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Mood disorders, including depressive and bipolar disorders, represent a multidimensional and prevalent group of psychiatric illnesses characterized by disturbances in emotion, cognition and metabolism. Maladaptive eating behaviors in mood disorders are diverse and warrant characterization in order to increase the precision of diagnostic criteria, identify subtypes and improve treatment strategies. The current narrative review synthesizes evidence for Eating Behavioral Phenotypes (EBP) in mood disorders as well as advancements in pathophysiological conceptual frameworks relevant to each phenotype. Phenotypes include maladaptive eating behaviors related to appetite, emotion, reward, impulsivity, diet style and circadian rhythm disruption. Potential treatment strategies for each phenotype are also discussed, including psychotherapeutic, pharmacological and nutritional interventions. Maladaptive eating behaviors related to mood disorders are relevant from both clinical and research perspectives, yet have been somewhat overlooked thus far. A better understanding of this aspect of mood disorders holds promise to improve clinical care in this patient group and contribute to the subtyping of these currently subjectively diagnosed and treated disorders.

Among medical disciplines, diagnosis in psychiatry depends highly upon descriptive signs and symptoms, rather than biomarkers. Clear descriptions of specific genetic etiologies have been lacking; genomic technologies, however, are rapidly changing that landscape. Notably, chromosomal microarrays-which detect gene copy number variants (CNVs)-are a recommended standard of care for neurodevelopmental disorders. As a result, an increasing number of patients now receive a clinical diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and an identified genetic etiological variant. However, psychiatric and genetic diagnoses are frequently communicated and managed as two disconnected diagnostic parameters. Here, we advocate for a transition model, allowing the integration of genetic etiological information-starting with diagnostically proven CNVs-within the DSM-5 classification framework.

In children undergoing genetic testing for physical health concerns, we examined how often the results also revealed information about their risk for neurodevelopmental disorders. The study sample consisted of 3056 genetic tests (1686 chromosomal microarrays--CMAs, and 1378 next-generation sequencing--NGS panels) ordered at a tertiary pediatric hospital because of a physical/congenital health problem. Tests ordered to investigate developmental concerns were excluded. Pathogenic, or likely pathogenic variants were manually reviewed for diagnostic likelihood, and for evidence of an association with a neurodevelopmental disorder (e.g., autism or intellectual disability). A total of 169 CMAs (10%) and 232 NGS panels (17%) had likely diagnostic results. More than half (52%) of all diagnostic results had established evidence of a neurodevelopmental disorder association. In summary, there is a high prevalence of neurodevelopmental implications from genetic tests ordered for physical/congenital indications. This broad clinical utility suggests a growing need for genetics-first developmental care pathways.

There are currently no approved medications for the core symptoms of autism spectrum disorder (ASD), and only limited data on the management of co-occurring mental health and behavioural symptoms. The purpose of this review is to synthesize recent trials on novel treatments in ASD, with a focus on research trends in the past 2 years.No new pharmacologic agents received regulatory approval for use in ASD. Several large randomized controlled trials (RCTs) had negative or ambiguous results (e.g. fluoxetine, oxytocin). A cross-over RCT of an oral cannabinoid suggested possible benefits for disruptive behaviours. Two large-scale multicentre trials of bumetanide were terminated early for lack of efficacy. Multicenter trials using repetitive transcranial magnetic stimulation are underway. Recent meta-analyses indicate that specific behavioural and psychological interventions can support social communication and treat anxiety. Numerous novel treatment targets informed by biological mechanisms are under investigation.Recent data support the use of behavioural and psychological interventions for social communication and anxiety in ASD; data are more limited regarding pharmacotherapy for core and associated symptoms. Next steps include replication of early findings, trials of new molecular targets, and the identification of novel biomarkers, including genetic predictors, of treatment response.

