Emergence Of Psychotic Symptoms Research Articles

Longitudinal Analysis of Brain Function-Structure Dependencies in 22q11.2 Deletion Syndrome and Psychotic Symptoms

BackgroundCompared with conventional unimodal analysis, understanding how brain function and structure relate to one another opens a new biologically relevant assessment of neural mechanisms. However, how function-structure dependencies (FSDs) evolve throughout typical and abnormal neurodevelopment remains elusive. The 22q11.2 deletion syndrome (22q11.2DS) offers an important opportunity to study the development of FSDs and their specific association with the pathophysiology of psychosis. MethodsPreviously, we used graph signal processing to combine brain activity and structural connectivity measures in adults, quantifying FSD. Here, we combined FSD with longitudinal multivariate partial least squares correlation to evaluate FSD alterations across groups and among patients with and without mild to moderate positive psychotic symptoms. We assessed 391 longitudinally repeated resting-state functional and diffusion-weighted magnetic resonance images from 194 healthy control participants and 197 deletion carriers (ages 7–34 years, data collected over a span of 12 years). ResultsCompared with control participants, patients with 22q11.2DS showed a persistent developmental offset from childhood, with regions of hyper- and hypocoupling across the brain. Additionally, a second deviating developmental pattern showed an exacerbation during adolescence, presenting hypocoupling in the frontal and cingulate cortices and hypercoupling in temporal regions for patients with 22q11.2DS. Interestingly, the observed aggravation during adolescence was strongly driven by the group with positive psychotic symptoms. ConclusionsThese results confirm a central role of altered FSD maturation in the emergence of psychotic symptoms in 22q11.2DS during adolescence. The FSD deviations precede the onset of psychotic episodes and thus offer a potential early indication for behavioral interventions in individuals at risk.

Neurobiochemical Disturbances in Psychosis and their Implications for Therapeutic Intervention.

Psychosis, marked by the emergence of psychotic symptoms, delves into the intricate dance of neurotransmitter dynamics, prominently featuring dopamine as a key orchestrator. In individuals living with psychotic conditions, the finely tuned balance of dopamine becomes disrupted, setting off a cascade of perceptual distortions and the manifestation of psychotic symptoms. A lot of factors can impact dopamine metabolism, further complicating its effects. From genetic predispositions to environmental stressors and inflammation, the delicate equilibrium is susceptible to various influences. The sensorium, the origin of incoming information, loses its intrinsic valence in this complex interplay. The concept of the "signal-to-noise ratio" encapsulates dopamine's role as a molecular switch in neural networks, influencing the flow of information serving the basic biological functions. This nuanced modulation acts as a cognitive prism, shaping how the world is perceived. However, in psychosis, this balance is disrupted, steering individuals away from a shared reality. Understanding dopamine's centrality requires acknowledging its unique status among neurotransmitters. Unlike strictly excitatory or inhibitory counterparts, dopamine's versatility allows it to toggle between roles and act as a cognitive director in the neural orchestra. Disruptions in dopamine synthesis, exchange, and receptor representation set off a chain reaction, impacting the delivery of biologically crucial information. The essence of psychosis is intricately woven into the delicate biochemical ballet choreographed by dopamine. The disruption of this neurotransmitter not only distorts reality but fundamentally reshapes the cognitive and behavioral field of our experience. Recognizing dopamine's role as a cognitive prism provides vital insights into the multifaceted nature of psychotic conditions, offering avenues for targeted therapeutic interventions aimed at restoring this delicate neurotransmitter balance.

Cognitive deficits profiles in the first-episode of schizophrenia, clinical high risk of psychosis, and genetically high-risk of psychosis.

