Affective psychosis and Prader–Willi syndrome

Previous studies have demonstrated that maladaptive behaviours are common amongst adults with Prader–Willi syndrome (PWS). Case reports have also previously demonstrated that psychosis can occur amongst adults with PWS. The present study was undertaken in order to gain a better understanding of the psychopathology of the psychosis of PWS. Twentythree out of 25 adults identified with PWS living in Northamptonshire, UK, agreed to participate. Comprehensive psychiatric assessments (using the PPSLD), and measures of adaptive and maladaptive behaviours (using the AAMR-ABS) were completed. Comparisons were made for the prevalence of psychiatric disorders against those from a previous epidemiological study of adults with intellectual disability of other aetiologies from a neighbouring county. The PWS group was found to have higher rates of affective disorders (a point prevalence of 17.4%), in which psychotic symptoms were common, but similar rates of schizophrenia/delusional disorders (4.3%) compared with the comparison group. Behaviour disorders were also common. Surprisingly, none of the PWS group was found to have generalized anxiety or phobic disorders. The diagnostic criteria for the episodes including psychotic symptoms are explored. The high rates of affective disorders is of clinical (i.e. treatment) importance as well as being of academic interest with regard to the genetics of psychiatric disorders.     

The course and outcome of psychiatric illness in people with Prader–Willi syndrome: implications for management and treatment

Background This study is part of a larger UK‐wide study investigating psychiatric illness in people with Prader–Willi syndrome (PWS), and describes the longitudinal aspect of psychiatric illness, in particular psychotic illness, and examines the use and role of psychotropic medication. Method A total of 119 individuals with genetically confirmed PWS were included in the study. An informant‐based questionnaire was administered for each participant to screen for a history of psychopathology. Those who screened positive were visited at their homes to obtain further information. This assessment included a full psychiatric history and mental state examination using the Psychiatric Assessment Schedule for Adults with Developmental Disability and the Operational Criteria Checklist for psychotic and affective illness to collect information regarding phenomenology and course of illness, and a modified life events questionnaire. At the end of the study period, informant‐based telephone interviews were again carried out, up to 2.5 years after the initial screening. Information regarding medication usage was collected. Results The results confirm previous findings that psychiatric illness in people with PWS resembles an affective disorder. Individuals with the maternal uniparental disomy genetic subtype had a more severe course of illness than those with the deletion genetic subtype in terms of a greater risk of recurrence, more episodes, higher incidence and a possibly poorer response to medication with more side‐effects. Individuals with a recurrent episode during the follow‐up period had a poorer course of illness. Selective serotonin reuptake inhibitor medication is frequently used, and beneficial effects may reflect fundamental pathological processes in PWS. Mood‐stabilizing medication was found to be of little benefit and reasons for this are examined. Conclusion The longitudinal course of psychiatric illness and response to medication in people with PWS is fully described. Further research is needed regarding the effect of psychotropic medications, particularly mood‐stabilizing medication. These data will enable informed decisions to be made regarding management options and provide information on the possible long‐term outcome of illness.     

Psychiatric disorders in people with 22q11.2 Deletion Syndrome: A population‐based prevalence study in Ireland

Background : 22q11.2 Deletion Syndrome (22q11.2 DS) is a common micro‐deletion syndrome associated with intellectual disability, brain abnormalities and a complex spectrum of psychiatric disorders in both adults and children. Many previous studies have shown that adults with 22q11.2 DS have approximately thirty times greater risk for the developing schizophrenia compared to the general population. Furthermore, studies of children and adolescents with 22q11.2 DS have found high rates of psychotic symptoms, ADHD and anxiety disorders. In this study we initially aim to characterize the psychiatric and neuropsychological phenotype of all individuals in Ireland with 22q11.2 DS and then correlate our findings with genetic association studies and brain imaging. We then intend to undertake a longitudinal study to assess for risk factors of future psychotic illness. Methods : Forty‐four individuals with 22q11.2 DS (Mean age = 14 years, SD = 9) were compared to 25 non‐affected sibling controls (Mean age = 12 years, SD = 4). Psychiatric phenotype assessment was performed using a range of standardized clinical assessments including, the Diagnostic Interview Schedule for Children (DISC), Psychotic Supplement of K‐SADS, Comprehensive Assessment of At Risk Mental State (CAARMS), the Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Child Behaviour Checklist (CBCL) and the Social Communication Questionnaire (SCQ). Results : Preliminary data indicates that individuals in the 22q11.2 DS group have a higher prevalence of psychiatric disorders including; ADHD (41%), psychotic symptoms (19%), schizophrenia (2.7%), specific phobias (38%), depressive episodes (11%), and anxiety disorders (32%). Conclusion : This is the first stage in a longitudinal follow‐up study of individuals with 22q11.2DS in Ireland. Our preliminary results are consistent with previous findings of high rates of psychiatric disorders in people with 22q11.2DS. The challenge remains to identify precursor symptoms in childhood that predicts the later development of psychiatric disorders, particularly schizophrenia in this vulnerable group.     

