Identification of the phenotype in psychiatric genetics

Summary Statistical procedures and molecular genetic techniques have attained a fine degree of resolution. Their ability to find disease genes has revolutionized medicine and raised hopes for breakthroughs in psychiatry. However, such breakthroughs may require an equally discriminating nosology. A psychiatric genetic nosology seeks to classify patients into categories that correspond to distinct genetic entities by addressing the problem of diagnostic accuracy: the degree to which a diagnosis correctly classifies people with and without a putative genetic illness. We review methods that deal with misclassification in genetic studies. These are clinical and epidemiological approaches that deal directly with how to define the observable manifestation of a putative genotype. We discuss two groups of methods: those that use known phenotypes and those that design new phenotypes.     

Familial infantile myoclonic epilepsy: clinical features in a large kindred with autosomal recessive inheritance

PURPOSE: To describe the clinical features of a large kindred with familial infantile myoclonic epilepsy (FIME) with autosomal recessive inheritance, and to discuss the nosology of the early infantile myoclonic epilepsies (IMEs). METHODS: The family descends from the intermarriage of two couples of siblings. In a previous study, we mapped the genetic locus to chromosome 16p13.We analyzed results of family records and personal history, psychomotor development, neurologic examination, epilepsy features, and EEG recordings for each subject. RESULTS: FIME has a strong penetrance (eight affected of 14 subjects) and a homogeneous clinical picture. Like the benign form of infantile myoclonic epilepsy (BIME), FIME is a true idiopathic IME with unremarkable history, no neurologic or mental impairment, good response to treatment, and normal interictal EEG pattern. Conversely, onset with generalized epileptic seizures without fever (four patients) or with fever (one patient), frequency and duration of the myoclonic seizures, occurrence of generalized tonic--clonic seizures (GTCSs) in all patients and persistence of seizures into adulthood are characteristics of the severe infantile myoclonic epilepsy (SIME). CONCLUSIONS: Clinical overlap probably exists among the myoclonic epilepsies of infancy. FIME differs from other forms of IME in its phenotypic features. The peculiar mode of inheritance is explained by the genetic background of the family. Genetic studies suggest linkage to chromosome 16 in familial cases of true IME.     

Nosology and diagnosis of Asperger''s syndrome

The autism spectrum disorders (ASD) have generated great interest among clinicians and researchers. Once considered rare, recent epidemiological data now suggests rates of up to 1 in 150 people. One of the most frequent of the ASD, Asperger's syndrome (AS), has been known as a disorder for as long as autism, which is easily the most visible of this group of conditions. Growing attention to and popularity of studying AS have made the nosology and diagnosis of the disorder a topic of growing concern in recent years. The purpose of this paper is to present an up-to-date analysis of the syndrome and the likelihood that it is actually a disorder distinct from high-functioning autism (HFA). This argument about how to diagnose people, either AS or HFA, hinges largely on the debate about whether distinct symptom patterns exist between AS and HFA and if AS can be reliably differentiated from HFA. A discussion of this topic, trends in research, and where the data appears to be leading diagnosticians is also presented, as well as research areas requiring further attention.     

Nosology and diagnosis of Rett Syndrome

Rett Syndrome is one of the least commonly occurring autism spectrum disorders (ASD), but certainly one of the most devastating. A genetic profile has been identified, but checklists still have an important role for prescreening, especially before expensive genetic testing, and to provide precise strengths and weaknesses with respect to the core features of the disorder. Furthermore, research is now demonstrating subprofiles of genetic mutation which may be linked to profiles of behavioral responding and general symptom profiles. We review the literature on the nosology and assessment of Rett Syndrome in light of these developments. Specific symptoms and assessment techniques are discussed and potential future research avenues are reviewed with an eye to strengths and weaknesses of the current knowledge base.     

The association of posttraumatic stress disorder,complex posttraumatic stress disorder,and borderline personality disorder from a network analytical perspective

BackgroundPosttraumatic Stress Disorder (PTSD), Complex PTSD, and Borderline Personality Disorder (BPD) share etiological risk factors and an overlapping set of associated symptoms. Since the ICD-11 proposal for trauma-related disorders, the relationship of these disorders has to be clarified. A novel approach to psychopathology, network analysis, allows for a detailed analysis of comorbidity on symptom level.MethodsSymptoms were assessed in adult survivors of childhood abuse (N = 219) using the newly developed ICD-11 Trauma-Questionnaire and the SCID-II. The psychopathological network was analyzed using the network approach.ResultsPTSD and Complex PTSD symptoms were strongly connected within disorders and to a lesser degree between disorders. Symptoms of BPD were weakly connected to others. Re-experiencing and dissociation were the most central symptoms.ConclusionsMental disorders are no discrete entities, clear boundaries are unlikely to be found. The psychopathological network revealed central symptoms that might be important targets for specific first interventions.     

