How does a real-world child psychiatric clinic diagnose and treat attention deficit hyperactivity disorder?

Aim: To investigate child and adolescent psychiatrists' (CAPs) attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) diagnoses and treatments in real-world clinical practice.

Methods: The medical records of 69 ADHD children (mean age = 9.5 years), newly referred to the ADHD clinic, were reviewed for their scores of parent- and teacher-reported Vanderbilt ADHD Diagnostic Rating Scales (VADRSs), CAPs' diagnoses of ADHD and ODD, and CAPs' treatment recommendations.

Gender-specific effects of comorbid depression and anxiety on the propensity to drink in negative emotional states.

Background And Aims: Depression and anxiety are often comorbid with alcoholism and contribute to craving and relapse. We aimed to estimate the prevalence of life-time diagnoses of major depressive disorder (MDD), substance-induced depression (SID), anxiety disorder (AnxD) and substance-induced anxiety (SIA), the effects of these comorbidities on the propensity to drink in negative emotional states (negative craving), and test whether these effects differ by sex.

Design: Secondary analyses of baseline data collected in a single-arm study of pharmacogenetic predictors of acamprosate response.

A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013.

Objective: This literature review assessed the burden of treatment-resistant depression in the United States by compiling published data about the clinical, societal, and economic outcomes associated with failure to respond to one or more adequate trials of drug therapy.

Methods: PubMed and the Tufts Cost-Effectiveness Analyses Registry were searched for English-language articles published between January 1996 and August 2013 that collected primary data about treatment-resistant depression. Two researchers independently assessed study quality and extracted data.

Treatment outcomes of depression: the pharmacogenomic research network antidepressant medication pharmacogenomic study.

Background: The effectiveness of selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder (MDD) is controversial.

Aims: The clinical outcomes of subjects with nonpsychotic MDD were reported and compared with the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study outcomes to provide guidance on the effectiveness of SSRIs.

Methods: Subjects were treated with citalopram/escitalopram for up to 8 weeks.

Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations.

Aims: Citalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT.

Methods: Our genome-wide association study was performed using samples from 435 MDD patients.

Does 5HTTLPR long allele prevent hospitalization? Test of Hardy-Weinberg equilibrium.

Many studies suggest an association of the serotonin transporter gene polymorphism (5HTTLPR) long allele with better antidepressant treatment response than the short allele. However, there is controversy over these findings. We hypothesized that if the long allele is associated with a better outcome, we would find fewer inpatients with the long allele compared with the short allele.

Clinical validity of cytochrome P450 metabolism and serotonin gene variants in psychiatric pharmacotherapy.

Adverse events, response failures and medication non-compliance are common in patients receiving medications for the treatment of mental illnesses. A systematic literature review assessed whether pharmacokinetic (PK) or pharmacodynamic (PD) responses to 26 commonly prescribed antipsychotic and antidepressant medications, including efficacy or side effects, are associated with nucleotide polymorphisms in eight commonly studied genes in psychiatric pharmacotherapy: CYP2D6, CYP2C19, CYP2C9, CYP1A2, CYP3A4, HTR2C, HTR2A, and SLC6A4. Of the 294 publications included in this review, 168 (57%) showed significant associations between gene variants and PK or PD outcomes.

Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting.

Objective: The objective was to evaluate the potential benefit of an integrated, five-gene pharmacogenomic test and interpretive report (GeneSight) for the management of psychotropic medications used to treat major depression in an outpatient psychiatric practice.

Methods: The open-label study was divided into two groups. In the first (unguided) group (n = 113), pharmacogenomic information was not shared until all participants completed the study.

SLC6A4 polymorphisms and age of onset in late-life depression on treatment outcomes with citalopram: a Sequenced Treatment Alternatives to Relieve Depression (STAR*D) report.

Objective: Age at onset of first major depressive episode (MDE) does not necessarily translate into different treatment outcomes to antidepressants in late-life depression. The influence of genetic variants may affect this relationship.

