Assessing evidence supporting cannabis harm reduction practices for adolescents at clinical high-risk for psychosis: a review and clinical implementation tool.

Cannabis use is consistently associated with both increased incidence of frank psychotic disorders and acute exacerbations of psychotic symptoms in healthy individuals and people with psychosis spectrum disorders. Although there is uncertainty around causality, cannabis use may be one of a few modifiable risk factors for conversion to psychotic disorders in individuals with Clinical High Risk for Psychosis (CHR-P) syndromes, characterized by functionally impairing and distressing subthreshold psychotic symptoms. To date, few recommendations beyond abstinence to reduce adverse psychiatric events associated with cannabis use have been made. This narrative review synthesizes existing scientific literature on cannabis' acute psychotomimetic effects and epidemiological associations with psychotic disorders in both CHR-P and healthy individuals to bridge the gap between scientific knowledge and practical mental health intervention. There is compelling evidence for cannabis acutely exacerbating psychotic symptoms in CHR-P, but its impact on conversion to psychotic disorder is unclear. Current evidence supports a harm reduction approach in reducing frequency of acute psychotic-like experiences, though whether such interventions decrease CHR-P individuals' risk of conversion to psychotic disorder remains unknown. Specific recommendations include reducing frequency of use, lowering delta-9-tetrahydrocannabinol content in favor of cannabidiol-only products, avoiding products with inconsistent potency like edibles, enhancing patient-provider communication about cannabis use and psychotic-like experiences, and utilizing a collaborative and individualized therapeutic approach. Despite uncertainty surrounding cannabis' causal association with psychotic disorders, cautious attempts to reduce acute psychosis risk may benefit CHR-P individuals uninterested in abstinence. Further research is needed to clarify practices associated with minimization of cannabis-related psychosis risk.

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

BACKGROUND: Choroid 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. METHODS: Clinical 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. RESULTS: Compared 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 [IL1ß (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)]. CONCLUSIONS: CHR 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.

Diminished differentiation of rewards in individuals at clinical high-risk for psychosis.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as "adaptive coding." Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally.

Disorganization in individuals at clinical high risk for psychosis: psychopathology and treatment response.

Disorganization is a nuclear dimension of psychosis, especially in schizophrenia. Despite its relevant association with poor prognosis and negative outcomes, it is still under-investigated compared to positive and negative symptoms, in particular at the onset of illness. This study explored disorganization in youth at Clinical High Risk for Psychosis (CHR-P) over a 2-year period. A sample of 180 CHR-P participants (50% males; 51.1% with baseline second-generation antipsychotic medication) recruited within a specialized CHR-P service completed the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Across the follow-up, we examined key associations of disorganization with other domains of psychopathology, functioning, and treatment response using Spearman's rank correlation coefficients and linear regression analyses. Our results showed a significant longitudinal reduction in disorganization severity levels across the follow-up. This decrease was significantly associated with improvements in negative symptoms and daily functioning, with a shorter duration of untreated psychiatric symptoms, and with baseline equivalent dose of antipsychotic medication. No significant longitudinal associations with other treatment component of the PARMS program were found. Our findings suggest a longitudinal improvement in disorganization dimension in CHR-P individuals, especially in the context of early interventions targeting reduction in the duration of untreated psychiatric symptoms and favoring a prompt antipsychotic therapy.

Screening for psychosis risk in primary mental health care services - Implementation, prevalence and recovery trajectories.

OBJECTIVES: Early interventions improve outcomes for people at high risk of psychosis and are likely to be cost saving. This group tends to seek help for emotional problems - depression and anxiety - via primary care services, where early detection methods are poor. We sought to determine prevalence rates of high risk for psychosis in UK primary care mental health services and clinical outcomes following routinely delivered psychological therapies. METHODS: We used a brief screen designed for settings with low base rates and significant time constraints to determine prevalence of high risk for psychosis in UK 'Talking Therapies' services. We examined socio-demographic characteristics, presenting problems and recovery trajectories for this group, compared with people not at risk of psychosis. RESULTS: A 2-item screen selected for specificity yielded a prevalence rate of 3% in primary care mental health services. People at elevated risk of psychosis were younger and more likely to report at least one long-term physical condition. This group presented with higher levels of depression, anxiety and trauma symptoms at assessment and were less likely to have recovered at the end of treatment, compared to people not at risk. CONCLUSIONS: Very brief screening tools can be implemented in busy health care settings. The 3% of referrals to UK primary care psychological therapies services at elevated risk of psychosis typically present with more severe symptoms and greater levels of comorbidity and may require augmented interventions to recover fully.

