Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32

PURPOSE The restricted genetic diversity and homogeneous molecular basis of Mendelian disorders in isolated founder populations have rarely been explored in epilepsy research. Our long-term goal is to explore the genetic basis of epilepsies in one such population, the Gypsies. The aim of this report is the clinical and genetic characterization of a Gypsy family with a partial epilepsy syndrome. METHODS Clinical information was collected using semistructured interviews with affected subjects and informants. At least one interictal electroencephalography (EEG) recording was performed for each patient and previous data obtained from records. Neuroimaging included structural magnetic resonance imaging (MRI). Linkage and haplotype analysis was performed using the Illumina IVb Linkage Panel, supplemented with highly informative microsatellites in linked regions and Affymetrix SNP 5.0 array data. RESULTS We observed an early-onset partial epilepsy syndrome with seizure semiology strongly suggestive of temporal lobe epilepsy (TLE), with mild intellectual deficit co-occurring in a large proportion of the patients. Psychiatric morbidity was common in the extended pedigree but did not cosegregate with epilepsy. Linkage analysis definitively excluded previously reported loci, and identified a novel locus on 5q31.3-q32 with an logarithm of the odds (LOD) score of 3 corresponding to the expected maximum in this family. DISCUSSION The syndrome can be classified as familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild intellectual deficit. The linked 5q region does not contain any ion channel-encoding genes and is thus likely to contribute new knowledge about epilepsy pathogenesis. Identification of the mutation in this family and in additional patients will define the full phenotypic spectrum.

Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia

BACKGROUND: Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence. These findings suggest that DNTBP1 may be involved in pathways that lead to multiple psychiatric phenotypes. In this study, we explored the association between DTNBP1 SNPs (single nucleotide polymorphisms) and multiple psychiatric phenotypes included in the Diagnostic Interview of Psychosis (DIP). METHODS: Five DTNBP1 SNPs, rs17470454, rs1997679, rs4236167, rs9370822 and rs9370823, were genotyped in 235 schizophrenia subjects screened for various phenotypes in the domains of depression, mania, hallucinations, delusions, subjective thought disorder, behaviour and affect, and speech disorder. SNP-phenotype association was determined with ANOVA under general, dominant/recessive and over-dominance models. RESULTS: Post hoc tests determined that SNP rs1997679 was associated with visual hallucination; SNP rs4236167 was associated with general auditory hallucination as well as specific features including non-verbal, abusive and third-person form auditory hallucinations; and SNP rs9370822 was associated with visual and olfactory hallucinations. SNPs that survived correction for multiple testing were rs4236167 for third-person and abusive form auditory hallucinations; and rs9370822 for olfactory hallucinations. CONCLUSION: These data suggest that DTNBP1 is likely to play a role in development of auditory related, visual and olfactory hallucinations which is consistent with evidence of DTNBP1 activity in the auditory processing regions, in visual processing and in the regulation of glutamate and dopamine activity

The acceptability, usability and short-term outcomes of Get Real: A web-based program for psychotic-like experiences (PLEs)

Background Psychotic-like experiences (PLEs) are subclinical delusional ideas and perceptual disturbances that have been associated with a range of adverse mental health outcomes. This study reports a qualitative and quantitative analysis of the acceptability, usability and short term outcomes of Get Real, a web program for PLEs in young people. Methods Participants were twelve respondents to an online survey, who reported at least one PLE in the previous 3 months, and were currently distressed. Ratings of the program were collected after participants trialled it for a month. Individual semi-structured interviews then elicited qualitative feedback, which was analyzed using Consensual Qualitative Research (CQR) methodology. PLEs and distress were reassessed at 3 months post-baseline. Results User ratings supported the program's acceptability, usability and perceived utility. Significant reductions in the number, frequency and severity of PLE-related distress were found at 3 months follow-up. The CQR analysis identified four qualitative domains: initial and current understandings of PLEs, responses to the program, and context of its use. Initial understanding involved emotional reactions, avoidance or minimization, limited coping skills and non-psychotic attributions. After using the program, participants saw PLEs as normal and common, had greater self-awareness and understanding of stress, and reported increased capacity to cope and accept experiences. Positive responses to the program focused on its normalization of PLEs, usefulness of its strategies, self-monitoring of mood, and information putting PLEs into perspective. Some respondents wanted more specific and individualized information, thought the program would be more useful for other audiences, or doubted its effectiveness. The program was mostly used in low-stress situations. Conclusions The current study provided initial support for the acceptability, utility and positive short-term outcomes of Get Real. The program now requires efficacy testing in randomized controlled trials.