Face Discrimination Skills in Prader-Willi Syndrome and Autism Spectrum Disorder

Individuals with Prader-Willi Syndrome (PWS) are at risk for autism spectrum disorder (ASD), including socialization problems. The PWS chromosome 15q11-13 maternal uniparental disomy (mUPD) subtype displays greater ASD symptoms than the paternal deletion (DEL) subtype. Since interpreting faces leads to successful socialization, we compared face discrimination in PWS with ASD to explore the socialization characteristics of these disorders. Although face processing impairment in ASD is well documented, PWS face processing research is limited. Forty-four PWS participants (14 DEL and 19 mUPD) and 17 participants with ASD were measured on face discrimination. PWS and ASD participants scored in the impaired functioning range. For primary findings, DEL and mUPD PWS genetic subtype groups did not differ. These findings suggest PWS individuals, regardless of subtype, show impaired face processing similar to ASD. This research highlights the need for additional research on social cognitive functioning in PWS to understand the role of 15q11-13 in ASD.     

Psychotic symptoms and paranoid ideation in a population-based sample of 95-year-olds.

OBJECTIVE: To examine the 1-year prevalence of psychotic symptoms and schizophrenia in nondemented 95-year-olds, and to examine the relation between psychotic symptoms and other psychiatric symptoms, sensory impairments, and cognitive functioning. PARTICIPANTS: The representative sample was 95-year-olds living in G?teborg, Sweden (N = 338). Individuals with dementia were excluded (N = 175), leaving 163 subjects for this study. DESIGN: This was a cross-sectional population study, including psychiatric and physical examinations, cognitive tests, and interviews with close informants. MEASUREMENTS: Diagnosis of schizophrenia, psychotic symptoms, paranoid ideation and dementia according to Diagnostic and Statistical Manual of Mental Disorders, Third Revision (DSM-III) were measured. Cognitive function was tested with the Mini-Mental State Exam. Other psychiatric symptoms were measured by the Comprehensive Psychopathological Rating Scale. RESULTS: The one-year prevalence of any psychotic symptom was 7.4% (95% confidence interval [CI] 3.8-12.5); including hallucinations 6.7% (95% CI 3.4-11.8) and delusions 0.6% (95% CI 0.0-3.4). Four (2.4%) individuals fulfilled DSM-III-R criteria for schizophrenia. Individuals with psychotic symptoms or paranoid ideation did not differ regarding cognitive functioning compared with individuals without these symptoms. Individuals with hallucinations and paranoid ideation had an increased frequency of previous paranoid personality traits compared with individuals without psychotic symptoms and paranoid ideation. No individuals with psychotic symptoms had a formal thought disorder, incoherence of speech, or flat affect. CONCLUSION: The authors found a high prevalence of psychotic symptoms, paranoid ideation, and schizophrenia in the very old. Most of the symptoms were elucidated by information from key informants, illustrating the importance of including relatives in the evaluation of elderly persons.     

Behavioral and psychiatric disorders in Prader-Willi syndrome: a population study in Japan

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder characterized by mental retardation and distinct physical, behavioral, and psychiatric features. Based on parents' questionnaires, we examined the prevalence of behavioral and psychiatric disorders of 165 persons with PWS aged 2-31 years in Japan. The data were analyzed comparing four different age groups with PWS: group 1, 2-5 years (n=34); group 2, 6-11 years (n=57); group 3, 12-17 years (n=45); and group 4, 18-31 years (n=29). Further, we compared the results of our PWS group 4 with those of 42 age-, gender-, and intelligence level-matched intellectual disability (ID) individuals without PWS. Our results showed that repetitive speech and stubbornness were prominent from early childhood and other behavioral problems such as hyperphagia, stealing food, temper tantrums, lying, and emotional lability tended to be more frequent with age among persons with PWS. Moreover, young adults with PWS have significantly higher rates of behavioral and psychiatric disorders than IDs without PWS, such as stubbornness, hyperphagia, temper tantrums, self-injurious behavior (skin picking), hypersomnia, inactivity, and delusion. Degree of obesity was not necessarily related to behavioral and psychiatric features associated with PWS. Our findings revealed that persons with PWS are more vulnerable to behavioral and psychiatric disorders particularly in young adulthood compared to those with ID from other etiologies in Japan.     

