Schizophrenia and multiple sclerosis

Similarities in clinical course, age of onset, geographical distribution, and immunological responses of patients with schizophrenia and multiple sclerosis (MS) suggest that these two common illnesses of young adults may belong to a similar class of disorders. This review examines some of the similarities and differences between these two disorders and suggests that epidemiological, immunological, and viral studies considered useful in the investigation of causal factors in multiple sclerosis may also be pertinent to the search for causes of schizophrenia.     

Multiple sclerosis and affective disorders

Affective disorders occurring in association with multiple sclerosis have been attributed both to the psychosocial impact of a chronic disabling illness and to the structural lesions of cerebral demyelination. A review of research evidence suggests that while there is a correlation between chronic depressive symptoms and both progressive disability and lack of social support, acute major depressive and manic episodes may be psychiatric manifestations of demyelinating lesions and may be the initial presenting symptoms of multiple sclerosis. Anti-inflammatory agents may be required in the management of acute psychiatric symptoms despite the fact that these agents have a propensity to precipitate psychotic episodes. Two case reports are presented to illustrate the clinical challenge of distinguishing between organic and functional affective illness in patients with multiple sclerosis. The interplay between biological and psychological aspects of multiple sclerosis in precipitating affective disorders is discussed, with implications for patient assessment and management.     

The comorbidity of anxiety disorders with personality,depressive, alcohol and drug disorders

Anxiety disorders seldom exist in isolation from personality traits and disorders, from depressive symptomatology, and from alcohol and drug use and abuse. This review examines the relationships between anxiety disorders and these often comorbid psychiatric disorders. While diagnostic systems such as DSM-III-R which describe multiple, discrete disorders highlight comorbidity and may have value for treatment outcome and other studies, they appear unlikely to generate useful aetiological explanations of the considerable overlap of psychiatric symptomatology seen in anxiety disorder patients.     

Disorders of muscle lipid metabolism: Diagnostic and therapeutic challenges

Disorders of muscle lipid metabolism may involve intramyocellular triglyceride degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or fatty acid β-oxidation. Three main diseases leading to permanent muscle weakness are associated with severe increased muscle lipid content (lipid storage myopathies): primary carnitine deficiency, neutral lipid storage disease and multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein deficiencies, and in recently described phosphatidic acid phosphatase deficiency. Respiratory chain disorders and congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation disorders due to the presence of secondary muscle lipidosis. The main biochemical tests giving clues for the diagnosis of these various disorders are measurements of blood carnitine and acylcarnitines, urinary organic acid profile, and search for intracytoplasmic lipid on peripheral blood smear (Jordan’s anomaly). Genetic analysis orientated by the results of biochemical investigation allows establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency may be treated after supplementation with carnitine, riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation disorders are currently developed, based on pharmacological treatment with bezafibrate, and specific diets enriched in medium-chain triglycerides or triheptanoin.     

Transient movement disorders and multiple sclerosis

Movement disorders associated with multiple sclerosis (MS) are uncommon, except for tremor. We report two patients with relapsing-remitting MS, who developed either dystonia or chorea during clinical exacerbation of their MS. The movement disorders resolved during treatment with adrenocorticotropin hormone (ACTH). Acute exacerbations of MS may be associated with transient movement disorders, which are responsive to ACTH.     

Overlap of gastrointestional symptom complexes in a US community

BACKGROUND: Although the Rome criteria define a number of individual functional gastrointestinal disorders, people may have symptoms of multiple disorders at the same time. In addition, therapies may be effective in subsets of people with specific disorders, yet at the same time help people with multiple disorders. AIM: To estimate the prevalence of combinations of gastrointestional (GI) symptom complexes. METHODS: A valid self report questionnaire which records GI symptoms was mailed to an age- and gender-stratified random sample of Olmsted County, MN residents aged 30-64 years. Standard definitions were used to identify people with gastro-oesophageal reflux, dyspepsia, irritable bowel syndrome (IBS), constipation and diarrhoea. The prevalence of people meeting multiple symptom complexes was estimated. Specifically, combinations of dyspepsia, IBS and constipation were compared to dyspepsia, IBS and diarrhoea. RESULTS: A total of 657 (69%) of 943 eligible subjects responded; 643 provided data for each of the necessary symptom questions. Each two-way combination of symptom group was present in between 4 and 9% of the population; each three-way combination was present in 1-4% of the population. The overlap between dyspepsia, IBS and constipation was similar to dyspepsia, IBS and diarrhoea, except body mass index was higher in the diarrhoea overlap group (P = 0.03). CONCLUSION: Symptom complex overlap is common in the community; for each condition, the majority of sufferers reported an additional symptom complex. This overlap of symptoms challenges the current paradigm that functional GI disorders represent multiple discreet entities.     