Cognitive deficits are core characteristics of schizophrenia, presenting before the emergence of psychotic symptoms. Individuals with a clinical high-risk for psychosis (CHR) and those with genetically high-risk of psychosis (GHR) also exhibit cognitive impairments. Nonetheless, it remains uncertain in which domains of cognitive impairments in these two groups were more similar to those of schizophrenia patients. Moreover, it is unclear which domains of impairment are caused by quality factors and which are more related to the state of disease. This research initiative aimed to extensively examine the distinct cognitive impairment profiles among the CHR, GHR, and first-episode schizophrenia (FES) cohorts. We compared the cognitive functions of the three groups and a healthy control group (HCs) using the MATRICS Consensus Cognitive Battery (MCCB). The participants for this study were recruited from the Beijing Anding Hospital of Capital Medical University. Our sample consisted of 56 patients with FES, 42 with CHR, 26 with GHR, and 62 HCs. The participants across all groups were matched in terms of gender, age, and level of education. Individuals with FES, GHR, and CHR showed significant impairment across the majority of MCCB domains, with the exception of visual learning, in comparison to HCs. None of the MCCB domains demonstrated a discerning ability to accurately differentiate between individuals with CHR and those with GHR. In the speed of processing and attention/vigilance domains, individuals with GHR and CHR exhibited scores between those of FES and HCs, with all group differences reaching statistical significance. This pattern of results indicates an intermediate level of cognitive function in individuals with GHR and CHR. Conversely, the levels of impairment observed in working memory and verbal learning were relatively consistent across all three groups: FES, CHR, and GHR. Notably, individuals in the CHR group exhibited performance akin to that of the HCs in the reasoning/problem-solving domain, while showing significant differences from the FES group, with the CHR individuals demonstrating better performance. Additionally, individuals with GHR displayed performance in social cognition similar to that of the HCs, while also demonstrating significant distinctions from the FES group, with the GHR individuals demonstrating better performance. Significant cognitive deficits exist in individuals with CHR, GHR, and FES, and these deficits vary across domains. Processing speed and attention/vigilance could potentially serve as robust biomarkers for identifying individuals at a risk of psychosis. The impairment observed in reasoning/problem-solving abilities might signify a qualitative trait, whereas deficits in social recognition could indicate a state characteristic specific to schizophrenia.

SCHIZOPHRENIA DURING THE COVID-19 PANDEMIC

The coronavirus disease 19 (COVID-19) pandemic is seriously affecting healthcare systems all over the world as well as public mental health; nevertheless, evidence about the COVID-19 pandemic's effects on people with schizophrenia and the emergence of psychotic symptoms is just now starting to emerge. Schi Recent findings : zophrenia patients exhibit worse COVID-19-related outcomes, including mortality, and are more susceptible to the disease. They exhibit minimal levels of knowledge and worry about the likelihood of infection, but they also displayed signicantly stable levels of psychotic symptoms and even an improvement in subjective well-being during the epidemic. In some cases, the onset of psychotic symptoms appears to be related to SARS-CoV-2, extended social isolation, and the propagation of false information. Clinicians should advise and educate their patient Summary: s on the hazards associated with COVID-19 and the SARS-CoV-2 infection as well as the steps that should be taken to prevent spreading the disease. Maintaining continuity of care is very important, especially for frail patients. Face-to-face visits are sometimes still necessary, despite the fact that telemedicine may be a useful help. Since viral involvement of the central nervous system appears to be relatively uncommon in COVID-19, the idea that viral infection directly contributes to the emergence of psychotic illnesses is currently under discussion

Aberrant Developmental Patterns of Gamma-Band Response and Long-Range Communication Disruption in Youths With 22q11.2 Deletion Syndrome.

Brain oscillations play a pivotal role in synchronizing responses of local and global ensembles of neurons. Patients with schizophrenia exhibit impairments in oscillatory response, which are thought to stem from abnormal maturation during critical developmental stages. Studying individuals at genetic risk for psychosis, such as 22q11.2 deletion carriers, from childhood to adulthood may provide insights into developmental abnormalities. The authors acquired 106 consecutive T1-weighted MR images and 40-Hz auditory steady-state responses (ASSRs) with high-density (256 channel) EEG in a group of 58 22q11.2 deletion carriers and 48 healthy control subjects. ASSRs were analyzed with 1) time-frequency analysis using Morlet wavelet decomposition, 2) intertrial phase coherence (ITPC), and 3) theta-gamma phase-amplitude coupling estimated in the source space between brain regions activated by the ASSRs. Additionally, volumetric analyses were performed with FreeSurfer. Subanalyses were conducted in deletion carriers who endorsed psychotic symptoms and in subgroups with different age bins. Deletion carriers had decreased theta and late-latency 40-Hz ASSRs and phase synchronization compared with control subjects. Deletion carriers with psychotic symptoms displayed a further reduction of gamma-band response, decreased ITPC, and decreased top-down modulation of gamma-band response in the auditory cortex. Reduced gamma-band response was correlated with the atrophy of auditory cortex in individuals with psychotic symptoms. In addition, a linear increase of theta and gamma power from childhood to adulthood was found in control subjects but not in deletion carriers. The results suggest that while all deletion carriers exhibit decreased gamma-band response, more severe local and long-range communication abnormalities are associated with the emergence of psychotic symptoms and gray matter loss. Additionally, the lack of age-related changes in deletion carriers indexes a potential developmental impairment in circuits underlying the maturation of neural oscillations during adolescence. The progressive disruption of gamma-band response in 22q11.2 deletion syndrome supports a developmental perspective toward understanding and treating psychotic disorders.

Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology

BackgroundThe cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA).MethodsThis work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by high-performance liquid chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored.ResultsIn the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzyme expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolite content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC.ConclusionsThus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.

Altered cortical thickness development in 22q11.2 deletion syndrome and association with psychotic symptoms

Schizophrenia has been extensively associated with reduced cortical thickness (CT), and its neurodevelopmental origin is increasingly acknowledged. However, the exact timing and extent of alterations occurring in preclinical phases remain unclear. With a high prevalence of psychosis, 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder that represents a unique opportunity to examine brain maturation in high-risk individuals. In this study, we quantified trajectories of CT maturation in 22q11DS and examined the association of CT development with the emergence of psychotic symptoms. Longitudinal structural MRI data with 1–6 time points were collected from 324 participants aged 5–35 years (N = 148 22q11DS, N = 176 controls), resulting in a total of 636 scans (N = 334 22q11DS, N = 302 controls). Mixed model regression analyses were used to compare CT trajectories between participants with 22q11DS and controls. Further, CT trajectories were compared between participants with 22q11DS who developed (N = 61, 146 scans), or remained exempt of (N = 47; 98 scans) positive psychotic symptoms during development. Compared to controls, participants with 22q11DS showed widespread increased CT, focal reductions in the posterior cingulate gyrus and superior temporal gyrus (STG), and accelerated cortical thinning during adolescence, mainly in frontotemporal regions. Within 22q11DS, individuals who developed psychotic symptoms showed exacerbated cortical thinning in the right STG. Together, these findings suggest that genetic predisposition for psychosis is associated with increased CT starting from childhood and altered maturational trajectories of CT during adolescence, affecting predominantly frontotemporal regions. In addition, accelerated thinning in the STG may represent an early biomarker associated with the emergence of psychotic symptoms.

What is the best approach for patients with prolonged duration of untreated psychosis (DUP) - about 2 clinical cases with dup longer than 10 years

IntroductionStudies have consistently found that many individuals with psychosis experience significant delays before receiving treatment. DUP refers to the period between the emergence of psychotic symptoms and the initiation of appropriate clinical treatment.ObjectivesTo review current knowledge on the best approach for patients with schizophrenia (SCZ) and prolonged DUP.MethodsNon-systematic review of literature through search on PubMed database, following the terms “DUP and treatment” and “impact of longer DUP”. Two clinical cases are described.ResultsThe clinical cases describe patients with SCZ with DUPs older than 10 years, in whom we could not achieve complete clinical remission after several therapeutic trials and whose prognosis was admitted as reserved. Longer DUP is an independent predictor of poorer outcome in SCZ, including the poor response to treatment and difficulty in achieving remission, predicting treatment resistance. Identifying treatment-resistant patients is crucial due to the importance of initiating clozapine as early as possible since the chances of responding are higher.ConclusionsDUP is a key prognostic variable in psychosis, revealing the significance of early treatment. Patients with long DUP should be regarded as at high risk of poor recovery. The detection of these patients enables clinicians to avoid unnecessary exposure to ineffective treatments while effective interventions are delayed. However, in view of adverse side effects of clozapine, future studies need to examine relevant predictors to detect accurately non-responders. We also suggest further studies to understand if there is correspondence between DUP and different stages of the disease that justify these results.

Impact of COVID-19 pandemic on persons with psychiatric disorders.

From the beginning of COVID-19 pandemic, concerns have been raised about its effect on mental health and on patients with psychiatric illnesses. A few reports suggest that patients with COVID-19 have increased symptoms of anxiety disorders, post-traumatic stress disorder, depression, increased substance use, and insomnia. There is an increased trend seen in flare-up of psychotic symptoms and new emergence of psychotic symptoms in previously healthy adults. There is extensive research available on the impact of COVID-19 on physical health, but there is a paucity of studies on the effects of COVID-19 on psychiatric illness.

