Individual differences in interoceptive accuracy and prediction error in motor functional neurological disorders: A DTI study

In motor functional neurological disorders (mFND), relationships between interoception (a construct of high theoretical relevance to its pathophysiology) and neuroanatomy have not been previously investigated. This study characterized white matter in mFND patients compared to healthy controls (HCs), and investigated associations between fiber bundle integrity and cardiac interoception. Voxel‐based analysis and tractography quantified fractional anisotropy (FA) in 38 mFND patients compared to 38 HCs. Secondary analyses compared functional seizures (FND‐seiz; n = 21) or functional movement disorders (n = 17) to HCs. Network lesion mapping identified gray matter origins of implicated fiber bundles. Within‐group mFND analyses investigated relationships between FA, heartbeat tracking accuracy and interoceptive trait prediction error (discrepancies between interoceptive accuracy and self‐reported bodily awareness). Results were corrected for multiple comparisons, and all findings were adjusted for depression and trait anxiety. mFND and HCs did not show any between‐group interoceptive accuracy or FA differences. However, the FND‐seiz subgroup compared to HCs showed decreased integrity in right‐lateralized tracts: extreme capsule/inferior fronto‐occipital fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, and thalamic/striatum to occipital cortex projections. These alterations originated predominantly from the right temporoparietal junction and inferior temporal gyrus. In mFND patients, individual differences in interoceptive accuracy and interoceptive trait prediction error correlated with fiber bundle integrity originating from the insula, temporoparietal junction, putamen and thalamus among other regions. In this first study investigating brain‐interoception relationships in mFND, individual differences in interoceptive accuracy and trait prediction error mapped onto multimodal integration‐related fiber bundles. Right‐lateralized limbic and associative tract disruptions distinguished FND‐seiz from HCs.     

Clinical applications of evoked potentials in neurological disorders

The functional integrity of the main sensorial systems and of the central motor pathways can be evaluated through multimodal evoked potentials and non-invasive transcranial stimulation of the motor cortex. In this review the authors summarize the main clinical indications of the afore said methods specifically in the field of the neurological disorders.     

Pharmacotherapy of adolescent substance use disorders: a review of the literature

OBJECTIVE: Substance use disorders (SUD) are increasingly conceptualized as developing during adolescence. Moreover, adolescent SUD are viewed as one of the most difficult mental health conditions to treat. The role of pharmacotherapy for adolescents with SUD is not well delineated. We systematically reviewed existing pharmacotherapy studies of adolescent SUD. METHODS: A computerized search of the literature addressing the pharmacotherapy of SUD in adolescents was performed. Data from relevant peer-reviewed scientific presentations were also included. RESULTS: Five case reports (n = 8 subjects), six open studies that primarily addressed SUD with comorbid psychiatric disorders (n = 73 subjects), and five placebo-controlled studies (n = 156 subjects) on the pharmacological treatment of youths with SUD were identified. Pharmacological agents appear to reduce comorbid psychopathology with a milder reduction in SUD symptoms. The most robust evidence exists for the treatment of SUD comorbid with affective disorders. There is a limited database supporting the use of agents to reduce substance craving and the preventative effects of pharmacotherapy on subsequent SUD development in adolescents with specific psychiatric disorders. CONCLUSION: Further controlled studies directed at reducing drug use and craving, and guiding the integration of pharmacotherapy and psychosocial interventions for SUD with the treatment of comorbid psychiatric illness, are necessary.     

Medical disorders affect health outcome and general functioning depending on comorbid major depression in the general population

OBJECTIVE: The objective of this study was to compare health-related quality of life (HR-QoL), disability/work productivity, and health care utilization in a variety of medical disorders with and without comorbid major depressive disorder (MDD) in the general population. METHODS: Twelve-month MDD (Composite International Diagnostic Interview) diagnosis was determined among 4181 participants from a community sample. Medical diagnoses (respiratory, cardiovascular, allergic, endocrine/metabolic, gastrointestinal, and neurological diseases) were made after medical examination. HR-QoL was evaluated with the MOS-SF-36. Outpatient doctor visits and disability/work productivity were assessed by self-report. RESULTS: Comorbid MDD was associated with a lower SF-36 mental summary score in all medical diagnoses and with a lower physical summary score in comorbid allergic and neurological disorders. The number of coexisting medical disorders was strongly related to lower physical and mental summary scores in cases without comorbid depression. The number of outpatient doctor visits increased by 42% when any of the medical disorders without comorbid MDD was present, and comorbid MDD was associated with a further 24-42% increase, depending on the medical disorder. Comorbid MDD was strongly associated with lower full-time working status (37.1% with MDD vs. 51.0% without MDD) and with a significant increase in disability days (45%) in the presence of any medical disorder. CONCLUSIONS: Findings have consequences for diagnostic and treatment procedures, as well as in relation to the importance of the number of medical disorders in future studies.     

