scispace - formally typeset
Search or ask a question

Showing papers in "Cns Spectrums in 2007"


Journal ArticleDOI
TL;DR: Findings suggest that the precuneus may play a central role in the neural network correlates of consciousness, and its activity seems to correlate with self-reflection processes, possibly involving mental imagery and episodic/autobiographical memory retrieval.
Abstract: This article reviews the rapidly growing literature on the functional anatomy and behavioral correlates of the precuneus, with special reference to imaging neuroscience studies using hamodynamic techniques. The precuneus, along with adjacent areas within the posteromedial parietal cortex, is among the most active cortical regions according to the "default mode" of brain function during the conscious resting state, whereas it selectively deactivates in a number of pathophysiological conditions (ie, sleep, vegetative state, drug-induced anesthesia), and neuropsychiatric disorders (ie, epilepsy, Alzheimer's disease, and schizophrenia) characterized by impaired consciousness. These findings, along with the widespread connectivity pattern, suggest that the precuneus may play a central role in the neural network correlates of consciousness. Specifically, its activity seems to correlate with self-reflection processes, possibly involving mental imagery and episodic/autobiographical memory retrieval.

304 citations


Journal ArticleDOI
TL;DR: Clinicians caring for persons with mitochondrial cytopathies should note the high prevalence of psychiatric problems, as this comorbidity might have etiological and therapeutic implications.
Abstract: Introduction:Mitochondria are intracellular organelles involved in adenosine triphosphate production. The literature has established the presence of mitochondrial dysfunction in some subjects with psychiatric disorders. Also, there are multiple reports of patients with mitochondrial dysfunction who have various psychiatric disorders. Although the literature on mitochondrial dysfunction and its relation to psychiatric disorders is growing, there remain many unanswered questions.Objective:To review subjects with mitochondrial cytopathies for prevalence of psychiatric comorbidity.Methods:For this study, 36 adults were interviewed. The Mini International Neuropsychiatric Interview and the Short-Form 36 Health Survey, version 1 were used.Results:Lifetime diagnoses included 54% major depressive disorder, 17% bipolar disorder, and 11% panic disorder. These prevalence rates are compared with the general population and subjects with cancer and epilepsy. Subjects with a comorbid psychiatric diagnosis were older (P=.05), had more hospital admissions (P=.02), more medical conditions (P=.01), and lower quality of life (P=.01) than subjects with mitochondrial disease alone.Conclusion:Clinicians caring for persons with mitochondrial cytopathies should note the high prevalence of psychiatric problems. Also, this comorbidity might have etiological and therapeutic implications.

174 citations


Journal ArticleDOI
TL;DR: There is no standard treatment for compulsive buying disorder, but group cognitive-behavioral models seem promising, and psychopharmacologic treatments are being actively studied.
Abstract: Compulsive buying disorder is characterized by excessive or poorly controlled preoccupations, urges, or behaviors regarding shopping and spending that lead to subjective distress or impaired functioning. Compulsive buying disorder is estimated to have a lifetime prevalence of 5.8% in the United States general adult population. In clinical settings, most individuals with compulsive buying disorder are women (approximately 80%). This gender difference may be artifactual. Compulsive buying disorder is typically chronic or intermittent, with an age of onset in the late teens or early 20s. Comorbid mood and anxiety disorders, substance use disorders, eating disorders, and other disorders of impulse control are common, as are Axis II disorders. The disorder occurs worldwide, mainly in developed countries with market-based economies, and it tends to run in families with mood disorders and substance abuse. There is no standard treatment for compulsive buying disorder, but group cognitive-behavioral models seem promising, and psychopharmacologic treatments are being actively studied. Other treatment options include simplicity circles, 12-step programs, financial counseling, bibliotherapy, marital therapy, and financial counseling. Directions for future research are discussed.

142 citations


Journal ArticleDOI
TL;DR: There is growing evidence, from both preclinical and clinical studies, that the dopamine system may also be involved in the pathogenesis of OCD, and that dopaminergic and serotonergic pathways play a role in the genesis and maintenance of obsessive-compulsive symptoms.
Abstract: The evidence for the involvement of the serotonergic system in the pathogenesis of obsessive-compulsive disorder (OCD) is circumstantial at best, despite being the focus for most pathophysiological research over the last 2 decades. This hypothesis was initially motivated by the observed differential efficacy of selective serotonin reuptake inhibitors in alleviating OCD symptoms. Direct evidence that serotonergic perturbations are implicated in the pathophysiology of OCD is still sparse. There is growing evidence, from both preclinical and clinical studies, that the dopamine system may also be involved in the pathogenesis of OCD, and that dopaminergic and serotonergic pathways play a role in the genesis and maintenance of obsessive-compulsive symptoms. The complex interactions between both systems, the phenotypic heterogeneity of the disorder, and the limitations of the available tests to probe both systems, make it as yet impossible to draw firm conclusions as to how these systems are implicated. Further studies with more selective pharmacologic agents and neurocognitive probes in humans, studies using deep brain stimulation in combination with neuroimaging, and the development of better animal models for OCD may further our understanding of this disabling condition.

