Natural language processing in psychiatry: the promises and perils of a transformative approach.

A person's everyday language can indicate patterns of thought and emotion predictive of mental illness. Here, we discuss how natural language processing methods can be used to extract indicators of mental health from language to help address long-standing problems in psychiatry, along with the potential hazards of this new technology.

Persistent genital arousal disorder: a special sense neuropathy.

INTRODUCTION: Persistent genital arousal (PGAD) is a syndrome of unprovoked sexual arousal/orgasm of uncertain cause primarily reported in female patients. Most patients are referred for mental-health treatment, but as research suggests associations with neurological symptoms and conditions, there is need to analyze cases comprehensively evaluated by neurologists. METHODS: The IRB waived consent requirements for this retrospective university-hospital study. We extracted and analyzed neurological symptoms, test, and treatment results from all qualifying participants' records and recontacted some for details. RESULTS: All 10 participants were female; their PGAD symptoms began between ages 11 to 70 years. Two patterns emerged: 80% reported daily out-of-context sexual arousal episodes (≤30/day) that usually included orgasm and 40% reported lesser, often longer-lasting, nonorgasmic arousals. Most also had symptoms consistent with sacral neuropathy-70% had urologic complaints and 60% had neuropathic perineal or buttock pain. In 90% of patients, diagnostic testing identified anatomically appropriate and plausibly causal neurological lesions. Sacral dorsal-root Tarlov cysts were most common (in 4), then sensory polyneuropathy (2). One had spina bifida occulta and another drug-withdrawal effect as apparently causal; lumbosacral disc herniation was suspected in another. Neurological treatments cured or significantly improved PGAD symptoms in 4/5 patients, including 2 cures. CONCLUSIONS: Although limited by small size and referral bias to neurologists, this series strengthens associations with Tarlov cysts and sensory polyneuropathy and suggests new ones. We hypothesize that many cases of PGAD are caused by unprovoked firing of C-fibers in the regional special sensory neurons that subserve sexual arousal. Some PGAD symptoms may share pathophysiologic mechanisms with neuropathic pain and itch.

Briquet syndrome revisited: implications for functional neurological disorder.

With the creation of the Somatic Symptom and Related Disorders category of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition in 2013, the functional neurological (symptom) disorder diagnostic criteria underwent transformative changes. These included an emphasis on 'rule-in' physical examination signs/semiological features guiding diagnosis and the removal of a required proximal psychological stressor to be linked to symptoms. In addition, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder, somatoform pain disorder and undifferentiated somatoform disorder conditions were eliminated and collapsed into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition somatic symptom disorder diagnosis. With somatic symptom disorder, emphasis was placed on a cognitive-behavioural (psychological) formulation as the basis for diagnosis in individuals reporting distressing bodily symptoms such as pain and/or fatigue; the need for bodily symptoms to be 'medically unexplained' was removed, and the overall utility of this diagnostic criteria remains debated. A consequence of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition restructuring is that the diagnosis of somatization disorder that encompassed individuals with functional neurological (sensorimotor) symptoms and prominent other bodily symptoms, including pain, was eliminated. This change negatively impacts clinical and research efforts because many patients with functional neurological disorder experience pain, supporting that the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition would benefit from an integrated diagnosis at this intersection. We seek to revisit this with modifications, particularly since pain (and a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder comorbidity, more specifically) is associated with poor clinical prognosis in functional neurological disorder. As a first step, we systematically reviewed the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder literature to detail epidemiologic, healthcare utilization, demographic, diagnostic, medical and psychiatric comorbidity, psychosocial, neurobiological and treatment data. Thereafter, we propose a preliminary revision to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition allowing for the specifier functional neurological disorder 'with prominent pain'. To meet this criterion, core functional neurological symptoms (e.g. limb weakness, gait difficulties, seizures, non-dermatomal sensory loss and/or blindness) would have 'rule-in' signs and pain (>6 months) impairing social and/or occupational functioning would also be present. Two optional secondary specifiers assist in characterizing individuals with cognitive-behavioural (psychological) features recognized to amplify or perpetuate pain and documenting if there is a pain-related comorbidity. The specifier of 'with prominent pain' is etiologically neutral, while secondary specifiers provide additional clarification. We advocate for a similar approach to contextualize fatigue and mixed somatic symptoms in functional neurological disorder. While this preliminary proposal requires prospective data and additional discussion, these revisions offer the potential benefit to readily identify important functional neurological disorder subgroups-resulting in diagnostic, treatment and pathophysiology implications.