Cariprazine in the Management of Negative Symptoms of Schizophrenia: State of the art and Future Perspectives

In schizophrenia, dopaminergic hyperactivity in the mesolimbic regions, or possibly even selectively so in the dorsal striatum, seems to cause the emergence of psychotic symptoms, whereas dopaminergic hypoactivity in cortical regions underlies the negative symptoms and cognitive deficits. Managing the negative symptoms is a major current challenge in the treatment of schizophrenia with a dearth of novel modalities to address this clinical issue. Cariprazine is a novel second-generation antipsychotic that specifically targets the D3 receptor mainly associated to negative symptoms. The review summarizes the main issues regarding negative symptom management and the role of cariprazine treatment.

Schizotypy, social stress and the emergence of psychotic-like states - A case for benign schizotypy?

Schizotypy is a personality-organisation related to schizophrenia-liability as well as the emergence of psychotic symptoms and psychotic-like experiences (PLEs) in non-schizophrenic individuals. It has been suggested that some non-schizophrenic individuals may exhibit PLEs frequently, but in a fashion that is not distressing but life-enhancing (“benign schizotypy”). In schizophrenia and at-risk individuals, however, psychotic symptoms are not only distressing, but also triggered stress.To further investigate questions of causality and examine how PLEs may present as distressing symptoms in some individuals and as benign experiences in others, we explored how schizotypy-facets moderated PLEs-variability under experimentally induced social stress.We performed a standardised social stress-paradigm in 107 healthy adults (77 female, 30 male; average age 22,5 years), measuring changes in psychometrically assessed PLEs and the moderation of changes under stress through positive, negative and disorganised schizotypy.Results suggest two discrete effects: On the one hand, individuals high in disorganised and negative schizotypy showed stress-dependent increases in PLEs; without added effects of positive schizotypy. On the other, individuals low in negative and disorganised schizotypy showed higher levels of PLEs solely as a function of positive schizotypy but not stress.We discuss these findings in light of the fully-dimensional model of schizotypy and hypothesize that PLEs in individuals high in schizotypy-facets suggested to convey risk-for-schizophrenia (negative and disorganised) may reflect qualitatively different entities than PLEs in individuals with low values in these facets, but high expressions of positive schizotypy (“happy schizotypes”). Additionally, we emphasize the importance of not overlooking the disorganised schizotypy-facet in related research.

Case report - Sertraline induced psychosis

Mrs. P was an 18-year-old female adolescent who met the DSM-V criteria for an episode of major depression without psychotic symptoms. The main complaints were depressed mood, loss of interest, irritability, decreased concentration, loss of appetite and weight. She was treated with sertraline 50mg per day and after 2 weeks she developed psychotic symptoms. The patient appeared to have no known predisposition to psychosis. After discontinuation of sertraline, psychotic symptoms resolved. The emergence of psychotic symptoms, in patients with non-psychotic mood disorders can have future implications for their prognosis.

Protective Factors for Psychotic Symptoms Among Poly-victimized Children.

BackgroundExperiencing victimization in early life has been repeatedly shown to be associated with the emergence of psychotic symptoms in childhood. However, most victimized children do not develop psychotic symptoms and why this occurs is not fully understood. This study investigated which individual, family-level, and wider community characteristics were associated with an absence of psychotic symptoms among children at risk for psychosis by virtue of their exposure to multiple victimization experiences (poly-victimization).MethodsParticipants were from the Environmental Risk Longitudinal Twin Study, a nationally representative cohort of 2232 UK-born twins. Exposure to maltreatment, bullying and domestic violence prior to age 12 was determined from interviews with mothers, children, and observations by research workers at ages 5, 7, 10, and 12. Children were interviewed about psychotic symptoms at age 12. Protective factors were measured at ages 5, 7, 10, and 12.ResultsChildhood poly-victimization was associated with age-12 psychotic symptoms (OR = 4.61, 95% CI 2.82–7.52), but the majority of poly-victimized children did not report symptoms (80.7%). Having a relatively high IQ, more positive atmosphere at home, and higher levels of neighborhood social cohesion were found to be protective against childhood psychotic symptoms among poly-victimized children and also in the whole sample. However, “protected” poly-victimized children displayed elevated levels of other mental health problems compared to nonvictimized children.ConclusionsChildren’s characteristics, family context, and the wider community were all found to protect children from developing early psychotic symptoms, even when they were victimized multiple times. These findings indicate targets for multilevel preventive interventions.