Design: Post hoc data set analysis of the association between variants in the promoter region (indel, rs25531) and within intron 2 (Stin2 VNTR) of the SCL6A4 gene and treatment outcomes among older participants in the first treatment arm of the Sequenced Treatment Alternatives to Relieve Depression trial (STAR*D).

A retrospective study of gender differences in depressive symptoms and risk of relapse in patients with alcohol dependence.

Background And Objectives: The aim of this study was to investigate potential gender differences in situations associated with heavy alcohol drinking.

Methods: Data from 395 alcohol dependent patients participating in the Mayo Clinic Intensive Addiction Program were evaluated. Each participant completed the inventory of drug taking situations (IDTS), Penn alcohol craving scale (PACS), patient health questionnaire (PHQ-9), and/or Beck depression inventory (BDI).

"Diminished" association between the serotonin transporter linked polymorphism (5HTTLPR) and body mass index in a large psychiatric sample.

Background: The role of the promoter polymorphism (5HTTLPR) of the serotonin transporter gene (SLC6A4) in psychiatric illnesses has been studied extensively. Serotonergic function also regulates many central nervous system, including appetite and feeding behaviors. The 5HTTLPR short allele was found to be associated with increased body mass index and obesity risk among the general population.

Alcohol craving as a predictor of relapse.

Background And Objectives: Alcoholism treatment interventions, both psychosocial and pharmacologic, aim to reduce cravings to drink. Yet, the role of craving in treatment outcomes remains unclear. This study evaluated craving intensity measured with the Penn Alcohol Craving Scale (PACS) at admission and discharge from residential treatment as a predictive factor of relapse after treatment.

Replication of genome wide association studies of alcohol dependence: support for association with variation in ADH1C.

Genome-wide association studies (GWAS) have revealed many single nucleotide polymorphisms (SNPs) associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism.

FKBP5 genetic variation: association with selective serotonin reuptake inhibitor treatment outcomes in major depressive disorder.

Objectives: FKBP51 (51 kDa immunophilin) acts as a modulator of the glucocorticoid receptor and a negative regulator of the Akt pathway. Genetic variation in FKBP5 plays a role in antidepressant response. The aim of this study was to comprehensively assess the role of genetic variation in FKBP5, identified by both Sanger and Next Generation DNA resequencing, as well as genome-wide single nucleotide polymorphisms (SNPs) associated with FKBP5 expression in the response to the selective serotonin reuptake inhibitor (SSRI) treatment of major depressive disorder.

Implementing genomic medicine in the clinic: the future is here.

Although the potential for genomics to contribute to clinical care has long been anticipated, the pace of defining the risks and benefits of incorporating genomic findings into medical practice has been relatively slow. Several institutions have recently begun genomic medicine programs, encountering many of the same obstacles and developing the same solutions, often independently. Recognizing that successful early experiences can inform subsequent efforts, the National Human Genome Research Institute brought together a number of these groups to describe their ongoing projects and challenges, identify common infrastructure and research needs, and outline an implementation framework for investigating and introducing similar programs elsewhere.

Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states.

Synthetic κ-opioid receptor (KOR) agonists induce dysphoric and pro-depressive effects and variations in the KOR (OPRK1) and prodynorphin (PDYN) genes have been shown to be associated with alcohol dependence. We genotyped 23 single nucleotide polymorphisms (SNPs) in the PDYN and OPRK1 genes in 816 alcohol-dependent subjects and investigated their association with: (1) negative craving measured by a subscale of the Inventory of Drug Taking Situations; (2) a self-reported history of depression; (3) the intensity of depressive symptoms measured by the Beck Depression Inventory-II. In addition, 13 of the 23 PDYN and OPRK1 SNPs, which were previously genotyped in a set of 1248 controls, were used to evaluate association with alcohol dependence.

