ABSTRACT
OBJECTIVE: Employing practice-based research methods, we addressed the need to examine the effectiveness of psychodynamic treatment as a supplement to the efficacy evidence offered by randomized clinical trials. METHOD: We used person-centered analyses to generate latent subgroups of clients (N = 118; M age = 40.92; 53.4% female; 81.4% Caucasian; 80.5% heterosexual) receiving contemporary relational psychotherapy (CRP) at a psychodynamic community mental health training clinic. RESULTS: Subgroups of clients reported a change in depression, social conflict, and anxiety symptomatology, and overall life satisfaction, depicted by significant quadratic growth curves. Findings also offered exploratory support for a theoretical proposition from CRP that improved relational functioning would correspond to improved affect dysregulation and overall life satisfaction. CONCLUSION: Clinical and training implications highlight the need to distinguish subgroups of "responders" and "nonresponders" to inform treatment.
Subject(s)
Anxiety Disorders/therapy , Depressive Disorder/therapy , Psychotherapy, Psychodynamic/methods , Treatment Outcome , Adult , Aged , Ambulatory Care Facilities , Female , Humans , Male , Middle Aged , Patient Satisfaction , Randomized Controlled Trials as Topic , Research Design , Young AdultABSTRACT
In 2009, we described the first generation of the chromosome 18 gene dosage maps. This tool included the annotation of each gene as well as each phenotype associated region. The goal of these annotated genetic maps is to provide clinicians with a tool to appreciate the potential clinical impact of a chromosome 18 deletion or duplication. These maps are continually updated with the most recent and relevant data regarding chromosome 18. Over the course of the past decade, there have also been advances in our understanding of the molecular mechanisms underpinning genetic disease. Therefore, we have updated the maps to more accurately reflect this knowledge. Our Gene Dosage Map 2.0 has expanded from the gene and phenotype maps to also include a pair of maps specific to hemizygosity and suprazygosity. Moreover, we have revamped our classification from mechanistic definitions (e.g., haplosufficient, haploinsufficient) to clinically oriented classifications (e.g., risk factor, conditional, low penetrance, causal). This creates a map with gradient of classifications that more accurately represents the spectrum between the two poles of pathogenic and benign. While the data included in this manuscript are specific to chromosome 18, they may serve as a clinically relevant model that can be applied to the rest of the genome.
Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 18/genetics , Gene Dosage/genetics , Genome, Human , Humans , Microtubule-Associated Proteins , PhenotypeABSTRACT
Since 18p- was first described in 1963, much progress has been made in our understanding of this classic deletion condition. We have been able to establish a fairly complete picture of the phenotype when the deletion breakpoint occurs at the centromere, and we are working to establish the phenotypic effects when each gene on 18p is hemizygous. Our aim is to provide genotype-specific anticipatory guidance and recommendations to families with an 18p- diagnosis. In addition, establishing the molecular underpinnings of the condition will potentially suggest targets for molecular treatments. Thus, the next step is to establish the precise effects of specific gene deletions. As we look forward to deepening our understanding of 18p-, our focus will continue to be on the establishment of robust genotype-phenotype correlations and the penetrance of these phenotypes. We will continue to follow our 18p- cohort closely as they age to determine the presence or absence of some of these diagnoses, including spinocerebellar ataxia (SCA), facioscapulohumeral muscular dystrophy (FSHD), and dystonia. We will also continue to refine the critical regions for other phenotypes as we enroll additional (hopefully informative) participants into the research study and as the mechanisms of the genes in these regions are elucidated. Mouse models will also be developed to further our understanding of the effects of hemizygosity as well as to serve as models for treatment development.
Subject(s)
Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/therapy , Chromosome Deletion , Chromosomes, Human, Pair 18/genetics , Abnormalities, Multiple/etiology , Animals , Genotype , Humans , Mice , PhenotypeABSTRACT
Providing clinically relevant prognoses and treatment information for people with a chromsome18q deletion is particularly challenging because every unrelated person has a unique region of hemizygosity. The hemizygous region can involve almost any region of 18q including between 1 and 101 genes (30 Mb of DNA). Most individuals have terminal deletions, but in our cohort of over 350 individuals 23% have interstitial deletions. Because of this heterogeneity, we take a gene by gene approach to understanding the clinical consequences. There are 196 genes on 18q. We classified 133 of them as dosage insensitive, 15 (8%) as dosage sensitive leading to haploinsufficiency while another 10 (5%) have effects that are conditionally haploinsufficient and are dependent on another factor, genetic or environmental in order to cause an abnormal phenotype. Thirty-seven genes (19%) have insufficient information to classify their dosage effect. Phenotypes attributed to single genes include: congenital heart disease, minor bone morphology changes, central nervous system dysmyelination, expressive speech delay, vesicouretreral reflux, polyposis, Pitt-Hopkins syndrome, intellectual disability, executive function impairment, male infertility, aural atresia, and high frequency sensorineural hearing loss. Additionally, identified critical regions for other phenotypes include: adolescent idiopathic scoliosis and pectus excavatum, Virchow-Robin perivascular spaces, small corpus callosum, strabismus, atopic disorders, mood disorder, IgA deficiency, nystagmus, congenital heart disease, kidney malformation, vertical talus, CNS dysmyelination growth hormone deficiency and cleft palate. Together these findings make it increasingly feasible to compile an individualized syndrome description based on each person's individuated genotype. Future work will focus on understanding molecular mechanisms leading to treatment.
Subject(s)
Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/therapy , Chromosome Deletion , Chromosomes, Human, Pair 18/genetics , Abnormalities, Multiple/etiology , Adolescent , Genotype , Humans , Male , PhenotypeABSTRACT
BACKGROUND: The Chromosome 18 Clinical Research Center has created a pediatrician-friendly virtual resource center for managing patients with chromosome 18 abnormalities. To date, children with rare chromosome abnormalities have been cared for either symptomatically or palliatively as a reaction to the presenting medical problems. As we enter an era of genomic-informed medicine, we can provide children, even those with individually unique chromosome abnormalities, with proactive medical care and management based on the most contemporary data on their specific genomic change. It is problematic for practicing physicians to obtain and use the emerging data on specific genes because this information is derived from diverse sources (e.g., animal studies, case reports, in vitro explorations) and is often published in sources that are not easily accessible in the clinical setting. METHODS: The Chromosome 18 Clinical Resource Center remedies this challenging problem by curating and synthesizing the data with clinical implications. The data are collected from our database of over 26 years of natural history and medical data from over 650 individuals with chromosome 18 abnormalities. RESULTS: The resulting management guides and video presentations are a first edition of this collated data specifically oriented to guide clinicians toward the optimization of care for each child. CONCLUSION: The chromosome 18 data and guides also serve as models for an approach to the management of any individual with a rare chromosome abnormality of which there are over 1,300 born every year in the US alone.