Comparing the broad socio-cognitive profile of youth with Williams syndrome and 22q11.2 deletion syndrome.

BACKGROUND: Numerous studies have assessed the socio-cognitive profile in Williams syndrome (WS) and, independently, in 22q11.2 deletion syndrome (22q11.2DS). Yet, a cross-syndrome comparison of these abilities between individuals with these two syndromes with known social deficits has not been conducted. METHODS: Eighty-two children participated in four study groups: WS (n = 18), 22q112.DS (n = 24), age-matched individuals with idiopathic developmental disability (IDD; n = 20) and typically developing (TD) controls (n = 20). Participants completed four socio-cognitive tests: facial emotion recognition, mental state attribution, differentiating real from apparent emotions and trait inference based on motives and actions-outcomes. RESULTS: The current findings demonstrate that children with WS were better in labelling happy faces compared with children with 22q11.2DS, partially reflecting their exaggerated social drive. In the false belief task, however, the WS and IDD groups performed poorly compared with the 22q11.2DS group, possibly due to their difficulty to interpret subtle social cues. When asked to identify the gap between real-negative vs. apparent-positive emotions, the 22q11.2DS group performed similarly to TD children but better than the WS group, possibly due to their anxious personality and their innate bias towards negatively valence cues. Finally, individuals with WS were more willing to become friends with a story character even when the character's motives were negative, reflecting their difficulty to avoid potentially harmful real-life situations. CONCLUSIONS: Overall, our multi-facet socio-cognitive battery uncovered strengths and weaknesses in social cognition that are syndrome-specific, shared among the genetic syndromes, or common to the three clinical groups compared with healthy controls. Our findings underscore the need to devise age-specific and condition-specific assessment tools and intervention programs towards improving these children's socio-cognitive deficits.

A tale worth telling: the impact of the diagnosis experience on disclosure of genetic disorders.

BACKGROUND: Research suggests children with genetic disorders exhibit greater coping skills when they are aware of their condition and its heritability. While the experiences parents have at diagnosis may influence their decision to disclose the diagnosis to their children, there is little research into this communication. The aim of the current study was to examine the relationship between the diagnosis experience and the disclosure experience for parents of children with developmental disorders of a known genetic aetiology: parents of children with 22q11.2 deletion syndrome (22q11DS) were compared with a group of parents with children affected with other genetic diagnoses, with a similar age of diagnosis (e.g. fragile X syndrome) and a group where diagnosis generally occurs early (i.e. Down syndrome). METHOD: The sample comprised 559 parents and caregivers of children with genetic developmental disorders, and an online survey was utilised. Items from the questionnaire were combined to create variables for diagnosis experience, parental disclosure experience, child's disclosure experience, and parental coping and self-efficacy. RESULTS: Across all groups parents reported that the diagnosis experience was negative and often accompanied by a lack of support and appropriate information. Sixty-eight per cent of those in the 22q11DS and 58.3% in the Similar Conditions groups had disclosed the diagnosis to their child, whereas only 32.7% of the Down syndrome group had. Eighty-six per cent of the Down syndrome group felt they had sufficient information to talk to their child compared with 44.1% of the Similar Conditions group and 32.6% of the 22q11DS group. Parents reported disclosing the diagnosis to their child because they did not want to create secrets; and that they considered the child's age when disclosing. In the 22q11DS and Similar Conditions groups, a poor diagnosis experience was significantly associated with negative parental disclosure experiences. In the Similar Conditions group, a poor diagnosis experience was also significantly associated with a more negative child disclosure experience. CONCLUSIONS: As expected this study highlights how difficult most parents find the diagnosis experience. Importantly, the data indicate that the personal experiences the parents have can have a long-term impact on how well they cope with telling their child about the diagnosis. It is important for clinicians to consider the long-term ramifications of the diagnosis experience and give the parents opportunities; through, for instance, psychoeducation to prepare for telling their child about the diagnosis. Further research is warranted to explore what type of information would be useful for parents to receive.

Association among income loss, financial strain and depressive symptoms during COVID-19: evidence from two longitudinal studies.

