New approach in the diagnosis and therapy of hyperphenylalaninemia

Background. Phenylketonuria is the most prevalent inborn error of aminoacid metabolism. Is an autosomal recessive disorder. It results from mutations in the phenylalanine hydroxilase (PAH) gene. Phenotypes can vary from mild hyperphenylalaninemia to a severe phenylketonuria wich, if untreated, results in severe mental retardation. Thanks to neonatal screening programmes, early detection and promp dietetic intervention (phenylalanine restricted diet lifelong) has allowed to avoid neurocognitive complications. Recently, a new therapy is become widely used: the oral supplementation with the PAH cofactor (BH4), wich can alleviate the diet burden. Genotype-phenotype correlation is a reliable tool to predict metabolic phenotype in order to establish a better tailored diet and to assess the potential responsiveness to BH4 therapy. Aim Molecular analysis of the PAH gene, evaluation of genotype-phenotype correlation and prediction of BH4 responsiveness in a group of HPA patients living in Emilia Romagna. Patients and methods. We studied 48 patients affected by PAH deficiency in regular follow-up to our Metabolic Centre. We performed the molecular analysis of these patients using genomic DNA extracted from peripheral blood samples Results. We obtained a full genotipic characterization of 46 patients. We found 87 mutant alleles and 35 different mutations, being the most frequent IVS10-11 G>A (19.3%), R261Q (9.1%), R158Q (9.1%), R408Q (6.8%) and A403V (5.7%), including 2 new ones (L287, N223Y) ever described previously. Notably, we found 15 mutations already identified in BH4-responsive patients, according to the literature. We found 42 different genotipic combinations, most of them in single patients and involving a BH4-responsive mutation. Conclusion. BH4 responsiveness is shown by a consistent number of PAH deficient hyperphenylalaninemic patients. This treatment, combined with a less restricted diet or as monotherapy, can reduce nutritional complications and improve the quality of life of these patients.

Im/possible Lives: Gender, Class, Self-Fashioning, and Affinal Solidarity in Modern South Asia

Drawing on ethnographic research and employing a micro-historical approach that recognizes not only the transnational but also the culturally specific manifestations of modernity, this article centers on the efforts of a young woman to negotiate shifting and conflicting discourses about what a good life might consist of for a highly educated and high caste Hindu woman living at the margins of a nonetheless globalized world. Newly imaginable worlds in contemporary Mithila,South Asia, structure feeling and action in particularly gendered and classed ways, even as the capacity of individuals to actualize those worlds and the “modern” selves envisioned within them are constrained by both overt and subtle means. In the context of shifting cultural anchors, new practices of silence, literacy, and even behaviors interpreted as “mental illness” may become tactics in an individual’s negotiation of conflicting self-representations. The confluence of forces at play in contemporary Mithila, moreover, is creating new structures of feeling that may begin to reverse long-standing locally held assumptions about strong solidarities between natal families and daughters, on the one hand, and weak solidarities between affinal families and new daughters-in-law, on the other.

The Blue Of

When I first started my thesis, I intended for my finished project to be a compilation of poems that aims to reflect and reveal several repeating themes of our society's collective unconscious, such as the relationship between the physical and spiritual aspects of being and the representation of women's lives, organized religion,adolescence, and mental illness. I proposed writing a chapbook of poetry that reflects an exploration of, and sensitivity to, the human unconscious mind, fears, and desires. Consulting other works of surreal, lyric, and confessional poetry, I sought to personallydevelop as both a poet and a psychology student. I made a conscious effort to avoid trying to attach a specific 'meaning' to each poem. I understand that, in poetry, the reader is never entirely aware of exactly what the poet is trying to convey. All the reader knows is what he or she sees in a given poem and how he or she responds to that poem. However, through working on my thesis I discovered that, while meaning may not be intentional in the drafting process, developing what the poem meant to me was central to the process of revision. Furthermore, I realized that I unconsciously returned to specific themes across various poems, something that was not apparent to me until I re-read my entire collection ...