Clinical utility of the at-risk for psychosis state beyond transition: A multidimensional network analysis.

To be relevant to healthcare systems, the clinical high risk for psychosis (CHR-P) concept should denote a specific (i.e., unique) clinical population and provide useful information to guide the choice of intervention. The current study applied network analyses to examine the clinical specificities of CHR-P youths compared to general help-seekers and non-CHR-P youth. 146 CHR-P (mean age = 14.32 years) and 103 non-CHR-P (mean age = 12.58 years) help-seeking youth were recruited from a neuropsychiatric unit and assessed using the Structured Interview for Psychosis-Risk Syndromes, Children's Depression Inventory, Multidimensional Anxiety Scale for Children, Global Functioning: Social, Global Functioning: Role, and Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale. The first network structure comprised the entire help-seeking sample (i.e., help-seekers network), the second only CHR-P patients (i.e., CHR-P network), and the third only non-CHR-P patients (i.e., non-CHR-P network). In the help-seekers network, each variable presented at least one edge. In the CHR-P network, two isolated "archipelagos of symptoms" were identified: (a) a subgraph including functioning, anxiety, depressive, negative, disorganization, and general symptoms; and (b) a subgraph including positive symptoms and the intelligence quotient. In the non-CHR-P network, positive symptoms were negatively connected to functioning, disorganization, and negative symptoms. Positive symptoms were less connected in the CHR-P network, indicating a need for specific interventions alongside those treating comorbid disorders. The findings suggest specific clinical characteristics of CHR-P youth to guide the development of tailored interventions, thereby supporting the clinical utility of the CHR-P concept.

Clinical and neurodevelopmental predictors of psychotic disorders in children and adolescents at clinical high risk for psychosis: the CAPRIS study.

BACKGROUND: The neurodevelopmental hypothesis of schizophrenia represents the disorder as an expression of an alteration during the brain development process early in life. Neurodevelopmental variables could become a trait marker, and the study of these variables in children and adolescents at clinical high risk for psychosis (CHR) could identify a specific cluster of patients who later developed psychosis. The aim of this study is to describe clinical and neurodevelopment predictors of transition to psychosis in child and adolescent participants at CHR. Naturalistic longitudinal two-center study of 101 CHR and 110 healthy controls (HC) aged 10-17. CHR participants were children and adolescents aged 10-17, meeting one or more of the CHR criteria assessed at baseline and at 18 months' follow-up. Neurodevelopmental variables assessed were obstetric complications, delay in principal development milestones, and presence of a neurodevelopment diagnosis. Pairwise comparisons, linear regressions, and binary logistic regression were performed.A transition rate of 23.3% at 1.5 years was observed. Participants who developed psychosis (CHR-P) showed higher rates of grandiosity and higher proportions of antipsychotic medication intake at baseline compared to participants who did not develop a psychotic disorder (CHR-NP). In terms of neurodevelopment alterations, CHR-P group showed a higher proportion of participants reporting delay in language development than the CHR-NP and HC groups. The odds of psychosis increased by 6.238 CI 95% [1.276-30.492] for a one-unit increase in having a positive score in grandiosity; they increased by 4.257 95% CI [1.293-14.023] for a one-unit increase in taking antipsychotic medication, and by 4.522 95% [1.185-64.180] for showing language development delay. However, the p-values did not reach significance after adjusting for multiple comparisons.A combination of clinical and neurodevelopmental alterations could help predict the transition to psychotic disorder in a CHR child and adolescent sample. Our results suggest the potential utility of collecting information about neurodevelopment and using these variable multifactorial models to predict psychosis disorders.