Medical emergency department utilization patterns among uninsured patients with psychiatric disorders

OBJECTIVE: This study examined medical emergency department utilization for patterns among uninsured patients with psychiatric disorders. METHODS: Billing records of 15,672 uninsured adult patients treated in the emergency department of an academic medical center in southeast Texas over a 12-month period were analyzed for information on demographic characteristics, diagnosis, number of emergency department visits, and hospitalization. RESULTS: Overall, 11.8% of the population was diagnosed as having at least one psychiatric disorder during an emergency department visit. Patients with psychiatric disorders had an increased risk of having multiple emergency department visits and hospitalization compared with patients without psychiatric disorders. The risk of multiple emergency department visits was particularly high for patients with either bipolar disorder or psychotic disorders. CONCLUSIONS: Uninsured patients with psychiatric disorders appear to be heavy users of medical emergency department services. These findings may be helpful in developing more efficient strategies to serve the mental health needs of the uninsured.     

Myasthenia gravis and multiple sclerosis

A case of multiple sclerosis is described in a patient who underwent thymectomy for myasthenia gravis. Clinical and laboratory data confirmed both diagnoses. This uncommon association, occuring in a patient from the Middle East where multiple sclerosis is rare, suggests that the disorders may have a common pathogeneses.     

A prospective-longitudinal study on the association of anxiety disorders prior to pregnancy and pregnancy- and child-related fears

This study aimed to investigate the relation between anxiety disorders prior to pregnancy and specific pregnancy- and child-related fears during pregnancy and after delivery. 306 expectant mothers were interviewed regarding anxiety (and depressive) disorders prior to pregnancy and pregnancy- and child-related fears (e.g. fear of labor pain, fear of infant injury) using the Composite International Diagnostic Interview for Women (CIDI-V). Pregnancy- and child-related fears were particularly pronounced in women with multiple anxiety disorders and women with comorbid anxiety and depressive disorders prior to pregnancy. Further analyses revealed associations between particular anxiety disorders and specific pregnancy- and child-related fears. Results remained stable when considering potential confounders such as maternal age, education, marital status, parity, prior abortion and preterm delivery or low birth weight. Our study suggests that especially women with multiple anxiety and/or comorbid depressive disorders may benefit from early targeted interventions to prevent an escalation of anxiety and fears over the peripartum period.     

MRI and the diagnosis of multiple sclerosis: expanding the concept of "no better explanation"

Although the diagnosis of multiple sclerosis relies on the demonstration of disease dissemination in space and time, the exclusion of other neurological disorders is also essential. The limited specificity of abnormalities disclosed by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients affected by other disorders. The available criteria for diagnosis of multiple sclerosis have not taken advantage of the potential of MRI to detect features "not suggestive" of multiple sclerosis. Recognition of such features in the work-up of patients suspected of having multiple sclerosis may reduce the likelihood of a false positive diagnosis of the disorder in some, while suggesting the correct alternative diagnosis in other patients. On the basis of this, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held to define a series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses. The presence of such red flags should alert clinicians to reconsider the differential diagnosis more extensively. In this review we will report on the conclusions of this international consensus, which should represent a first step beyond the concept of "no better explanation", and inform future diagnostic criteria for multiple sclerosis.     

Current Treatment of Selected Pediatric Sleep Disorders

While pediatric sleep disorders are relatively common, treatments are often not straightforward. There is often a paucity of gold standard studies and data available to guide clinicians, treatments may yield arguably incomplete results, interventions may require chronic use, and/ or involve multiple modalities including behavioral interventions that require high parental and family commitment. This review points out diagnostic differences compared to adults and focuses on current therapy for selected common pediatric sleep disorders including sleep disordered breathing/ obstructive sleep apnea, narcolepsy, and restless legs syndrome. Other common pediatric sleep disorders, such as insomnia and parasomnias, are not covered.     