An imagery-based road map to tackle maladaptive motivation in clinical disorders

There is now a widespread recognition of the importance of mental imagery in a range of clinical disorders (1). This provides the potential for a transdiagnostic route to integrate some aspects of these disorders and their treatment within a common framework. This opinion piece argues that we need to understand why imagery is such a central and recurring feature, if we are to progress theories of the origin and maintenance of disorders. This will aid us in identifying therapeutic techniques that are not simply targeting imagery as a symptom, but as a manifestation of an underlying problem. As papers in this issue highlight, imagery is a central feature across many clinical disorders, but has been ascribed varying roles. For example, the involuntary occurrence of traumatic memories is a diagnostic criterion for PTSD (2), and it has been suggested that multisensory imagery of traumatic events normally serves a functional role in allowing the individual to reappraise the situation (3), but that this re-appraisal is disabled by extreme affective responses. In contrast to the disabling flashbacks associated with PTSD, depressed adults who experience suicidal ideation often report “flash forward” imagery related to suicidal acts (4), motivating them to self-harm. Socially anxious individuals who engage in visual imagery about giving a talk in public become more anxious and make more negative predictions about future performance than others who engage in more abstract, semantic processing of the past event (5). People with Obsessive Compulsive Disorder (OCD) frequently report imagery of past adverse events, and imagery seems to be associated with severity (6). The content of intrusive imagery has been related to psychotic symptoms (7), including visual images of the catastrophic fears associated with paranoia and persecution. Imagery has been argued (8) to play a role in the maintenance of psychosis through negative appraisals of imagined voices, misattribution of sensations to external sources, by the induction of negative mood states that trigger voices, and through maintenance of negative schemas. In addiction and substance dependence, Elaborated Intrusion (EI) Theory (9, 10) emphasizes the causal role that imagery plays in substance use, through its role in motivating an individual to pursue goals directed toward achieving the pleasurable outcomes associated with substance use...

The designed environment and how it affects brain morphology and mental health

Background The environment is inextricably related to mental health. Recent research replicates findings of a significant, linear correlation between a childhood exposure to the urban environment and psychosis. Related studies also correlate the urban environment and aberrant brain morphologies. These findings challenge common beliefs that the mind and brain remain neutral in the face of worldly experience. Aim There is a signature within these neurological findings that suggests that specific features of design cause and trigger mental illness. The objective in this article is to work backward from the molecular dynamics to identify features of the designed environment that may either trigger mental illness or protect against it. Method This review analyzes the discrete functions putatively assigned to the affected brain areas and a neurotransmitter called dopamine, which is the primary target of most antipsychotic medications. The intention is to establish what the correlations mean in functional terms, and more specifically, how this relates to the phenomenology of urban experience. In doing so, environmental mental illness risk factors are identified. Conclusions Having established these relationships, the review makes practical recommendations for those in public health who wish to use the environment itself as a tool to improve the mental health of a community through design.

Lost in space: The place of the architectural milieu in the aetiology and treatment of schizophrenia

Purpose – Psychological and epidemiological literature suggests that the built environment plays both causal and therapeutic roles in schizophrenia, but what are the implications for designers? The purpose of this paper is to focus on the role the built environment plays in psycho‐environmental dynamics, in order that negative effects can be avoided and beneficial effects emphasised in architectural design. Design/methodology/approach – The approach taken is a translational exploration of the dynamics between the built environment and psychotic illness, using primary research from disciplines as diverse as epidemiology, neurology and psychology. Findings – The built environment is conceived as being both an agonist and as an antagonist for the underlying processes that present as psychosis. The built environment is implicated through several means, through the opportunities it provides. These may be physical, narrative, emotional, hedonic or personal. Some opportunities may be negative, and others positive. The built environment is also an important source of unexpected aesthetic stimulation, yet in psychotic illnesses, aesthetic sensibilities characteristically suffer from deterioration. Research limitations/implications – The findings presented are based on research that is largely translated from very different fields of enquiry. Whilst findings are cogent and logical, much of the support is correlational rather than empirical. Social implications – The WHO claims that schizophrenia destroys 24 million lives worldwide, with an exponential effect on human and financial capital. Because evidence implicates the built environment, architectural and urban designers may have a role to play in reducing the human costs wrought by the illness. Originality/value – Never before has architecture been so explicitly implicated as a cause of mental illness. This paper was presented to the Symposium of Mental Health Facility Design, and is essential reading for anyone involved in designing for improved mental health.

