Artificial intelligence (AI) is explored as a tool to expand access to mental health care, offering support and self-disclosure. To date, the perspectives of individuals with schizophrenia on AI have been absent from the medical literature. This exploratory study represents an effort to report schizophrenia patient perspectives on AI chatbots through a focus group.

We conducted an exploratory, cross-sectional, qualitative study using semi-structured focus groups at a large academic health center in New York City. Participants included patients with schizophrenia spectrum disorders (n = 17), caregivers (n = 7), and providers (n = 4). Discussions explored familiarity with AI, privacy, and perceived utility of a hypothetical AI companion tool. Transcripts were analyzed using thematic analysis.

Five themes were identified in this exploratory analysis: (1) ‘Available When No One Else Is’, reflecting participants’ recognition of AI as a potentially accessible source of between-visit support; (2) ‘What Would It Do?’ capturing uncertainty about AI’s role; (3) ‘How Can I Trust It?’ highlighting trust as the central barrier, shaped by privacy concerns and schizophrenia-specific vulnerabilities; (4) ‘A Tool, Not a Therapist’, emphasizing that AI was acceptable only as a supplement to, not a replacement for, human care; and (5) ‘Keep It Low-Risk’, describing the narrow range of acceptable use cases, limited to supportive functions.

These exploratory findings suggest that AI is perceived as both a promising adjunct to care and a potential risk in schizophrenia. Implementation should emphasize transparency, trust, and clear boundaries, with AI designed to support, not replace, existing care.

Prenatal maternal stress is a known risk factor for later emotional problems, yet not all exposed offspring develop psychopathology. Executive functioning and prefrontal cortex structure and activity may buffer these effects, but it remains unclear whether genetic predispositions in these domains moderate associations with adolescent internalizing symptoms.

We examined 3,111 adolescents (1,881 females, 1,230 males). Prenatal stress was measured via a cumulative index across four domains. Internalizing symptoms were self-reported at ages 14 and 16. Genetic predisposition for executive functioning was indexed using a polygenic score (PGS) derived from adult samples, applied here to estimate genetic predisposition for executive functioning in adolescence. We also estimated a prefrontal cortex PGS based on cortical thickness and activation in six prefrontal regions, with a composite index derived from the first principal axis summarizing these measures.

Higher prenatal stress was significantly associated with more internalizing symptoms in adolescence. Female sex and maternal genetic risk for internalizing symptoms were also associated with higher symptom levels. Neither genetic disposition for executive functioning nor prefrontal cortex moderated this association overall. However, a weak interaction emerged at age 16, indicating that a genetic disposition for higher executive functioning was associated with greater internalizing symptoms under high stress exposure.

Prenatal maternal stress predicted increased adolescent internalizing symptoms, with limited evidence for moderation by genetic predisposition for executive functioning. Higher genetic potential for executive functioning may confer increased sensitivity to early stress under certain developmental conditions.

Charting developmental abnormalities in future psychotic disorder could help identify pathogenic processes. Head circumference (HC) is a proxy for brain size. Studies of HC and its developmental trajectories in future psychotic disorder cases and across the psychosis spectrum are inconclusive. It is important to determine whether deviations in HC are specific or reflect a general growth disorder.

We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to chart HC trajectories from birth to 15 years in individuals with operationally-defined psychotic disorder (N = 62), psychotic experiences (PE; N = 339) and controls (N = 3,527). We extracted total intracranial volume (TIV) from MRI data on a subset (N = 347) scanned at age 20.

HC at birth, 7 and 15 years was correlated with TIV at age 20 (r’s = 0.45–0.77). The psychotic disorder group had consistently smaller HC from birth through to adolescence (B = −0.26, p = 0.02). Females with PE had smaller HC across childhood and adolescence (B = −0.27, p = 0.016), while males with PE had consistently larger HC (B = 0.35, p = 0.023). The effects did not change when controlling for maternal and pregnancy-related characteristics but attenuated after controlling for height, except in males with PE.

Deviations in head and hence brain size across the psychosis spectrum likely reflect a more general growth abnormality. Future studies should examine factors regulating growth during early life in relation to psychosis, including sex, to understand underlying mechanisms.

