"I did what?" Zolpidem and the courts

Zolpidem is a widely prescribed nonbenzodiazepine hypnotic medication available in the United States since 1992. Attention has been drawn recently to its potential to cause sleep-related, complex behaviors such as sleepwalking and sleep driving. These automatic behaviors have led to a deluge of legal claims. To the authors' knowledge, this is the first review in the forensic literature of the legal ramifications of zolpidem. In this article, the medical literature will be reviewed to explore the current understanding of zolpidem's specific psychopharmacology. Case law will be explored to determine how the courts have handled the claims surrounding sleep-related, complex behaviors alleged to be caused by zolpidem. Finally, a summary of recommendations will be provided for forensic psychiatrists who are asked to be experts in these cases.     

Insulin-like growth factor I and Alzheimer's disease: therapeutic prospects?

The search for a cure of Alzheimer's dementia is restless. In recent years, unexpected epidemiological data showing a protective effect of anti-inflammatory and cholesterol-lowering drugs gave way to clinical trials with these compounds. Now, a newly described mechanism indicating that brain amyloid clearance is modulated by serum insulin-like growth factor I may also lead to new trials with this growth factor. Insulin-like growth factor I is an abundant circulating hormone with potent central actions whose levels in serum appear to be altered in Alzheimer's patients. Amyloid clearance, a potential therapeutic target in Alzheimer's disease was mostly neglected until recent antiamyloid therapies proved to involve a peripheral amyloid sink. Although more work in animal models are required, the evidence available strongly indicates that insulin-like growth factor I therapy in Alzheimer's dementia may be addressing pathogenic processes.     

“Stories I tell my patients”the cork and buoy

With this issue, the journal completes its tenth year! To commemorate this achievement, we will be printing a comprehensive "Ten Year Index" in Volume 11, at the beginning of next year.     

Grandpa and I have dystrophinopathy?: approach to asymptomatic hyperCKemia

This report describes three males from a single kinship, ages 7, 8, and 67 years with clinically asymptomatic dystrophinopathy. The index case was an 8-year-old male evaluated for asymptomatic but persistently elevated serum creatine kinase levels. Muscle biopsy demonstrated a mild myopathy, without necrotic fibers. Immunostaining for dystrophin revealed a slight reduction in sarcolemmal reactivity for the amino terminus of dystrophin. Dystrophin gene analysis revealed a deletion of exon 45 to exon 51. Genetic analysis identified two other affected males (age 7 years and 67 years), as well as four female carriers in the same family. The 7-year-old male had mildly increased creatine kinase levels with normal muscle strength. The 67-year-old grandfather had normal neuromuscular examination and serum creatine kinase levels. Asymptomatic dystrophinopathy in late adulthood is exceptionally rare, and highlights the importance of consideration of dystrophin mutation analysis in patients with hyperCKemia, even in the absence of muscle weakness.     

Where am I? The neurological correlates of self and other

Although still controversial, there is growing evidence that information about the self is processed in the right hemisphere, specifically the right frontal lobe. It has also been hypothesized that self-awareness and mental state attribution (inferences about the mental experience of others) are part of a similar neurocognitive process [Am. J. Primatol. 2 (1982) 237]. Here we measured blood oxygen level-dependent (BOLD) activity when viewing self-faces and when thinking about the mental states of others. We found significant activation in right superior, middle, and inferior frontal gyri when activation associated with self-face processing was compared with activation associated with familiar famous face processing. Mental state attribution, as measured by a computerized version of the Mind in the Eyes--Revised Test, was associated with activation in the right superior and middle frontal gyri, medial superior frontal gyrus, and left middle frontal gyrus and superior temporal gyrus/temporal pole. Self-face recognition and mental state attribution were colocalized to the middle and superior frontal gyri in the right hemisphere. These data support a model developed over two decades ago by Gallup [Am. J. Primatol. 2 (1982) 237] that posits that self-awareness and mental state attribution are part of a shared neurocognitive suite of processing and that neural architecture implicated in processing knowledge about the self is called upon when inferring knowledge in others.     