Background22q11.2 deletion syndrome (22q11DS), one of the most common recurrent copy number variant disorders, is associated with dopaminergic abnormalities and increased risk for psychotic disorders.AimsGiven the elevated prevalence of substance use and dopaminergic abnormalities in non-deleted patients with psychosis, we investigated the prevalence of substance use in 22q11DS, compared with that in non-deleted patients with psychosis and matched healthy controls.MethodThis cross-sectional study involved 434 patients with 22q11DS, 265 non-deleted patients with psychosis and 134 healthy controls. Psychiatric diagnosis, full-scale IQ and COMT Val158Met genotype were determined in the 22q11DS group. Substance use data were collected according to the Composite International Diagnostic Interview.ResultsThe prevalence of total substance use (36.9%) and substance use disorders (1.2%), and weekly amounts of alcohol and nicotine use, in patients with 22q11DS was significantly lower than in non-deleted patients with psychosis or controls. Compared with patients with 22q11DS, healthy controls were 20 times more likely to use substances in general (P < 0.001); results were also significant for alcohol and nicotine use separately. Within the 22q11DS group, there was no relationship between the prevalence of substance use and psychosis or COMT genotype. Male patients with 22q11DS were more likely to use substances than female patients with 22q11DS.ConclusionsThe results suggest that patients with 22q11DS are at decreased risk for substance use and substance use disorders despite the increased risk of psychotic disorders. Further research into neurobiological and environmental factors involved in substance use in 22q11DS is necessary to elucidate the mechanisms involved.Declaration of interestNone.

Background Pediatric brain tumor survivors (PBTS) are at risk of experiencing social competence challenges, but only a limited number of studies have used a qualitative approach to understand their social relationships. We examined PBTS responses to social interview questions within the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2), which includes questions related to their understanding of their own relationships, as well as the construct of friendship more generally. Methods Twenty-four PBTS (ages 9–17 years; M = 14.2 years from diagnosis; 50% male; 42% received radiation treatment) completed the ADOS-2. ADOS-2 social interview responses were recorded and transcribed verbatim. Themes were derived using an inductive thematic analysis approach. Results PBTS reported that they considered trust, acceptance, respect, emotional support, and spending time together to be important aspects of friendships in general. When describing their own social relationships, some PBTS noted a lack of intimacy or closeness, spending time with their friends almost exclusively at school, with structured activities outside of school being an additional basis for friendship. Challenges to their social relationships included loneliness and reliance on family for social support, experiences of teasing and bullying, social skills deficits, and lack of insight into social situations. Conclusion Although PBTS were able to acknowledge many important qualities of friendships in general (e.g., trust, emotional support), these were not necessarily reported in their own friendships. PBTS also appeared to have difficulty identifying whether someone was their friend. These findings offer potential opportunities for supporting PBTS in achieving friendships consistent with their conception of this important relationship.

Advances in laboratory testing have significantly increased the detection of rare genetic etiologies of neurodevelopmental psychiatric disorders (NPD), particularly developmental delay / intellectual disability, autism spectrum disorder, and schizophrenia. Establishing a genetic diagnosis has important medical and personal utility for individuals with these conditions. Diagnostic genetic tests for NPD are clinically available but under-utilized outside of medical genetics settings. Without clear multidisciplinary consensus recommendations, active involvement of medical specialists working with NPD patients, and practical education and training, the implementation of genetic testing for NPD will continue to lag behind other areas of medicine. In the long-term, collaborative efforts to address educational, logistical, and workforce obstacles will improve patient care and pave the way for targeted, effective NPD treatments.

Objective: Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships.\ud \ud Methods: This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing.\ud \ud Results: The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits.\ud \ud Conclusions: Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.

Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.

Background Only little is information is available about the needs and preferences regarding care and treatment of people who are going through a psychosis for the first time. A first psychotic episode is often an intense experience, which may not directly be recognized as a mental health problem. Given the unfamiliarity with the available options of care, it probably differs from subsequent psychoses. In order to design first psychosis programs to optimally meet patients preferences, we need to learn the care needs of these usually young people. Furthermore, peoples’ needs during the first psychosis, and the need for care after a psychotic episode have to be explored, in order to be able picking up life again after complete or incomplete remission. Methods Qualitative interviews were conducted with people (n = 20) who are in complete or partial remission after their first psychosis about their personal care needs. Interviews were conducted by an experience expert and a researcher together and lasted between 1 and 3 hours. Interviews were non-structured, but a basic set of 5 topics was used. Results Preliminary results of the interviews conducted so far (n = 14) show that people with a first psychosis have a great need for information about the symptoms they are suffering from. In addition, they believe that medication is an important ‘cornerstone’ to get rid of their symptoms. Furthermore, nearly all participants hope to be able to stop medication in the near future. Admission to a ward is in most cases experienced as frightening. One person indicated that the tranquility during admission was very welcome. At this stage, experience experts are not being reached out to yet, nor is there a clear need for social work in this stage of the disease. During and shortly after their first psychosis, the interviewees especially appreciate the support of family and close friends. Discussion Clear information about a first psychosis was mentioned as the first need. Family and close friends are most appreciated as “auxiliary troops”. Family support is therefore an important contributor in care for patients suffering from psychosis. Medication was appreciated as an important cornerstone, but only to induce remission, not as a mean for maintenance treatment. Admission was by most patients experienced as stressful. Additional research is recommended to further map what information this should be exactly, and how to bring it to the patient and his relatives.