The influential predictive processing theory of psychosis posits that symptoms arise from an imbalanced weighting of predictions (priors) and sensory evidence, yet studies present conflicting results. This is particularly problematic as findings from single tasks with modest sample sizes are frequently used to advance a theory for a generalized altered reliance on priors in psychosis.

This study presents a random-effects, multi-level meta-analysis (PROSPERO CRD42024574379) evaluating evidence for aberrant reliance on priors in psychosis across perceptual tasks. The search identified articles in Embase, MEDLINE, APA PsycINFO, and APA PsycArticles published between 1st January 2005—31st October 2024, with risk of bias assessed using the Newcastle-Ottawa Scale. Included articles (34 results from 27 studies) compared adults with schizophrenia-spectrum psychosis (SZ; n = 904) to healthy controls (n = 1,039) on behavioral measures representing reliance on priors.

Results provided no evidence for atypical reliance on priors in psychosis (g = .03, 95% CI [−0.27, 0.34]; p = .818) or associations with delusions (6 results; SZ = 183; r = −.16, 95% CI [−0.51, 0.19]; p = .293) or hallucinations (10 results; SZ = 370; r = .04, 95% CI [−0.28, 0.36]; p = .780). In contrast with the theory that psychosis differentially affects priors at different levels of the cognitive hierarchy, a sub-group analysis indicated that a two-level hierarchical model of priors did not reconcile conflicting results (F (1,32) = 0.1, p = .758).

These findings do not suggest that psychosis is associated with a generalized predictive processing deficit spanning multiple aspects of perception.

Individuals with schizophrenia spectrum disorders (SSDs) frequently exhibit low levels of physical activity (PA) and mood disturbances, both of which contribute to functional impairment and poorer long-term outcomes. Despite growing evidence linking PA and affective regulation, little is known about the real-time, bidirectional relationship between these domains in SSD.

In this multicenter observational study (DiAPAson project), 120 patients with SSD and 113 age- and sex-matched healthy controls (HC) underwent a 7-day ecological assessment combining smartphone-based Ecological Momentary Assessment (EMA; 8 prompts/day) and continuous wrist-worn actigraphy. We analyzed the dynamic associations between PA and mood using generalized linear mixed models (GLMMs) and Bayesian models with lagged temporal structures.

GLMMs revealed significantly lower daily mood in SSD compared to HC (estimate = −0.33, 95% CI: −0.53 to −0.12; p = .002), but no significant day-level association between PA and mood. In contrast, Bayesian models uncovered robust within-day, bidirectional associations in HC such that higher PA levels were followed by higher subsequent mood and, conversely, better mood predicted higher subsequent PA (PA → mood: posterior probability = 99.9%; mood → PA: 89.6%). In SSD, these within-day couplings were attenuated and more heterogeneous across individuals (PA → mood: 87.2%; mood → PA: 67.5%).

PA and mood are dynamically and bidirectionally linked within short temporal windows throughout the day, with stronger coupling in HC than in SSD. The substantial individual variability observed in SSD highlights the need for personalized, sensor-informed interventions, as aggregated analyses may obscure clinically relevant microtemporal dynamics.

Functional impairment in psychosis often persists despite symptomatic remission. There is a paucity of research examining early-course psychosocial functioning trajectories, and none has been conducted to examine relationship between the trajectories and prospective long-term functional outcomes in early psychosis sample.

We conducted 12-year follow-up of a randomized controlled trial on extended early intervention for first-episode psychosis to identify early-course social-occupational functioning trajectories and their baseline predictors and associations with 12-year outcomes. Participants who completed Social and Occupational Functioning Scale (SOFAS) scores at three or more timepoints between baseline and 3-year follow-up were included in the study. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Latent growth mixture modeling was employed to derive early-course social-occupational functioning trajectories based on SOFAS scores over 3-year follow-up.

A total of 148 participants were included in this study, with 106 patients having completed the 12-year follow-up. Our results identified four distinct trajectories, including persistently-good class, gradually-improved class, suboptimal-stable class, and persistently-poor class. Patients in persistently-poor class had more severe negative symptoms at baseline compared to patients in persistently-good class. Patients with persistently-poor trajectory had worse long-term outcomes than those with other classes in the majority of functional measures at 12-year follow-up.

The majority of patients were classified in early-stage suboptimal or poor functional trajectories. Above one-fourth of the participants exhibited persistently-poor social-occupational functioning trajectory, which predicted worse functional outcomes at 12-year follow-up. These findings highlighted the importance of tracking functional changes during the initial years of illness.