Cognitive predictors of transition and remission of psychosis risk syndrome in a child and adolescent sample: longitudinal findings from the CAPRIS study.

Cognitive impairments are proposed as predictors in the differentiation between subjects with psychosis risk syndrome (PRS) who will develop a psychotic disorder (PRS-P) and those who will not (PRS-NP). More in-depth study of the PRS-NP group could contribute to defining the role of cognitive alterations in psychosis. This study aims to analyze cognition of children and adolescents with PRS in terms of their clinical outcome at 18-month follow-up (psychosis, remission, and non-remission) and of determinate predictors of transition to psychosis and remission of PRS. The method is two-site, naturalistic, longitudinal study design, with 98 help-seeking adolescents with PRS and 64 healthy controls (HC). PRS-P (n = 24) and PRS-NP (n = 74) participants were clinically and cognitively assessed at baseline, and when full-blown psychotic disorder had developed or at 18-month follow-up. PRS-P subjects showed lower scores at baseline in processing speed, visuospatial memory, attention, and executive function (cognitive flexibility/processing speed) compared to HC. PRS-NP subjects showed lower baseline scores in verbal working memory and verbal fluency compared to HC. This deficit is also observed in the PRS group of participants still presenting attenuated psychotic symptoms at 18-month follow-up, while PRS subjects in remission showed a similar cognitive profile to HC subjects. Baseline score on processing speed, measured with a coding task, appeared to be a predictive variable for the development of a psychotic disorder. Performance in verbal working memory was predictive of remission in the PRS-NP. Post hoc comparisons indicate the need for careful interpretation of cognitive markers as predictors of psychosis. Cognitive impairments are present in both PRS-P and PRS-NP. Those individuals who recover from PRS show baseline cognitive performance comparable to the HC group. Together with sociodemographic variables, this observation could help in the differentiation of a variety of PRS trajectories in children and adolescents.

Debate: The prevention of psychosis in child and adolescent mental health services.

Psychopathological conditions in adolescence and young adulthood often result from an altered neurodevelopment already phenotypically expressed in childhood. Child and adolescent mental health services are ideally placed to intercept in the developmental trajectories of younger adolescents and contribute to the early detection of a risk for psychosis, as proposed by Salazar de Pablo and Arango (2023, Child and Adolescent Mental Health), opening a debate to which we contribute. The early detection of a specific risk for psychosis and of a broader risk for severe mental illness requires an understanding of the clinical staging of psychosis, neurodevelopmental antecedents of severe mental illness and of heterotypic trajectories between childhood phenotypes and adult disorders.

Reduced magnetic mismatch negativity: a shared deficit in psychosis and related risk.

BACKGROUND: Abnormal auditory processing of deviant stimuli, as reflected by mismatch negativity (MMN), is often reported in schizophrenia (SCZ). At present, it is still under debate whether this dysfunctional response is specific to the full-blown SCZ diagnosis or rather a marker of psychosis in general. The present study tested MMN in patients with SCZ, bipolar disorder (BD), first episode of psychosis (FEP), and in people at clinical high risk for psychosis (CHR). METHODS: Source-based MEG activity evoked during a passive auditory oddball task was recorded from 135 patients grouped according to diagnosis (SCZ, BD, FEP, and CHR) and 135 healthy controls also divided into four subgroups, age- and gender-matched with diagnostic subgroups. The magnetic MMN (mMMN) was analyzed as event-related field (ERF), Theta power, and Theta inter-trial phase coherence (ITPC). RESULTS: The clinical group as a whole showed reduced mMMN ERF amplitude, Theta power, and Theta ITPC, without any statistically significant interaction between diagnosis and mMMN reductions. The mMMN subgroup contrasts showed lower ERF amplitude in all the diagnostic subgroups. In the analysis of Theta frequency, SCZ showed significant power and ITPC reductions, while only indications of diminished ITPC were observed in CHR, but no significant decreases characterized BD and FEP. CONCLUSIONS: Significant mMMN alterations in people experiencing psychosis, also for diagnoses other than SCZ, suggest that this neurophysiological response may be a feature shared across psychotic disorders. Additionally, reduced Theta ITPC may be associated with risk for psychosis.

