Very early onset and greater vulnerability in schizophrenia: A clinical and neuroimaging study

Margari, Francesco; Presicci, Anna; Petruzzelli, Maria Giuseppina; Ventura, Paolo; Cuonzo, Franca Di; Palma, M.; Margari, Lucia

doi:10.2147/ndt.s2484

Cited by 13 publications

(10 citation statements)

References 25 publications

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“…The proportion of patients with EOS is only around 4% of all schizophrenia patients [1]. Those with EOS show an insidious onset, more severe premorbid neurodevelopmental abnormalities, more frequent terrifying visual hallucinations, constant blunted affects, a higher rate of familial psychopathology, minor response to treatment, poorer outcome [2] and more severe cognitive performance [3,4] compared with adult-onset schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Genetic Association of TCF4 and AKT1 Gene Variants with the Age at Onset of Schizophrenia

Chow

Tee²,

Yong³

et al. 2016

Neuropsychobiology

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Background: Age at onset (AAO) is a known prognostic indicator for schizophrenia and is hypothesized to correlate with cognition and symptom severity. TCF4 and AKT1 are schizophrenia risk genes involved in cognitive functions. The current study examined the interactive effects of TCF4 and AKT1 variants with gender, family history of psychiatric disorders and ethnicity on the AAO of schizophrenia. Methods: This study consisted of 322 patients with schizophrenia meeting the DSM-IV criteria. Six single nucleotide polymorphisms (SNPs) of TCF4 (rs12966547, rs8766, rs2958182, rs9960767, rs10401120 and rs17512836) and seven AKT1 SNPs (rs2498804, rs3803304, rs2494732, rs3730358, rs1130214, rs2498784 and rs3803300) were genotyped using the TaqMan® SNP genotyping-based assays method. The relationship of AAO with each variant was investigated using analyses of covariance. Results: Among the TCF4 variants, rs12966547 (p = 0.024) and rs8766 (p = 0.021) were significantly associated with earlier AAO. We found a lower average AAO in patients with the AA genotype of rs12966547, while the CT genotype of rs8766 was demonstrated to have a protective effect on AAO. For rs8766, there was significant gene × gender interaction (p = 0.012) in influencing AAO. However, these results were not significant after false discovery rate correction. Significant gene × ethnicity interactions were observed to influence AAO (p < 0.05). The Kaplan-Meier curve of the minor AA genotype of rs12966547 displayed a significant trend (p = 0.008) for onset after 19 years of age. Similarly, the minor CC genotype of rs8766 showed a significantly (p = 0.034) lower AAO compared to the TT genotype. Conclusion: Our analyses suggest that individual risk genotypes may influence the risk of schizophrenia in an age-specific manner.

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Section: Introductionmentioning

confidence: 99%

Genetic Association of TCF4 and AKT1 Gene Variants with the Age at Onset of Schizophrenia

Chow

Tee²,

Yong³

et al. 2016

Neuropsychobiology

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“…Familial studies have indicated that parents of youth with EOS have higher rates of schizophrenia spectrum disorders than parents of patients with adult-onset illness and relatives of children and adolescents with ADHD (Margari et al, 2008;Nicolson et al, 2003). The risk of developing schizophrenia is about ten times higher if a first-degree relative has the illness.…”

Section: Geneticsmentioning

confidence: 99%

“…Yet, family involvement and intervention become particularly critical when treating a child with EOS as they most likely reside with their family and are dependent upon them to support and access treatment (Asarnow et al, 2004). Familyfocused interventions require an understanding of this system, particularly since familial studies have indicated that parents of individuals with EOS have higher rates of schizophrenia and schizophrenia spectrum disorders than parents of patients with adult-onset illness, and relatives of children and adolescents with ADHD (Margari et al, 2008;Nicolson et al, 2003). Parents of youth with EOS also experience higher levels of social isolation, introversion, suspiciousness, and hostility than parents of children with autism and ADHD (Nicolson et al, 2003).…”

Section: Family Interventionsmentioning

confidence: 99%

Identifying, Assessing, and Treating Early Onset Schizophrenia at School

Pearrow

Jimerson

2010

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“…Additionally, clinical group differences in the N100 repetition suppression response were considered separately in subsamples of participants between 5 and 12 years and 13 and 17 years of age to explore whether very early presentation of CHR or PS is accompanied by more marked plasticity deficits. Research suggests that very early onset psychosis (i.e., emerging before the age of 13 years) shows more severe premorbid neurodevelopmental abnormalities and poorer treatment response and outcomes than later onset psychosis [ 46 – 48 ]. We hypothesized a progression in plasticity dysfunction from HC to CHR to PS groups.…”

Section: Introductionmentioning

confidence: 99%

N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth

et al. 2016

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Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones − mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life.

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Very early onset and greater vulnerability in schizophrenia: A clinical and neuroimaging study

Cited by 13 publications

References 25 publications

Genetic Association of <b><i>TCF4</i></b> and <b><i>AKT1</i></b> Gene Variants with the Age at Onset of Schizophrenia

Genetic Association of <b><i>TCF4</i></b> and <b><i>AKT1</i></b> Gene Variants with the Age at Onset of Schizophrenia

Identifying, Assessing, and Treating Early Onset Schizophrenia at School

N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth

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