Posttraumatic stress disorder (PTSD) exhibits disrupted functional organization of brain networks involving sensory and association cortices. Connectome studies reveal a principal unimodal-to-transmodal gradient in the brain functional network that supports the spectrum from sensation to cognition. However, the disruption of the connectome gradient in PTSD and its associated transcriptional and neurotransmitter patterns remains poorly understood.

Using resting-state functional magnetic resonance imaging data from a cohort of 86 non-comorbid adult patients with PTSD caused by an earthquake and 86 trauma-exposed non-PTSD (TENP) controls who experienced the same disaster, we examined PTSD-related changes in the principal connectome gradient, their links to symptom severity and sex/age interactions, and brain-wide associations between gradient changes and microscale transcriptomic and neurotransmitter maps and macroscale cognitive function.

Compared with TENP controls, PTSD exhibited global topographic abnormalities in the principal unimodal-to-transmodal gradient, and focal aberrance mainly in the unimodal (visual network) and transmodal systems (limbic, ventral attention, and frontoparietal networks). Sex had no significant effects, while gradient decrease in the subcortical network is more prominent in adolescents with PTSD than adults. The PTSD-related gradients colocalized with brain-wide gene expression enriched in mitochondria and DNA/RNA metabolic process and corresponded with the distribution of dopamine, opioid, noradrenaline, and cholinergic neurotransmitter systems.

These findings highlight the dysfunctional connectome hierarchy in PTSD and its association with transcriptomic and molecular profiles, suggesting that early traumatization may more significantly impact the development of subcortical network. This work provides insight into the neurobiological basis of PTSD and indicates potential biomarkers for prediction and prevention.

Although recent stressful life events (SLEs) have been implicated as a risk factor for schizophrenia, prospective evidence and the underlying immunometabolic mechanisms remain unclear. This study investigated the association between recent SLEs and schizophrenia risk and explored the potential mediating role of immunometabolic markers.

Data were drawn from the UK Biobank prospective cohort. Cox proportional hazards models, linear mixed-effects models, and mediation analyses were applied.

We included 493,294 participants (mean [SD] age, 56.55 [8.09] years; 45.56% male) free of schizophrenia at baseline, among whom 492 schizophrenia cases were identified over a median follow-up of 13.91 years. Exposure to any recent SLEs was associated with a 49% higher risk of schizophrenia, with evidence of a dose–response relationship (e.g. highest SLE score group: HR, 7.15, 95% CI: 5.74–9.11). Among individual SLE types, ‘serious illness, injury, or assault to yourself’ and ‘financial difficulties’ showed the strongest associations with schizophrenia risk. Recent SLEs were associated with alterations in multiple immunometabolic markers, several of which were also significantly associated with schizophrenia risk. Mediation analyses indicated that specific immunometabolic markers (e.g. C-reactive protein and degree of unsaturation) partially mediated the association between recent SLEs and subsequent schizophrenia risk, with proportion mediated estimates of 9.0% and 11.7%, respectively.

In this cohort of predominantly middle-aged and older adults, recent SLEs were associated with increased subsequent schizophrenia risk. Immunometabolic pathways may partially underlie this association, supporting further investigation of integrated psychosocial and biological approaches to schizophrenia risk stratification.

Childhood trauma increases the risk for psychosis. However, mechanisms underlying this relationship remain unclear. In the present study, we aimed to investigate whether negative cognitive self-schemas or basic self-disturbance mediate the association between childhood trauma subtypes (abuse and neglect) and psychotic experiences in patients with psychotic disorders, unaffected siblings, and healthy controls.

This study was performed in a subsample of 110 patients, 120 siblings, and 48 healthy controls within the Genetic Risk and Outcome of Psychosis (GROUP) study. Parallel mediation models were used while correcting for age and sex. Abuse and neglect were measured with the childhood trauma questionnaire (CTQ), psychotic experiences with the Community Assessment of Psychic Experiences (CAPE), self-disturbance phenomena with the Self-Experience Lifetime Frequency Scale (SELF), and negative self-schemas with the Brief Core Schemas Scale (BCSS).

