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Biomedical subjects

Gerome Breen

Publications and source records attributed to Gerome Breen.

5 recordsLinked to original sources
PubMed2025

Genome-wide association study of adolescent-onset depression.

Adolescent depression is a heritable psychiatric condition with rising global prevalence and severe long-term outcomes, yet its biological underpinnings remain poorly understood. We conducted the first genome-wide association study of adolescent-onset depression, comprising 102,428 cases (diagnosis or clinical symptom thresholds) and 286,911 controls, including diverse ancestries. Cross-ancestry meta-analysis identified 52 independent variants across 17 loci; European-only analysis found 61 variants at 29 loci, with a SNP-based heritability of 9.8%. Comparative analyses revealed two genes unique to adolescent-onset versus lifetime depression, enriched in neuronal subtypes, and two genes as potential drug repurposing targets. Polygenic scores were associated with adolescent-onset depression across ancestries, persistent depression trajectories, more severe outcomes, as well as reduced cortical volume, surface area and white matter integrity. Genetic correlation and Mendelian randomisation analyses support shared genetic liability and causal links with early puberty and modifiable health and behavioural risk factors. These findings uncover novel genetic loci and refine biological pathways underlying adolescent-onset depression, revealing age-specific mechanisms and early intervention opportunities.

Journal Article↗
PubMed2004

Two peptidase activities decrease in treated bipolar disorder not schizophrenic patients.

BACKGROUND: Inhibition of prolyl oligopeptidase (PO) in primary neuronal cultures has been shown to reverse the effect of the common mood-stabilizers lithium, valproic acid and carbamazepine. In clinical studies, abnormal plasma PO activity has been associated with bipolar disorder (BD) and schizophrenia. However, this association is complicated by the discovery in bovine plasma of a Z-Pro-prolinal-insensitive peptidase (ZIP), a novel enzyme that cleaves the same substrate as PO. METHODS: We developed an assay to distinguish between ZIP and PO and measured both activities in plasma from 48 BD and 50 schizophrenic patients undergoing treatment and compared them with 50 control subjects. RESULTS: ZIP activity is restricted to blood plasma, whereas PO activity is present in the cytosol of lymphocytes, but can also be detected in blood plasma. Significant decreases in their plasma activities were found between treated BD (p = 0.007 and 0.03 respectively) but not schizophrenic (p > 0.05) patients and controls. CONCLUSIONS: We have found that the enzyme activity previously reported as plasma PO actually comprises two enzymes, PO and ZIP. This study shows a statistically significant decrease of both enzymes in BD patients undergoing lithium treatment. No statistically significant change in PO or ZIP activity is observed in schizophrenic patients.

Antipsychotic Agents↗
PubMed2003

Association of APOE gene with schizophrenia in Chinese: a possible risk factor in times of malnutrition.

Five hundred and seventy nine Chinese patients with schizophrenia who met DSMIV criteria for the disorder were genotyped for alleles epsilon 2,3,4 of apolipoprotein E (APOE) gene. All were recruited from inpatients and outpatients attending a large mental health centre in Shanghai. Results were compared to APOE data on 1528 controls drawn from the same area. Major differences in APOE genotype ratios and allele frequencies were observed between the patients and controls. The patients with schizophrenia had highly significantly (p<0.0001) increased epsilon 4/-genotypes and allele frequencies, and decreased epsilon 3/3 genotypes and epsilon 3 allele frequencies compared to controls. The effect was independent of sex and/or age of onset of illness, but strongly influenced by date of birth. Significant differences were restricted to individuals with schizophrenia born either before 1949 or during the period 1958-1967. Both were times of severe food shortages and malnutrition. We suggest that APOE may operate as an additional risk factor for schizophrenia in individuals subjected to fetal and/or early postnatal malnutrition.

Adult↗
PubMed2002

Novel and alternate SNP and genetic technologies.

There are many different genotyping technologies and chemistries. Other articles in this special issue focus on nanotechnology, bioinformatics, DNA chips and genotyping methods. This article focuses on four method categories not featured elsewhere in this, or the following special issue: (1) melting curve-based technologies such as dynamic allele-specific hybridization (DASH), melting curve single nucleotide polymorphism (McSNP), fluorescent resonance energy transfer (FRET), hybridization-based melting curves, and homogeneous assay formats based on melting curves; (2) non-PCR-dependent assays such as the oligonucleotide ligation assay and Invader, and isothermal amplification techniques such as rolling circle amplification; (3) rapid whole genome sequencing with methods such as the use of single molecule arrays and molecular resonance sequencing; (4) and other promising novel technologies.

Alternative Splicing↗