Manganese Intoxication

We have reported two cases of chronic manganese poisoning. Case 1 followed exposure to manganese fumes in cutting and burning manganese steel. Case 2 resulted from exposure to dusts of manganese dioxide, an ingredient used in glazing of ceramics. There were initial difficulties in establishing the correct diagnosis. Prominent clinical features were severe and persistent chronic depressive psychosis (Case 1), transient acute brain syndrome (Case 2) and the presence of various extrapyramidal symptoms in both cases.Manganese intoxication has not previously been reported as occurring in California. With increasing use of the metal, the disease should be considered in the differential diagnosis of neurologic and psychiatric disease.Our observations were made in the period 1964 through 1968. Recently the prognosis of victims of manganese poisoning has been improved dramatically by the introduction of levodopa as a therapeutic agent.     

Anti-Ri-associated paraneoplastic cerebellar degeneration. Report of a case and revision of the literature

Paraneoplastic cerebellar degeneration associated with anti-Ri antibodies mainly presents with opsoclonus-myoclonus-ataxia. We report here the case of a patient with anti-Ri-antibody paraneoplastic syndrome, who presented four years after treatment for small-cell lung cancer (SCLC) with oscillopsia and gait disorder. On neurological examination vertical nystagmus, ataxic gait and postural tremor of all four limbs was detected. He died one year after the onset of the symptoms because of a acute exacerbation of his severe chronic obstructive pulmonary disease. No SCLC relapse or new cancer has been detected during the one-year follow-up period.To our knowledge, our patient is the first case of anti-Ri associated disorder with oscillopsia and vertical nystagmus as the initially prominent clinical features. The findings of this case study support the variability of anti-Ri-antibody-associated paraneoplastic syndrome. Further studies must be directed to better characterize the mechanisms underlying this syndrome. Finally, paraneoplastic neurological syndromes should be kept in mind also when a neoplastic disease is not demonstrated.     

Improving outcomes of first‐episode psychosis: an overview

Outcomes of psychotic disorders are associated with high personal, familiar, societal and clinical burden. There is thus an urgent clinical and societal need for improving those outcomes. Recent advances in research knowledge have opened new opportunities for ameliorating outcomes of psychosis during its early clinical stages. This paper critically reviews these opportunities, summarizing the state‐of‐the‐art knowledge and focusing on recent discoveries and future avenues for first episode research and clinical interventions. Candidate targets for primary universal prevention of psychosis at the population level are discussed. Potentials offered by primary selective prevention in asymptomatic subgroups (stage 0) are presented. Achievements of primary selected prevention in individuals at clinical high risk for psychosis (stage 1) are summarized, along with challenges and limitations of its implementation in clinical practice. Early intervention and secondary prevention strategies at the time of a first episode of psychosis (stage 2) are critically discussed, with a particular focus on minimizing the duration of untreated psychosis, improving treatment response, increasing patients’ satisfaction with treatment, reducing illicit substance abuse and preventing relapses. Early intervention and tertiary prevention strategies at the time of an incomplete recovery (stage 3) are further discussed, in particular with respect to addressing treatment resistance, improving well‐being and social skills with reduction of burden on the family, treatment of comorbid substance use, and prevention of multiple relapses and disease progression. In conclusion, to improve outcomes of a complex, heterogeneous syndrome such as psychosis, it is necessary to globally adopt complex models integrating a clinical staging framework and coordinated specialty care programmes that offer pre‐emptive interventions to high‐risk groups identified across the early stages of the disorder. Only a systematic implementation of these models of care in the national health care systems will render these strategies accessible to the 23 million people worldwide suffering from the most severe psychiatric disorders.     

Vitamin E and neurologic function in man

Despite the well-known detrimental effect of vitamin E deficiency on the nervous system of many experimental animal models for decades, only over the past decade has vitamin E become recognized as essential for the maintenance of the structure and function of the human nervous system. This discovery of the neurologic role of vitamin E in man is due primarily to the identification of a degenerative neurologic syndrome in children and adults with chronic vitamin E deficiency caused by gastrointestinal diseases impairing fat and vitamin E absorption. A compelling body of clinical, neuropathologic, and therapeutic response evidence conclusively demonstrates that vitamin E deficiency is responsible for the neurologic disorder seen in such patients. In addition, an inborn error in vitamin E metabolism, the Isolated Vitamin E Deficiency Syndrome, causes vitamin E deficiency and similar neurologic degeneration in the absence of fat malabsorption. Guidelines for the evaluation and treatment of vitamin E deficiency in relevant clinical circumstances are provided. The possible role of vitamin E in treating other neurologic diseases is discussed.     