BACKGROUND: The COVID-19 pandemic has major ramifications for global health and the economy, with growing concerns about economic recession and implications for mental health. Here we investigated the associations between COVID-19 pandemic-related income loss with financial strain and mental health trajectories over a 1-month course. METHODS: Two independent studies were conducted in the U.S and in Israel at the beginning of the outbreak (March-April 2020, T1; N = 4 171) and at a 1-month follow-up (T2; N = 1 559). Mixed-effects models were applied to assess associations among COVID-19-related income loss, financial strain, and pandemic-related worries about health, with anxiety and depression, controlling for multiple covariates including pre-COVID-19 income. FINDINGS: In both studies, income loss and financial strain were associated with greater depressive symptoms at T1, above and beyond T1 anxiety, worries about health, and pre-COVID-19 income. Worsening of income loss was associated with exacerbation of depression at T2 in both studies. Worsening of subjective financial strain was associated with exacerbation of depression at T2 in one study (US). INTERPRETATION: Income loss and financial strain were uniquely associated with depressive symptoms and the exacerbation of symptoms over time, above and beyond pandemic-related anxiety. Considering the painful dilemma of lockdown versus reopening, with the tradeoff between public health and economic wellbeing, our findings provide evidence that the economic impact of COVID-19 has negative implications for mental health. FUNDING: This study was supported by grants from the National Institute of Mental Health, the US-Israel Binational Science Foundation, Foundation Dora and Kirsh Foundation.

The interaction between neurocognitive functioning, subthreshold psychotic symptoms and pharmacotherapy in 22q11.2 deletion syndrome: A longitudinal comparative study.

BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is the most common genetic syndrome associated with schizophrenia. The goal of this study was to evaluate longitudinally the interaction between neurocognitive functioning, the presence of subthreshold psychotic symptoms (SPS) and conversion to psychosis in individuals with 22q11DS. In addition, we attempted to identify the specific neurocognitive domains that predict the longitudinal evolution of positive and negative SPS, as well as the effect of psychiatric medications on 22q11DS psychiatric and cognitive developmental trajectories. METHODS: Forty-four participants with 22q11DS, 19 with Williams syndrome (WS) and 30 typically developing (TD) controls, age range 12-35years, were assessed at two time points (15.2±2.1months apart). Evaluation included the Structured Interview for Prodromal Symptoms (SIPS), structured psychiatric evaluation and the Penn Computerized Neurocognitive Battery (CNB). RESULTS: 22q11DS individuals with SPS had a yearly conversion rate to psychotic disorders of 8.8%, compared to none in both WS and TD controls. Baseline levels of negative SPS were associated with global neurocognitive performance (GNP), executive function and social cognition deficits, in individuals with 22q11DS, but not in WS. Deficits in GNP predicted negative SPS in 22q11DS and the emergence or persistence of negative SPS. 22q11DS individuals treated with psychiatric medications showed significant improvement in GNP score between baseline and follow-up assessments, an improvement that was not seen in untreated 22q11DS. CONCLUSIONS: Our results highlight the time-dependent interplay among positive and negative SPS symptoms, neurocognition and pharmacotherapy in the prediction of the evolution of psychosis in 22q11DS.

Velocardiofacial manifestations and microdeletions in schizophrenic inpatients.

Velocardiofacial syndrome (VCFS) is associated with an increased frequency of schizophrenia and other types of psychiatric morbidity. In this study, we tried to identify a subgroup of schizophrenic patients with deletions in the VCFS region of the long arm of chromosome 22. For that purpose, we screened the records of two major general hospitals for patients with abnormalities characteristic of VCFS, such as cardiac anomalies and cleft palate, and cross-checked the data with the register of psychiatric hospitalizations in four psychiatric hospitals. Of the 24 patients that qualified, only seven patients could be studied. An additional eight schizophrenic inpatients were ascertained clinically, based on a working VCFS Clinical Scale. FISH studies and molecular analyses, using polymorphic markers from the VCFS region, documented hemizygosity of 22q11 in three out of 15 patients (20.0%). Increased awareness of psychiatrists to signs of VCFS among patients with psychiatric illnesses is encouraged, in order to direct molecular studies effectively. In order to cut down the cost of testing, we suggest screening suspected patients with a single marker, such as D22S941, and to study further only those who have a single electrophoretic band.