Botulinum Toxin Type A for the Treatment of Equinus Deformity in to Patients With Mucopolysaccharidosis Type II

Mucopolysaccharidoses are lysosomal storage disorders that are caused by a deficiency in the enzymes that degrade glycosaminoglycans. The accumulation of glycosaminoglycans affects multiple systems, resulting in coarse facial features, short stature, organomegaly, and variable neurological changes from normal intelligence to severe mental retardation and spasticity. Effects on the musculoskeletal system include dysostosis multiplex, joint stiffness, and muscle shortening. This article reports 2 patients with mucopolysaccharidosis type II (Hunter syndrome) who showed progressive equinus deformity of the feet. Both patients were treated with intramuscular botulinum toxin type A injections in the gastrocnemius and the soleus muscles, followed by serial casting. In both patients, passive range of motion, muscle tone, and gait performance were significantly improved. Botulinum toxin type A injections followed by serial casting are a therapeutic option for contractures in patients with mucopolysaccharidosis. However, the long-term effects and the effect of application in other muscles remain unknown.

The Cultural Construction Of Posttraumatic Stress Disorder: Sociopolitical Responses To Psychological Trauma In American And Vie

In my thesis, I incorporate both psychological research and personal narratives in order to explain why, in the aftermath of the Vietnam War, the United States officially recognized Post-Traumatic Stress Disorder while the Vietnamese government did not. The absence of Vietnamese studies on the impact of PTSD on veterans, in comparison to the abundance of research collected on American soldiers, is reflective not of a disparity in the actual prevalence of the disorder, but of the influence of political policy on the scope of Vietnamese psychology. Personal narratives from Vietnamese civilians and soldiers thus reveal accounts of trauma otherwise hidden due to the absence of Vietnamese psychological research. Although these two nations conspicuously differed in their respective responses to the prevalence of psychological trauma in war veterans, these responses demonstrated that both the recognition and rejection of PTSD was a result of sociopolitical factors: political ideologies, rather than scientific reasons, dictated whether the postwar trajectory of psychological research focused on fully exploring the impact of PTSD on veteran populations. The association of military defeat with psychological trauma thus fixed attention on certain groups of veterans, including former American and South Vietnamese soldiers, while ignoring the impact of trauma on veterans of the Viet Cong and North Vietnamese Army. The correlation of a soldier¿s ideological background with psychological trauma, rather than exposure to actual traumatic experiences, demonstrates that cultural and sociopolitical factors are far more influential in the construction of PTSD than objective indicators of the disorder¿s prevalence. Culturally-constructed responses to disorders such as PTSD therefore account for the subjective treatment of mental illness. The American and Vietnamese responses to veterans suffering from PTSD both demonstrated that the evidence of mental health problems in an individual does not guarantee an immediate or appropriate diagnosis and treatment regimen. External authorities whose primary aims are not necessarily concerned with the objective treatment of all victims of mental illness subjectively dictate mental health care policy, and therefore risk ignoring or marginalizing the needs of individuals in need of proper treatment.

[How can the mentally ill achieve sustained employment? Supported employment versus pre-vocational training]

People with severe mental disorders are often without work, although work may have a positive effect on their health. The paper presents some results in this field from the German S3 guidelines on psychosocial therapies. In terms of evidence-based medicine supported employment (SE - first place then train) has proven to be most effective. Nevertheless, SE is still rare in Germany. Pre-vocational training, however, follows the concept first train then place and is offered in rehabilitation of the mentally ill (RPK) centres in Germany. There is some evidence that the programs are beneficial for users. The UN Convention for the Rights of Persons with Disabilities outlines an obligation for work on an equal basis with others and for vocational training. So far, the German mental health system only partly meets these requirements.

Changing ‘Multi-Problem Families’ – Developing a Multi-Contextual Systemic Approach

Over the past 30 years the Marlborough Family Service in London has pioneered multi-family work with marginalized families presenting simultaneously with abuse and neglect, family violence, substance misuse, educational failure and mental illness. The approach is based on a systemic multi-contextual mode and this chapter describes the evolving work, including the establishment of the first permanent multiple family day setting, specifically designed for and solely dedicated to the work with seemingly ‘hopeless’ families. The ingredients of ‘therapeutic assessments’ of parents and families are outlined and the importance of initial network meetings with professionals and family members is emphasized.

Physician perceptions of risk regarding mood disorders and pharmacological management during pregnancy: What is current practice?