Benzodiazepines abstinence syndrome with psychotic symptoms: Case report

IntroductionSeveral studies point to the importance that the complex formed by GABA and the benzodiazepine receptor play for cerebral dopaminergic transmission and, hence, to the pathophysiology of psychotic symptoms. The decrease in GABA neuratransmisión or the hypofunction of the system in the hippocampus, cortex and other limbic prefrontal or subcortical regions has consequences as emotional dysregulation, cognitive impairment and development of positive psychotic symptoms.ObjectivesWe intended to show an additional practical example to the limited literature available based on a case linking the emergence of psychotic symptoms due to acute benzodiazepine withdrawal.MethodsWe present the case of a 21 year old man who was sent to the emergency room of our hospital after an episode of aggressiveness on the street. The patient showed a psychotic schizophrenic syndrome with significant emotional and behavioural impact with aggressive and bizarre movements. In parallel, restlessness, sweating, tremor, increased blood pressure and tachycardia were observed. Symptoms had started abruptly two hours earlier. The patient companion explained that he usually took Alprazolam at an of over 40 mg per day. He had decided to give up this consumption abruptly four days earlier.DiscussionGABAergic deficits cause the imbalance between excitatory and inhibitory neurotransmission that may relate the pathophysiology of psychotic symptoms. The dysfunction of the GABAergic cortical interneurons could affect to the modulating response from the association cortex, which, could also relate with the appearance of these symptoms.ConclusionThis case could relate a decrease in GABAergic transmission with the appearance of psychotic symptoms.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Confusion between symptom and disease. Parkinson vs meningioma

IntroductionParkinson's disease is caused by decreased dopaminergic neurons of the substantia nigra. Psychosis occurs between 20 and 40% of patients with Parkinson's disease. Dopaminergic drugs act as aggravating or precipitating factor. Before the introduction of levodopa patients had described visual hallucinations but the frequency was below 5%.ObjectiveIllustrated importance of treatment, reassessment after its introduction and refractoriness to answer; as well as the importance of a differential diagnosis at the onset of psychotic symptoms later in life.MethodClinical case: female patient 75 years tracking Neurology by parkinsonism in relation to possible early Parkinson disease. She was prescribed rasagiline treatment. Begins to present visual and auditory hallucinations, delusional self-referential and injury. She had no previous psychiatric history. She went on several occasions to the emergency room, where the anti-Parkinson treatment is decreased to the withdrawal point and scheduled antipsychotics did not answer. Doses of antipsychotics are increased despite which symptoms persist and even increase psychotic symptoms. In this situation it is agreed to extend the study. Subsequently an NMR of the skull where the image is suggestive of a right occipital meningioma appears.Results/conclusionsWith the emergence of psychotic symptoms later in life it will be important to ask a broad differential diagnosis, since in a large number of cases will be secondary to somatic or to drug therapies.Parkinsonism can be a symptom of occipital meningioma, presenting in the psychotic clinic. Refractoriness, on one hand to the suspension of treatment for Parkinson's disease, such as poor response to antipsychotics, did extend the study, which ultimately gave us the diagnosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Predictors of long term use of psychiatric services of patients with recent-onset schizophrenia: 12\xa0years follow-up

BackgroundThe aim of study was to investigate predictors of long term use of psychiatric services of patients with recent-onset schizophrenia.MethodsA cohort of 50 clinically stable patients with recent-onset schizophrenia was included in a randomized controlled trial comparing early integrated treatment with treatment as usual. Recent onset was defined as emergence of psychotic symptoms for the first time during the preceding 2 years. The follow up period was from the date of randomization and until 12 years after termination of treatment trial, 14 years forward.ResultsScore on Brief psychiatric rating scale both at baseline and after 2 years of treatment, suicide attempts during 2 years of treatment and being an inpatient during 2 years of treatment were significant predictors of long term use of services.ConclusionHigh score on Brief psychiatric rating scale, suicide attempts and being admitted as inpatient early in the course of schizophrenia are possible predictors of long term use of services.Trial registrationClinicalTrials.gov NCT00184509. Registered 15 September 2005.