Bone age in adolescents with schizophrenia and obsessive-compulsive disorder.

The bone age (BA), height and weight of 20 adolescents with schizophrenia and 21 matched adolescents with obsessive-compulsive disorder (COD) were measured. The BA of the schizophrenic patients was significantly higher than their chronological age (CA)(p < 0.05), while the OCD subjects' BA was non-significantly lower than their CA. In addition, the difference between CA and BA (delta ages) in the schizophrenic adolescents was significantly different from the delta ages of the OCD adolescents (p , 0.05). Gender did not significantly affect BA or delta ages. A positive correlation (r = 0.5, p < 0.01) was obtained between CA and delta ages in the schizophrenic patients but not in the OCD patients. Both groups were within the normal range of weight and height percentiles.

Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome.

Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion in the long arm of chromosome 22 and is associated with an increased frequency of schizophrenia and bipolar mood disorder. The purpose of this study was to investigate the genetic, physical, developmental and psychiatric features of schizophrenic patients with VCFS microdeletion. It describes the clinical findings in four schizophrenic inpatients with the characteristic chromosomal deletion. The four patients displayed delayed motor development, language deficits, learning disabilities, mental retardation, early age of onset, chronic and disabling course of illness and poor response to classical neuroleptic drugs and electroconvulsive therapy. Two patients benefited from treatment with clozapine. We suggest that schizophrenic patients with a history of delayed motor development, early onset of the disorder, history of learning disability, mental retardation, congenital cardiac anomalies and/or hypernasal speech should be screened for the velo-cardio-facial syndrome deletion. The implications of this study for psychiatric phenotype, nosology, disease mechanism, and possible new treatments in the future are discussed.

Defense mechanisms in severe adolescent anorexia nervosa.

OBJECTIVE: To compare ego defense mechanisms in adolescents with anorexia nervosa and other major psychiatric disorders, to defenses in healthy adolescents. METHOD: Thirty-seven patients with anorexia nervosa, 30 with major depressive disorder, 20 with obsessive-compulsive disorder, 53 with borderline personality disorder, 60 with schizophrenia, and 81 healthy controls were assessed with Pfeffer's Ego Defense Scale. RESULTS: Regression, denial, projection, repression, introjection, and total defenses were common to all psychiatric patients and distinguished them from normal adolescents. In addition to these defenses, anorectic patients also used intellectualization more frequently than normal adolescents and psychiatric patients. They used sublimation more than other psychiatric patients. Patients with disorders, apart from obsessive-compulsive disorder, that are considered to be often comorbid with anorexia did not have different defense than schizophrenic patients. CONCLUSIONS: Anorectic adolescents overutilize relatively more mature defenses than do psychiatrically ill adolescents, and they overutilize immature defenses compared with normal adolescents. This combination of mature and immature defenses may be related to the uniquely heterogeneous ego functioning seen in anorectic patients, and it may provide insight into the nature of the psychopathology of anorexia nervosa. It also could have important psychotherapeutic and prognostic value.

Correlation of suicidal and violent behavior in different diagnostic categories in hospitalized adolescent patients.

OBJECTIVE: To determine the relative importance of aggression and depression in adolescent suicide within different diagnostic categories. METHOD: One hundred sixty-three consecutive admissions to an adolescent psychiatric inpatient unit were assessed using a semistructure diagnostic instrument, the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Scores for depression, suicidal behaviors, and violent behaviors were calculated from this assessment. RESULTS: Anorexia nervosa and conduct disorder patients had the highest suicidal behavior scores. In addition, patients with conduct disorder were significantly more violent than patients with major depressive disorder, and scores on the Violent Behavior Scale correlated with suicidal symptoms but not with depressive symptoms. CONCLUSION: Aggression may be as important in some kinds of suicidal behaviors as is depression. Thus it seems that there are hypothetically at least two types of suicidal behaviors during adolescence: a wish to die (depression) and a wish not to be here for a time (impulse control). The first type of suicidal behavior characterizes that seen in disorders with prominent depression such as major depressive disorder and anorexia nervosa, and the second characterizes disorders of impulse control such as conduct disorder.