Personality disorders and violence potential

Violence associated with personality disorders is usually best viewed separately from psychiatric diagnosis, as a syndrome of violence rather than a syndrome of diagnosis. The authors describe eight categories of violence associated with personality disorders that may help clinicians choose treatment or management techniques: purposeful, instrumental violence; purposeful, non-instrumental violence; purposeful, targeted, defensive violence; targeted, impulsive violence; nontargeted, impulsive violence incidental to emotional escape; random but purposeful violence; violence related to perceived or feared loss or abandonment; and violence related to chronic paranoia or related misconceptions. The categories are not completely mutually exclusive, nor do they represent a "decision tree." We also point out three important principles about the relationship between personality disorders and violence: 1) Personality disorders are rarely ego dystonic; 2) Most patients and violent situations that come to clinical attention involve comorbid conditions. 3) Violence and violence risk are often associated with intoxication.     

Depression and neurological disorders

PURPOSE OF REVIEW: Clinical studies support a bidirectional link between depression and neurological diseases. Here we review the most recent findings supporting the hypothesis that major depression is a medical illness of the brain which can be elicited by neurological illnesses. RECENT FINDINGS: In the last year major improvements in brain-imaging techniques allowed correlations to be demonstrated between functional and structural brain abnormalities in specific brain areas (prefrontal cortex, hippocampus, cingulate gyrus) and the presence and severity of affective disorders, thus suggesting a neural basis for their onset and progression. Similar lesions, caused by neurological diseases, have been found to correlate with the presence of depression in neurological illnesses, but literature on the topic is still lacking. Depression in neurological disorders responds to the same treatments available for idiopathic major depression, but patients seem to have different sensitivities to side effects depending on their specific neurological syndrome. Most available data come from case reports and open trials. SUMMARY: 'Psychiatric' and 'neurologic' depression seem to share common abnormalities in specific brain areas, but sound brain-imaging studies of the neural correlates of depression in neurological disorders are still lacking. Available treatments are efficacious, but no clear-cut guidelines about the best drugs and dosages can be defined because double-blind placebo-controlled studies are still scarce.     

Electroconvulsive therapy in movement disorders: an update

Electroconvulsive therapy (ECT) is a well-recognized treatment for psychiatric illness, primarily depressive disorders. Its use in patients with neurological illnesses is steadily increasing. Older reviews indicate that ECT may also benefit Parkinson's disease and similar movement disorders independent of its effects on comorbid psychiatric disorders. In this updated review, recent literature regarding ECT and movement disorders is summarized from 1990 to 2000. Considerable evidence indicates that ECT improves motor symptoms of Parkinson's disease in patients with and without mood disorders. A few case reports, ranging from one to six patients per disorder, suggest that ECT may ameliorate the motor symptoms of other movement disorders. ECT affects a variety of neurotransmitters that play a role in these diseases. Limitations of current reports are reviewed, and recommendations for further investigation are made.     

Cortical spreading depression and the pathogenesis of brain disorders: a computational and neural network-based investigation

This paper reviews our recent studies of the role of cortical spreading depression (CSD) in the pathogenesis of brain disorders. Our investigation is a computational one, involving the development and utilization of a complex neuro-metabolic model of the interactions assumed to occur in the cortex during the passage of multiple CSD waves. Incorporating these neuro-metabolic changes of CSD within a neural network model of normoxic cortex produces cortical activation patterns during the passage of a CSD wave that, projected onto the visual fields, resemble the visual hallucinations observed during the migraine aura. When focal ischemia is simulated with the model, the evoked CSD waves are found to affect the expansion of the infarction into the ischemic penumbra. Our findings support the hypothesis that CSD does play an important pathogenic role in these and other neurological disorders, and suggest additional experimental studies that may further substantiate it.     