Prader–Willi syndrome: new insights in the behavioural and psychiatric spectrum

Prader–Willi syndrome (PWS) is a genetic disorder caused by the loss of the paternal contribution of the proximal part (15q11–q13) of the long arm of chromosome 15 (i.e. deletion, disomy and imprinting mutation). The syndrome is associated with distinct physical dysmorphism, as well as with specific behavioural and psychopathological characteristics. Psychiatric symptoms in adolescence and adulthood have been described, including acute cycloid psychosis, and obsessive compulsive, bipolar and pervasive developmental disorders. At the Centre for Human Genetics in Leuven, Belgium, 53 individuals (31 children and adolescents, and 22 adults) have been followed up for 15 years by a special multidisciplinary team. Attention was given to their medical, cognitive, behavioural and emotional development, and the evolution of psychiatric disorders in adolescence and adulthood. This study describes the psychiatric problems in four patients diagnosed with acute cycloid psychosis and traces their development from infancy to adolescence. Four other individuals needed psychiatric evaluation and treatment, and could be diagnosed as having unspecified bipolar disorder, also termed unstable mood disorder. Both groups were compared, and significant differences in early development and later evolution into adulthood were noted. The individuals with PWS who later developed psychotic episodes were described as active and extrovert toddlers, and showed autistic behaviour during their primary school education. Their intellectual functioning was in the moderate to severely retarded range. The individuals with PWS who later developed an unstable mood disorder were described as rather passive and introvert toddlers, and they presented less disturbed behaviour during their primary school education. The intellectual functioning of these subjects was in the normal to borderline range.     

Tobacco smoking among people living with a psychotic illness: The second Australian survey of psychosis

Objective: The aims of this study were to (a) describe patterns of tobacco smoking among Australians living with a psychotic illness and (b) explore the association between smoking and measures of psychopathology, psychiatric history, psychosocial functioning, physical health, substance use and demographic characteristics. Methods: Data were from 1812 participants in the 2010 Australian Survey of High Impact Psychosis. Participants were aged 18-64 years and resided in seven mental health catchment sites across five states of Australia. Bivariate statistics were used to compare smokers with non-smokers on the measures of interest, and to compare ICD-10 diagnostic categories on measures of smoking prevalence, nicotine addiction and quitting history. Multivariate logistic regression was used to test whether (a) demographics and psychiatric history were associated with having ever smoked and (b) whether symptoms and psychosocial functioning were independently associated with current smoking, after controlling for demographics, psychiatric history and substance use. Results: The prevalence of current tobacco smoking was 66.6% (72% of men and 59% of women); lifetime prevalence was 81%. In univariate analyses, individuals with a diagnosis of schizophrenia or schizoaffective disorder were most likely to be smoking tobacco (70%) and were more nicotine dependent. Smokers reported worse perceived physical health, lower body mass index and waist circumference, and more lifetime medical conditions. A younger age of illness onset, male gender and low education were associated with having ever smoked. Associations with current smoking included low education, male gender, no formal employment, worse negative symptoms, higher daily caffeine consumption, and alcohol dependence and substance abuse/dependence. Conclusions: The prevalence of tobacco smoking is high amongst people with a psychotic disorder, and is associated with adverse mental health symptoms as well as high rates of other substance use, poorer subjective physical health, and a higher risk of the many known health consequences of smoking.     

The course of depressive symptoms and prescribing patterns of antidepressants in schizophrenia in a one-year follow-up study

BackgroundAntidepressants are frequently prescribed in patients with psychotic disorders, but little is known about their effects in routine clinical practice. The objective was to investigate the prescribing patterns of antidepressants in relation to the course of depressive symptoms in patients with psychotic disorders.MethodsA cohort of 214 Dutch patients with psychotic disorders received two assessments of somatic and psychiatric health, including a clinician-rated screening for depressive symptoms, as part of annual routine outcome monitoring.ResultsDepressive symptoms were prevalent among 43% (93) of the patients. Antidepressants were prescribed for 40% (86) of the patients and the majority 83% (71) continued this therapy after one year. Multivariable analysis showed that patients with more severe psychopathology had a higher risk to develop depressive symptoms the following year (OR [95% CI] = 0.953 [0.912–0.995]). For patients with depressive symptoms at baseline, polypharmacy was a potential risk factor to keep having depressive symptoms (OR [95% CI] = 1.593 [1.123–2.261]). Antidepressant use was not an independent predictor in both analyses.ConclusionsRoutine outcome monitoring in patients with psychotic disorders revealed a high prevalence of depressive symptoms. Antidepressants were frequently prescribed and continued in routine clinical practice.     