Therapeutic responses to tricyclic antidepressants and related drugs in non-affective disorder patient populations

Although therapeutic responsiveness to tricyclic antidepressants has been primarily associated with the affective disorders, clinical investigations in the last decade have suggested that non-affective disorders such as panic disorder, obsessive-compulsive disorder, anxiety disorder, bulimia, enuresis, migraine, and the chronic pain syndrome may also respond to tricyclics and other antidepressants. This therapeutic responsiveness may sometimes be related to improvement in secondary depressive symptoms, but may also clearly occur in the absence of secondary depression; in particular, improvement in the core symptoms of at least some of these disorders may occur without a change in mood. Furthermore, many patients with these disorders display psychobiologic abnormalities that show many similarities, but also some differences, compared to those observed in patients with affective disorders, despite the frequent absence of affective symptoms. While an improvement in subclinical or "masked" depression remains one hypothesis linking tricyclic responsiveness and shared biological abnormalities in this diverse group of diagnostic entities, an alternative hypothesis (the "ven disorder" hypothesis) is presented, suggesting the possibility that tricyclic and other antidepressant-responding patients have a core disorder with common psychobiologic abnormalities but multiple clinical and diagnostic presentations. An alternative hypothesis (the "shotgun" hypothesis) suggests that the multiple actions of tricyclics (e.g. on adrenergic receptors vs. muscarinic receptors vs. serotonin system changes) may each be differentially important in the therapeutic outcome in patients with specific or predominant problems in one or another of these areas. An examination of both the similarities and differences among the non-affective, tricyclic-responsive disorders and the affective disorders may provide clues about the important psychobiologic elements in these disorders, and to the mode of action of tricyclic antidepressants and related drugs across the psychiatric disorder spectrum.     

The sensitivity of the K6 as a screen for any disorder in community mental health surveys: a cautionary note.

OBJECTIVE: Short screening instruments, which exclude respondents unlikely to have psychiatric disorders, can make epidemiologic surveys shorter and more cost-effective. The Kessler 6-Item Psychological Distress Scale (K6), a measure of generalized distress, has been proposed for this role and has shown good agreement with the Composite International Diagnostic Interview (CIDI). However, performance of the K6 may vary for individual disorders or combinations of disorders. In this report, we examine the ability of the K6 to detect disorders among respondents in different diagnostic categories. METHOD: We used data from Cycle 1.2 of the Canadian Community Health Survey to assemble 5 groups of respondents with different 12-month psychiatric disorders (n = 4481). A sixth group comprised those with 2 or more disorders. We examined the sensitivity of the K6 among respondents with an individual disorder as well as those with multiple disorders. RESULTS: The sensitivity of the K6 varies significantly by disorder; it is highest among respondents with multiple disorders and lowest among those with agoraphobia only. CONCLUSIONS: Use of the K6 as a screen for the CIDI is likely to result in biased prevalence estimates. However, both instruments should be compared with a third standard to fully assess the benefits and drawbacks of their combination.     

Affective disorders in children and adolescents: addressing unmet need in primary care settings.

Affective disorders are common among children and adolescents but may often remain untreated. Primary care providers could help fill this gap because most children have primary care. Yet rates of detection and treatment for mental disorders generally are low in general health settings, owing to multiple child and family, clinician, practice, and healthcare system factors. Potential solutions may involve 1) more systematic implementation of programs that offer coverage for uninsured children; 2) tougher parity laws that offer equity in defined benefits and application of managed care strategies across physical and mental disorders; and 3) widespread implementation of quality improvement programs within primary care settings that enhance specialty/primary care collaboration, support use of care managers to coordinate care, and provide clinician training in clinically and developmentally appropriate principles of care for affective disorders. Research is needed to support development of these solutions and evaluation of their impacts.     

Risk factors for behavioral and emotional disorder in preadolescent children

The relationship between risk factors and behavioral and emotional disorder was examined in 792 11-year-old children. Background characteristics such as sex, maternal depression, marital status of the parents, and reading problems distinguished between children with and without disorder. It also appeared that disorder was related to the number of risk factors experienced. This study, like others, failed to provide strong support for differences in background characteristics among children with different diagnoses. This may reflect the degree of overlap among disorders, because even children with only a single disorder may not be entirely free of the symptomatology of other disorders. For this reason it is important to assess children for multiple disorders or at least consider impaired functioning in other dimensions.     

Bipolar disorder and comorbid anxiety disorders in children and adolescents

Recent attention has focused on the association between bipolar disorder and comorbid anxiety disorders in children and adolescents. There is a high rate of comorbidity between bipolar disorder and anxiety disorders in children and youths. Often, a child or adolescent with bipolar disorder has multiple comorbid anxiety disorders. In general, anxiety disorders precede the development of bipolar disorder in children. Comorbid disorders may worsen the course of each individual disorder. Pharmacologic management of the comorbid anxiety disorder is complicated by potential mood destabilization in a child or adolescent with bipolar disorder.     