Tardive dyskinesia.

Tardive dyskinesia is a potentially irreversible syndrome of involuntary hyperkinetic movements that occur in predisposed persons receiving extended neuroleptic (antipsychotic) drug therapy. It is usually characterized by choreoathetoid dyskinesias in the orofacial, limb, and truncal regions, but subtypes of this syndrome may include tardive dystonia and tardive akathisia. Although the mechanisms underlying the pathogenesis and pathophysiology of this disorder are unproven, altered dopaminergic functions will likely play a role in any explanation of it. Tardive dyskinesia develops in 20% of neuroleptic-treated patients, but high-risk groups such as the elderly have substantially higher rates. Risk factors include age, female sex, affective disorders, and probably those without psychotic diagnoses, including patients receiving drugs with antidopaminergic activity for nausea or gastrointestinal dysfunction for extended periods. Total drug exposure is positively correlated with tardive dyskinesia risk. Management strategies include a careful evaluation of both the psychiatric and neurologic states, a broad differential diagnosis, and adjustment of neuroleptic agents to the lowest effective dose that controls psychosis and minimizes motor side effects. No drug therapy is uniformly safe and effective for treating this disorder. A favorable long-term outcome of improvement or resolution correlates with younger age, early detection, lower drug exposure, and duration of follow-up.     

Autistic-Like Traits in Adult Patients with Mood Disorders and Schizophrenia

Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of evaluating autistic-like traits/symptoms underlying adult-onset psychiatric disorders for the best-suited treatment. Further studies with a prospective design and larger samples are needed.     

Psychiatric morbidity in patients with alcoholic liver disease.

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients'' likelihood of complying with such advice.     

Psychotic mania in glucose-6-phosphate-dehydrogenase-deficient subjects

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with acute psychosis, catatonic schizophrenia, and bipolar disorders by previous inconclusive reports. A particularly disproportionate rate of enzyme deficiency was found in manic schizoaffective patients from 662 lithium patients surveyed in Sardinia. The purpose of this study was to describe clinical characteristics which may be potentially associated with G6PD deficiency. METHODS: Characteristics of episodes, course of illness, family pattern of illness, laboratory tests, and treatment response of 29 G6PD-deficient subjects with a Research Diagnostic Criteria diagnosis of manic schizoaffective disorder were abstracted from available records. RESULTS: The most peculiar pattern was that of acute recurrent psychotic manic episodes, mostly characterized by loosening of associations, agitation, catatonic symptoms, and/or transient confusion, concurrent hyperbilirubinemia, positive psychiatric family history, and partial response to long-term lithium treatment. CONCLUSIONS: A relationship between psychiatric disorder and G6PD deficiency is to be searched in the bipolar spectrum, particularly among patients with a history of acute episodes with psychotic and/or catatonic symptoms or with transient confusion.     

Treatment needs of prisoners with psychiatric disorders.

OBJECTIVE--To describe the prevalence of psychiatric disorder and the treatment needs of sentenced prisoners in England and Wales. DESIGN--Population survey based on a 5% sample of men serving prison sentences. SETTING--Sixteen prisons for adult males and nine institutions for male young offenders representative of all prisons in prison type, security levels, and length of sentences. SUBJECTS--406 young offenders and 1478 adult men, 404 and 1365 of whom agreed to be interviewed. MAIN OUTCOME MEASURES--History of psychiatric disorder, clinical diagnosis of psychiatrist, and required treatment. RESULTS--652 (37%) men had psychiatric disorders diagnosed, of whom 15 (0.8%) had organic disorders, 34 (2%) psychosis, 105 (6%) neurosis, 177 (10%) personality disorder, and 407 (23%) substance misuse. 52 (3%) were judged to require transfer to hospital for psychiatric treatment, 96 (5%) required treatment in a therapeutic community setting, and a further 176 (10%) required further psychiatric assessment or treatment within prison. CONCLUSIONS--By extrapolation the sentenced prison population includes over 700 men with psychosis, and around 1100 who would warrant transfer to hospital for psychiatric treatment. Provision of secure treatment facilities, particularly long term medium secure units, needs to be improved. Services for people with personality, sexual, and substance misuse disorders should be developed in both prisons and the health service.     