Mild traumatic brain injury: Is DTI ready for the courtroom?

Important advances in neuroscience and neuroimaging have revolutionized our understanding of the human brain. Many of these advances provide new evidence regarding compensable injuries that have been used to support changes in legal policy. For example, we now know that regions of the brain involved in decision making continue to develop into the mid-20s, and this information weighs heavily in determining that execution or automatic sentence of life without the possibility of parole for someone younger than 18 years old, at the time of the crime, violates the 8th Amendment prohibition against "cruel and unusual punishment." The probative value of other testimony regarding neuroimaging, however, is less clear, particularly for mild traumatic brain injury (mTBI), also known as concussion. There is nonetheless some evidence that new imaging technologies, most notably diffusion tensor imaging (DTI), may be useful in detecting mTBI. More specifically, DTI is sensitive to detecting diffuse axonal brain injuries in white matter, the most common brain injury in mTBI. DTI is, in fact, the most promising technique available today for such injuries and it is beginning to be used clinically, although it remains largely within the purview of research. Its probative value is also not clear as it may be both prejudicial and misleading given that standardization is not yet established for use in either the clinic or the courtroom, and thus it may be premature for use in either. There are also concerns with the methods and analyses that have been used to provide quantitative evidence in legal cases. It is within this context that we provide a commentary on the use of neuroimaging in the courtroom, most particularly DTI, and the admissibility of evidence, as well as the definition and role of expert testimony. While there is a great deal of evidence demonstrating cognitive impairments in attention, processing speed, memory, and concentration from neuropsychological testing following mTBI, we focus here on the more recent introduction of DTI imaging in the courtroom. We also review definitions of mTBI followed by admissibility standards for scientific evidence in the courtroom, including Daubert criteria and two subsequent cases that comprise the so-called Daubert trilogy rulings on the admissibility of expert testimony. This is followed by a brief review of neuroimaging techniques available today, the latter with an emphasis on DTI and its application to mTBI. We then review some of the court rulings on the use of DTI. We end by highlighting the importance of neuroimaging in providing a new window on the brain, while cautioning against the premature use of new advances in imaging in the courtroom before standards are established in the clinical arena, which are informed by research. We also discuss further what is needed to reach a tipping point where such advances will provide important and meaningful data with respect to their probative value.

Bridging the Great Divide: What Can Neurology Learn From Psychiatry?

Neurology and psychiatry share common historical origins and rely on similar tools to study brain disorders. Yet the practical integration of medical and scientific approaches across these clinical neurosciences remains elusive. Although much has been written about the need to incorporate emerging systems-level, cellular-molecular, and genetic-epigenetic advances into a science of mind for psychiatric disorders, less attention has been given to applying clinical neuroscience principles to conceptualize neurologic conditions with an integrated neurobio-psycho-social approach. In this perspective article, the authors briefly outline the historically interwoven and complicated relationship between neurology and psychiatry. Through a series of vignettes, the authors then illustrate how some traditional psychiatric conditions are being reconceptualized in part as disorders of neurodevelopment and awareness. They emphasize the intersection of neurology and psychiatry by highlighting conditions that cut across traditional diagnostic boundaries. The authors argue that the divide between neurology and psychiatry can be narrowed by moving from lesion-based toward circuit-based understandings of neuropsychiatric disorders, from unidirectional toward bidirectional models of brain-behavior relationships, from exclusive reliance on categorical diagnoses toward transdiagnostic dimensional perspectives, and from silo-based research and treatments toward interdisciplinary approaches. The time is ripe for neurologists and psychiatrists to implement an integrated clinical neuroscience approach to the assessment and management of brain disorders. The subspecialty of behavioral neurology & neuropsychiatry is poised to lead the next generation of clinicians to merge brain science with psychological and social-cultural factors. These efforts will catalyze translational research, revitalize training programs, and advance the development of impactful patient-centered treatments.