Should I stay or should I go? Personality Assessment Inventory and Rorschach indices of early withdrawal from psychotherapy

The Personality Assessment Inventory (PAI) and the Rorschach were used to investigate differences between patients who withdrew early from university-based outpatient psychodynamic psychotherapy and those who continued in treatment. The study employs two sets of analyses, one utilizing the complete sample (N = 101) and a second comprised of comparison pairs matched on the specific therapist delivering treatment (n = 36 for Rorschach; n = 38 for PAI). It was hypothesized that early withdrawers would score higher on the PAI Treatment Rejection Scale (RXR) and the PAI Treatment Process Index (TPI) than treatment continuers. It was also hypothesized that early treatment withdrawers will have better overall interpersonal relationships, less need for closeness and intimacy, less available psychological resources and more current stimulus demands, and lower levels of psychological/cognitive disturbance as measured by the Rorschach. In addition, differences between the two groups on PAI treatment and clinical scales and subscales were examined. Results indicated that PAI RXR differentiated between the two groups (p< .05) in the expected direction. Limited differences between withdrawers and continuers were found on the Rorschach and other PAI scales. Potential explanations for the findings as well as a discussion of clinical applicability are presented.     

What do we mean by "conscious" and "aware"?

The concepts of consciousness and awareness are multifaceted, and steeped in cultural and intellectual history. This paper explores their complexities by way of a series of contrasts: (1) states of consciousness, such as wakefulness and sleep are contrasted with awareness, a term that picks out the contents of consciousness: these range across all our psychological capacities; the scientific background of the two concepts is briefly outlined; (2) consciousness is contrasted to self-consciousness, itself a complex term embracing self-detection, self-monitoring, self-recognition, theory of mind and self-knowledge; (3) "narrow" and "broad" senses of consciousness are contrasted, the former requiring mature human awareness capable of guiding action and self-report, the latter involving the much broader capacity to acquire and exploit knowledge; (4) an "inner" conception of consciousness, by which awareness is essentially private and beyond the reach of scientific scrutiny, is contrasted with an "outer" conception which allows that consciousness is intrinsically linked with capacities for intelligent behaviour; (5) finally "easy" and "hard" questions of consciousness are distinguished, the former involving the underlying neurobiology of wakefulness and awareness, the latter the allegedly more mysterious process by which biological processes generate experience: Whether this final distinction is valid is a focus of current debate. Varied interests converge on the study of consciousness from the sciences and the humanities, creating scope for interdisciplinary misunderstandings, but also for a fruitful dialogue. Health professionals treating disorders of consciousness should be aware both of its scientific complexities and of its broad cultural background, which influences the public understanding of these conditions.     

"Fatigue" in multiple sclerosis. Development and and validation of the "Würzburger Fatigue Inventory for MS"

BACKGROUND: Fatigue is one of the most common, yet poorly defined, disabling symptoms in patients with multiple sclerosis (MS). Several fatigue scales have been developed, but rigorous psychometric methods have not always been applied and validation was mainly based on small numbers of patients. We therefore assembled a new fatigue scale from a set of widely used scales and assessed its psychometric properties in a large sample of MS patients. PATIENTS AND METHODS: Fatigue was assessed in 158 MS patients by four published quantitative scales: the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), MS-specific Fatigue Severity Scale (MFSS), and Visual Analogue Scale. From these a new fatigue scale, the Würzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS), was assembled. It contains 17 items with values from 0 to 4. The WEIMuS scale was validated in a subgroup of 67 patients and a control group of 68 patients. RESULTS: The MFIS and FSS but not the MFSS showed high internal consistency and split-half reliability. After applying factor analysis within the scales, fairly reliable and valid items originally found in the MFIS and FSS were selected to construct the final 17-item WEIMuS scale, which showed a high degree of reliability. In the validation study, varimax rotated factor analysis extracted two main factors corresponding to both cognitive and physical fatigue. CONCLUSION: The new, two-dimensional WEIMuS showed good psychometric properties, is easy to use, and may therefore be a useful tool for the assessment of MS-associated fatigue. Multiple sclerosis patients suffer from different types of fatigue which could be attributed to cognitive and physical fatigue. Thus, MS-associated fatigue is different from common tiredness.     