In patients, negative self-schemas fully mediated the association between abuse and psychotic experiences, whereas self-disturbance partly mediated the effect of neglect on psychotic experiences. In siblings, both negative self-schemas and self-disturbance fully mediated the association between abuse/neglect and psychotic experiences. In controls, only negative self-schemas mediated the association between abuse and neglect and psychotic experiences.

Our findings suggest that negative self-schemas and self-disturbance phenomena are relevant factors in explaining the association between childhood trauma and psychotic experiences across illness liability groups. Further research is needed to explore the causal pathways between trauma, negative self-schemas, self-disturbance phenomena, and psychotic experiences.

Methamphetamine is a highly addictive psychostimulant associated with widespread neurobiological alterations. While the acute and chronic effects on the brain have been extensively studied in animal models, far less is known about its impact on the human brain, particularly in the context of inhibitory processing.

Seventy-two participants (35 who regularly use methamphetamine) completed a paired-pulse somatosensory gating paradigm during magnetoencephalography (MEG). Immediately before the first stimulation of each trial, participants viewed either a substance-related or neutral image. The resulting responses were imaged, and time series were extracted from the peak voxel in the whole-brain maps, which was centered on the contralateral postcentral gyrus. Gating ratios (Stimulation 2/Stimulation 1) were subjected to a linear mixed-effect model, and spontaneous activity in the same voxel was assessed.

We found a significant group-by-condition interaction and a main effect of group, with the latter indicating that controls had significantly stronger gating across both task conditions compared to the methamphetamine group. Interestingly, the interaction revealed that only those in the methamphetamine group exhibited weaker gating in the substance-cue compared to the neutral image condition. Furthermore, gating indices were predictive of processing speed above and beyond the effect of group, while spontaneous gamma during the baseline was elevated in the methamphetamine group compared to controls.

Adults who use methamphetamine exhibit altered gating responses and elevated spontaneous gamma activity in the somatosensory cortices, likely reflecting disruptions in GABAergic circuitry. Substance-related cues accentuated gating deficits, suggesting that cue reactivity may compromise sensory inhibition in this population.

Early motor and language milestones are key indicators of neurodevelopment, yet their associations with later autism traits and attention-deficit/hyperactivity disorder (ADHD) symptoms remain poorly understood. Neurobiological mechanisms linking early developmental delays to these conditions are not well established. Here, we investigate associations between early developmental milestones, resting-state functional connectivity (rsFC), and neurodevelopmental traits in a large adolescent sample.

Data were drawn from the Adolescent Brain Cognitive Development study (ABCD) and included 6,663 participants (age range = 8.92–11.08 years; mean age = 9.92 years; 48.42% female). Developmental measures included roll over, sit without assistance, walk without assistance, speech development, gross motor development, and coordination. Autism traits were assessed using the Social Responsiveness Scale, and ADHD symptoms were assessed using the Attention Problems subscale of the Child Behavior Checklist. rsFC was examined within and between cortical and subcortical regions. Linear mixed-effects (LME) models and Bayesian mediation analyses assessed associations between developmental measures, rsFC, and neurodevelopmental traits.

LME models revealed shared and condition-specific associations. Poor coordination was associated with higher autism traits and ADHD symptoms, whereas delayed speech development was associated with autism traits, and delayed walking without assistance with ADHD symptoms. We found negligible evidence that rsFC measures mediated associations between early developmental milestones and neurodevelopmental traits. Indirect effects were modest, accounting for less than 2% of associations with autism traits, although somewhat larger effects were observed for ADHD symptoms.

These findings suggest overlapping developmental pathways, with intrinsic connectivity reflecting downstream neural processes rather than primary mediating mechanisms.

Selective serotonin reuptake inhibitors (SSRIs) represent an effective treatment for major depressive disorder (MDD). This study employed glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) to compare glutamate-sensitive signals in the prefrontal cortex and hippocampus of MDD patients before and after SSRI treatment.

The study included 35 unmedicated MDD patients and 39 healthy controls (HCs) who underwent baseline GluCEST imaging, using magnetization transfer ratio asymmetry (MTRasym) values to reflect regional glutamate levels. Twenty MDD patients completed follow-up GluCEST imaging after 8 weeks of SSRI treatment. Depressive symptoms were assessed using the Hamilton Rating Depression Scale (HAMD).