Mood disorders are the most common form of mental illness and one of the leading causes of morbidity worldwide. Major depressive disorder and bipolar disorder have a lifetime prevalence of 16.2% and 4.4%, respectively. Women comprise a substantial proportion of this population, and an estimated 500,000 pregnancies each year involve women with a psychiatric condition. Management with psychotropic medications is considered standard of care for most patients with mood disorders. However, many of these medications are known human teratogens. Because pregnant women with mood disorders face a high risk of relapse if unmanaged, the obstetrician faces a unique challenge in providing the best care to both mother and baby. It has been suggested that many obstetricians overestimate the teratogenic risks associated with psychotropic medications, while concurrently underestimating the risks associated with unmanaged mood disorders. This may be due a knowledge gap regarding the most current teratogen information, and lack of official management guidelines. Therefore, the purpose of this study is to determine the current knowledge base of obstetricians regarding the teratogenic effects of common psychotropic medications, as wells as to capture current management practices for pregnant women with mood disorders. A total of 117 Texas obstetricians responded to a survey regarding teratogen knowledge and management practice. It was common for respondents to encounter women who disclose both having a mood disorder and taking a psychotropic medication during pregnancy. Many respondents did not utilize up-to-date drug counseling resources, and were unaware of or over-estimated the teratogenic risks of common medications used to treat mood disorders. Finally, many respondents reported wanting to refer pregnant patients with mood disorders to psychiatrists for co-management, but are reportedly restricted in doing so due to accessibility or insurance issues. This study demonstrates that there is a knowledge gap among obstetricians regarding the teratogenicity of common psychotropic medications utilized to manage a patient population they frequently encounter. Further, obstetricians have vastly different risk perceptions of these medications, resulting in various management approaches and recommendations. Future research should focus on establishing standard practice guidelines, as well as better accessibility to psychiatric services for pregnant women.

Characteristics and experiences of past participants in the Texas Peer Assistance Program for Nurses

There are nearly 200,000 licensed practicing nurses in the state of Texas, representing one-tenth of the nations' workforce. The prevalence of substance abuse among nurses is estimated to range between six and 20 percent in this professional group.^ Since March 1987, the Texas Peer Assistance Program for Nurses (TPAPN) has offered intervention, education, support and monitoring to nurses in Texas whose practice has become impaired due to substance abuse and/or mental illness. Since then approximately 44 percent of nurses who voluntarily signed participation agreements successfully completed the program; fifty-six percent have not. One determinant of completion for those nurses identified as chemically dependent is abstinence from mood altering substances. Other helping professions report higher rates of abstinence two years following treatment.^ The purpose of this study was to investigate the relationship between relapse, demographics, treatment variables, work setting, "stress" indicators and support factors for nurses who participated in TPAPN. A questionnaire was mailed to 1000 randomly selected nurses who had signed agreements since 1987 and were no longer active in the program. More than 41% of the questionnaires were returned undeliverable.^ Recipients of the questionnaire were known only to TPAPN, never to the investigator. All information was received anonymously except when the participant chose to sign the questionnaire. A cover letter explaining the study and inviting participation was enclosed. Completion and return of the questionnaire was considered consent to participate.^ Findings demonstrated a significant relationship between relapse and opiates as the drug of choice for past participants in the Texas Peer Assistance Program for Nurses. Significant associations were found among factors such as control at work, support, physical complaints, job security, self-esteem and employment in this sample. Respondents shared copious written comments about their experiences in TPAPN. These data were analyzed using qualitative methods and compared with similar studies of recovering nurses. Further research with nurses whose practice has been affected by abuse of chemical and mental illness is warranted. ^

Psychiatric severity and behavior change in alcoholism

Individuals who are diagnosed with a chronic mental illness and an alcohol use disorder comprise a high risk population that challenges the mental health care system. Effective treatment for the dually diagnosed, who are characterized by heterogeneity in their psychiatric diagnoses, their substance use patterns, and their current degree of dysfunction, presents a challenge. Several integrated treatment models have been developed that attempt to concurrently treat patients' psychiatric and substance abuse problems. At this point in the development of these "dual diagnosis" programs, treatment planning is hindered by a lack of knowledge about the relation of psychiatric severity to the process of recovery from alcohol abuse and dependence.^ The present study sought to advance the field's understanding of the relation between psychiatric severity and the process of behavior change through an examination of the relation between dimensions of psychiatric severity and Prochaska and DiClemente's Transtheoretical Model (TTM) constructs. The TTM, which focuses on identifying the processes of change that appear to underlie the modification of addictive behaviors, provides a way of conceptualizing and measuring specific elements relevant to the desired behavior change. Knowledge of the relation between these constructs and psychiatric severity will enable treatment planners to develop dual diagnosis programs which target clients' needs with a much higher level of specificity.^ One hundred-thirty two alcohol dependent patients in a dual diagnosis treatment program were assessed on psychiatric severity (defined as number of symptoms and level of distress resulting from symptoms) and the Transtheoretical Model constructs. The constructs include stages and processes of change for alcohol use, alcohol decisional balance, and alcohol abstinence self-efficacy. Results indicate that the TTM variable of "temptation to drink" is most strongly related to psychiatric severity: the more psychiatric distress a person is experiencing, the more he or she is tempted to drink. The "cons" of drinking were also related to psychiatric severity, indicating that participants who were experiencing more psychiatric distress also endorsed as important a higher number of the negative aspects of drinking.^ Additional aims of this investigation were to determine whether participants' scores on the Transtheoretical Model variables were associated with their: (a) severity of drinking, defined as frequency, quantity and consequences of use, (b) previous psychiatric and substance abuse treatment episodes, and (c) functional impairment. Associations were found among these variables and each of the key constructs of the Transtheoretical Model. Each association is explored in detail and implications for treatment programming are discussed. ^