Vulnerability to psychosis increases the risk of depression. Results of the RADEP study

We studied prevalence of depressive symptoms in primary care (PrC) and in psychiatric outpatient care (PsC), and how psychotic and manic symptoms are associated with current depressive symptoms. Altogether 563 patients attending PrC and 163 patients attending PsC filled in a questionnaire including the Depression Scale (DEPS), the Mood Disorder Questionnaire (MDQ) and questions on psychotic symptoms from the Composite International Diagnostic Interview (CIDI). Patients with depressive symptoms (DEPS score > 8) were interviewed by phone using the same checklist 6 months after baseline examination. From the PrC sample, 19.5% and from the PsC sample 73.0% were DEPS positive. In the PrC but not in the PsC sample, patients' background associated strongly with occurrence of depressive symptoms. Both at baseline and at follow-up, depressive symptoms correlated significantly with psychotic and manic symptoms. In multivariate analyses, when the effects of background, health and functioning were taken into account, baseline depressive symptoms associated significantly with lifetime psychotic symptoms. Depressive symptoms at follow-up associated significantly with psychotic symptoms during the follow-up period. In the PrC sample, this association was significant even when the effect of baseline depressive symptoms was controlled. About one-fifth of patients attending primary care and about three-quarters of patients attending psychiatric outpatient patient care suffer from depressive symptoms. Vulnerability to psychosis, indicated by occurrence of psychotic symptoms, increases the risk of and slower recovery from depressive symptoms in the patients attending primary care. Therefore, vulnerability to psychosis should be evaluated when treatment intervention for patients with depressive symptoms is planned.     

The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms

OBJECTIVE: To examine psychopathology and influence of intelligence level on psychiatric symptoms in children with the 22q11.2 deletion syndrome (22q11DS). METHOD: Sixty patients, ages 9 through 18 years, were evaluated. Assessments followed standard protocols, including structured and semistructured interviews of parents, videotaped psychiatric interview, and intelligence assessment of the child. Intelligence level, psychiatric symptoms, and classification provided the main outcome. RESULTS: High rates of autism spectrum disorders (30 of 60, 50.0%) and psychotic symptoms (16 of 60, 26.7%) were found in this sample. In 7 of 60 (11.7%), the psychotic symptoms interfered with behavior and caused considerable distress. In these cases, the diagnosis of a psychotic disorder was applied. The average age of the children with psychotic symptoms at time of assessment was 14.2 years. Although it is likely that the high rate of psychopathology in this sample is to some extent associated with the lower level of cognitive function, a major effect of the degree of cognitive impairment on psychiatric morbidity was not found. CONCLUSION: Autism spectrum disorders and subthreshold autistic symptomatology are common in children with 22q11DS. Furthermore, a high rate of psychosis and psychotic symptoms is found in this childhood sample, suggesting an early onset of psychosis in 22q11DS patients. Autistic and psychotic disorders should be considered to be main elements of the behavioral phenotype of 22q11DS children.     

Divergent structural brain abnormalities between different genetic subtypes of children with Prader–Willi syndrome

Background

Prader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses.

Methods

High resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite.

Results

Both children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD.

Conclusions

Children with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD.     

Prader–Willi syndrome and psychotic symptoms: 2. A preliminary study of prevalence using the Psychopathology Assessment Schedule for Adults with Development Disability checklist

The Psychopathology Assessment Schedule for Adults with Developmental Disability (PAS-ADD) checklist was used to screen for psychotic symptoms among people with Prader–Willi syndrome (PWS) aged 16 years and over. The scoring instructions for the PAS-ADD checklist were modified to take account of knowledge about the behavioural phenotype of PWS. Using modified scoring, 6.3% of the 95 people for whom checklists were completed had a possible psychotic disorder in the month before the assessment was made. The results should be treated as a crude estimate of the prevalence of psychotic symptoms associated with PWS in adult life in view of potential biases in the sample reported. These findings lend some support to the hypothesis that PWS has a non-chance association with psychotic symptoms and that the association is not entirely accounted for by the increased prevalence of psychosis associated with intellectual disability.     