Obsessive-compulsive spectrum disorders

The obsessive-compulsive spectrum is an important concept referring to a number of disorders drawn from several diagnostic categories that share core obsessive-compulsive features. These disorders can be grouped by the focus of their symptoms: bodily preoccupation, impulse control, or neurological disorders. Although the disorders are clearly distinct from one another, they have intriguing similarities in phenomenology, etiology, pathophysiology, patient characteristics, and treatment response. In combination with the knowledge gained through many years of research on obsessive-compulsive disorder (OCD), the concept of a spectrum has generated much fruitful research on the spectrum disorders. It has become apparent that these disorders can also be viewed as being on a continuum of compulsivity to impulsivity, characterized by harm avoidance at the compulsive end and risk seeking at the impulsive end. The compulsive and impulsive disorders differ in systematic ways that are just beginning to be understood. Here, we review these concepts and several representative obsessive-compulsive spectrum disorders including both compulsive and impulsive disorders, as well as the three different symptom clusters: OCD, body dysmorphic disorder, pathological gambling, sexual compulsivity, and autism spectrum disorders.     

Comorbid depression and anxiety spectrum disorders

The relationship between depression and anxiety disorders has long been a matter of controversy. The overlap of symptoms associated with these disorders makes diagnosis, research, and treatment particularly difficult. Recent evidence suggests genetic and neurobiologic similarities between depressive and anxiety disorders. Comorbid depression and anxiety are highly prevalent conditions. Patients with panic disorder, generalized anxiety disorder, social phobia, and other anxiety disorders are also frequently clinically depressed. Approximately 85% of patients with depression also experience significant symptoms of anxiety. Similarly, comorbid depression occurs in up to 90% of patients with anxiety disorders. Patients with comorbid disorders do not respond as well to therapy, have a more protracted course of illness, and experience less positive treatment outcomes. One key to successful treatment of patients with mixed depressive and anxiety disorders is early recognition of comorbid conditions. Antidepressant medications, including the selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors, are highly effective in the management of comorbid depression and anxiety. The high rates of comorbid depression and anxiety argue for well-designed treatment studies in these populations. Depression and Anxiety 4:160–168, 1996/1997. © 1997 Wiley-Liss, Inc.     

Multilevel convergence of interoceptive impairments in hypertension: New evidence of disrupted body–brain interactions

Interoception, the sensing of visceral body signals, involves an interplay between neural and autonomic mechanisms. Clinical studies into this domain have focused on patients with neurological and psychiatric disorders, showing that damage to relevant brain mechanisms can variously alter interoceptive functions. However, the association between peripheral cardiac‐system alterations and neurocognitive markers of interoception remains poorly understood. To bridge this gap, we examined multidimensional neural markers of interoception in patients with early stage of hypertensive disease (HTD) and healthy controls. Strategically, we recruited only HTD patients without cognitive impairment (as shown by neuropsychological tests), brain atrophy (as assessed with voxel‐based morphometry), or white matter abnormalities (as evidenced by diffusion tensor imaging analysis). Interoceptive domains were assessed through (a) a behavioral heartbeat detection task; (b) measures of the heart‐evoked potential (HEP), an electrophysiological cortical signature of attention to cardiac signals; and (c) neuroimaging recordings (MRI and fMRI) to evaluate anatomical and functional connectivity properties of key interoceptive regions (namely, the insula and the anterior cingulate cortex). Relative to controls, patients exhibited poorer interoceptive performance and reduced HEP modulations, alongside an abnormal association between interoceptive performance and both the volume and functional connectivity of the above regions. Such results suggest that peripheral cardiac‐system impairments can be associated with abnormal behavioral and neurocognitive signatures of interoception. More generally, our findings indicate that interoceptive processes entail bidirectional influences between the cardiovascular and the central nervous systems.     

Anxiety disorders and schizophrenia

Anxiety symptoms and disorders have long been described in schizophrenia. This article reviews the epidemiology, phenomenology, and neurobiologic underpinnings of comorbid anxiety symptoms and disorders in schizophrenia. Recent literature was obtained by Medline searches using key words relating to schizophrenia and anxiety symptoms or disorders. There is some evidence that anxiety may be a core symptom dimension in schizophrenia, although further work is required. There is evidence that comorbid obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, and social anxiety disorder are all more common than expected by chance in schizophrenia, although additional work is needed to determine the mechanisms that underlie these associations and their clinical implications. In the interim, however, the data emphasize the importance of assessing and treating comorbid anxiety symptoms and disorders in schizophrenia.     