A functional polymorphism in the disrupted-in schizophrenia 1 gene is associated with chronic fatigue syndrome

AimsDisrupted-in schizophrenia 1 (DISC1), identified in a pedigree with a familial psychosis with the chromosome translocation (1:11), is a putative susceptibility gene for psychoses such as schizophrenia and major depressive disorder (MDD). Patients with chronic fatigue syndrome (CFS) report having continuous severe fatigue and many overlapping symptoms with MDD; however, the mechanism and effective treatment of CFS are still unclear. We focused on the overlapping symptoms between CFS and MDD and performed an association study of the functional single-nucleotide polymorphism (SNP) in the DISC1 gene with CFS.Main methodsVenous blood was drawn from CFS patients and controls and genomic DNA was extracted from the whole blood according to standard procedures. Ser704Cys DISC1 SNP was genotyped using the TaqMan 5′-exonuclease allelic discrimination assay.Key findingsWe found that the Cys704 allele of Ser704Cys SNP was associated with an increased risk of CFS development compared with the Ser704 allele.SignificanceDISC1 Ser704Cys might be a functional variant that affects one of the mechanisms implicated in the biology of CFS. Some patients with CFS showed a phenotype similar to that of patients with MDD, but further studies are needed to clarify the biological mechanism, because this study is of a rather preliminary nature. Despite the variety of patients with CFS, DISC1 Ser704Cys has an association with CFS, which may also suggest that DISC1 plays a central role in the induction of various psychiatric diseases.     

Neurologic disorders responsive to folic acid therapy.

Six women aged 31 to 70 years had folate deficiency and neuropsychiatric disorders. The three with acquired folate deficiency were depressed and had permanent muscular and intellectual fatigue, mild symptoms of restless legs, depressed ankle jerks, diminution of vibration sensation in the legs, stocking-type hypoesthesia and long-lasting constipation; D-xylos absorption was abnormal. The bone marrow was megaloblastic in only one patient, and she and one other had atrophy of the jejunal mucosa. The third was a vegan. All three recovered after folic acid therapy. The other three were members of a family with the restless legs syndrome, fatigability and diffuse muscular pain. One also had subacute combined degeneration of the spinal cord and kidney disease but no megaloblastosis; she improved spectacularly after receiving large daily doses of folic acid. The other two also had minor neurologic signs, controlled with 5 to 10 mg of folic acid daily. Unrecognized and treatable folate deficiency (with low serum folic acid values but normal erythrocyte folate values) may be the basis of a well defined syndrome of neurologic, psychiatric and gastroenterologic disorders, and the restless legs syndrome may represent the main clinical expression of acquired and familial (or inborn) folate deficiency in adults.     

Systems biology approach to Wilson’s disease

Wilson’s disease (WD) is a severe disorder of copper misbalance, which manifests with a wide spectrum of liver pathology and/or neurologic and psychiatric symptoms. WD is caused by mutations in a gene encoding a copper-transporting ATPase ATP7B and is accompanied by accumulation of copper in tissues, especially in the liver. Copper-chelation therapy is available for treatment of WD symptoms and is often successful, however, significant challenges remain with respect to timely diagnostics and treatment of the disease. The lack of genotype-phenotype correlation remains unexplained, the causes of fulminant liver failure are not known, and the treatment of neurologic symptoms is only partially successful, underscoring the need for better understanding of WD mechanisms and factors that influence disease manifestations. Recent gene and protein profiling studies in animal models of WD began to uncover cellular processes that are primarily affected by copper accumulation in the liver. The results of such studies, summarized in this review, revealed new molecular players and pathways (cell cycle and cholesterol metabolism, mRNA splicing and nuclear receptor signaling) linked to copper misbalance. A systems biology approach promises to generate a comprehensive view of WD onset and progression, thus helping with a more fine-tune treatment and monitoring of the disorder.     

The impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management

Sexual dysfunction often accompanies severe psychiatric illness and can be due to both the mental disorder itself and the use of psychotropic treatments. Many sexual symptoms resolve as the mental state improves, but treatment‐related sexual adverse events tend to persist over time, and are unfortunately under‐recognized by clinicians and scarcely investigated in clinical trials. Treatment‐emergent sexual dysfunction adversely affects quality of life and may contribute to reduce treatment adherence. There are important differences between the various compounds in the incidence of adverse sexual effects, associated with differences in mechanisms of action. Antidepressants with a predominantly serotonergic activity, antipsychotics likely to induce hyperprolactinaemia, and mood stabilizers with hormonal effects are often linked to moderate or severe sexual dysfunction, including decreased libido, delayed orgasm, anorgasmia, and sexual arousal difficulties. Severe mental disorders can interfere with sexual function and satisfaction, while patients wish to preserve a previously satisfactory sexual activity. In many patients, a lack of intimate relationships and chronic deterioration in mental and physical health can be accompanied by either a poor sexual life or a more frequent risky sexual behaviour than in the general population. Here we describe the influence of psychosis and antipsychotic medications, of depression and antidepressant drugs, and of bipolar disorder and mood stabilizers on sexual health, and the optimal management of patients with severe psychiatric illness and sexual dysfunction.     

Evidence for a Shared Etiological Mechanism of Psychotic Symptoms and Obsessive-Compulsive Symptoms in Patients with Psychotic Disorders and Their Siblings

The prevalence of obsessive-compulsive disorder in subjects with psychotic disorder is much higher than in the general population. The higher than chance co-occurrence has also been demonstrated at the level of subclinical expression of both phenotypes. Both extended phenotypes have been shown to cluster in families. However, little is known about the origins of their elevated co-occurrence. In the present study, evidence for a shared etiological mechanism was investigated in 3 samples with decreasing levels of familial psychosis liability: 987 patients, 973 of their unaffected siblings and 566 healthy controls. The association between the obsessive-compulsive phenotype and the psychosis phenotype c.q. psychosis liability was investigated. First, the association was assessed between (subclinical) obsessive-compulsive symptoms and psychosis liability. Second, in a cross-sib cross-trait analysis, it was examined whether (subclinical) obsessive-compulsive symptoms in the patient were associated with (subclinical) psychotic symptoms in the related unaffected sibling. Evidence was found for both associations, which is compatible with a partially shared etiological pathway underlying obsessive-compulsive and psychotic disorder. This is the first study that used a cross-sib cross-trait design in patients and unaffected siblings, thus circumventing confounding by disease-related factors present in clinical samples.     

Psychological aspects of lower urinary tract infections in women.

OBJECTIVE--To determine whether women with the urethral syndrome can be distinguished from those with urinary tract infection by case notes, clinical symptoms, or psychiatric state. DESIGN--Longitudinal survey of consecutive women presenting with dysuria and frequency. SETTING--General practice and community. SUBJECTS--58 patients with the urethral syndrome and 44 patients with a urinary tract infection, mean age 39.9 years. MAIN OUTCOME MEASURES--Results of analysis of serial midstream urine specimens, patients'' self rated physical symptoms and responses to 60 item general health questionnaire at presentation and after resolution of symptoms, and results of psychiatric assessment with the clinical psychiatric interview. RESULTS--4 of 42 patients with a urinary tract infection had recently changed sexual partner compared with none of 58 with the urethral syndrome. Dysuria and nocturia were more common in patients with urinary tract infections than those with the urethral syndrome (mean (SD) score for dysuria 5.37 (2.39) v 4.57 (2.13), p less than 0.05; nocturia in 39/44 (88%) patients v 40/58 (69%), chi 2 = 5.5, p less than 0.02). Both groups showed transient high levels of distress which resolved with the physical symptoms, but no psychiatric difference distinguished them. CONCLUSION--The urethral syndrome is not associated with increased psychiatric morbidity.     

Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome.

OBJECTIVE: To test the efficacy of a graded aerobic exercise programme in the chronic fatigue syndrome. DESIGN: Randomised controlled trial with control treatment crossover after the first follow up examination. SETTING: Chronic fatigue clinic in a general hospital department of psychiatry. SUBJECTS: 66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep disturbance. INTERVENTIONS: Random allocation to 12 weeks of either graded aerobic exercise or flexibility exercises and relaxation therapy. Patients who completed the flexibility programme were invited to cross over to the exercise programme afterwards. MAIN OUTCOME MEASURE: The self rated clinical global impression change score, "very much better" or "much better" being considered as clinically important. RESULTS: Four patients receiving exercise and three receiving flexibility treatment dropped out before completion. 15 of 29 patients rated themselves as better after completing exercise treatment compared with eight of 30 patients who completed flexibility treatment. Analysis by intention to treat gave similar results (17/33 v 9/33 patients better). Fatigue, functional capacity, and fitness were significantly better after exercise than after flexibility treatment. 12 of 22 patients who crossed over to exercise after flexibility treatment rated themselves as better after completing exercise treatment 32 of 47 patients rated themselves as better three months after completing supervised exercise treatment 35 of 47 patients rated themselves as better one year after completing supervised exercise treatment. CONCLUSION: These findings support the use of appropriately prescribed graded aerobic exercise in the management of patients with the chronic fatigue syndrome.     