WHEN DOES THE TROUBLE START? OBESITY, DIABETES RISKS AND METABOLIC DISTURBANCES IN YOUNG PEOPLE WITH PSYCHOSIS

People with psychotic disorders have higher mortality rates compared to the general population. Most deaths are due to cardiovascular (CV) disease, reflecting high rates of CV risk factors such as obesity and diabetes. Treatment with antipsychotic drugs is associated with weight gain in clinical trials. However, there is little information about how these drugs affect children and young people, and how early in the course of treatment the elevation in CV risk factors begins. This information is essential in understanding the costs and benefits of these treatments in young people, and establishing preventive and early intervention services to address physical health comorbidities. This symposium reports both prospective and naturalistic data from children and adolescents treated with antipsychotic drugs. These studies demonstrate that adverse effects on cardiometabolic measures, notably BMI and insulin resistance, become apparent very soon after treatment is initiated. Further, children and adolescents appear to be even more sensitive to these effects than adults. Population-wide studies are also informative. Danish data showing that young people exposed to antipsychotics have a higher risk of diabetes, compared with young people who had a psychiatric diagnosis but were not exposed to antipsychotic drugs, will be presented. In addition, an Australian comparison between a large, nationally representative sample of people with psychosis and a general population sample shows that higher rates of obesity and other cardiometabolic abnormalities are already evident in people with psychosis by the age of 25 years. Young people living with psychosis are already disadvantaged by the demands of living with mental illness, stigma, and social factors such as unemployment and low income. The addition of obesity, diabetes and other comorbidities adds a further burden. The data presented highlights the need for careful selection of antipsychotic drugs, regular monitoring of physical health and early intervention when weight gain, glucose dysregulation, or other cardiometabolic abnormalities are detected.

High-Dose Benzodiazepine Dependence: A Qualitative Study of Patients' Perceptions on Initiation, Reasons for Use, and Obtainment

BACKGROUND High-dose benzodiazepine (BZD) dependence is associated with a wide variety of negative health consequences. Affected individuals are reported to suffer from severe mental disorders and are often unable to achieve long-term abstinence via recommended discontinuation strategies. Although it is increasingly understood that treatment interventions should take subjective experiences and beliefs into account, the perceptions of this group of individuals remain under-investigated. METHODS We conducted an exploratory qualitative study with 41 adult subjects meeting criteria for (high-dose) BZD-dependence, as defined by ICD-10. One-on-one in-depth interviews allowed for an exploration of this group's views on the reasons behind their initial and then continued use of BZDs, as well as their procurement strategies. Mayring's qualitative content analysis was used to evaluate our data. RESULTS In this sample, all participants had developed explanatory models for why they began using BZDs. We identified a multitude of reasons that we grouped into four broad categories, as explaining continued BZD use: (1) to cope with symptoms of psychological distress or mental disorder other than substance use, (2) to manage symptoms of physical or psychological discomfort associated with somatic disorder, (3) to alleviate symptoms of substance-related disorders, and (4) for recreational purposes, that is, sensation-seeking and other social reasons. Subjects often considered BZDs less dangerous than other substances and associated their use more often with harm reduction than as recreational. Specific obtainment strategies varied widely: the majority of participants oscillated between legal and illegal methods, often relying on the black market when faced with treatment termination. CONCLUSIONS Irrespective of comorbidity, participants expressed a clear preference for medically related explanatory models for their BZD use. We therefore suggest that clinicians consider patients' motives for long-term, high-dose BZD use when formulating treatment plans for this patient group, especially since it is known that individuals are more compliant with approaches they perceive to be manageable, tolerable, and effective.

