Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated With Psychopathology Across Independent Cohorts.

Background: Patients with early psychosis (EP) (within 3 years after psychosis onset) show significant variability, which makes predicting outcomes challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, which limits the development of early interventions.

Methods: A data-driven approach, partial least squares correlation, was used across 2 independent datasets to examine multivariate relationships between white matter properties and symptomatology and to identify stable and generalizable signatures in EP.

Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

Background: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions.

Methods: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP.

PET-measured human dopamine synthesis capacity and receptor availability predict trading rewards and time-costs during foraging.

Foraging behavior requires weighing costs of time to decide when to leave one reward patch to search for another. Computational and animal studies suggest that striatal dopamine is key to this process; however, the specific role of dopamine in foraging behavior in humans is not well characterized. We use positron emission tomography (PET) imaging to directly measure dopamine synthesis capacity and D and D receptor availability in 57 healthy adults who complete a computerized foraging task.

In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis.

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI).

Clinical correlation but no elevation of striatal dopamine synthesis capacity in two independent cohorts of medication-free individuals with schizophrenia.

Dysregulation of dopamine systems has been considered a foundational driver of pathophysiological processes in schizophrenia, an illness characterized by diverse domains of symptomatology. Prior work observing elevated presynaptic dopamine synthesis capacity in some patient groups has not always identified consistent symptom correlates, and studies of affected individuals in medication-free states have been challenging to obtain. Here we report on two separate cohorts of individuals with schizophrenia spectrum illness who underwent blinded medication withdrawal and medication-free neuroimaging with [F]-FDOPA PET to assess striatal dopamine synthesis capacity.

Polymorphism in the ZNF804A Gene and Variation in D and D/D Dopamine Receptor Availability in the Healthy Human Brain: A Dual Positron Emission Tomography Study.

Background: The rs1344706 single nucleotide polymorphism in the ZNF804A gene has been associated with risk for psychosis in multiple genome-wide association studies, yet mechanisms underlying this association are not known. Given preclinical work suggesting an impact of ZNF804A on dopamine receptor gene transcription and clinical studies establishing dopaminergic dysfunction in patients with schizophrenia, we hypothesized that the ZNF804A risk single nucleotide polymorphism would be associated with variation in dopamine receptor availability in the human brain.

Methods: In this study, 72 healthy individuals genotyped for rs1344706 completed both [F]fallypride and [C]NNC-112 positron emission tomography scans to measure D/D and D receptor availability, respectively.

Heritability of Functional Connectivity in Resting State: Assessment of the Dynamic Mean, Dynamic Variance, and Static Connectivity across Networks.

Recent efforts to evaluate the heritability of the brain's functional connectome have predominantly focused on static connectivity. However, evaluating connectivity changes across time can provide valuable insight about the inherent dynamic nature of brain function. Here, the heritability of Human Connectome Project resting-state fMRI data was examined to determine whether there is a genetic basis for dynamic fluctuations in functional connectivity.

Relationships between intrinsic functional connectivity, cognitive control, and reading achievement across development.

There are vast individual differences in reading achievement between students. Besides structural and functional variability in domain-specific brain regions, these differences may partially be explained by the organization of domain-general functional brain networks. In the current study we used resting-state functional MRI data from the Philadelphia Neurodevelopmental Cohort (PNC; N = 553; ages 8-22) to examine the relation between performance on a well-validated reading assessment task, the Wide Range Achievement Word Reading Test (WRAT-Reading) and patterns of functional connectivity.

State-Dependent Functional Dysconnectivity in Youth With Psychosis Spectrum Symptoms.

Psychosis spectrum disorders are conceptualized as neurodevelopmental disorders accompanied by disruption of large-scale functional brain networks. Dynamic functional dysconnectivity has been described in patients with schizophrenia and in help-seeking individuals at clinical high risk for psychosis. Less is known, about developmental aspects of dynamic functional network connectivity (dFNC) associated with psychotic symptoms (PS) in the general population.

Structural Brain Alterations in Youth With Psychosis and Bipolar Spectrum Symptoms.

Objective: Adults with established diagnoses of serious mental illness (bipolar disorder and schizophrenia) exhibit structural brain abnormalities, yet less is known about how such abnormalities manifest earlier in development.

Method: Cross-sectional data publicly available from the Philadelphia Neurodevelopmental Cohort (PNC) were analyzed. Structural magnetic resonance neuroimaging data were collected on a subset of the PNC (N = 989; 9-22 years old).

Disruptions in White Matter Maturation and Mediation of Cognitive Development in Youths on the Psychosis Spectrum.

Background: Psychosis onset typically occurs in adolescence, and subclinical psychotic experiences peak in adolescence. Adolescence is also a time of critical neural and cognitive maturation. Using cross-sectional data from the Philadelphia Neurodevelopmental Cohort, we examined whether regional white matter (WM) development is disrupted in youths with psychosis spectrum (PS) features and whether WM maturation mediates the relationship between age and cognition in typically developing (TD) youths and youths with PS features.

Presynaptic Dopamine Synthesis Capacity in Schizophrenia and Striatal Blood Flow Change During Antipsychotic Treatment and Medication-Free Conditions.

Standard-of-care biological treatment of schizophrenia remains dependent upon antipsychotic medications, which demonstrate D receptor affinity and elicit variable, partial clinical responses via neural mechanisms that are not entirely understood. In the striatum, where D receptors are abundant, antipsychotic medications may affect neural function in studies of animals, healthy volunteers, and patients, yet the relevance of this to pharmacotherapeutic actions remains unresolved. In this same brain region, some individuals with schizophrenia may demonstrate phenotypes consistent with exaggerated dopaminergic signaling, including alterations in dopamine synthesis capacity; however, the hypothesis that dopamine system characteristics underlie variance in medication-induced regional blood flow changes has not been directly tested.

Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established.

ADHD comorbidity can matter when assessing cortical thickness abnormalities in patients with bipolar disorder.

Objectives: Attention-deficit hyperactivity disorder (ADHD) is prevalent in patients with bipolar disorder (BP), but very few studies consider this when interpreting magnetic resonance imaging findings. No studies, to our knowledge, have screened for or controlled for the presence of ADHD when examining cortical thickness in patients with BP. We used a 2 × 2 design to evaluate the joint effects of BP and ADHD on cortical thickness and uncover the importance of ADHD comorbidity in BP subjects.

Anterior cingulate activation relates to local cortical thickness.

Few studies have examined the relationship between local anatomic thickness of the cortex and the activation signals arising from it. Using structural and functional MRI, we examined whether a relationship exists between cortical thickness and brain activation. Twenty-eight participants were asked to perform the Go/NoGo response inhibition task known to activate the anterior cingulate and the prefrontal cortex.