Motor precision deficits in clinical high risk for psychosis.

Motor deficits appear prior to psychosis onset, provide insight into vulnerability as well as mechanisms that give rise to emerging illness, and are predictive of conversion. However, to date, the extant literature has often targeted a complex abnormality (e.g., gesture dysfunction, dyskinesia), or a single fundamental domain (e.g., accuracy) but rarely provided critical information about several of the individual components that make up more complex behaviors (or deficits). This preliminary study applies a novel implicit motor task to assess domains of motor accuracy, speed, recognition, and precision in individuals at clinical high risk for psychosis (CHR-p). Sixty participants (29 CHR-p; 31 healthy volunteers) completed clinical symptom interviews and a novel Serial Interception Sequence Learning (SISL) task that assessed implicit motor sequence accuracy, speed, precision, and explicit sequence recognition. These metrics were examined in multilevel models that enabled the examination of overall effects and changes in motor domains over blocks of trials and by positive/negative symptom severity. Implicit motor sequence accuracy, speed, and explicit sequence recognition were not detected as impacted in CHR-p. When compared to healthy controls, individuals at CHR-p were less precise in motor responses both overall (d = 0.91) and particularly in early blocks which normalized over later blocks. Within the CHR-p group, these effects were related to positive symptom levels (t = - 2.22, p = 0.036), such that individuals with higher symptom levels did not improve in motor precision over time (r's = 0.01-0.05, p's > 0.54). CHR-p individuals showed preliminary evidence of motor precision deficits but no other motor domain deficits, particularly in early performance that normalized with practice.

Links of platelet glutamate and glutathione metabolism with attenuated positive and negative symptoms in depressed patients at clinical high risk for psychosis.

Aim of the study is to reveal clinical and biological correlations in patients with adolescent depression and attenuated psychotic symptoms. Activity of platelet enzymes involved in glutamate-, glutathione- and energy metabolism was evaluated in control group and in the patients, because these systems are suspected as related to pathogenesis of psychosis. Adolescents (78 men, 16-25 years old) hospitalized with the first acute depressive state composed two groups: with prevalence of attenuated psychotic positive or negative symptoms (Gr1 and Gr2, 48 and 30 patients, respectively). Control group comprised 20 mentally healthy men of 19-25 years old. Gr1 differed significantly from Gr2 in scores by the Scale of Prodromal Symptoms (SOPS) for positive symptoms, p < 0.001, for disorganization symptoms, p < 0.003, and for total SOPS score, p < 0.001, before the treatment started. When patients from either Gr1 or Gr2 were compared with the control group, significantly decreased baseline activities of platelet glutamate dehydrogenase (GDH), glutathione reductase (GR) and glutathione S-transferase (GST) were found (p < 0.0001). Different correlations were found between baseline enzymatic activities in Gr1 and Gr2: GDH activity correlated with GR activity in Gr1 (R = 0.37), and with GST activity in Gr2 (R = 0.70). Significant correlations were found only in Gr2 between the delta of scores by SOPS negative symptoms (SOPS-N) under treatment and baseline GDH, GST, and GR activities (R = - 0.36, R = - 0.60, and R = 0.38, respectively). The found correlations of the baseline enzymatic activity levels with the value of the decrease (delta) in SOPS-N scores under the treatment represent interest for the prediction of the pharmacotherapy efficiency.

Quality of life and its predictors in first-episode schizophrenia and individuals at clinical high-risk for psychosis.