Apolipoprotein E genotype and schizophrenia

Schizophrenic disorders are complex genetic disorders and may involve multiple genes of small effect. The presence of apolipoprotein E (apoE) is associated with several neuropsychiatric disorders. Previous studies on apoE genotype distribution in schizophrenia have reported conflicting findings. We studied the genotype frequencies in a large group of schizophrenic patients. The genotype distribution was significantly different between the schizophrenic patients and the control subjects. Persons who were sigma3 carriers have an increased risk of schizophrenia. This result suggests that apoE isoforms may play a functional role in the pathogenesis of schizophrenic disorders. Some possible mechanisms regarding the effect of apoE on the development of schizophrenia are discussed.     

Transdiagnostic impairment of cognitive control in mental illness

Intact cognitive control or executive function has characteristic patterns in both behavior and functional neurocircuitry. Functional neuroimaging studies have shown that a frontal-cingulate-parietal-insular (i.e., “multiple demand”) network forms a common functional substrate undergirding successful adaptation to diverse cognitive processing demands. Separate work on intact neurocognitive performance implicates a higher order factor that largely explains performance across domains and may reflect trait cognitive control capacity. In the current review we highlight findings from respective psychiatric disorders (i.e., psychotic, bipolar and unipolar depressive, anxiety, and substance use disorders) suggesting that cognitive control perturbations amidst psychopathology are most pronounced within these common brain and behavioral indices of adaptive cognitive functioning and moreover, are evident across disorders (i.e., transdiagnostically). Specifically, within each of the disorder classes impairments are consistent in the multiple demand network across a wide range of cognitive tasks. While severity varies between disorders, broad as opposed to domain-specific impairments consistently emerge in neurocognitive performance. Accumulating findings have revealed that phenotypically diverse psychiatric disorders share a common factor or vulnerability to dysfunction that is in turn related to broad neurocognitive deficits. Furthermore, we have observed that regions of the multiple demand network, which overlap with the salience network (dorsal anterior cingulate and bilateral anterior insula) are characterized by reduced gray matter transdiagnostically and predict weaker neurocognitive performance. In summary, transdiagnostic (as opposed to disorder-specific) patterns of symptomatic distress and neurocognitive performance deficits, concurrent with parallel anomalies of brain structure and function may largely contribute to the real-world socio-occupational impairment common across disorders.     

The neuropsychiatry of multiple sclerosis.

This review describes the many neuropsychiatric abnormalities associated with multiple sclerosis (MS). These may be broadly divided into 2 categories: disorders of mood, affect, and behaviour and abnormalities affecting cognition. With respect to the former, the epidemiology, phenomenology, and theories of etiology are described for the syndromes of depression, bipolar disorder, euphoria, pathological laughing and crying, and psychosis attributable to MS. The section discussing cognition reviews the prevalence and nature of cognitive dysfunction, with an emphasis on abnormalities affecting multiple domains of memory, speed of information processing, and executive function. The detection, natural history, and cerebral correlates of cognitive dysfunction are also discussed. Finally, treatment pertaining to all these disorders is reviewed, with the observation that translational research has been found wanting when it comes to providing algorithms to guide clinicians. Guidelines derived from general psychiatry still largely apply, although they may not always be most effective in patients with neurologic disorders. The importance of future research addressing this imbalance is emphasized, for neuropsychiatric sequelae add significantly to the morbidity associated with MS.     

The co‐morbidity of personality disorder and clinical syndromes in prisoners

Objectives Our aim was to examine patterns of Axis II co‐morbidity using data from the national survey of psychiatric morbidity among prisoners in England and Wales. Methods A one‐in‐five sub‐sample of participants in a survey of psychiatric morbidity among prisoners in England and Wales was interviewed using the Schedule for Clinical Assessment in Neuropsychiatry and the Structured Clinical Interview for the fourth edition of the Diagnostic and Statistical Manual of Mental Health Disorders Axis II personality disorders (PD). Logistic regression analysis was conducted adjusting for confounders of associations with co‐morbid psychopathology disorders, age and gender. Results The most prevalent Axis II disorders in the sample were anti‐social, paranoid and borderline PD. Following logistic regression, anti‐social and borderline PD demonstrated high levels of co‐morbidity with both Axis I and other Axis II disorders, narcissistic PD with other Axis II, and paranoid and avoidant PD with Axis I disorders. Conclusions Certain Axis II disorders may increase the risk for lifetime Axis I disorders. Although appropriate statistical procedures reduce the level of Axis II co‐morbidity, some patterns may be artefacts of a diagnostic system encouraging multiple diagnostic categories. Copyright © 2009 John Wiley & Sons, Ltd