Suicidal adolescents and ego defense mechanisms.

OBJECTIVES: To identify defense mechanisms that characterize adolescents with a range of suicidal behaviors and to differentiate them from nonsuicidal adolescents. METHODS: Fifty-five suicidal adolescent inpatients admitted for a definite suicide attempt were compared with 87 adolescent inpatients who had no history of suicide attempt or ideation and 81 nonpatients. Defense mechanisms were assessed by the Ego Defense Scale (EDS) which is part of a larger semistructured interview, the Child Suicide Potential Scale (CSPS), and by a self-report questionnaire, the Life Style Index (LSI). The CSPS was also used to quantity violent and suicidal behaviors. RESULTS: On the LSI suicidal adolescent patients scored higher on denial, displacement, repression, and total defenses than the nonpatients. On the EDS they scored higher on regression, denial, projection, introjection, repression, and total defenses and lower on sublimation. LSI scores on displacement (higher) and on compensation (lower) distinguished suicidal from nonsuicidal inpatients. Denial and regression correlated positively and sublimation correlated negatively with both suicidal and violent behaviors. Introjection and repression correlated with suicidal behavior only. CONCLUSIONS: Overuse of displacement is connected with increased risk for suicidal and aggressive behaviors, while sublimation is probably a protective factor. In addition, several immature ego defenses possibly amplify aggression, which then is directed against the self by the maladaptive overuse of introjection, displacement, and repression.

Death concepts in suicidal adolescents.

OBJECTIVE: To investigate the relationship between components of death concept (preoccupation with death, death as a pleasant state, and death as final) and suicidal behavior in adolescents. METHOD: The death concepts of 51 suicidal inpatients, 102 nonsuicidal inpatients, 36 emergency room suicidal subjects, and 81 normal controls were compared using Pfeffer's Child Suicide Potential Scale. In addition, the IQ level as well as emotions that potentially influence the death concept were measured. RESULTS: Both groups of suicidal adolescents evaluated death as more pleasant than the nonsuicidal groups. All the study groups equally perceived death as a final state. Suicidal inpatients were more preoccupied with death than nonsuicidal inpatients, but surprisingly among all study groups, including normal controls, the emergency room suicidal subjects were the least preoccupied with death. Partialing out depression, anxiety, and aggression specifically augmented the association between preoccupation with death and suicidality. Thus the relationship between death concept and suicidality appears to be a direct one. No correlation was found between suicidality and intelligence level. CONCLUSIONS: Elements of death concept distinguish suicidal from nonsuicidal as well as between hospitalized versus nonhospitalized suicidal adolescents. Thus the death concept evaluation is potentially valuable in the assessment of adolescents with a high risk for suicide.

Evidence for the involvement of the hippocampus in the pathophysiology of schizophrenia.

The hippocampus, a medial temporal lobe structure, is often considered to play an important role in the pathophysiology of schizophrenia. Recent developments of neuroimaging and molecular postmortem techniques have significantly increased our ability to study the role of discrete brain regions in the pathophysiology of schizophrenia. This article describes animal models, structural, histological, molecular biology, and neuropsychological evidence for the involvement of the hippocampus in the pathophysiology of schizophrenia. The major findings in schizophrenic patients are decreased volumes, hypometabolism, and cytoarchitectural abnormalities which are more robust on the left hippocampus, as well as verbal memory impairment. It is yet to be determined whether these changes are neurodevelopmental or neurodegenerative in nature. Overall, these findings indicate that there are subtle changes in the hippocampus of schizophrenic patients. More comprehensive and focused hippocampal research in schizophrenia is required to elucidate the contribution of this intriguing brain structure to the pathophysiology of schizophrenia.

Measurement of aggression in psychiatric patients.