BACKGROUND: This is a cross-sectional study comparing the degree of subjective quality of life (QOL) impairment and its predictive factors in first-episode schizophrenia (FES) and individuals at clinical high-risk (CHR) for psychosis. METHODS: Seventy-seven FES, 59 CHR, and 64 healthy controls (HC) were included. The QOL of all participants was assessed using the World Health Organization Quality of Life (WHOQOL)-Brief Form (BREF). Psychiatric symptoms of individuals with FES were assessed with the Positive and Negative Syndrome Scale (PANSS), five factors were further identified through factor analysis; for individuals with CHR and HC, the Scale of Prodromal Symptoms (SOPS) was used. RESULTS: The total and four sub-domain scores of the WHOQOL-BREF in the FES and CHR groups were lower than those of the HC group. The overall and psychological health scores in the CHR group were lowest. In the FES group, after applying Bonferroni's correction, there is a negative correlation between the total QOL scores and anxiety/depressive symptom scores (r = -0.34, P = 0.003). The stepwise multiple regression analysis showed that the QOL of both FES and CHR group were negatively affected by anxiety/depressive symptoms and unemployment (P < 0.05). CONCLUSIONS: Compared with FES, CHR individuals are more dissatisfied with their QOL. Although diagnostic assessment of FES and CHR relies heavily on positive symptoms, the QOL is more affected by anxiety/depressive symptoms and social functioning.

Childhood Maltreatment and Its Association with Cognitive Ability in Young People Suspected to Be at Clinical High Risk of Psychosis.

INTRODUCTION: Childhood maltreatment is associated with both reduced cognitive functioning and the development of psychotic symptoms. However, the specific relationship between childhood maltreatment, cognitive abilities and (pre)psychotic symptoms remains unclear. Therefore, the aim of this study was to investigate the association between childhood maltreatment and tasks of verbal memory and processing speed in a help-seeking sample of an early detection of psychosis service. METHODS: A total of 274 participants consisting of 177 clinical high risk (CHR) for psychosis subjects and 97 clinical controls (CC) with subthreshold CHR underwent a battery of neurocognitive assessments measuring the latent variables verbal memory and processing speed. Additionally, the Trauma and Distress Scale (TADS) was administered to assess varying childhood maltreatment subtypes. Structural equation modeling (SEM) was used to examine associations between verbal memory, processing speed, and maltreatment subtypes. Other factors in the model were age, gender, clinical group (CHR or CC), and the presence of different CHR criteria. RESULTS: Physical abuse was associated with lower scores in verbal memory and processing speed. The explained variance in the SEM reached up to 9.5% for verbal memory and 24.9% for processing speed. Both latent variables were each associated with the presence of cognitive-perceptive basic symptoms. Lower verbal memory was additionally associated with the clinical high-risk group, and processing speed capacity was associated with higher age and female gender. CONCLUSION: Childhood physical abuse in particular was associated with poorer performance on verbal memory and processing speed across both groups of CHR and CC with subthreshold CHR symptoms. This adds to the current literature on reduced cognitive abilities when childhood maltreatment had occurred, albeit subtype dependent. Our findings, together with high prevalence rates of childhood maltreatment in patients with psychosis or CHR states, along with the presence of cognitive deficits in these patients, highlight the importance of not only assessing cognition but also childhood maltreatment in managing these patients. Future research should investigate the specific biological mechanisms of childhood maltreatment on verbal memory and processing speed in CHR subjects, as neurobiological alterations might explain the underlying mechanisms.

Age-related change in cortical thickness in adolescents at clinical high risk for psychosis: a longitudinal study.

Progression to psychosis has been associated with increased cortical thinning in the frontal, temporal and parietal lobes in individuals at clinical high risk for the disorder (CHR-P). The timing and spatial extent of these changes are thought to be influenced by age. However, most evidence so far stems from adult samples. Longitudinal studies are essential to understanding the neuroanatomical changes associated to transition to psychosis during adolescence, and their relationship with age. We conducted a longitudinal, multisite study including adolescents at CHR-P and healthy controls (HC), aged 10-17 years. Structural images were acquired at baseline and at 18-month follow-up. Images were processed with the longitudinal pipeline in FreeSurfer. We used a longitudinal two-stage model to compute the regional cortical thickness (CT) change, and analyze between-group differences controlling for age, sex and scan, and corrected for multiple comparisons. Linear regression was used to study the effect of age at baseline. A total of 103 individuals (49 CHR-P and 54 HC) were included in the analysis. During follow-up, the 13 CHR-P participants who transitioned to psychosis exhibited greater CT decrease over time in the right parietal cortex compared to those who did not transition to psychosis and to HC. Age at baseline correlated with longitudinal changes in CT, with younger individuals showing greater cortical thinning in this region. The emergence of psychosis during early adolescence may have an impact on typical neuromaturational processes. This study provides new insights on the cortical changes taking place prior to illness onset.