Validation of DSM-IV Model of Psychiatric Syndromes in Children with Autism Spectrum Disorders

The objective of this study was to assess the internal construct validity of the DSM-IV as a conceptual model for characterizing behavioral syndromes in children with ASD. Parent and teachers completed the Child Symptom Inventory-4, a DSM-IV-referenced rating scale, for 6-to-12 year old clinic referrals with an ASD (N = 498). Ratings were submitted to confirmatory factor analysis and models were assessed for fit. Results were also compared to those obtained for a sample of non-ASD psychiatric outpatient school-age children. Fit indices ranged from acceptable to good for the ASD samples and compared well to those obtained in typically developing children. Findings lend support to the notion that DSM-IV syndromes may be an appropriate conceptual model for characterizing psychopathology in ASD.     

Alcohol Use Disorders in ICD‐11: Past,Present, and Future

The Eleventh Revision of the International Classification of Diseases (ICD‐11) was formally published in May 2019. Alcohol use disorders form a key part of the section of Disorders due to Substance Use and Addictive Behaviours. This review describes and discusses the alcohol diagnoses within this section of ICD‐11, including Alcohol Dependence, Harmful Pattern of Use of Alcohol, and entities such as Alcohol Intoxication, Alcohol Withdrawal, and several alcohol‐induced mental disorders, and briefly covers Hazardous Alcohol Use, which is listed separately as a health risk factor. We summarize the historical background to the development of these diagnoses, including work within the World Health Organization since the 1970s, and the corresponding diagnoses in the current ICD‐10. The process by which ICD‐11 diagnoses have been made is described and may be summarized as a conceptual–pragmatic–confirmatory one. The available empirical data supporting the ICD‐11 diagnoses are presented, particularly in relation to the diagnostic guidelines for Alcohol Dependence. Comparison is made with the corresponding diagnoses in ICD‐10 and their nearest counterparts in the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders. Field testing of the ICD‐11 diagnoses is currently in progress. A plea is made for matching of diagnoses, diagnostic guidelines/criteria, and the assessment tools intended to capture these diagnoses.     

Schizoaffective disorder–an ongoing challenge for psychiatric nosology

Objective

Schizoaffective disorder is a common diagnosis in mental health services. The present article aims to provide an overview of diagnostic reliability, symptomatology, outcome, neurobiology and treatment of schizoaffective disorder.

Method

Literature was identified by searches in “Medline” and “Cochrane Library”.

Results

The diagnosis of schizoaffective disorder has a low reliability. There are marked differences between the current diagnostic systems. With respect to psychopathological symptoms, no clear boundaries were found between schizophrenia, schizoaffective disorder and affective disorders. Common neurobiological factors were found across the traditional diagnostic categories. Schizoaffective disorder according to ICD-10 criteria, but not to DSM-IV criteria, shows a more favorable outcome than schizophrenia. With regard to treatment, only a small and heterogeneous database exists.

Conclusion

Due to the low reliability and questionable validity there is a substantial need for revision and unification of the current diagnostic concepts of schizoaffective disorder. If future diagnostic systems return to Kraepelin's dichotomous classification of non-organic psychosis or adopt a dimensional diagnostic approach, schizoaffective disorder will disappear from the psychiatric nomenclature. A nosological model with multiple diagnostic entities, however, would be compatible with retaining the diagnostic category of schizoaffective disorder.     

Relationship between social anxiety disorder and body dysmorphic disorder

Social anxiety disorder (SAD) and body dysmorphic disorder (BDD) are two separate, but conceptually overlapping nosological entities. In this review, we examine similarities between SAD and BDD in comorbidity, phenomenology, cognitive biases, treatment outcome, and cross-cultural aspects. Our review suggests that SAD and BDD are highly comorbid, show a similar age of onset, share a chronic trajectory, and show similar cognitive biases for interpreting ambiguous social information in a negative manner. Furthermore, research from treatment outcome studies have demonstrated that improvements in SAD were significantly correlated with improvements in BDD. Findings from cross-cultural research suggest that BDD may be conceived as a subtype of SAD in some Eastern cultures. Directions for future research and clinical implications of these findings are discussed.