The enzyme catechol-O-methyltransferase (COMT) transfers a methyl group from S-adenosylmethionine to the benzene ring of catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. This review focuses on the association between the genetic polymorphisms of COMT gene and psychiatric disorders.
Catechol O-Methyltransferase ; genetics ; Humans ; Mental Disorders ; genetics ; Polymorphism, Genetic

Schizophrenia is a common but complex mental disorder affected by multiple factors. Forensic psychiatric assessment of schizophrenia involves evaluations on many aspects, but there is no effective biological identification index for schizophrenia. Researches indicate that dysfunction of dopaminergic neurotransmission plays an important role in the pathogenesis of schizophrenia. Our study reviews the classification, genetic structure of dopamine receptors and the recent pertinent studies between the dopamine receptors and schizophrenia and its forensic significance.
Forensic Medicine ; Humans ; Mental Disorders ; Polymorphism, Genetic ; Psychotic Disorders ; Receptors, Dopamine/genetics* ; Schizophrenia/genetics* ; Schizophrenic Psychology

Cholecystokinin (CCK) is a brain-gut peptide with broad biological activities. It is one of the main regulating hormones in the digestive system, and it plays an important physiological role in the central and peripheral nervous system as a neurotransmitter or a neuromodulator. Recently, many reports have demonstrated that there were a number of SNPs on CCK gene, of which -45C/T and -196G/A showed certain correlation with a variety of psychiatric states such as schizophrenia, depressive disorder, suicidal behavior, Parkinson's disease, etc. These SNPs may be used in paternity testing and personal identification. In addition, it may also become one of the auxiliary indicators in some special cases of forensic pathology.
Cholecystokinin/genetics* ; Forensic Medicine ; Humans ; Mental Disorders/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Psychiatric Status Rating Scales

INTRODUCTIONNeurological soft signs (NSS) are suggested as a candidate endophenotype for schizophrenia. This article aims to review relevant literature and discuss the role of NSS in understanding schizophrenia.

METHODSThis is an update on a review article published in 2003. Articles from 2003 onwards were specifically reviewed and discussed with relevance to the role of NSS as endophenotype for schizophrenia.

RESULTSConsistent data suggest an excess of NSS in schizophrenic patients. NSS appear to be related to schizophrenic symptoms, in particular negative symptoms and disorganisation. Information on NSS and demographic correlates is scarce, and the confounding effects between age, education and intelligence on NSS constitute an important gap in current knowledge. Longitudinal data suggest NSS as both a trait and state variable in the course of disease. NSS are not specific with regard to diagnosis, although there are claims that individual sub-components may be more specific. The weight of evidence raises question on the specificity of NSS for schizophrenia.

CONCLUSIONSThe usefulness and feasibility of NSS as a specific endophenotype target for schizophrenia is unclear. However, NSS remain an important feature and symptom correlate of schizophrenia. Future research should focus on delineating the effects of NSS from those of confounding demographic variables, and the stability of NSS over the course of illness to elucidate its role in schizophrenia.

Humans ; Mental Disorders ; Neurologic Examination ; Phenotype ; Risk Factors ; Schizophrenia ; diagnosis ; genetics ; Sensitivity and Specificity

OBJECTIVETo assess the association between aggressive behaviors and 15 short tandem repeats (STRs) loci.

METHODSPeripheral blood samples from 541 army men with aggressive behaviors and 459 healthy individuals were collected. All sample were amplified with a AmpFlSTR Identifiler(TM) system and separated by electrophoresis to compare the genotypic and allelic frequencies of 15 STRs (CSF1PO, D2S1338, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, FGA, THO1, TPOX and vWA) in the two groups.

RESULTSA significant difference was found in allelic and genotypic frequencies at loci D2S1338 and D19S433 (P< 0.01) between the two groups, but not for the remaining 13 STR loci (P> 0.05). Univarite analysis also showed a significant difference for allele 16, genotypes 19-22, 22-24 on D2S1338 and genotypes 13-14.2 on D19S433 between the two groups (P= 0.0018, P= 0.0001, P= 0.0003, P= 0.0000), with the OR values being 7.380 (95%CI: 1.701-32.028), 0.051(95%CI: 0.007-0.388), 13.933(95%CI: 1.845-105.717), 0.349 (95%CI: 0.216-0.564), respectively.