N-Acetylaspartate and Choline Metabolites in Cortical and Subcortical Regions in Clinical High Risk Relative to Healthy Control Subjects: An Exploratory 7T MRSI Study.

N-acetylaspartate (NAA) and choline (Cho) are two brain metabolites implicated in several key neuronal functions. Abnormalities in these metabolites have been reported in both early course and chronic patients with schizophrenia (SCZ). It is, however, unclear whether NAA and Cho's alterations occur even before the onset of the disorder. Clinical high risk (CHR) individuals are a population uniquely enriched for psychosis and SCZ. In this exploratory study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to examine differences in total NAA (tNAA; NAA + N-acetylaspartylglutamate [NAAG]) and major choline-containing compounds, including glycerophosphorylcholine and phosphorylcholine [tCho], over the creatine (Cre) levels between 26 CHR and 32 healthy control (HC) subjects in the subcortical and cortical regions. While no tCho/Cre differences were found between groups in any of the regions of interest (ROIs), we found that CHR had significantly reduced tNAA/Cre in the right dorsal lateral prefrontal cortex (DLPFC) compared to HC, and that the right DLPFC tNAA/Cre reduction in CHR was negatively associated with their positive symptoms scores. No tNAA/Cre differences were found between CHR and HC in other ROIs. In conclusion, reduced tNAA/Cre in CHR vs. HC may represent a putative molecular biomarker for risk of psychosis and SCZ that is associated with symptom severity.

Thalamic dysconnectivity in the psychosis risk syndrome and early illness schizophrenia.

BACKGROUND: Schizophrenia (SZ) is associated with thalamic dysconnectivity. Compared to healthy controls (HCs), individuals with SZ have hyperconnectivity with sensory regions, and hypoconnectivity with cerebellar, thalamic, and prefrontal regions. Despite replication of this pattern in chronically ill individuals, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset. METHODS: Resting-state functional magnetic resonance imaging data were collected from psychosis risk syndrome (PRS) youth (n = 45), early illness SZ (ESZ) (n = 74) patients, and HCs (n = 85). Age-adjusted functional connectivity, seeded from the thalamus, was compared among the groups. RESULTS: Significant effects of group were observed in left and right middle temporal regions, left and right superior temporal regions, left cerebellum, and bilateral thalamus. Compared to HCs, ESZ demonstrated hyperconnectivity to all temporal lobe regions and reduced connectivity with cerebellar, anterior cingulate, and thalamic regions. Compared to HCs, PRS demonstrated hyperconnectivity with the left and right middle temporal regions, and hypoconnectivity with the cerebellar and other thalamic regions. Compared to PRS participants, ESZ participants were hyperconnected to temporal regions, but did not differ from PRS in hypoconnectivity with cerebellar and thalamic regions. Thalamic dysconnectivity was unrelated to positive symptom severity in ESZ or PRS groups. CONCLUSIONS: PRS individuals demonstrated an intermediate level of thalamic dysconnectivity, whereas ESZ showed a pattern consistent with prior observations in chronic samples. These cross-sectional findings suggest that thalamic dysconnectivity may occur prior to illness onset and become more pronounced in early illness stages.

Basic self-disturbance trajectories in clinical high risk for psychosis: a one-year follow-up study.

