We modeled both psychopathology and executive function (EF) as bi-factor models to study if EF impairments are transdiagnostic or relate to individual syndromes, and concurrently, if such associations are with general EF or specific EF impairments.

Data were obtained from the Tracking Adolescents’ Individual Lives Survey (TRAILS; N = 2230). Psychopathology was assessed with parent-report questionnaires at ages 11, 14, 16, and 19, and EF with tasks from the Amsterdam Neuropsychological Tasks program at ages 11 and 19. Bi-factor models were fitted to the data using confirmatory factor analysis. Correlations were estimated to study the associations between general or specific components of both psychopathology and EF.

A bi-factor model with a general psychopathology factor, alongside internalizing (INT), externalizing, attention deficit/hyperactivity (ADHD), and autism spectrum (ASD) problem domains, and a bi-factor model with a general EF factor, alongside specific EFs were adequately fitting measurement models. The best-fitting model between EF and psychopathology showed substantial associations of specific EFs with the general psychopathology factor, in addition to distinct patterns of association with ASD, ADHD, and INT problems.

By studying very diverse psychopathology domains simultaneously, we show how EF impairments cross diagnostic boundaries. In addition to this generic relation, ADHD, ASD, and INT symptomatology show separable profiles of EF impairments. Thus, inconsistent findings in the literature may be explained by substantial transdiagnostic EF impairments. Whether general EF or specific EFs are related to psychopathology needs to be further studied, as differences in fit between these models were small.

Patients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors.

Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC.

Compared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA.

UHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity.

Subjects at ‘ultra high risk’ (UHR) for developing psychosis have differences in white matter (WM) compared with healthy controls. WM integrity has not yet been investigated in UHR subjects in relation to the development of subsequent psychosis. Hence, we investigated a prospective cohort of UHR subjects comparing whole brain fractional anisotropy (FA) of those later developing psychosis (UHR-P) to those who did not (UHR-NP).

We recruited 37 subjects fulfilling UHR criteria and 10 healthy controls. Baseline 3 Tesla magnetic resonance imaging (MRI) scans and Positive and Negative Syndrome Scale (PANSS) ratings were obtained. UHR subjects were assessed at 9, 18 and 24 months for development of frank psychosis. We compared baseline FA of UHR-P to controls and UHR-NP subjects. Furthermore, we related clinical data to MRI outcome in the patient population.

Of the 37 UHR subjects, 10 had transition to psychosis. UHR-P subjects showed significantly lower FA values than control subjects in medial frontal lobes bilaterally. UHR-P subjects had lower FA values than UHR-NP subjects, lateral to the right putamen and in the left superior temporal lobe. UHR-P subjects showed higher FA values, compared with UHR-NP, in the left medial temporal lobe. In UHR-P, positive PANSS negatively correlated to FA in the left middle temporal lobe. In the total UHR group positive PANSS negatively correlated to FA in the right superior temporal lobe.

UHR subjects who later develop psychosis have differences in WM integrity, compared with UHR subjects who do not develop psychosis and to healthy controls, in brain areas associated with schizophrenia.