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Concept: Classification of mental disorders

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BACKGROUND: Some patients report a preoccupation with a specific aversive human sound that triggers impulsive aggression. This condition is relatively unknown and has hitherto never been described, although the phenomenon has anecdotally been named misophonia. METHODOLOGY AND PRINCIPAL FINDINGS: 42 patients who reported misophonia were recruited by our hospital website. All patients were interviewed by an experienced psychiatrist and were screened with an adapted version of the Y-BOCS, HAM-D, HAM-A, SCL-90 and SCID II. The misophonia patients shared a similar pattern of symptoms in which an auditory or visual stimulus provoked an immediate aversive physical reaction with anger, disgust and impulsive aggression. The intensity of these emotions caused subsequent obsessions with the cue, avoidance and social dysfunctioning with intense suffering. The symptoms cannot be classified in the current nosological DSM-IV TR or ICD-10 systems. CONCLUSIONS: We suggest that misophonia should be classified as a discrete psychiatric disorder. Diagnostic criteria could help to officially recognize the patients and the disorder, improve its identification by professional health carers, and encourage scientific research.

Concepts: Medical terms, Greek loanwords, Mental disorder, Clinical psychology, Psychiatry, Cross-cultural psychiatry, Classification of mental disorders, American Psychiatric Association

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Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Concepts: Genetics, Genome-wide association study, Mental disorder, Schizophrenia, Bipolar disorder, Suicide, Schizoaffective disorder, Classification of mental disorders

8

This study sought to estimate i) the prevalence of the co-occurrence of, ii) the association between, and iii) the sequence of onset of chronic pain and mental disorders in adolescents. We used weighted data (N=6483) from the National Comorbidity Survey Replication Adolescent Supplement (participants' age: 13-18 years). Lifetime chronic pain was assessed by adolescent self-report, lifetime DSM-IV mental disorders by the WHO CIDI, complemented by parent report. Among the study’s subjects, 1600 out of 6476 (25.93%) had experienced any type of chronic pain and any mental disorder in their lifetime. All types of pain were related to mental disorders. The most substantial temporal associations were those with onset of mental disorders preceding onset of chronic pain, including those between affective disorders and headaches and any chronic pain; between anxiety disorders and chronic back/neck pain, headaches, and any chronic pain; between behavior disorders and headaches and any chronic pain; and between any mental disorder and chronic back/neck pain, headaches, and any chronic pain.

Concepts: Psychology, Mental disorder, Abnormal psychology, Schizophrenia, Mental illness diagnosis by DSM and ICD, Classification of mental disorders

4

The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development, and susceptibility to schizophrenia and bipolar disorder. To advance the understanding of BRD1 and its role in mental disorders, we characterized the protein and chromatin interactions of the BRD1 isoforms, BRD1-S and BRD1-L.

Concepts: DNA, Gene expression, Mental disorder, Schizophrenia, Disability, Suicide, Schizoaffective disorder, Classification of mental disorders

3

Background Previous research suggests that many people receiving mental health treatment do not meet criteria for a mental disorder but are rather ‘the worried well’. Aims To examine the association of past-year mental health treatment with DSM-IV disorders. Method The World Health Organization’s World Mental Health (WMH) Surveys interviewed community samples of adults in 23 countries (n = 62 305) about DSM-IV disorders and treatment in the past 12 months for problems with emotions, alcohol or drugs. Results Roughly half (52%) of people who received treatment met criteria for a past-year DSM-IV disorder, an additional 18% for a lifetime disorder and an additional 13% for other indicators of need (multiple subthreshold disorders, recent stressors or suicidal behaviours). Dose-response associations were found between number of indicators of need and treatment. Conclusions The vast majority of treatment in the WMH countries goes to patients with mental disorders or other problems expected to benefit from treatment.

Concepts: Psychology, Medical ethics, Mental health, Mental disorder, Schizophrenia, Psychiatry, World Health Organization, Classification of mental disorders

2

The Scale to Assess Unawareness in Mental Disorder (SUMD) is widely used in clinical trials and epidemiological studies but more rarely in clinical practice because of its length (74 items). In clinical practice, it is necessary to provide shorter instruments. The aim of this study was to investigate the validity and reliability of the abbreviated version of the SUMD.

Concepts: Epidemiology, Clinical trial, Psychometrics, Validity, Reliability, Mental disorder, Test, Classification of mental disorders

2

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM–whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article took up the first two questions. Part II will take up the second two questions. Question 3 deals with the question as to whether DSM-V should assume a conservative or assertive posture in making changes from DSM-IV. That question in turn breaks down into discussion of diagnoses that depend on, and aim toward, empirical, scientific validation, and diagnoses that are more value-laden and less amenable to scientific validation. Question 4 takes up the role of pragmatic consideration in a psychiatric nosology, whether the purely empirical considerations need to be tempered by considerations of practical consequence. As in Part 1 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances.