Apathy: a neurocircuitry model based on frontotemporal dementia.

Apathy is a symptom shared among many neurological and psychiatric disorders. However, the underlying neurocircuitry remains incompletely understood. Apathy is one of the core features of behavioural variant frontotemporal dementia (bvFTD), a neurodegenerative disease presenting with heterogeneous combinations of socioaffective symptoms and executive dysfunction. We reviewed all neuroimaging studies of apathy in frontotemporal dementia (FTD) attempting to refine a neurocircuitry model and inform clinical definitions. Levels of apathy have been consistently shown to correlate with the severity of executive dysfunctions across a wide range of diseases, including FTD. Some authors view 'energisation'-the loss of which is central in apathy-as a core executive function. Apathy in FTD is most robustly associated with atrophy, hypometabolism and/or hypoperfusion in the dorsolateral prefrontal cortex, the anterior and middle cingulate cortex, the orbitofrontal cortex and the medial and ventromedial superior frontal gyri. Data also suggest that abnormalities in connecting white matter pathways and functionally connected more posterior cortical areas could contribute to apathy. There is a lack of consistency across studies due to small samples, lenient statistical thresholds, variable measurement scales and the focus on apathy as a unitary concept. Integrating findings across studies, we revise a neurocircuitry model of apathy divided along three subcomponents (cognition/planning, initiation, emotional-affective/motivation) with specific neuroanatomical and cognitive substrates. To increase consistency in clinical practice, a recommendation is made to modify the bvFTD diagnostic criteria of apathy/inertia. More generally, we argue that bvFTD constitutes a disease model to study the neurocircuitry of complex behaviours as a 'lesion-based' approach to neuropsychiatric symptoms observed across diagnostic categories.

Protecting the Health and Finances of the Elderly With Early Cognitive Impairment.

The projected expansion of the nation's elderly population necessitates the revision of health care and policy strategies for safeguarding the health and assets of this community. The elderly are at greatly increased risk for developing mild cognitive impairment and Alzheimer's disease. These conditions are associated with diminished complex decision-making abilities that adversely affect patients, their families, and society, even during early stages of Alzheimer's disease. We present three composite patient histories that demonstrate problems routinely encountered by families, health care providers, and legal professionals during the course of early AD and MCI. We review the prevalence of cognitive and behavioral symptoms associated with MCI and early AD. Obstacles to early detection of cognitive decline, limitations of current testing modalities and benefits of earlier detection are discussed. Central themes common to medical and judicial approaches toward capacity assessment are discussed. We argue that an emphasis on earlier detection will result in benefits for patient health and result in financial savings to patients and the country as a whole. Finally, we recommend national guidelines for the evaluation of task-specific decision-making capacities to reduce the variability of outcome and improve quality of evaluations found among medical professionals, forensic evaluators, and legal actors.

Approach to atypical Alzheimer's disease and case studies of the major subtypes.

Alzheimer's disease (AD) has long been recognized as a heterogeneous illness, with a common clinical presentation of progressive amnesia and less common "atypical" clinical presentations, including syndromes dominated by visual, aphasic, "frontal," or apraxic symptoms. Our knowledge of atypical clinical phenotypes of AD comes from clinicopathologic studies, but with the growing use of in vivo molecular biomarkers of amyloid and tau pathology, we are beginning to recognize that these syndromes may not be as rare as once thought. When a clinician is evaluating a patient whose clinical phenotype is dominated by progressive aphasia, complex visual impairment, or other neuropsychiatric symptoms with relative sparing of memory, the differential diagnosis may be broader and a confident diagnosis of an atypical form of AD may require the use of molecular biomarkers. Despite the evolving sophistication in our diagnostic tools, and the acknowledgment of atypical AD syndromes in the 2011 revised diagnostic criteria for AD, the assessment of such patients still poses substantial challenges. We use a case-based approach to review the clinical and imaging phenotypes of a series of patients with typical and atypical AD, and discuss our current approach to their evaluation. One day, we hope that regardless of whether a patient exhibits typical or atypical symptoms of AD pathology, we will be able to identify the condition at a prodromal phase and institute a combination of symptomatic and disease-modifying therapies to support cognitive processes, function, and behavior, and slow or halt progression to dementia.