(The American Journal of Human Genetics 101, 616–622; October 5, 2017) This article has been retracted at the request of the authors. In this article, we claimed the presence of nested inversion polymorphisms, spanning the LCR22-B/D or LCR22-C/D locus. We detected an increased frequency of inversions in the chromosomes of the parental genome in which the 22qll.2 rearrangement occurred. Since this publication, we have continued working on an improved map of the 22qll Iocus. During these efforts, we were unable to confirm the presence of the inversion polymorphism. We proved the polymorphism to be absent and the original data to be biased. Absence of a double-blinded control left complex observations open to interpretation and hampered objective analysis. With this crucial flaw uncovered, we no longer support these data and are retracting the article. We apologize to the scientific community, the readers of AJHG, and the families who were involved in this research.

The role of rare genetic variants, in particular copy number variants (CNVs), in the etiology of neurodevelopmental disorders is becoming increasingly clear. While the list of these disorder-related CNVs continues to lengthen, it has also become clear that in nearly all genetic variants the proportion of carriers who express the associated phenotype is far from 100%. To understand this variable penetrance of CNVs it is important to realize that even the largest CNVs represent only a tiny fraction of the entire genome. Therefore, part of the mechanism underlying the variable penetrance of CNVs is likely the modulatory impact of the rest of the genome. In the present study we used the 22q11DS as a model to examine whether the observed penetrance of intellectual impairment-one of the main phenotypes associated with 22q11DS-is modulated by the intellectual level of their parents, for which we used the parents' highest level of education as a proxy. Our results, based on data observed in 171 children with 22q11DS in the age range of 5-15 years, showed a significant association between estimated parental cognitive level and intelligence in offspring (full scale, verbal and performance IQ), with the largest effect size for verbal IQ. These results suggest that possible mechanisms involved in the variable penetrance observed in CNVs include the impact of genetic background and/or environmental influences. © 2016 Wiley Periodicals, Inc.