Association of GATA4 sequence variation with alcohol dependence.

To further explore reports of association of alcohol dependence and response to acamprosate treatment with the GATA4 rs13273672 single nucleotide polymorphism (SNP), we genotyped this and 10 other GATA4 SNPs in 816 alcohol-dependent cases and 1248 controls. We tested for association of alcohol dependence with the 11 SNPs individually and performed a global test for association using a principle components analysis. Our analyses demonstrate significant association between GATA4 and alcohol dependence at the gene level (P = 0.

Testing a diathesis-stress model: potential genetic risk factors for development of distress in context of acute leukemia diagnosis and transplant.

Objective: Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes, specifically in the context of stressful life events. We hypothesized that this single-nucleotide polymorphism will predict the development of psychological distress among patients diagnosed with acute leukemia and preparing for hematopoietic stem cell transplant (HSCT). We also explored the relationship of other genetic factors to psychological distress, including 5HTTLPR and STin2, FKBP5, and the CRHR1 TAT haplotype.

Ethanol withdrawal-induced brain metabolites and the pharmacological effects of acamprosate in mice lacking ENT1.

Acamprosate is clinically used to treat alcohol-dependent patients. While the molecular and pharmacological mechanisms of acamprosate remain unclear, it has been shown to regulate γ-aminobutyric acid (GABA) or glutamate levels in the cortex and striatum. To investigate the effect of acamprosate on brain metabolites in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), we employed in vivo 16.

Merging pharmacometabolomics with pharmacogenomics using '1000 Genomes' single-nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics.

Objective: We set out to test the hypothesis that pharmacometabolomic data could be efficiently merged with pharmacogenomic data by single-nucleotide polymorphism (SNP) imputation of metabolomic-derived pathway data on a 'scaffolding' of genome-wide association (GWAS) SNP data to broaden and accelerate 'pharmacometabolomics-informed pharmacogenomic' studies by eliminating the need for initial genotyping and by making broader SNP association testing possible.

Methods: We previously genotyped 131 tag SNPs for six genes encoding enzymes in the glycine synthesis and degradation pathway using DNA from 529 depressed patients treated with citalopram/escitalopram to pursue a glycine metabolomics 'signal' associated with selective serotonine reuptake inhibitor response. We identified a significant SNP in the glycine dehydrogenase gene.

Prospectively assessed early life experiences in relation to cortisol reactivity in adolescents at risk for asthma.

Altered cortisol reactivity in individuals with asthma likely increases the risk of inflammation in the face of stress. Understanding antecedents of cortisol reactivity enhances knowledge of factors affecting asthma. Forty-eight subjects genetically predisposed for asthma, recruited from a study that assessed them from birth, completed a laboratory stress procedure and self-report measures at ages 17-19 years.

Investigation of serotonin transporter gene (SLC6A4) by child abuse history interaction with body mass index and diabetes mellitus of White female depressed psychiatric inpatients.

Background: The serotonin transporter gene promoter polymorphism (5HTTLPR) and child abuse have been associated with an increased risk for depression. We previously reported the long/long (l/l) genotype of 5HTTLPR being associated with higher heart rate among patients with a history of child abuse compared with those without a history of child abuse, whereas the short allele carriers did not have heart rate differences dependent on child abuse history. This time, we extended our investigation to other outcomes with body mass index (BMI), and diabetes mellitus (DM) diagnosis.

Relationship between FKBP5 polymorphisms and depression symptoms among kidney transplant recipients.

Background: Several polymorphisms in FK506 Binding Protein gene (FKBP5) and a history of child abuse have been shown to be associated with an increased risk for posttraumatic stress disorder (PTSD). It has also been demonstrated that the same polymorphisms of FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. However, there are only limited numbers of studies replicating the polymorphisms as vulnerability factors for the development of mental illnesses, such as PTSD and depression after stressful life event, especially with a specific incidence, such as kidney transplant surgery.