Role of calcium, glutamate and NMDA in major depression and therapeutic application

Major depression is a common, recurrent mental illness that affects millions of people worldwide. Recently, a unique fast neuroprotective and antidepressant treatment effect has been observed by ketamine, which acts via the glutamatergic system. Hence, a steady accumulation of evidence supporting a role for the excitatory amino acid neurotransmitter (EAA) glutamate in the treatment of depression has been observed in the last years. Emerging evidence indicates that N-methyl-D-aspartate (NMDA), group 1 metabotropic glutamate receptor antagonists and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) agonists have antidepressant properties. Indeed, treatment with NMDA receptor antagonists has shown the ability to sprout new synaptic connections and reverse stress-induced neuronal changes. Based on glutamatergic signaling, a number of therapeutic drugs might gain interest in the future. Several compounds such as ketamine, memantine, amantadine, tianeptine, pioglitazone, riluzole, lamotrigine, AZD6765, magnesium, zinc, guanosine, adenosine aniracetam, traxoprodil (CP-101,606), MK-0657, GLYX-13, NRX-1047, Ro25-6981, LY392098, LY341495, D-cycloserine, D-serine, dextromethorphan, sarcosine, scopolamine, pomaglumetad methionil, LY2140023, LY404039, MGS0039, MPEP, 1-aminocyclopropanecarboxylic acid, all of which target this system, have already been brought up, some of them recently. Drugs targeting the glutamatergic system might open up a promising new territory for the development of drugs to meet the needs of patients with major depression.

Internet-based self-help for schizophrenia – risks and chances

Purpose: Schizophrenia is a severe mental disorder which is accompanied by an enormous individual and societal burden. Despite established efficacy of cognitive behavioral therapy (CBT) for schizophrenia, its dissemination into routine mental health care remains poor. Internet-based cognitive behavioral therapy in a self-help format helps to narrow the treatment gap in many mental disorders. Are Internet-based self-help programs, which are based on the principles of CBT, also feasible and viable for patients with schizophrenia? Methods: Mental health professionals (target N=50) as well as individuals with schizophrenia spectrum disorders (target N=50) reported their opinion regarding potential chances and risks of Internet-based self-help for schizophrenia in an online survey. Results: The preliminary data analysis of n=30 health professionals revealed a general acceptance of Internet-based programs for schizophrenia (53% acceptable, 47% acceptable after empirical evaluation) and specific contraindications (e.g., severe psychotic symptoms; 73%). People with schizophrenia highlighted the attractiveness of self-help interventions due to a wish for empowerment and for opportunities to strengthen self-efficacy. Conclusions: Risks, limitations and chances of Internet-based programs for patients with schizophrenia will be discussed.

Translation and cultural adaptation of the Stigma-Devaluation scale for use among family caregivers of mentally ill relatives in Jordan

Background/significance. Mental illness stigma is a matter of great concern to family caregivers. Few research studies have been conducted in the Arab World on family caregivers' perception of stigma associated with caring for a mentally ill relative. Review of the literature on measurement of the concept of stigma related to caring for a mentally ill relative yielded no instrument appropriate for use in a Jordanian sample. Reliable and valid instruments to measure stigma perception among family caregivers are needed for research and practice, particularly in Arabic speaking populations. ^ Purpose. The purposes of this study were: (1) translate the Stigma-Devaluation scale (SDS) into Arabic, modifying it to accurately reflect the cultural parameters specific to Jordan, and (2) test the reliability, the content and construct validity of the Arabic version of the SDS for use among a sample of family members of mentally ill relatives in Jordan. ^ Design. Methodologic, cross-sectional. ^ Methods. The SDS was translated into Arabic language, modified and culturally adapted to the Jordanian culture by a translation model which incorporates a cultural adaptation process. The Arabic SDS was evaluated in a sample of 164 family caregivers in the outpatient mental health clinic in Irbid-Jordan. Cronbach's alpha estimation of internal consistency was used to assess the reliability of the SDS. Construct validity was determined by confirmatory factor analysis (CFA). Measurements of content validity and reading level of the Arabic SDS were included. ^ Findings. Content Validity Index was determined to be 1.0. Reading level of the Arabic SDS was considered at a 6th grade or lower Cronbach's alpha coefficient of the modified Arabic SDS total scale was .87. Initial results of CFA did not fully support the proposed factor structures of the SDS or its subscales. After modifications, the indices indicated that the modified model of each subscale had satisfactory fit. ^ Conclusion. This study provided psychometric evidence that the modified Arabic SDS translated and culturally adapted instrument, is valid and conceptually consistent with the content of the original English SDS in measuring stigma perception among families of mentally ill relatives in Jordan. ^