At baseline, the MTRasym values in the left hippocampus and bilateral prefrontal cortex were significantly lower in MDD patients compared to the HCs. Following SSRI treatment, the 20 MDD patients who completed follow-up showed significantly increased MTRasym values in the bilateral hippocampus and bilateral prefrontal cortex relative to baseline. Uncorrected correlation analyses showed that treatment-related differences in MTRasym values in the left hippocampus and left prefrontal cortex were associated with changes in HAMD-17 total score, sleep disturbance, and retardation scores.

GluCEST imaging suggested abnormal glutamate-sensitive signals in the prefrontal cortex and hippocampus of patients with MDD. SSRI treatment was associated with increased GluCEST signals across all regions of interest. The observed associations between regional GluCEST signal changes and symptom changes further suggest a potential role of glutamatergic-related modulation in the therapeutic effects of SSRIs.

Reinforcement motivation, particularly heightened punishment sensitivity and its imbalance relative to reward sensitivity (“motivational bias”), can predict outcomes in anorexia nervosa (AN). However, previous studies did not account for affective symptoms, which are intertwined with reinforcement processes and illness trajectory. This study examined whether affective symptoms explain outcomes beyond reinforcement motivation.

Adolescent girls and young women with AN (n = 192; Mage = 16.33 years, SD = 2.61) completed self-report measures of punishment/reward sensitivity, depressive symptoms, and trait anxiety at treatment admission and at 1-year follow-up. Outcomes included ED symptoms, body mass index, and multidimensional recovery (Morgan–Russell outcome assessment schedule). Cross-sectional comparisons included long-term recovered individuals (n = 154) and healthy controls (n = 440); longitudinal associations were tested using nested linear regression.

Patients with AN and recovered individuals showed elevated punishment sensitivity (η2ₚ = 0.19) and stronger motivational bias (punishment>reward; η2ₚ = 0.17). At baseline, reinforcement motivation and affective symptoms showed limited predictive utility. Longitudinally, shifts in motivational bias were associated with ED symptoms and multidimensional outcomes (|β| > 0.248, pFDR < .002), whereas changes in affective symptoms were the most robust and consistently associated predictors (|β| > 0.173, pFDR < .017).

Depressive symptom improvement emerged as the key predictor of outcome, showing stronger associations with follow-up ED symptoms and psychosocial functioning than reinforcement motivation. While changes in reinforcement motivation accompanied ED outcomes, affective symptom change was more predictive across outcomes. These findings emphasize the importance of prioritizing affective processes within developmentally tailored AN treatment frameworks.

Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) commonly co-occur and have overlapping genetic liabilities. Less is known regarding the phenomenology and genetics of ADHD in a cohort enriched for SUDs and the extent to which ADHD genetic liability contributes to SUD risk when controlling for substance specific genetic risk.

We used data from the Yale-Penn cohort, which comprises ~14,000 individuals ascertained for SUDs and/or as controls. Psychiatric and substance use phenotypes were ascertained from the semi-structured assessment for drug dependence and alcohol survey for all participants. Polygenic scores (PGSs) were developed for ADHD and multiple substance-related traits using summary statistics from large genome-wide association studies on participants with genetic data (N = 10,275).

Participants who met DSM-IV Criteria for ADHD had significantly increased odds for every DSM-5 SUD analyzed, greater polysubstance use, and younger age of onset of substance use. Among participants of European-like ancestry, ADHD PGS was associated with multiple SUDs, even after controlling for substance-specific PGS. Of the substance-related PGS, only the smoking initiation PGS was associated with ADHD diagnosis and criterion count and only among individuals of European-like ancestry.

In this sample, ADHD was associated with increased risk for SUDs and earlier onset of substance use. Additionally, genetic liability to ADHD was independently associated with multiple SUDs and SUD criteria counts. PGS for substance-related traits tended to be less significantly associated with ADHD. Further studies in large, diverse populations are needed to enhance our understanding of these associations.

Associations between childhood streptococcal upper respiratory infections and subsequent psychiatric outcomes have been described for over 25 years, although clinical evidence remains limited. This study explored psychiatric outcomes after pediatric streptococcal versus non-streptococcal upper respiratory tract infections.

