Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

Abstract

Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the wellestablished abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These earlyonset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to earlyonset schizophrenia cases. However, patients with earlyonset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders.

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

“…[1][2][3][4]38 We and others postulate that if onset of psychosis coincides with active maturational changes in a brain structure, then development of that particular brain structure will be most affected by the disease. 4,22 The current study indicates that if SSD starts after early adolescence, no differences are found in the parietal cortex of cases and controls. The parietal cortex reaches peak maturity in late childhood (around 7.5 y in girls and 9 in boys 4 ), and parietal abnormalities are present in very early-onset psychosis such as childhood-onset schizophrenia.…”

“…Some studies have not found any differences between first-episode SSD and AFP patients, and many others do not include diagnostic subgroup comparisons. 22 Hence this finding warrants further replication. A previous study in first-episode AFP and schizophrenia patients aged 18-40 years also showed brain deficits confined to the subgenual cingulate in this specific subgroup.…”

“…[8][9][10][11][12][13][14][15][16][17][18][19] This pattern has also been reported in patients with first-episode affective psychoses (AFP), with alterations being larger and more widespread in the SSD group. 8,12,[20][21][22] Previous studies assessing the effect of age at FEP on brain structure suggest that earlier onset is associated with greater disruption of structural brain development. 7,[23][24][25][26] However, interpretation of these results may be hampered by using age as a linear variable and disregarding the nonlinear relationship of age with brain development, 24,26 stratifying cases into several onset (adolescent/adult) groups instead of treating age as a continuous variable, 23,25 and using a narrow age-range sample of patients which does not encompass important stages of brain development.…”

Dissociable auditory mismatch response and connectivity patterns in adolescents with schizophrenia and adolescents with bipolar disorder with psychosis: A magnetoencephalography study

“…The P3 is commonly believed to be an endogenous neuronal component that is dependent on the level of attention and arousal as well as the context in which a stimulus occurs (Polich, 2007). We acknowledge that this interpretation may be wrong, however, the existence of dissociable effects at latencies usually associated with higher order mechanisms may further support the notion that in adolescence, an active period of brain re-organization, different developmental pathways are materializing in schizophrenia and bipolar disorder with psychosis (Arango et al, 2014).…”

“…It is thought that at a neuronal population level this reflects a maturation of the excitatory inhibitory balance in the temporal regions. Mapping changes in adolescence may, therefore, represent a uniquely sensitive way to understand the MMN response in schizophrenia and bipolar disorder against the developmental course of adolescence (e.g., Arango et al, 2014) Following our previous work (Dima et al, 2012) we used Magnetoencephalography (MEG) to quantify the MMN neuronal response in adolescents with schizophrenia (ASZ), in adolescents with bipolar disorder with psychosis (ABP) and in normally developing adolescents. MEG is able to image the brain at high temporal resolution, where the spatial resolution is typically better than EEG, thereby offering the potential to better delineate neural correlates of these disorders.…”