Duplication 15q14 → pter: a rare chromosomal abnormality underlying bipolar affective disorder

Reif, Andreas; Kress, W.; Wurm, Karl; Benninghoff, Jens; Pfuhlmann, Bruno; Lesch, Klaus‐Peter

doi:10.1016/j.eurpsy.2004.03.001

Cited by 8 publications

(4 citation statements)

References 8 publications

(9 reference statements)

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“…In medication‐free adults with BD, reduced Cho concentrations have also been shown in the left dorsolateral prefrontal cortex compared to HC (36). In our study, reductions in vermal myo ‐Ino and Cho may reflect hypometabolism (37) or an early neurodegenerative process that parallels volumetric reductions seen in the cerebellum of individuals who have already developed BD (9, 10).…”

Section: Discussionmentioning

confidence: 64%

Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder

et al. 2011

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Objectives We aimed to compare concentrations of N-acetyl aspartate, myo-inositol, and other neurometabolites in the cerebellar vermis of offspring at risk for bipolar disorder (BD) and healthy controls to examine whether changes in these neuronal metabolite concentrations occur in at-risk offspring prior to the onset of mania. Methods A total of 22 children and adolescents aged 9–17 years with a familial risk for bipolar I or II disorder [at-risk offspring with non-bipolar I disorder mood symptoms (AR)], and 25 healthy controls (HC) were examined using proton magnetic resonance spectroscopy at 3T to study metabolite concentrations in an 8-cc voxel in the cerebellar vermis. Results Decreased myo-inositol and choline concentrations in the vermis were seen in the AR group compared to HC (p < 0.01). Conclusions Decreased cellular metabolism and interference with second messenger pathways may be present in the cerebellar vermis in youth at risk for BD as evident by decreased myo-inositol and choline concentrations in this region. These results may be limited by a cross-sectional design, co-occurring diagnoses, and medication exposure. Longitudinal studies are necessary to determine whether early neurochemical changes can predict the development of mania. Improved methods for identifying children with certain neurochemical vulnerabilities may inform preventive and early intervention strategies prior to the onset of mania.

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Section: Discussionmentioning

confidence: 64%

Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder

et al. 2011

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“…Another informative patient with bipolar affective disorder and duplication of chromosome 15q14/pter, and thus partial trisomy 15, has been followed longitudinally for over 15 years (Reif et al, 2004). This patient also presents with dysmorphic features, positive pyramidal tract signs, hypotonia, awkward movements, and intellectual impairment (Reif et al, 2004). Interestingly, trisomy 15 mosaicism is known to cause a PWS phenotype, which is often characterized by cycloid psychosis and bipolar affective disorder (Liu et al, 2001).…”

Section: Psychiatric Disordersmentioning

confidence: 99%

Genomic Rearrangements and Gene Copy-Number Alterations as a Cause of Nervous System Disorders

Lee

Lupski

2006

Neuron

250

206

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Genomic disorders are a group of human genetic diseases caused by genomic rearrangements resulting in copy-number variation (CNV) affecting a dosage-sensitive gene or genes critical for normal development or maintenance. These disorders represent a wide range of clinically distinct entities but include many diseases affecting nervous system function. Herein, we review selected neurodevelopmental, neurodegenerative, and psychiatric disorders either known or suggested to be caused by genomic rearrangement and CNV. Further, we emphasize the cause-and-effect relationship between gene CNV and complex disease traits. We also discuss the prevalence and heritability of CNV, the correlation between CNV and higher-order genome architecture, and the heritability of personality, behavioral, and psychiatric traits. We speculate that CNV could underlie a significant proportion of normal human variation including differences in cognitive, behavioral, and psychological features.

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“…For example, it is noteworthy that human RyR genes, RYR1 and RYR3, are encoded at sites, 19q13 and 15q14–15, respectively, which have been implicated as risk loci for bipolar disorder in genome-wide association studies (Reif et al, 2004; Francks et al, 2010; Green et al, 2013). Alternatively, these targets may be involved in side effects of ADs such as ventricular tachycardia (Thanacoody and Thomas, 2005; Zima et al, 2008).…”

Section: Drug Elucidation Drives Discovery Researchmentioning

confidence: 99%

Drug elucidation: invertebrate genetics sheds new light on the molecular targets of CNS drugs

et al. 2014

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Many important drugs approved to treat common human diseases were discovered by serendipity, without a firm understanding of their modes of action. As a result, the side effects and interactions of these medications are often unpredictable, and there is limited guidance for improving the design of next-generation drugs. Here, we review the innovative use of simple model organisms, especially Caenorhabditis elegans, to gain fresh insights into the complex biological effects of approved CNS medications. Whereas drug discovery involves the identification of new drug targets and lead compounds/biologics, and drug development spans preclinical testing to FDA approval, drug elucidation refers to the process of understanding the mechanisms of action of marketed drugs by studying their novel effects in model organisms. Drug elucidation studies have revealed new pathways affected by antipsychotic drugs, e.g., the insulin signaling pathway, a trace amine receptor and a nicotinic acetylcholine receptor. Similarly, novel targets of antidepressant drugs and lithium have been identified in C. elegans, including lipid-binding/transport proteins and the SGK-1 signaling pathway, respectively. Elucidation of the mode of action of anesthetic agents has shown that anesthesia can involve mitochondrial targets, leak currents, and gap junctions. The general approach reviewed in this article has advanced our knowledge about important drugs for CNS disorders and can guide future drug discovery efforts.

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Duplication 15q14 → pter: a rare chromosomal abnormality underlying bipolar affective disorder

Cited by 8 publications

References 8 publications

Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder

Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder

Genomic Rearrangements and Gene Copy-Number Alterations as a Cause of Nervous System Disorders

Drug elucidation: invertebrate genetics sheds new light on the molecular targets of CNS drugs

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