Prise en charge du premier épisode psychotique : le patient partenaire

Early recognition and effective management of the first episode of psychosis in a patient with schizophrenia or schizoaffective disorder is key in preventing further psychotic episodes. Patients’ denial of illness makes it difficult to establish early diagnosis and makes them unwilling to accept treatment after first episodes of psychosis. Many different reasons lead to poor compliance, resulting in high relapse rates within five years of recovery from the first episode, the risk of suicide, increased risk of violence, and increased impairment of occupational and social functioning. Second generation antipsychotic drugs prescribed at the early stages of illness represents a major advancement in the management of schizophrenia, with a lower propensity to develop extrapyramidal symptoms and tardive dyskinesia. These agents have become the preferred treatment option in most patients. Low doses of these medications at the early stages of the illness appear to help patients accept their illnesses better in the medium and long terms. Long-acting injectable formulations of atypical antipsychotic drugs (long-acting risperidone injection) offer the benefit of the efficacy and tolerance of the newer agents, together with the security of consistent delivery. This new potential treatment option for first-episode psychosis patients is the focus of this review. However, the advantages of such formulations clearly depend on patient acceptance of an injection and family support. Therefore, the attitude of the medical team impacts the patient’s attitude toward the injection. More attention must be focused on user and provider attitudes as well as treatment satisfaction. However, important issues must still be addressed, including the need for better solutions that address treatment non-compliance.     

Longitudinal study of outcome of chronic fatigue syndrome.

OBJECTIVE--To examine the predictors of long term outcome for patients with the chronic fatigue syndrome. DESIGN--Cohort study. SUBJECTS--139 subjects previously enrolled in two treatment trials; 103 (74%) were reassessed a mean of 3.2 years after start of the trials. SETTING--University hospital referral centre. MAIN OUTCOME MEASURES--Age at onset, duration of illness, psychological and immunological status at initial assessment. Ongoing symptom severity, levels of disability, and immunological function at follow up. RESULTS--65 subjects had improved but only six reported no current symptoms. An alternative medical diagnosis had been made in two and psychiatric illness diagnosed in 20. The assignment of a primary psychiatric diagnosis at follow up and the strength of the belief that a physical disease process explained all symptoms at entry to the trials both predicted poor outcome. Age at onset of illness, duration of illness, neuroticism, premorbid psychiatric diagnoses, and cell mediated immune function did not predict outcome. CONCLUSION--Though most patients with the chronic fatigue syndrome improve, a substantial proportion remain functionally impaired. Psychological factors such as illness attitudes and coping style seem more important predictors of long term outcome than immunological or demographic variables.     

Tourette syndrome: clinical and psychological aspects of 250 cases.

Tourette syndrome is a common hereditary neuropsychiatric disorder consisting of multiple tics and vocal noises. We summarize here clinical aspects of 250 consecutive cases seen over a period of 3 years. The sex ratio was four males to one female, and the mean age of onset was 6.9 years. Only 10% were Jewish, indicating that it is not more prevalent in Ashkenazi Jews. Only 33% had compulsive swearing (coprolalia), indicating that this is not necessary for the diagnosis. The most frequent initial symptoms were rapid eye-blinking, facial grimacing, and throat-clearing. In this series, it was clear that Tourette syndrome is a psychiatric as well as a neurological disorder. Significant discipline problems and/or problems with anger and violence occurred in 61%, and 54% had attention-deficit disorder with hyperactivity. Some degree of exhibitionism was present in 15.9% of males and 6.1% of females. Obsessive-compulsive behavior was seen in 32%. Other than tics and vocal noises, the most common parental complaints were of short temper and everything being a confrontation. There were no significant clinical differences between familial and sporadic cases. Whenever a child presents with a learning disorder, attention-deficit disorder, or significant discipline or emotional problems, the parents should be questioned about the presence of tics or vocal noises in the patient and other family members.