See What I’m Saying? Expertise and Verbalisation in Perception and Imagery of Complex Scenes

How does describing a previously viewed picture affect our memory for it? Does verbalisation affect our eye movements even when the picture has disappeared? When viewing a photograph, the sequences of eye movements we make (‘scanpaths’) are influenced by both bottom-up visual saliency and top-down cognitive knowledge. Recognition memory is enhanced and the similarity of scanpaths at encoding and recognition is greater for domain-specific pictures. A similarity in scanpaths is also observed during imagery but to a greatly reduced degree. This study explored whether scanpath similarity could be improved by verbalising one’s memory of the picture and whether the previously observed domain-specific advantage was still present when no bottom-up information was available. Specialists and controls were shown a set of photographs, and after each one had to either visualise it or describe it from memory. The stimuli were complex scenes, half of which contained a domain-specific object. Recognition accuracy was increased by post-stimulus verbalisation, and specialists demonstrated an advantage for stimuli that contained domain-relevant information. Saliency influenced both verbal feedback and eye movements but was moderated by domain expertise. Scanpaths were more similar when pictures were described compared to when imagined, and specialists produced more similar scanpaths when describing domain-specific pictures, compared to control pictures and control participants.     

Does telomere length mediate associations between inbreeding and increased risk for bipolar I disorder and schizophrenia?

We have recently found that consanguinity is a risk factor for bipolar I disorder (BP1) and schizophrenia (SZ) in Egypt. Inbreeding has been associated with increased cellular stress and impaired physiological function in plants and animals. Previous studies have reported that telomere length (TL), an index of oxidative stress and cellular senescence is significantly reduced among patients with SZ or mood disorders compared with control individuals. Hence we evaluated TL as a possible mediator of the observed association between consanguinity and BP1/SZ risk. Patients with BP1 (n = 108), or SZ (n = 60) were compared with screened adult controls in separate experiments. TL was estimated using a quantitative PCR (qPCR) based assay. The inbreeding coefficient/consanguinity rate was estimated in two ways: using 64 DNA polymorphisms (‘DNA-based’ rate); and from family history data (‘self report’). Significant correlation between TL and DNA based inbreeding was not observed overall, though suggestive trends were present among the SZ cases. No significant case-control differences in TL were found after controlling for demographic variables. In conclusion, reduced TL may not explain a significant proportion of observed associations between consanguinity and risk for BP1/SZ.     

Clinical and neuropsychological correlates of insight in schizophrenia and bipolar I disorder: does diagnosis matter?

BACKGROUND: Lack of insight is a well-recognized feature of schizophrenia and is associated with symptom severity and cognitive impairments. However, the diagnostic specificity of insight variables and their correlates is not known. To assess this specificity, we compared awareness of illness and neuropsychological function between patients with chronic schizophrenia and bipolar I disorder. METHOD: We assessed insight, level of psychopathology, and cognitive performance on a neuropsychological test battery in 37 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar I disorder, 32 patients with schizophrenia, and 31 healthy subjects for comparison. RESULTS: There was no significant difference between the 2 diagnostic groups on general illness awareness. However, patients with bipolar disorder had better awareness of their symptoms and their pathologic nature compared to patients with schizophrenia. Similar patterns of association emerged between insight and clinical variables. General unawareness was associated with clinical severity, especially of the affective type, and working memory deficits (Wechsler Adult Intelligence Scale digit span) in both diagnostic groups. The contribution of other cognitive deficits to insight differed across the groups. Misattribution differed from the other aspects of insight in its relative independence of clinical and neurocognitive correlates. Both patient groups were neurocognitively impaired, with the schizophrenia group performing significantly worse on conceptual ability, verbal learning, visuospatial processing, and motor speed. CONCLUSIONS: The results suggest that differences in general insight in major mental disorders may be explained by symptom severity and working memory function rather than the specific diagnosis. Subcomponents of insight are influenced by different factors emphasizing the need to consider insight as multidimensional.     

Anti-beta2-glycoprotein I antibodies--when and how should they be measured?

The biological criteria of the antiphospholipid syndrome defined at the Sapporo meeting in 1998 included the presence of lupus anticoagulant (LA) and/or anticardiolipin antibodies at medium and high titers. During the 48th SSC meeting held in Boston July 2002, it was proposed to modify these criteria. Four patient groups were defined, the first one comprising LA and anti-β₂glycoprotein I antibodies (aβ₂GPI), the second one LA only, the third one aβ₂GPI only and the fourth one other antiphospholipid antibodies such as antiprothrombin, anticardiolipin, antiphosphatidylethanolamine, etc. This proposition raised the issue of the association of aβ₂GPI with APS clinical criteria (thrombosis and pregnancy morbidity). In some studies, a strong association between IgG aβ₂GPI and thrombosis was found, whereas in others this association could not be demonstrated. In the obstetrical field, few studies are available and no clear conclusion can be drawn yet. However, for thrombosis or pregnancy morbidity, it has been shown that in up to 10% of patients, aβ₂GPI are the sole antibodies present and therefore the diagnosis of APS would be missed in these patients. In addition, some studies suggest that the severity of disease is dependent on the number of positive tests and on their titers. We recommend aβ₂GPI assays to be included in the panel of antiphospholipid screening tests. However, the standardisation of aβ₂GPI assays has to be improved in order to ensure better comparability between the studies.     