Comments on: "The role of the social environment in psychiatric research: Outstanding challenges and future directions by Dana March, James Kirkbride, Wim Veling"

On 17 March 2009, we hosted a live discussion of fresh new ideas in the epidemiology of schizophrenia. Discussion leaders Dana March of Columbia University, James Kirkbride of the University of Cambridge, and Wim Veling of Parnassia Psychiatric Institute delivered a wide-ranging discussion of social factors such as migration, ethnicity, and urbanicity, but also asked how this research could benefit from genetic insights. Finally, they discussed possible biological mechanisms that might transduce social factors into psychosis

Changes in cannabis use among psychotic clients without specialised substance use treatment

The need to address substance use among people with psychosis has been well established. However, treatment studies targeting substance use in this population have reported mixed results. Substance users with psychosis in no or minimal treatment control groups achieve similar reductions in substance use compared to those in more active substance use treatment, suggesting a role for natural recovery from substance use. This meta-analysis aims to quantify the amount of natural recovery from substance use within control groups of treatment studies containing samples of psychotic substance users, with a particular focus on changes in cannabis use. A systematic search was conducted to identify substance use treatment studies. Meta-analyses were performed to quantify reductions in the frequency of substance use in the past 30 days. Significant but modest reductions (mean reduction of 0.3–0.4 SD across the time points) in the frequency of substance use were found at 6 to 24 months follow up. The current study is the first to quantify changes in substance use in samples enrolled in no treatment or minimal treatment control conditions. These findings highlight the potential role of natural recovery from substance use among individuals with psychosis, although they do not rule out effects of regression to the mean. Additionally, the results provide a baseline from which to estimate likely changes or needed effects sizes in intervention studies. Future research is required to identify the processes underpinning these changes, in order to identify strategies that may better support self-management of substance use in people with psychosis.

The profile of psychiatric symptoms exacerbated by methamphetamine use

Background Methamphetamine use can produce symptoms almost indistinguishable from schizophrenia. Distinguishing between the two conditions has been hampered by the lack of a validated symptom profile for methamphetamine-induced psychiatric symptoms. We use data from a longitudinal cohort study to examine the profile of psychiatric symptoms that are acutely exacerbated by methamphetamine use. Methods 164 methamphetamine users, who did not meet DSM-IV criteria for a lifetime primary psychotic disorder, were followed monthly for one year to assess the relationship between days of methamphetamine use and symptom severity on the 24-item Brief Psychiatric Rating Scale. Exacerbation of psychiatric symptoms with methamphetamine use was quantified using random coefficient models. The dimensions of symptom exacerbation were examined using principal axis factoring and a latent profile analysis. Results Symptoms exacerbated by methamphetamine loaded on three factors: positive psychotic symptoms (suspiciousness, unusual thought content, hallucinations, bizarre behavior); affective symptoms (depression, suicidality, guilt, hostility, somatic concern, self-neglect); and psychomotor symptoms (tension, excitement, distractibility, motor hyperactivity). Methamphetamine use did not significantly increase negative symptoms. Vulnerability to positive psychotic and affective symptom exacerbation was shared by 28% of participants, and this vulnerability aligned with a past year DSM-IV diagnosis of substance-induced psychosis (38% vs. 22%, _2 (df1) = 3.66, p = 0.056). Conclusion Methamphetamine use produced a symptom profile comprised of positive psychotic and affective symptoms, which aligned with a diagnosis of substance-induced psychosis, with no evidence of a negative syndrome.