This retrospective cohort study used TriNetX, a global federated health research network of over 150 million deidentified electronic medical records. We compared children aged 3–16 with a diagnosis of acute upper respiratory infection (ICD-10 J00-J06) and a Streptococcus pyogenes test result (positive or negative) within 2 weeks, propensity matched on 70 baseline variables. Main outcomes were the 1-year incidence of any psychiatric disorder, obsessive-compulsive disorder (OCD), tic disorder, anxiety, and restricted oral intake.

Before matching, 464,513 children were streptococcal positive and 1,023,171 children were streptococcal negative. After matching, there were 456,221 children in each cohort (48% female). The streptococcal-positive cohort had a reduced risk of any psychiatric disorder (RR 0.92 [0.90, 0.94]), restricted oral intake (0.81 [0.77, 0.86]), and anxiety disorder (0.94 [0.91, 0.97]) at 1 year. Risk of OCD (RR 0.98 [0.86, 1.12]) and tic disorder (RR 0.95 [0.87, 1.04]) was not significantly different between the two cohorts.

This large-scale cohort study found no evidence that exposure to S. pyogenes is associated with increased risk of the measured psychiatric outcomes.

Depression affects over 400 million adults worldwide and is associated with substantial morbidity and mortality. Although symptoms vary in their responsiveness to treatment, clinical trials typically report total scores, obscuring symptom-level effects. Despite collaborative care’s effectiveness for depression in primary care, its impact on individual depressive symptoms among racially and socioeconomically diverse patients remains unclear.

We conducted a secondary analysis of the eIMPACT trial of 216 primary care patients (Mage = 59 years; 78% women; 50% Black; 46% with income <$10,000/year). Participants were randomized to 12 months of modernized collaborative care (internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants) or usual primary care. Two path analytic models estimated simultaneous item-level effects on the Hopkins Symptom Checklist-20 (SCL-20) and Patient Health Questionnaire-9 (PHQ-9).

The intervention outperformed usual care on 15 of 20 SCL-20 items and 7 of 9 PHQ-9 items. Seventeen symptoms – including hopelessness, anxious distress, depressed mood, self-blame, worthlessness, disturbed sleep, and fatigue – showed moderate-to-large between-group improvement (βs = −0.50 to −0.70). Smaller but significant gains were observed for six other symptoms (βs = −0.35 to −0.49). No significant advantage emerged for suicidality, loneliness, sexual dysfunction, appetite change, or psychomotor symptoms (βs = −0.03 to −0.37).

Modernized collaborative care improves most depressive symptoms in diverse primary care patients, though cross-measure persistent symptoms highlight clinically consequential domains that may be obscured by total scores. Symptom-level analyses may help identify persistent symptom domains requiring targeted adjunctive treatment to optimize recovery.

22q11.2 deletion syndrome (22q11DS) is strongly associated with aberrant neurodevelopment, including decreased cognitive functioning and schizophrenia spectrum disorders (SSDs). While the different core domains of IQ have distinct clinical ramifications, their collective profile has not been well-characterized in 22q11DS. Here, in the largest 22q11DS sample to date, we elucidate the overall IQ profile, including Verbal and Performance IQ (VIQ and PIQ), Processing Speed (PS), and Working Memory (WM), including associations with developmental stage and SSDs.

We included 1,328 individuals with 22q11DS from the International Brain and Behavior Consortium. We derived an overall IQ profile using VIQ, PIQ, PS, and WM scores at initial assessment, from age-appropriate Wechsler scales. Using both cross-sectional and longitudinal IQ data from a subset (n = 496; 37.35%) of individuals, we examined IQ profiles across three age groups and compared profiles between individuals with and without SSDs.

IQ profiles in 22q11DS exhibited differences between IQ domains (p < 0.001), ranked from relatively strongest to weakest: PS > WM > VIQ > PIQ. This profile was similar across age groups, with scores highest in children, lower in adolescents, and lowest in adults. Individuals without SSDs had higher IQ scores than those with SSDs (p < 0.001), with no significant domain-specific effects.

The results indicate a tendency toward a characteristic IQ profile in 22q11DS, regardless of SSD status. A clinical implication of these divergent IQ domains, in particular the relative weakness in PIQ, is that functional expectations are likely to be overestimated. The domain-specific differences across age-groups highlight the need for repeated and comprehensive cognitive assessments in this high-risk population, and may suggest differing underlying mechanisms that require further investigation.