CONCLUSIOND2S1338 and D19S433 may be associated with aggressive behavior. Allele 16 and genotype 22-24 on D2S1338 may be susceptible factors for the disease, whilst genotypes 19-22 on D2S1338 and 13-14.2 on D19S433 may confer a protective effect on it.

Adult ; Aggression ; Alleles ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Mental Disorders ; genetics ; Microsatellite Repeats

The development of molecular biology has brought many changes in psychiatry. Molecular biology makes us possible to know the cause of mental disorders that provide the way to prevent the disorders, and to develop various accurate diagnostic and treatment methods for mental disorders. The author discusses the concept, cause, and treatment of mental disorders in the aspect of molecular biology. Importing the methods of molecular biology into psychiatry, we can anticipate to get a number of the goals of psychiatric genetics, including identification of specific susceptibility genes, clarification of the pathophysiological processes whereby these genes lead to symptoms, establishment of epigenetic factors that interact with these genes to produce disease, validation of nosological boundaries that more closely reflect the actions of these genes, and development of effective preventive and therapeutic interventions based on genetic counselling, gene therapy, and modification of permissive or protective environmental influences. In addition to their capacity to accelerate the discovery of new molecules participationg in the nervous system's response to disease or to self-administered drugs, molecular bilolgical strategies can also be used to determine how critical a particular gene product may be in mediating a cellular event with behavioral importance. Molecular biology probably enables us discover the environmental factors of mental disorders and allow rational drug design and gene therapies for mental disorders, by isolation of gene products that facilitate a basic understanding of the pathogenesis of these disorders. A specific genetic linkage may suggest a novel class of drugs that has not yet been tried. With respect to gene therapy, the hypothetical method would use a gene delivery system, most likely a modified virus, to insert a functional copy of a mutant gene into those brain cells that require the gene for normal function.
Brain ; Drug Design ; Epigenomics ; Genes, vif ; Genetic Linkage ; Genetic Therapy ; Genetics ; Mental Disorders ; Molecular Biology ; Negotiating

OBJECTIVE: To evaluate the relationship between the tyrosine hydroxylase (TH) gene and mental disorder by comparing the two TH gene SNP points (extron 3 and intron 9) of patients with mental disorders and normal human. METHODS: DNA extracted from specimens of patients and normal subjects were quantified by using Real-time PCR. RESULTS: (1) G334A distribution was: G=0.133, A=0.867 in patients with schizophrenia, G=0.116, A=0.884 in patients with depression, and G=0.214, A=0.786 in normal group. (2) C5162G distribution was: C=0.962, G=0.038 in patients with schizophrenia, C=0.959, G=0.041 in patients with depression, and C=0.961, G=0.039 in normal group. CONCLUSION There are statistically significant differences in G334A locus between normal people and patients with mental disorders, but no statistically significant differences in C5162G locus.
Depressive Disorder/genetics* ; Female ; Forensic Genetics ; Humans ; Male ; Mental Disorders/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Schizophrenia/genetics* ; Tyrosine 3-Monooxygenase/genetics*

To determine the frequency of chromosomal abnormalities in a child psychiatric population, and to evaluate possible associations between types of abnormalities and patient's clinical characteristics, cytogenetic examination was performed on 604 patients. Demographic data, reasons for karyotyping, clinical signs, and other patient characteristics were assessed and correlated with the results from karyotyping. Chromosomal abnormalities were found in 69 patients (11.3%); these were structural in 49 cases and numerical in 20. Inversion of chromosome nine was found in 15 subjects, trisomy of chromosome 21 in 11, and fragile X in five patients. When karyotyping was performed because of intellectual impairment or multiple developmental delay, significantly more abnormalities were found than average; when performed because autistic disorder was suspected, the number of abnormalities was significantly fewer. There were no differences in clinical variables between structural and numerical abnormalities, nor among nine types of chromosomal abnormalities, except that numerical abnormalities and polymorphism were found at a later age, and that walking was more delayed and IQ was lower in patients with Down syndrome. Clinicians should be aware of the possible presence of chromosomal abnormalities in child psychiatric populations; the close collaboration with geneticists and the use of more defined guidelines for cytogenetic investigation are important.
Adolescence ; Autistic Disorder/genetics ; Autistic Disorder/diagnosis ; Child ; Child, Preschool ; Developmental Disabilities/genetics* ; Developmental Disabilities/diagnosis ; Down Syndrome/genetics* ; Down Syndrome/diagnosis ; Female ; Fragile X Syndrome/genetics* ; Fragile X Syndrome/diagnosis ; Human ; Karyotyping ; Male ; Mental Disorders/genetics* ; Mental Disorders/diagnosis ; Mental Retardation/genetics ; Mental Retardation/diagnosis