Basic self-disturbance (BSD) has been proposed as a driver of symptom development in schizophrenia spectrum disorders (SSDs). In a one-year follow-up of 32 patients (15-30 years) at putative risk for psychosis, we investigated trajectories of BSD levels from baseline to follow-up, and associations between clinical characteristics at baseline and follow-up, including follow-up levels of BSD (assessed with the EASE). Clinical high risk (CHR) for psychosis status and symptom severity were assessed with the SIPS/SOPS scales and also according to the cognitive basic symptoms high-risk criteria (COGDIS). DSM-IV diagnoses, functioning and other clinical characteristics were assessed with standard clinical instruments. Higher severity of negative symptoms and meeting COGDIS criteria at baseline were associated with higher BSD levels at follow-up. All measured at follow-up, higher BSD levels correlated with higher severity of positive, negative, disorganization and general symptoms, and with a lower level of global functioning. We found higher BSD levels at follow-up in subjects with schizotypal personality disorder (SPD) at baseline (n = 5) and in SSDs at follow-up (n = 12, including nine with SPD). Mean BSD levels decreased significantly from baseline to follow-up, but individual trajectories varied considerably. Increased BSD levels were associated with higher baseline BSD levels, non-remission of positive symptoms and functional decline. Overall, the current study indicates that subgroups in the CHR population with a higher risk of non-remission or deterioration may be identified by supplementing CHR criteria with assessment of BSD and negative symptoms.

Dorsolateral Prefrontal Cortex Glutamate/Gamma-Aminobutyric Acid (GABA) Alterations in Clinical High Risk and First-Episode Schizophrenia: A Preliminary 7-T Magnetic Resonance Spectroscopy Imaging Study.

Converging lines of evidence suggest that an imbalance between excitation and inhibition is present in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia (SCZ). Gamma-aminobutyric-acid (GABA) and, to a lesser extent, glutamate (Glu) abnormalities were reported in the DLPFC of SCZ patients, especially on the right hemisphere, by post-mortem studies. However, in vivo evidence of GABA, Glu, and Glu/GABA DLPFC abnormalities, particularly on the right side and the early stages of illness, is limited. In this preliminary study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to investigate bilateral Glu/Creatine (Cre), GABA/Cre, and Glu/GABA in the DLPFC of sixteen first episode schizophrenia (FES), seventeen clinical high risk (CHR), and twenty-six healthy comparison (HC) subjects. FES and CHR had abnormal GABA/Cre and Glu/GABA in the right DLPFC (rDLPFC) compared with HC participants, while no differences were observed in the left DLPFC (lDLPFC) among the three groups. Furthermore, HC had higher Glu/GABA in rDLPFC compared to lDLPFC (R > L), whereas the opposite relationship (R < L) was observed in the DLPFC Glu/GABA of FES patients. Altogether, these findings indicate that GABA/Cre and Glu/GABA DLPFC alterations are present before illness manifestation and worsen in FES patients, thus representing a putative early pathophysiological biomarker for SCZ and related psychotic disorders.

Burden Experienced by Primary Caregivers of Children With Psychotic Disorders and at Clinical High Risk for Psychosis.

BACKGROUND: Despite the existing research exploring caregiver burden in adult psychosis, few studies have examined the experience of providing care to children diagnosed with psychotic disorders (PDs) and those identified as having clinical high risk for psychosis (CHR-P). OBJECTIVE: This study measured the level of burden in caregivers of children with PD and CHR-P and examined associated risk factors, including social support, caregiver-child relationship, severity of illness, and frequency of psychiatric hospitalizations. METHODS: A total of 56 caregivers completed validated measures and provided demographic information. Measures included the Zarit Burden Interview, the Multidimensional Scale of Perceived Social Support, the Behavior Assessment System for Children, Third Edition, Parenting Relationship Questionnaire-Child and Adolescent Form (BASC-3 PRQ-CA), and the Clinical Global Impression-Severity scale. RESULTS: The majority of caregivers were women (86%), mothers (84%), White (63%), married (66%), working full-time (50%), college-educated (79%), and whose mean age was 45.7 years (SD = 8.09). Nearly half of the caregivers (45%) reported a high level of caregiver burden, 39% rated their burden in the mild to moderate range, and 16% reported little to no burden. There was no significant difference in mean burden between PD and CHR-P groups. Higher caregiver burden was associated with lower levels of social support (r = -.408, p = .002), lower levels of parenting confidence (r = -.514, p < .001), higher levels of relational frustration (r = .612, p < .001), and higher severity of illness (r = .316 p = .025). CONCLUSIONS: These findings underscore the critical unmet need for support for caregivers of children with PD and CHR-P. Applications to clinical practice are discussed.