Department Utilization After Outpatient Surgery for Sports-Related Injuries.

The purpose of this study was to identify the most common reasons for and risk factors associated with postoperative emergency department (ED) utilization after orthopaedic procedures for sports-related injuries. Using the 2014 to 2016 New York and Florida State Databases from the Healthcare Cost and Utilization Project, outpatient procedures for sports-related injuries were identified. Patient records were tracked across care settings within each state to determine the rate and reasons of postoperative ED utilization within 90 days after the index surgery. Multiple logistic regression models were used to identify risk factors associated with ED visits at 0 to 7 days, 8 to 30 days, 31 to 90 days postoperatively. A total of 28,192 surgery visits for sports-related injuries were identified, with knee arthroscopy with partial meniscectomy (18.48%) and arthroscopic anterior cruciate ligament reconstruction (17.04%) as the two most common procedures treating sports injuries. The overall postoperative ED utilization rates were 1.6% (0 to 7 days postoperative), 1.3% (8 to 30 days) and 2.1% (31 to 90 days). The main cause of ED visits was markedly different during each postoperative period: mainly musculoskeletal pain (36.3%) during 0 to 7 days, either musculoskeletal pain (17%) or injury (16.6%) during 8 to 30 days, and injury (24.2%) during 31 to 90 days. Sports with the highest ED utilization in descending order were basketball, football, ice/snow sports, walking/running, cycling, and soccer. Relative to open procedures, arthroscopic procedures were 0.71 times as likely to result in a postoperative ED visit. Independent predictors of ED utilization up to 90 days postoperatively included renal failure, chronic pulmonary disease, psychosis, diabetes, and alcohol abuse. Rate of ED utilization after outpatient surgery for sports-related injuries is low (<2.2%), with postoperative musculoskeletal pain and reinjury as the two most common causes, highlighting the importance of postoperative pain management and injury prevention. Arthroscopic procedures showed markedly lower ED utilization compared with open surgery, although not indicative of overall superiority. III, Retrospective Cohort Study.

The short-, medium-, and long-term prevalence of physical health comorbidities in first-episode psychosis: a systematic review protocol

Background Individuals with first-episode psychosis (FEP) face an increased risk of physical comorbidities, notably cardiovascular diseases, metabolic disorders, respiratory disorders, and certain types of cancer. Previous reviews report pooled physical health prevalence from chronic psychosis and FEP groups. By contrast, this review will focus on antipsychotic-naïve FEP cohorts and incorporate data from observational longitudinal studies and antipsychotic intervention studies to understand the progression of physical health comorbidities from the onset to later stages of psychosis. This review aims to systematically examine the short-, medium-, and long-term period prevalence of these comorbidities in FEP and variations related to demographic factors. Methods A systematic review will be conducted using the PRISMA and MOOSE guidelines. Medline, Embase, PsycINFO, and CINAHL+, as well as Clinical Trials gov.uk, OpenGrey, WHO International Clinical Trials Registry Platform, Current Controlled Trials, United States National Institute of Health Trials Registry, and the Irish Health Repository, will be searched from inception. Longitudinal studies exploring physical health outcomes in FEP cohorts and antipsychotic intervention studies monitoring health outcomes in antipsychotic naïve FEP individuals will be eligible for inclusion. Two reviewers will independently screen titles, abstracts, and full-text articles. Bias in individual studies will be assessed using the JBI Critical Appraisal Checklist. A meta-analysis of the short-, medium-, and long-term prevalence of cardiovascular, metabolic, cancer, and respiratory outcomes and a narrative synthesis will be conducted. If possible, a meta-regression on the impact of demographic variables will be conducted. Conclusions This systematic review will clarify the progression of physical health comorbidities in FEP, informing early intervention strategies and policies for this population. Subsequent findings will be submitted to a leading journal, supplemented by a recovery education module for patient groups and a lay summary for wider dissemination. Registration The study was registered in PROSPERO, the International Prospective Register of Systematic Reviews (CRD42023431072; 17/06/2023).

The dark side of head trauma: Chronic psychosis revealed

The dark side of head trauma: Chronic psychosis revealed

66 A Recurrent Pattern of Posterior Vermis-Predominant Cerebellar Hypoplasia (Not Dandy-Walker) Occurring with Psychosis-Schizophrenia