OBJECTIVE: To explore the genetic basis for a child with febrile seizures. METHODS: Peripheral venous blood samples were taken from the child and his parents for the analysis of chromosomal karyotype and dynamic variant of the FMR1 gene. The family trio was also subjected to target capture and next generation sequencing (NGS) with a gene panel related to developmental retardation, mental retardation, language retardation, epilepsy and special facial features. RESULTS: The child was found to have a normal karyotype by conventional cytogenetic analysis (400 bands). No abnormal expansion was found with the CGG repeats of the FMR1 gene. NGS revealed that the child has carried a heterozygous c.864+1 delG variant of the MEF2C gene, which may lead to abnormal splicing and affect its protein function. The same variant was found in neither parent, suggesting that it has a de novo origin. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.864+1delG variant of MEF2C gene was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION MEF2C, as the key gene for chromosome 5q14.3 deletion syndrome which was speculated as a cause for febrile seizures, has an autosomal dominant effect. The c.864+1delG variant of the MEF2C gene may account for the febrile seizures in this patient.
Child ; Chromosome Deletion ; Chromosome Disorders ; Epilepsy ; Fragile X Mental Retardation Protein ; Humans ; Intellectual Disability/genetics* ; Karyotyping ; MEF2 Transcription Factors/genetics*

OBJECTIVETo review the main neuropsychiatric disorders and cognitive deficits in patients with Cushing's disease (CD) and the associated pathophysiological mechanisms underlying CD. These mechanistic details may provide recommendations for preventing or treating the cognitive impairments and mood disorders in patients with CD.

DATA SOURCESData were obtained from papers on psychiatric and cognitive complications in CD published in English within the last 20 years. To perform the PubMed literature search, the following keywords were input: cushing's disease, cognitive, hippocampal, or glucocorticoids.

STUDY SELECTIONStudies were selected if they contained data relevant to the topic addressed in the particular section. Because of the limited length of this article, we have frequently referenced recent reviews that contain a comprehensive amalgamation of literature rather than the actual source papers.

RESULTSPatients with active CD not only suffer from many characteristic clinical features, but also show some neuropsychiatric disorders and cognitive impairments. Among the psychiatric manifestations, the common ones are emotional instability, depressive disorder, anxious symptoms, impulsivity, and cognitive impairment. Irreversible effects of previous glucocorticoid (GC) excess on the central nervous system, such as hippocampal and the basal ganglia, is the most reasonable reason. Excess secretion of cortisol brings much structural and functional changes in hippocampal, such as changes in neurogenesis and morphology, signaling pathway, gene expression, and glutamate accumulation. Hippocampal volume loss can be found in most patients with CD, and decreased glucose utilization caused by GCs may lead to brain atrophy, neurogenesis impairment, inhibition of long-term potentiation, and decreased neurotrophic factors; these may also explain the mechanisms of GC-induced brain atrophy and hippocampal changes.

CONCLUSIONSBrain atrophy and hippocampal changes caused by excess secretion of cortisol are thought to play a significant pathophysiological role in the etiology of changes in cognitive function and psychiatric disturbances. The exact mechanisms by which GCs induce hippocampal volume loss are not very clear till now. So, further investigations into the mechanisms by which GCs affect the brain and the effective coping strategy are essential.

Brain-Derived Neurotrophic Factor ; genetics ; Cognition Disorders ; etiology ; Glucocorticoids ; physiology ; Hippocampus ; pathology ; physiology ; Humans ; Mental Disorders ; etiology ; Neurogenesis ; Pituitary ACTH Hypersecretion ; complications ; pathology ; physiopathology ; Quality of Life ; Signal Transduction