Low self-esteem and psychiatric patients: Part I – The relationship between low self-esteem and psychiatric diagnosis

Background

The objective of the current study was to determine the prevalence and the degree of lowered self-esteem across the spectrum of psychiatric disorders.

Method

The present study was carried out on a consecutive sample of 1,190 individuals attending an open-access psychiatric outpatient clinic. There were 957 psychiatric patients, 182 cases with conditions not attributable to a mental disorder, and 51 control subjects. Patients were diagnosed according to DSM III-R diagnostic criteria following detailed assessments. At screening, individuals completed two questionnaires to measure self-esteem, the Rosenberg self-esteem scale and the Janis and Field Social Adequacy scale. Statistical analyses were performed on the scores of the two self-esteem scales.

Results

The results of the present study demonstrate that all psychiatric patients suffer some degree of lowered self-esteem. Furthermore, the degree to which self-esteem was lowered differed among various diagnostic groups. Self-esteem was lowest in patients with major depressive disorder, eating disorders, and substance abuse. Also, there is evidence of cumulative effects of psychiatric disorders on self-esteem. Patients who had comorbid diagnoses, particularly when one of the diagnoses was depressive disorders, tended to show lower self-esteem.

Conclusions

Based on both the previous literature, and the results from the current study, we propose that there is a vicious cycle between low self-esteem and onset of psychiatric disorders. Thus, low self-esteem increases the susceptibility for development of psychiatric disorders, and the presence of a psychiatric disorder, in turn, lowers self-esteem. Our findings suggest that this effect is more pronounced with certain psychiatric disorders, such as major depression and eating disorders.

     

Outpatients with schizophrenia and bipolar I disorder: Do they differ in their cognitive and social functioning?

The authors used a battery of cognitive and social functioning measures to evaluate stable outpatients with schizophrenia (n=74) and bipolar I disorder (n=26) who were receiving care at community and rehabilitation programs. The groups did not differ significantly on 36 of 41 measures. For most variables, comparisons between groups yielded effect sizes of <0.5. These results suggest that individuals with bipolar I disorder receiving community and rehabilitation services have many social and cognitive deficits that are as severe as those in schizophrenia.     

Is there a link between atypical and early-onset "unipolar" depression and bipolar II disorder?

The aim of the present study was to determine whether there is a link between "unipolar" depression with atypical features and early onset, and bipolar II disorder, using atypical features and early onset as markers of bipolarity. A total of 158 consecutive unipolar and 234 bipolar II major depressive episode (MDE) outpatients were interviewed using the Structured Clinical Interview for DSM-IV (SCID). Patients were divided into those with and without atypical features, and into those with and without early onset. Comparisons were made on variables reported to distinguish bipolar from unipolar: age of onset, recurrences, atypical features, depressive mixed state (MDE plus three or more concurrent hypomanic symptoms [DMX3]), and bipolar II family history. Compared to bipolar II patients, patients with atypical unipolar were not significantly different regarding age of onset, DMX3, recurrences, and bipolar II family history. Compared to non-atypical unipolar patients, atypical unipolar patients had a significantly different age of onset. Nonatypical unipolar patients, versus bipolar II patients, were significantly different regarding age of onset, recurrences, DMX3, and bipolar II family history. Early onset unipolar, versus bipolar II, were not significantly different regarding atypical features, recurrences, DMX3, and bipolar II family history. Later onset unipolar patients, versus bipolar II patients, were significantly different regarding atypical features, recurrences, DMX3, and bipolar II family history. These results support a link of atypical and early-onset "unipolar" depression with bipolar II disorder, and support Pages and Dunner's suggestion to combine bipolar II and recurrent unipolar into a single group.