To the Editor: Catatonia is a motor dysregulation syndrome with multiple etiologies and is associated with a variety of neurologic disorders, general medical conditions, and reactions to medications.1–3 Recent studies suggest that catatonia should be conceptualized as an independent syndrome, which facilitates accurate diagnosis and appropriate anticatatonic treatments.2 Catatonia typically responds to anticonvulsants, mainly benzodiazepines, and electroconvulsive therapy (ECT).2 However, the therapeutic value of benzodiazepines and ECT in chronic catatonia is less well established.4 Only 20% to 30% of schizophrenic patients with catatonic symptoms respond to benzodiazepines. Thus, identifying those patients with potentially reversible symptoms is important. Here, we report the case of a patient with chronic catatonia who presented with a chronic fluctuating course of idiopathic catatonia and responded well to subsequent ECT. Case report. Ms A, a 25-year-old Dutch woman, was admitted to our clinic due to the uncertainty of the diagnosis and to exclude a somatic origin of symptoms. She was initially diagnosed with DSM-IV major depressive disorder with psychotic symptoms at age 22 years and over time had been prescribed quetiapine, initially 100 mg/d and subsequently 50 mg/d for 11 days, at which time she was switched to citalopram 20 mg/d and subsequently 10 mg/d for 6 months (Table 1). Meanwhile, at another psychiatric hospital, a diagnosis of conversion disorder was suggested, with psychotic disorder as a possible differential diagnosis. Table 1. Illness and Treatment Course of the Female Patient With Chronic Catatonia When she was presented to our unit in October 2009, the patient was mute and displayed posturing, rigidity, staring, severe ambitendency, withdrawal, negative thoughts, and frequent grimacing. She ate and drank only modestly, with much support. Furthermore, the pattern of symptoms was extremely fluctuating. Physical examination revealed cogwheel rigidity of the arms and emerging contractures of the hands, as well as increased reflexes of the arms and legs. Furthermore, there was an occurrence of waxy flexibility as well as acrocyanosis with a slow capillary refill of the toes, interpreted as venous stasis with immobility. A duplex ultrasound examination excluded circulatory stenosis or arterial anomalies and a rheumatoid origin of symptoms. Neurologic and internal examinations excluded a potential somatic origin of the disorder. A few days after admission, due to the suspected catatonia, treatment with oxazepam 50 mg 4 times daily was commenced. After 4 weeks of clinical observation, the diagnosis of chronic catatonia was established and ECT treatment was started due to an inadequate response to the benzodiazepine treatment. Initially, ECT treatment was bilateral, twice a week (Thymatron System IV, Somatics, LLC, Lake Bluff, Illinois; bilateral, impulse width 0.5 msec, energy set first 53 treatments 5% to 100% and second 15 treatments 5% to 35%, adequate seizure duration > 20 sec EMG). The patient showed slow, but gradual, improvements in speech, motoric function, mime, and social contact. The frequency of ECT treatments was therefore increased to 3 times a week, producing further improvements. Because ECT induced severe difficulty with information encoding, the frequency of ECT was, after 25 bilateral ECT treatment sessions, reduced to twice a week. The patient responded with a deterioration of symptoms such as less communication and increased muscle tension. Therefore, after 3 weeks the frequency of ECT was reinstated to 3 times a week, resulting in symptom improvement. Clinical symptoms improved significantly with ECT, and activities of daily routine improved steadily. However, when ECT was fully stopped in June 2010, symptoms deteriorated again, with the patient showing less communication, increased muscle tension, increased ambitendency, and decreased initiative. Meanwhile, a psychotic disorder with catatonia or catatonic schizophrenia was considered, and ECT was restarted twice a week along with the addition of olanzapine (up to 10 mg/d). With this treatment, she was able to speak in whole sentences, started to walk spontaneously, and showed more initiative and less ambitendency. In August 2010, the clinical symptoms improved gradually and she was discharged with a prescription of olanzapine 10 mg/d and ECT twice a week. Between January and June 2011, the patient was further followed at the outpatient clinic of a regional hospital. To the best of our knowledge, this unique case showed that, despite an insidious onset and an atypical, fluctuating course of catatonic symptoms, the diagnosis of catatonia should be considered and, as in acute catatonia, ECT can be effective in chronic catatonia. Studies of more patients with similar presentation are needed to develop an empirically based treatment approach.

Constitutional translocations at the same 22q11.21 low copy repeat B (LCR-B) breakpoint involved in the recurrent t(11;22) are relatively abundant. A novel 46,XY,t(8;22)(q24.13;q11.21) rearrangement was investigated to determine whether the recurrent LCR-B breakpoint is involved. Investigations demonstrated an inversion of the 3Mb region typically deleted in patients with the 22q11.2 deletion syndrome. The 22q11.21 inversion appears to be mediated by low copy repeats, and is presumed to have taken place prior to translocation with 8q24.13. Despite predictions based on inversions observed in other chromosomes harboring low copy repeats, this 22q11.2 inversion has not been observed previously. The current studies utilize novel laser microdissection and MLPA (multiplex ligation-dependent probe amplification) approaches, as adjuncts to FISH, to map the breakpoints of the complex rearrangements of 22q11.21 and 8q24.21. The t(8;22) occurs between the recurrent site on 22q11.21 and an AT-rich site at 8q24.13, making it the fifth different chromosomal locus characterized at the nucleotide level engaged in a translocation with the unstable recurrent breakpoint at 22q11.21. Like the others, this breakpoint occurs at the center of a palindromic sequence. This sequence appears capable of forming a perfect 145 bp stem–loop. Remarkably, this site appears to have been involved in a previously reported t(3;8) occurring between 8q24.13 and FRA3B on 3p14.2. Further, the fragile site-like nature of all of the breakpoint sites involved in translocations with the recurrent site on 22q11.21, suggests a mechanism based on delay of DNA replication in the initiation of these chromosomal rearrangements.