Age at First Episode Modulates Diagnosis-Related Structural Brain Abnormalities in Psychosis

Abstract

Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12-35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15-20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18-20 y). The AFP group also had age-constant (12-35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis.

Gray matter differences between affective and non-affective first episode psychosis: A review of Magnetic Resonance Imaging studies

“…Specifically, greater cortical thinning in the left inferior frontal gyrus, left cuneus, right middle temporal gyrus and right superior temporal sulcus was observed in NA-FEP compared to A-FEP (Qiu et al, 2013). Moreover, Pina-Camacho et al (2016) found that earlier age at NA-FEP patients had significantly smaller frontal volumes and thinner frontal, temporal, parietal, medial orbitofrontal, insular cortices as well as smaller middle frontal gyrus volumes and thinner precuneus than A-FEP .…”

“…With regard to cortical regions, four MRI studies investigated the presence of cortical thickness differences between A-FEP and NA-FEP (Pina-Camacho et al, 2016;Qiu et al, 2013;Ansell et al, 2015;(Nakamura et al, 2007). However, only two MRI studies reported significant results (Pina-Camacho et al, 2016;Qiu et al, 2013). Specifically, greater cortical thinning in the left inferior frontal gyrus, left cuneus, right middle temporal gyrus and right superior temporal sulcus was observed in NA-FEP compared to A-FEP (Qiu et al, 2013).…”

Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder—a systematic review of the magnetic resonance neuroimaging literature

“…BD > SZ in presubiculum and subiculumMathew et al 35 2014337/219/142/188PChronicMedicatedMedial temporal lobeFree Surfer3BD = HC > SZ and SAD in medial temporal cortex volume, SZ < BD < HC in hippocampal subfieldsKnochel et al 38 201421/21/0/21ChronicMedicatedHippocampusVBM3Hippocampal volume HC > BD > SZFindikili et al 122 201530/17/0/17ChronicMedicatedPineal glandROI (manual tracing)1.5Mean pineal gland volume SZ < BD < HCNenandic et al 41 201534/34/0/17PChronicMedicatedWhole brainVBM3HC > SZ prefrontal cortex and insula, temporal cortex, thalamus, and cerebellum. SZ < BD in hippocampus, DLPFC, and cerebellumKittel-Schneider et al 45 201518/23/0/30P/NPFEMedicatedAmygdalaROI (manual tracing)1.5HC > BD > SZ in amygdala volumeLaidi et al 123 201552/32/0/115P/NPChronicMedicatedCerebellumFree Surfer3SZ < HC = BD in cerebellar volumeSong et al 34 201535/71/0/44PChronicOff medicationWhole brainVBM3HC > SZ precentral gyrus, caudate, and cerebellum; HC > BD middle frontal gyrus, fusiform gyrus; BD > SZ cerebellum, temporal lobe, basal gangliaPina-Camacho et al 53 2015157/92/0/32/72PFEMedicatedWhole brainVBM, Free Surfer1.5/3HC > SZ in frontal and temporal lobe, SZ > HC in basal ganglia. HC > BD ACC, BD > HC in caudate and temporal lobe thicker temporal cortexShepherd et al 124 201534/28/12/30ChronicMedicatedWhole brainVBM3HC > SZ in hippocampus and frontal cortex.…”

The association between season of birth, age at onset, and clozapine use in schizophrenia

“…Furthermore, possible biological markers for a poor prognosis have been found in early‐onset schizophrenia. Patients who had their first episode before age 15–20 showed a significantly decreased volume and thickness of the frontal lobe, a decreased volume of the temporal lobe, and an enlarged volume of the ventricular system and the basal ganglia . Pauly et al.…”