The Dialectic Between Empathy and Violence: An Opportunity for Intervention?

The authors provide a comprehensive review of the neurobiology of empathy and compare this with the neurobiology of psychopathic predatory violence-the most extreme deficit of empathy. This suggests that the specific areas of the prefrontal cortex and limbic system, which have been associated with violent behavior, also appear to subserve the capacity for empathy. Damage to these regions may result in the emergence of aggression, but not of empathy, suggesting a structurally inverse relationship between the two. The authors examine the evidence for a dialectic between empathy and predatory violence and explore the implications for early interventions with empathy training in treatment-resistant psychopathy.

Retrospective Analysis of the Short-Term Safety of ECT in Patients With Neurological Comorbidities: A Guide for Pre-ECT Neurological Evaluations.

Pre-ECT neurology consultations are often requested to determine the relative risk of the procedure in patients with neurological comorbidities, but there is limited data to guide clinicians. The authors performed a retrospective chart review of all consecutive inpatients at McLean Hospital who underwent a pre-ECT neurological evaluation between January 2012 and June 2014 (N=68). ECT was safe and effective in patients with a wide variety of neurological diseases. Only one minor event was related to a neurological comorbidity, and there were no serious neurological complications. Based on the latest evidence, the authors provide guidance on the pre-ECT evaluation with respect to neurologic status.

Neuropsychiatric symptoms in primary progressive aphasia: phenomenology, pathophysiology, and approach to assessment and treatment.

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by insidious and progressive loss of language. Current diagnostic criteria require symptoms to be largely restricted to language dysfunction for at least the first 2 years of the syndrome. However, as the disorder progresses - and sometimes even in the early stages - patients with PPA may exhibit neuropsychiatric symptoms. In this article, we review the phenomenology and frequency of neuropsychiatric symptoms in PPA. Among the few studies of this topic that have been performed, there is consistent agreement that neuropsychiatric symptoms are not uncommon among PPA patients. In some cases, particularly the semantic variant of PPA, symptoms are similar to those found in the behavioral variant of frontotemporal dementia. We further review the approach to assessment of behavioral symptoms in PPA and their possible management strategies, and speculate regarding their potential neurobiological substrates.

Bapineuzumab and solanezumab for Alzheimer's disease: is the 'amyloid cascade hypothesis' still alive?

INTRODUCTION: The 'amyloid cascade hypothesis' remains the leading hypothesis to explain the pathophysiology of Alzheimer's disease (AD). Immunotherapeutic agents have been developed to remove the neurotoxic amyloid ß42 protein and prevent the hypothesized amyloid ß42-induced neurotoxicity and neurodegeneration. The most notable of these immunotherapies are bapineuzumab and solanezumab. AREAS COVERED: This article briefly reviews the experimental agents in development for treatment of AD and then discusses the results of bapineuzumab and solanezumab in AD patients, as reported in preclinical studies, clinical trials and press releases. EXPERT OPINION: Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA). Solanezumab's two Phase III trials in AD patients failed to meet endpoints when analyzed independently. However, analysis of pooled data from both trials showed a significant reduction in cognitive decline in mild AD patients. The improvement was associated with an increase in plasma amyloid-ß (Aß) levels and a low incidence of ARIA in solanezumab-treated patients. The marginal benefits of solanezumab are encouraging to support continued evaluation in future studies, and offer small support in favor of the ongoing viability of the 'amyloid cascade hypothesis' of AD.

The clinical significance of bilateral basal ganglia calcification presenting with mania and delusions.

The authors present the case of a 37-year-old man who developed a psychotic manic episode and was found to have bilateral basal ganglia calcification (BGC). The authors present this case report along with a discussion of the literature on the neuropsychiatry of BGC.