Concepts: Mental disorder, Abnormal psychology, Schizophrenia, Borderline personality disorder, Psychiatry, Diagnostic and Statistical Manual of Mental Disorders, Classification of mental disorders, American Psychiatric Association

1

Misophonia, a phenomenon first described in the audiology literature, is characterized by intense emotional reactions (e.g., anger, rage, anxiety, disgust) in response to highly specific sounds, particularly sounds of human origin such as oral or nasal noises made by other people (e.g., chewing, sniffing, slurping, lip smacking). Misophonia is not listed in any of the contemporary psychiatric classification systems. Some investigators have argued that misophonia should be regarded as a new mental disorder, falling within the spectrum of obsessive-compulsive related disorders. Other researchers have disputed this claim. The purpose of this article is to critically examine the proposition that misophonia should be classified as a new mental disorder. The clinical and research literature on misophonia was examined and considered in the context of the broader literature on what constitutes a mental disorder. There have been growing concerns that diagnostic systems such as DSM-5 tend to over-pathologize ordinary quirks and eccentricities. Accordingly, solid evidence is required for proposing a new psychiatric disorder. The available evidence suggests that (a) misophonia meets many of the general criteria for a mental disorder and has some evidence of clinical utility as a diagnostic construct, but (b) the nature and boundaries of the syndrome are unclear; for example, in some cases misophonia might be simply one feature of a broader pattern of sensory intolerance, and © considerably more research is required, particularly work concerning diagnostic validity, before misophonia, defined as either as a disorder or as a key feature of some broader syndrome of sensory intolerance, should be considered as a diagnostic construct in the psychiatric nomenclature. A research roadmap is proposed for the systematic evaluation as to whether misophonia should be considered for future editions of DSM or ICD.

Concepts: Psychology, Mental disorder, Psychiatry, Classification of mental disorders

1

Research in the field of mental health consequences of abortion is characterized by methodological limitations. We used exact matching on carefully selected confounders in a prospective cohort study of 325 women who had an abortion of an unwanted pregnancy and compared them 1-to-1 to controls who did not have this experience. Outcome measures were incidence and recurrence of common DSM-IV mental disorders (mood, anxiety, substance use disorders, and the aggregate measure ‘any mental disorder’) as measured with the Composite International Diagnostic Interview (CIDI) version 3.0, in the 2.5-3 years after the abortion. Although non-matched data suggested otherwise, women in the abortion group did not show significantly higher odds for incidence of ‘any mental disorder’, or mood, anxiety and substance use disorders, compared to matched controls who were similar in background variables but did not have an this experience. Having an abortion did not increase the odds for recurrence of the three disorder categories, but for any mental disorder the higher odds in the abortion group remained significant after matching. It is unlikely that termination of an unwanted pregnancy increases the risk on incidence of common mental disorders in women without a psychiatric history. However, it might increase the risk of recurrence among women with a history of mental disorders.

Concepts: Psychology, Pregnancy, Mental health, Mental disorder, Abnormal psychology, Psychiatry, Cross-cultural psychiatry, Classification of mental disorders

1

Elevated peripheral proline is associated with psychiatric disorders, and there is evidence that proline is a neuromodulator. The proline dehydrogenase (PRODH) gene, which encodes the enzyme that catalyzes proline catabolism, maps to human chromosome 22q11.2, a region conferring risk of schizophrenia. In the Prodh-null mouse, an interaction between elevated peripheral proline and another 22q11.2 gene, catechol-O-methyltransferase (COMT), on neurotransmission and behavior has been reported. We explored the relationship between fasting plasma proline levels and COMT Val(158)Met genotype on symptoms (positive, negative and total) in schizophrenia patients. In an exploratory study we also examined symptom change in patients with bipolar disorder. There was a significant interaction between peripheral proline and COMT on negative symptoms in schizophrenia (P<0.0001, n=95). In COMT Val/Val patients, high proline was associated with low Scale for the Assessment of Negative Symptom (SANS) scores. In contrast, high proline was associated with high SANS scores in patients carrying a Met allele. The relationship between proline and COMT also appears to modify negative symptoms across psychiatric illness. In bipolar disorder, a significant interaction was also observed on negative-symptom change (P=0.007, n=43). Negative symptoms are intractable and largely unaddressed by current medications. These data indicate a significant interaction between peripheral proline and COMT genotype, influencing negative symptoms in schizophrenia and bipolar disorder. That high proline has converse effects on symptoms by COMT genotype, may have implications for therapeutic decisions.

Concepts: Genetics, Mental disorder, Schizophrenia, Borderline personality disorder, Disability, Suicide, Schizoaffective disorder, Classification of mental disorders