Clinical characteristics of 80 subjects with KCNQ2-related encephalopathy: Results from a family-driven survey.

Variants of KCNQ2 are associated with a wide spectrum of disorders, ranging from Self-limiting Neonatal Epilepsy (SelNE) to Early Onset Developmental and Epileptic Encephalopathy (KCNQ2-DEE). Comorbidities associated with this end of the spectrum have been seldomly described and their impact on the life of patients and their families is yet to be investigated. Collaborating with caregivers from different European family associations, we have developed a questionnaire aimed at investigating the onset and frequency of epileptic seizures, anti-seizure medications (ASM), hospitalizations, stages of development, and comorbidities. Responses from 80 patients, 40 males, from 14 countries have been collected. Median age 7.6 years (4 months - 43.6 years). Of 76 epileptic patients (93.6%), 55.3% were seizure-free with a mean age at last seizure of 26.7 months. Among patients with active epilepsy, those older have a lower frequency of seizures (p > 0.05). We were able to identify three different clusters of varying severity (Mild, Severe, Profound), based on neurodevelopmental features and symptoms, excluding epilepsy. Patients in a higher severity cluster had a higher mean number of comorbidities, which had a higher impact on families. Notably, patients in different clusters presented different epilepsy onset and courses. This study constitutes the most extensive data collection of patients with KCNQ2-DEE, with a focus on comorbidities in a wide age group. The participation of caregivers helps to define the impact of the disease on the lives of patients and families and can help identify new primary and secondary outcomes beyond seizures in future studies.

Attachment styles and personality disorders as predictors of symptom course.

Adult attachment styles and personality disorders (PDs) show some conceptual and empirical overlap and both may complicate the course of symptoms among psychiatric patients. In this naturalistic prospective study, 149 patients with affective, anxiety, substance use, and other disorders were interviewed shortly after entering treatment, which included psychotherapy, pharmacotherapy, or both. Follow-up interviews were conducted 6 and 12 months later. Attachment styles, DSM-III-R PDs, and symptoms were assessed using structured interviews and consensus ratings. At intake, borderline, avoidant, and dependent PD features correlated consistently with symptom severity and secure attachment correlated inversely with two of four symptom scales. Secure attachment was linked with greater relative improvement in global functioning and a more benign course of anxiety symptoms over 6 months. Borderline PD features predicted less relative improvement of depressive symptoms over 6 months. These findings clarify the relations between attachment styles and PD features and they point to potential mediators of treatment response.

The reliability and validity of two structured diagnostic interviews for personality disorders.

BACKGROUND: The reliability and validity of Axis II diagnoses were investigated in a sample of 108 patients with nonpsychotic Axis I disorders. METHODS: Patients were assessed for personality disorders (PDs) with either the Personality Disorder Examination (PDE) or the Structured Interview for DSM-III-R Personality (SIDP-R). Validity was examined by comparing interview diagnoses with "best-estimate" consensus diagnoses assigned by a panel of judges. RESULTS: Interrater reliabilities were excellent when using continuous data (eg, total or cluster scores; intra-class correlation coefficients, .82 to .92); they were lower with categorical diagnoses (eg, any PD vs no PD; kappa = 0.55 and 0.58 with the two interviews). Validity coefficients (ie, kappa values reflecting agreement between the interviews and the consensus diagnosis) for the decision of any PD vs no PD were 0.18 (56% agreement) with the PDE and 0.37 (75% agreement) with the SIDP-R; validity coefficients for identifying cases of "marked" PD were 0.21 (62% agreement) with the PDE and 0.24 (60% agreement) with the SIDP-R. CONCLUSIONS: There have been important advances in the development of structured interviews for Axis II diagnoses, but the findings suggest a continued need to be thoughtful about their strengths and weaknesses before accepting their results as definitive diagnostic tests. The findings also demonstrated some of the advantages of continuous vs categorical data.

Parental hypertension, affect, and cardiovascular response to cognitive challenge.

This investigation examined the cardiovascular and affective reactions of offspring of hypertensive and normotensive parents on exposure of subjects to a frustrating cognitive task. Subjects were 44 normotensive, male undergraduate volunteers, 22 with and 22 without a parental history of hypertension. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) measurements were recorded under resting (baseline) conditions and during subjects' performance of a 3-min mental arithmetic task. Subjects were also administered state forms of the State-Trait Anxiety and Anger Inventories following baseline measurements and immediately after the experimental task. Results indicated that relative to sons of normotensive parents, offspring of hypertensives showed significantly greater HR and DBP elevations during mental arithmetic. However, neither task performance nor task-related changes on the state measures of anxiety and anger varied reliably with differences in parental status. When subjects were divided into groups of high- and low-affect (i.e., anxiety, anger) responders, the HR reactions of persons having hypertensive and normotensive parents were found to differ significantly only among subjects who reported experiencing the most appreciable anxiety--and to a lesser extent, anger--when performing the mental arithmetic task. This finding suggests that persons at familial risk for hypertension possess a heightened cardiovascular response "potential" which is expressed, in part, in relation to concomitant affective experiences of the individual.