Objective:Schizophrenia (SCZ) is a neuropsychiatric disorder with strong genetic heritability and predicted genetic heterogeneity, but limited knowledge regarding the underlying genetic risk variants. Classification into phenotype-driven subgroups or endophenotypes is expected to facilitate genetic analysis. Here, we report a teen boy with chronic psychosis and cerebellar hypoplasia (CBLH) and analyze data on 16 reported individuals with SCZ or chronic psychosis not otherwise specified associated with cerebellar hypoplasia to look for shared features.Participants and Methods:We evaluated an 18-year-old boy with neurodevelopmental deficits from early childhood and onset of hallucinations and other features of SCZ at 10 years who had mild vermis-predominant CBLH on brain imaging. This prompted us to review prior reports of chronic psychosis or SCZ with cerebellar malformations using paired search terms including (1) cerebellar hypoplasia, Dandy-Walker malformation, Dandy-Walker variant, or mega-cisterna magna with (2) psychosis or SCZ. We found reports of 16 affected individuals from 13 reports. We reviewed clinical features focusing on demographic information, prenatal-perinatal history and neuropsychiatric and neurodevelopmental phenotypes, and independently reviewed brain imaging features.Results:All 17 individuals had classic psychiatric features of SCZ or chronic psychosis as well as shared neurodevelopmental features not previously highlighted including a downward shift in IQ of about 20 points, memory impairment, speech-language deficits, attention deficits and sleep disturbances. The brain imaging findings among these individuals consistently showed posterior vermis predominant CBLH with variable cerebellar hemisphere hypoplasia and enlarged posterior fossa (a.k.a. mega-cisterna magna). None had features of classic DWM.Conclusions:In 17 individuals with chronic psychosis or SCZ and cerebellar malformation, we found a high frequency of neurodevelopmental disorders, a consistent brain malformation consisting of posterior vermis-predominant (and usually symmetric) CBLH, and no evidence of prenatal risk factors. The consistent phenotype and lack of prenatal risk factors for CBLH leads us to hypothesize that psychosis or schizophrenia associated with vermis predominant CBLH comprises a homogeneous subgroup of individuals with chronic psychosis/schizophrenia that is likely to have an underlying genetic basis. No comprehensive targeted gene panel for CBLH has yet been defined, leading us to recommend trio-based exome sequencing for individuals who present with this combination of features.

Receptor-Independent Therapies for Forensic Detainees with Schizophrenia-Dementia Comorbidity.

Forensic institutions throughout the world house patients with severe psychiatric illness and history of criminal violations. Improved medical care, hygiene, psychiatric treatment, and nutrition led to an unmatched longevity in this population, which previously lived, on average, 15 to 20 years shorter than the public at large. On the other hand, longevity has contributed to increased prevalence of age-related diseases, including neurodegenerative disorders, which complicate clinical management, increasing healthcare expenditures. Forensic institutions, originally intended for the treatment of younger individuals, are ill-equipped for the growing number of older offenders. Moreover, as antipsychotic drugs became available in 1950s and 1960s, we are observing the first generation of forensic detainees who have aged on dopamine-blocking agents. Although the consequences of long-term treatment with these agents are unclear, schizophrenia-associated gray matter loss may contribute to the development of early dementia. Taken together, increased lifespan and the subsequent cognitive deficit observed in long-term forensic institutions raise questions and dilemmas unencountered by the previous generations of clinicians. These include: does the presence of neurocognitive dysfunction justify antipsychotic dose reduction or discontinuation despite a lifelong history of schizophrenia and violent behavior? Should neurolipidomic interventions become the standard of care in elderly individuals with lifelong schizophrenia and dementia? Can patients with schizophrenia and dementia meet the Dusky standard to stand trial? Should neurocognitive disorders in the elderly with lifelong schizophrenia be treated differently than age-related neurodegeneration? In this article, we hypothesize that gray matter loss is the core symptom of schizophrenia which leads to dementia. We hypothesize further that strategies to delay or stop gray matter depletion would not only improve the schizophrenia sustained recovery, but also avert the development of major neurocognitive disorders in people living with schizophrenia. Based on this hypothesis, we suggest utilization of both receptor-dependent and independent therapeutics for chronic psychosis.

Magnetic Resonance Spectroscopy Studies of Brain Energy Metabolism in Schizophrenia: Progression from Prodrome to Chronic Psychosis.

Schizophrenia (SZ) is a debilitating mental illness; existing treatments are partially effective and associated with significant side effect burden, largely due to our limited understanding of disease mechanisms and the trajectory of disease progression. Accumulating evidence suggests that metabolic changes associated with glucose metabolism, mitochondrial dysfunction, and redox imbalance play an important role in the pathophysiology of schizophrenia. However, the molecular mechanisms associated with these abnormalities in the brains of schizophrenia patients and the ways in which they change over time remain unclear. This paper aims to review the current literature on molecular mechanisms and in vivo magnetic resonance spectroscopy (MRS) studies of impaired energy metabolism in patients at clinical high risk for psychosis, with first-episode SZ, and with chronic SZ. Our review covers research related to high-energy phosphate metabolism, lactate, intracellular pH, redox ratio, and the antioxidant glutathione. Both first-episode and chronic SZ patients display a significant reduction in creatine kinase reaction activity and redox (NAD + /NADH) ratio in the prefrontal cortex. Chronic, but not first-episode, SZ patients also show a trend toward increased lactate levels and decreased pH value. These findings suggest a progressive shift from oxidative phosphorylation to glycolysis for energy production over the course of SZ, which is associated with redox imbalance and mitochondrial dysfunction. Accumulating evidence indicates that aberrant brain energy metabolism associated with mitochondrial dysfunction and redox imbalance plays a critical role in SZ and will be a promising target for future treatments.