A two-year follow-up study of chronic fatigue syndrome comorbid with psychiatric disorders

Aims:  Chronic fatigue syndrome patients often have comorbid psychiatric disorders such as major depressive disorders and anxiety disorders. However, the outcomes of chronic fatigue syndrome and the comorbid psychiatric disorders and the interactions between them are unknown. Therefore, a two-year prospective follow-up study was carried out on chronic fatigue syndrome patients with comorbid psychiatric disorders.
Methods:  A total of 155 patients who met the Japanese case definition of chronic fatigue syndrome were enrolled in this study. Comorbid psychiatric disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria. Patients with comorbid psychiatric disorders received psychiatric treatment in addition to medical therapy for chronic fatigue syndrome. Seventy patients participated in a follow-up interview approximately 24 months later.
Results:  Of the 70 patients with chronic fatigue syndrome, 33 patients were diagnosed as having comorbid psychiatric disorders including 18 major depressive disorders. Sixteen patients with psychiatric disorders and eight patients with major depressive disorders did not fulfill the criteria of any psychiatric disorders at the follow up. As for chronic fatigue syndrome, nine out of the 70 patients had recovered at the follow up. There is no significant influence of comorbid psychiatric disorders on the outcome of chronic fatigue syndrome.
Conclusions:  Chronic fatigue syndrome patients have a relatively high prevalence of comorbid psychiatric disorders, especially major depressive disorders. The outcomes of chronic fatigue syndrome and psychiatric disorders are independent. Therefore treatment of comorbid psychiatric disorders is necessary in addition to the medical treatment given for chronic fatigue syndrome.     

Brain mechanisms underlying the placebo effect in neurological disorders

The potential of placebo treatments to alleviate a variety of medical conditions has long been recognised. Although the placebo effect is widely known, the physiological mechanisms underlying this phenomenon are not well understood. This review focuses on the existing evidence for placebo responses in different neurological conditions, including pain, Parkinson's disease, depression, sleep and immune-mediated disorders. Special attention is paid to the neural changes associated with placebo treatments, as revealed by in vivo neurophysiological and functional neuroimaging studies. Converging evidence suggests that placebo analgesia is linked to the activation of the endogenous opioid analgesia network, whilst dopaminergic pathways seem to play a central role in the placebo effect in movement disorders and neuroimmunomodulation. Further research on the placebo response is needed, both to improve the efficacy of its application in clinical practice and to shed more light on the complexity of mind-body interactions.     

Brief report: Comorbid psychiatric disorders of autistic disorder

Conclusion The behavioral and/or psychiatric symptoms in autistic people as described above have been viewed by many professionals dealing with autistic populations as associated features of autism that may result from these individuals' inability to cope with the environmental demands and physical discomfort. Traditionally, in treating individuals with autism, special education intervention including behavioral modifications has been the main emphasis. Such an approach has made some progress in milder and uncomplicated cases of autism. However, if many of these behavioral and/or psychiatric symptoms in those with more severe associated features can be viewed as symptoms of various comorbid psychiatric disorders, there are data suggesting that with an appropriate evaluation, predrug workups, a specific diagnosis, and multiple measures of outcome, pharmacotherapy can be a safe and efficacious adjunct treatment for some symptoms in autistic persons. Nevertheless, the data presented here were obtained mainly from autistic children. A great deal of work remains to be done Future research should put more emphasis on developing agreeable, reliable, and valid diagnostic instruments for identifying comorbid psychiatric disorders in autistic people. Future research should also emphasize employing a randomized double-blind placebo-controlled crossover design, as well as involving multicenters and using uniformed diagnostic criteria to study autistic adolescents and adults.     