This article analyzes, describes, and characterizes the methods used for measuring aggression in studies on psychiatric patients. The authors reviewed all studies published between 1985 and 1994 in seven major psychiatric journals and found 103 studies on adult aggression and 43 on childhood and adolescent aggression. Almost half (44.7%) of the adult studies and 23.3% of the child and adolescent studies did not use any structured instrument; the remainder used a total of 52 different instruments, indicating that the methodology in this area is not well established. The methods used for measuring aggression were mainly of three types: observational measures; self-report questionnaires; and structured chart reviews. Each of these tools is described herein, with special focus on reliability and validity. Overall the reliability of the various scales is high, but the empirical validity is rather poor. In choosing a suitable method for measuring aggression, researchers should take into account the direction of investigation (e.g. state vs. trait aggression, dynamic or biological aspects of aggression) and the target population. Practical suggestions in this regard are offered.

Bipolar affective disorder heralding cerebral demyelination in adreno-myelo-leukodystrophy.

A young male with adrenomyeloleukodystrophy (AMLD), diagnosed at the age of 25 years, presented with signs of bipolar affective disorder (BPD) concomitant with radiological findings of central demyelination. There was a marked deterioration of the earlier relatively benign neurological dysfunction, leading to fatal bulbar syndrome. The association of BPD with central demyelination in AMLD is in agreement with previously reported cases of this and other types of multifocal central demyelination diseases.

Impulsivity as a correlate of suicidal behavior in adolescent psychiatric inpatients.

One hundred and eighteen inpatient adolescents in a psychiatric hospital were evaluated to determine the relationship of aggression, self injury, and suicidal behavior to impulsivity. It was hypothesized that all these variables would be significantly and positively correlated with one another. This hypothesis was in part based on the results of psychobiological research that found serotonin dysfunction to be the common denominator of these psychopathological dimensions. As predicted, a significant correlation was found between the measures of suicidal behavior, aggressive behavior, and impulsivity. This correlation between suicidal behavior and impulsivity remained after partialing out the factor of aggression. Furthermore, the correlations between impulsivity and suicidality appeared greater in males than in females. Since male suicide attempters are more likely to eventually commit suicide than female suicide attempters, these findings may have a bearing on suicide prediction.

The complexity of molecular genetic research in psychiatric disorders: advances and pitfalls.

This article describes the major techniques in molecular genetics, i.e., parametric and nonparametric linkage analyses, association studies and quantitative trait loci approaches. Some major molecular findings in schizophrenia, bipolar affective disorder and Alzheimer disease are presented. Aspects of the complexity of molecular genetic research in psychiatric disorders are discussed, including the relationship between genotype and phenotype, and between etiology and pathophysiology. Molecular findings in two genetic neuropsychiatric disorders, fragile X syndrome and Huntington's disease are described. These findings provoke some critical thoughts regarding future directions in psychiatric molecular research.

A comparative study of the neuropsychiatric and neurocognitive phenotype in two microdeletion syndromes: velocardiofacial (22q11.2 deletion) and Williams (7q11.23 deletion) syndromes.

PURPOSE: 22q11.2 deletion syndrome (22q11.2DS) and Williams syndrome (WS) are common neurogenetic microdeletion syndromes. The aim of the present study was to compare the neuropsychiatric and neurocognitive phenotypes of 22q11.2DS and WS. METHODS: Forty-five individuals with 22q11.2DS, 24 with WS, 22 with idiopathic developmental disability (DD) and 22 typically developing (TD) controls were compared for the rates of psychiatric disorders as well as cognitive executive and visuospatial functions. RESULTS: We found that while anxiety, mood and disruptive disorders had an equally high prevalence among individuals with 22q11.2DS, WS and DDs, the 22q11.2DS group had the highest rates of psychotic disorders and the WS group had the highest rates of specific phobia. We also found that the WS group demonstrated more severe impairments in both executive and visuospatial functions than the other groups. WS and 22q11.2DS subjects had worse Performance-IQ than Verbal-IQ, a feature typical of non-verbal learning disorders. CONCLUSION: These findings offer a wide perspective on unique versus common phenotypes in 22q11.2DS and WS.