Vulnerability to psychosis in patients attending primary and psychiatric care. Results of the RADEP study

We studied occurrence of psychotic symptoms and their associations with occurrence of depressive and manic symptoms; 563 patients attending primary care (PrC) and 163 patients attending psychiatric outpatient care (PsC) completed a questionnaire including lists of psychotic, manic and depressive symptoms, and patients with depressive symptoms were interviewed using the same questionnaire 6 months after baseline examination. Of PrC patients, 8.5% and of PsC patients, 36.2% reported at least seven lifetime psychotic symptoms. During the 6-month follow-up, the corresponding figures were 0.22% for PrC and 2.84% for PsC patients. Among PrC patients, men, young, never-married, students and unemployed reported more psychotic symptoms than others. In multivariate analyses, occurrence of psychotic symptoms was associated with young age, never being married, poor functioning and former psychiatric treatment, as well as with occurrence of manic and depressive symptoms. Psychotic symptoms are rather prevalent in primary care and very common in psychiatric care. In primary care, vulnerability to psychosis is associated with the patient's background more strongly than in psychiatric care. Concurrent occurrence of psychotic symptoms with manic and depressive symptoms is common.     

Vulnerability to psychosis in patients attending primary and psychiatric care. Results of the RADEP study

We studied occurrence of psychotic symptoms and their associations with occurrence of depressive and manic symptoms; 563 patients attending primary care (PrC) and 163 patients attending psychiatric outpatient care (PsC) completed a questionnaire including lists of psychotic, manic and depressive symptoms, and patients with depressive symptoms were interviewed using the same questionnaire 6 months after baseline examination. Of PrC patients, 8.5% and of PsC patients, 36.2% reported at least seven lifetime psychotic symptoms. During the 6-month follow-up, the corresponding figures were 0.22% for PrC and 2.84% for PsC patients. Among PrC patients, men, young, never-married, students and unemployed reported more psychotic symptoms than others. In multivariate analyses, occurrence of psychotic symptoms was associated with young age, never being married, poor functioning and former psychiatric treatment, as well as with occurrence of manic and depressive symptoms. Psychotic symptoms are rather prevalent in primary care and very common in psychiatric care. In primary care, vulnerability to psychosis is associated with the patient's background more strongly than in psychiatric care. Concurrent occurrence of psychotic symptoms with manic and depressive symptoms is common.     

Aging-related diagnostic variations: need for diagnostic criteria appropriate for elderly psychiatric patients.

It is commonly thought and taught that most psychiatric disorders other than dementia are much less prevalent among the elderly than among younger adults. This perception is based on a relatively small number of published epidemiologic investigations of the incidence and prevalence of mental illnesses in elderly populations. Most of these studies have had a number of methodologic problems, including improper definitions and diagnostic criteria for older persons. A likely consequence of these misconceptions is that clinically significant and potentially treatable mental illnesses might be overlooked, misdiagnosed, and mistreated in elderly patients. Studies in community samples suggest that many older adults who experience clinically significant psychopathology do not fit easily into our existing nomenclature, and yet are disabled. There is a need to develop aging-appropriate diagnostic criteria for major psychiatric disorders. In this article, we discuss the potential causes of this diagnostic confusion. Four specific classes of disorders-mood (specifically depressive) disorders, schizophrenia (and related psychotic disorders), anxiety disorders, and substance use disorders-are discussed as examples. Finally, we suggest some future steps for clarifying this diagnostic confusion.     

Characteristics Associated with Presence of Depressive Symptoms in Adults with Autism Spectrum Disorder

Evidence suggests that individuals with autism spectrum disorders (ASD) often exhibit associated psychiatric symptoms, particularly related to depression. The current study investigated whether individual characteristics, specifically, severity of ASD symptoms, level of cognitive ability, and/or presence of other psychiatric disorders, are associated with occurrence of depressive symptoms in adults with ASD. Forty-six adults with ASD were administered a standardized psychiatric history interview. Twenty participants (43%) endorsed depressive symptoms. It was found that individuals with less social impairment, higher cognitive ability, and higher rates of other psychiatric symptoms, were more likely to report depressive symptoms. These characteristics may be vulnerability factors for the development of depression, and should be considered when screening and treating adults with ASD.