Psychosis as a continuous phenotype in the general population: the thin line between normality and pathology.

Psychosis as a continuous phenotype in the general population: the thin line between normality and pathology.

Long-range dysconnectivity in frontal and midline structures is associated to psychosis in 22q11.2 deletion syndrome.

Patients affected by 22q11.2 deletion syndrome (22q11DS) present a characteristic cognitive and psychiatric profile and have a genetic predisposition to develop schizophrenia. Although brain morphological alterations have been shown in the syndrome, they do not entirely account for the complex clinical picture of the patients with 22q11DS and for their high risk of psychotic symptoms. Since Friston proposed the "disconnection hypothesis" in 1998, schizophrenia is commonly considered as a disorder of brain connectivity. In this study, we review existing evidence pointing to altered brain structural and functional connectivity in 22q11DS, with a specific focus on the role of dysconnectivity in the emergence of psychotic symptoms. We show that widespread alterations of structural and functional connectivity have been described in association with 22q11DS. Moreover, alterations involving long-range association tracts as well as midline structures, such as the corpus callosum and the cingulate gyrus, have been associated with psychotic symptoms in this population. These results suggest common mechanisms for schizophrenia in syndromic and non-syndromic populations. Future directions for investigations are also discussed.

Developmental trajectories of executive functions in 22q11.2 deletion syndrome.

Background22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder associated with a specific cognitive profile. Higher-order cognitive skills like executive functions (EF) are reported as a relative weakness in this population. The present study aimed to delineate the developmental trajectories of multiple EF domains in a longitudinal sample using a broader age range than previous studies. Given the high incidence of psychotic symptoms in 22q11.2DS, we also compared the development of EF in participants with/without comorbid psychotic symptoms. Given the importance of EF in daily life, the third aim of the study was to characterize the link between EF and adaptive functioning.MethodsThe sample consisted of 95 individuals with 22q11.2DS and 100 typically developing controls aged 6–26 years. A large proportion of the sample (55.38 %) had multiple time points available. Between-group differences in the developmental trajectories of three subdomains of EF (verbal fluency, working memory, and inhibition) were examined using mixed models regression analyses. Analyses were repeated comparing only the 22q11.2DS group based on the presence/absence of psychotic symptoms to investigate the influence of executive dysfunction on the emergence of psychotic symptoms. Hierarchical stepwise regression analyses were also conducted to investigate the predictive value of EF on adaptive functioning.ResultsWe observed lower performance on EF domains, as well as atypical development of working memory and verbal fluency. Participants who presented with negative symptoms exhibited different developmental trajectories of inhibition and working memory. Adaptive functioning level was not significantly predicted by EF scores.ConclusionsThe present study highlighted domain-specific atypical trajectories of EF in individuals with 22q11.DS and explored the link with psychotic symptoms. However, no relation between EF and adaptive functioning was observed.

Longitudinal study of premorbid adjustment in 22q11.2 deletion (velocardiofacial) syndrome and association with psychosis.

Velocardiofacial syndrome, also known as 22q11.2 deletion syndrome (22q11DS), is associated with an increased risk of major psychiatric disorders, including schizophrenia. The emergence of psychotic symptoms in individuals with schizophrenia in the general population is often preceded by a premorbid period of poor or worsening social and/or academic functioning. Our current study evaluated premorbid adjustment (via the Cannon-Spoor Premorbid Adjustment Scale [PAS]) and psychotic symptoms (via the Structured Interview for Prodromal Symptoms and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version) in youth with 22q11DS (N = 96), unaffected siblings (N = 40), and community controls (N = 50). The PAS scores indicated greater maladjustment during all developmental periods in individuals with 22q11DS compared to the controls. Many participants with 22q11DS had chronically poor (n = 33) or deteriorating (n = 6) PAS scores. In 22q11DS, chronically poor PAS trajectories and poor childhood and early adolescence academic domain and total PAS scores significantly increased the risk of prodromal symptoms or overt psychosis. Taking into account the catechol-O-methyltransferase (COMT) genotype, the best predictor of (prodromal) psychosis was the early adolescence academic domain score, which yielded higher sensitivity and specificity in the subgroup of youth with 22q11DS and the high-activity (valine) allele. PAS scores may help identify individuals at higher risk for psychosis.