Diagnosis and treatment of mood disorders in persons with epilepsy

PURPOSE OF REVIEW: Epilepsy is a common, disabling neurological disorder associated with increased rates of comorbid psychiatric disorders as compared with the general population. RECENT FINDINGS: Mood disorders, especially major depression, appear to be more prevalent in persons with epilepsy than in those with the other chronic disorders and the general population. Depression may have more influence on quality of life than do cognitive and seizure factors. Although psychological, social, and vocational disabilities contribute to mood dysfunction in epilepsy, functional neuroimaging studies have consistently shown correlation of presence of cerebral abnormalities with increased severity of symptoms of depression. Most persons with epilepsy are not routinely screened for depression, and depression is subsequently treated in only a minority of patients. Although serotonin receptor density is greatest in brain regions commonly associated with epilepsy, such as the mesial temporal and prefrontal areas, no controlled trials have investigated the efficacy of serotonin reuptake inhibitors in persons with epilepsy. Optimal methods to identify and treat depression in epilepsy require substantial further research. SUMMARY: Depression is a common comorbid condition with significant negative effects on health status in persons with epilepsy, but additional understanding of the disorder is needed to improve diagnosis and treatment.     

Cortical spreading depression and the pathogenesis of brain disorders: A computational and neural network-based investigation

Abstract

This paper reviews our recent studies of the role of cortical spreading depression (CSD) in the pathogenesis of brain disorders. Our investigation is a computational one, involving the development and utilization of a complex neuro-metabolic model of the interactions assumed to occur in the cortex during the passage of multiple CSD waves. Incorporating these neuro-metabolic changes of CSD within a neural network model of normoxic cortex produces cortical activation patterns during the passage of a CSD wave that, projected onto the visual fields, resemble the visual hallucinations observed during the migraine aura. When focal ischemia is simulated with the model, the evoked CSD waves are found to affect the expansion of the infarction into the ischemic penumbra. Our findings support the hypothesis that CSD does play an important pathogenic role in these and other neurological disorders, and suggest additional experimental studies that may further substantiate it. [Neurol Res 2001; 23: 447-456]     

Deep brain stimulation in neuropsychiatric disorders

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus, subthalamic nucleus, and internal globus pallidus has been put forth as an alternative to surgical ablation for the treatment of movement disorders. In this paper, the authors discuss the history and putative physiologic mechanisms underlying DBS of these target regions. The authors then review empirical findings pertaining to the effects of DBS on neurological symptoms, cognitive functioning, and psychiatric symptoms in Parkinson's disease and essential tremor, the disorders for which the procedure has been most extensively applied. Finally, emerging and potential novel areas of application of DBS for the treatment of neuropsychiatric disorders and symptoms are discussed.     

Deep brain stimulation in neuropsychiatric disorders

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus, subthalamic nucleus, and internal globus pallidus has been put forth as an alternative to surgical ablation for the treatment of movement disorders. In this paper, the authors discuss the history and putative physiologic mechanisms underlying DBS of these target regions. The authors then review empirical findings pertaining to the effects of DBS on neurological symptoms, cognitive functioning, and psychiatric symptoms in Parkinson’s disease and essential tremor, the disorders for which the procedure has been most extensively applied. Finally, emerging and potential novel areas of application of DBS for the treatment of neuropsychiatric disorders and symptoms are discussed.     

Comorbid psychiatric disorders in late life depression.

In late life depression, common comorbid psychiatric disorders are alcohol use, anxiety, and personality disorders. Elderly depressed patients are three to four times more likely to have an alcohol use disorder compared with nondepressed elderly subjects, with a prevalence of 15%-30% in patients with late life major depression. While the presence of a comorbid alcohol use disorder may worsen the prognosis for geriatric depression, limited data suggest that successful treatment of depression combined with reducing alcohol use leads to the best possible outcomes. Most studies show that the overall prevalence of anxiety disorders, particularly panic disorder and obsessive-compulsive disorder, is low in geriatric depression, but generalized anxiety disorder may not be uncommon. It remains unclear if the presence of a comorbid anxiety disorder impacts on the treatment and prognosis of late life major depression. Personality disorders occur in 10%-30% of patients with late life major depression or dysthymic disorder, particularly in patients with early onset depressive illness. Cluster C disorders, including the avoidant, dependent, and obsessive-compulsive subtypes predominate, while Cluster B diagnoses, including borderline, narcissistic, histrionic and antisocial, are rare. Overall, the research database on comorbid psychiatric disorders in major and nonmajor late life depression is relatively sparse. Since comorbid psychiatric disorders affect clinical course and prognosis, and may worsen long-term disability in late life depression, considerably more research in this field is needed.