139 citations


Journal ArticleDOI
TL;DR: The authors review the evidence on the impact of PG on families, marriages, and offspring, and make recommendations for future research targeting these problems.
Abstract: Pathological gambling (PG) is widely reported to have negative consequences on marriages, families, and children. Empirical evidence is only now accumulating but when put together with anecdotal information, the extent of these problems is clear. PG contributes to chaos and dysfunction within the family unit, disrupts marriages, leading to high rates of separation and divorce, and is associated with child abuse and neglect. Divorce rates are high, not surprising in light of reports that these marriages are often abusive. Research shows that the families of pathological gamblers are filled with members who gamble excessively, suffer from depressive or anxiety disorders, and misuse alcohol, drugs, or both. Families of persons with PG are also large, a variable independently related to family dysfunction. The authors review the evidence on the impact of PG on families, marriages, and offspring, and make recommendations for future research targeting these problems.

132 citations


Journal ArticleDOI
TL;DR: The first in the series of articles is to broaden knowledge and interest in neuroanatomy, with a special reference to some key brain structures that are important for neuropsychiatry, and reviews the ventral striatum.
Abstract: Over the next 2 years, CNS Spectrums will be publishing a series of articles on neuroanatomy. The purpose of these articles is to broaden knowledge and interest in neuroanatomy, with a special reference to some key brain structures that are important for neuropsychiatry. Interest in nuclear structures and hodology, in connectivity and circuitry between brain regions, and in neurochemical associations has increased in the last 3 decades due to new neuroanatomical staining methods, brain imaging, and new treatments, such as deep brain stimulation.These columns will enliven an understanding of the clinical neuroscience interface but also provide a solid framework of contemporary neuroanatomy for psychiatrists and neurologists.The first in the series reviews the ventral striatum. Henk J. Groenewegen, MD, PhD, in a column dedicated to the late Lennart Heimer, MD, reveals the importance of this structure and its connectivity for a contemporary understanding of brain-behavior relationships. In earlier conceptions, the basal ganglia were solely related to motor function, uninvolved with emotion or cognition. This conception arose from a misunderstanding of basic neuroanatomy, which has been unravelled by careful neuroanatomical studies in the last 30 years with new tissue staining and tracing techniques.The basal ganglia are the main target structures of the limbic system, hence the motion in emotion.

122 citations


Journal ArticleDOI
TL;DR: Clinicians should be familiar with the extent of problematic Internet use and the data regarding the efficacies and tolerabilities of available treatments, according to epidemiological and clinical perspectives.
Abstract: Impulse-control disorders have received relatively little attention from the mental health community. An increasing awareness of the prevalence and impact of these disorders is emerging. Among impulse control disorders, problematic Internet use has been considered and examined. Prevalence estimate studies indicate that problematic Internet use is experienced across geographic locations by many individuals of diverse backgrounds. This review examines problematic Internet use from epidemiological and clinical perspectives. Clinicians should be familiar with the extent of problematic Internet use and the data regarding the efficacies and tolerabilities of available treatments.

118 citations


Journal Article
TL;DR: Recommendations are provided for patients and physicians based on collaborative care interventions that may be useful for improving the current management of depressive disorders and the importance of factors other than antidepressant medication per se for achieving treatment effectiveness is demonstrated.
Abstract: Major depressive disorder (MDD) is often a chronic, recurrent, and debilitating disorder with a lifetime prevalence of 16.2% and a 12-month prevalence of 6.6% in the United States. The disorder is associated with high rates of comorbidity with other psychiatric disorders and general medical illnesses, lower rates of adherence to medication regimens, and poorer outcomes for chronic physical illness. While 51.6% of cases reporting MDD received health care treatment for the illness, only 21.7% of all MDD cases received minimal guideline-level treatment. Because the overwhelming majority of patients with depressive disorders are seen annually by their primary care physicians, the opportunity to diagnose and treat patients early in the course of their illness in the primary care setting is substantial, though largely unfulfilled by our current health care system. The goal of treatment is 2-fold: early and complete remission of symptoms of depression and eventual recovery to premorbid levels of functioning in response to acute-phase treatment, and prevention of relapse during the continuation phase or recurrence during the maintenance phase. However, only 25% to 50% of patients with MDD adhere to their antidepressant regimen for the length of time recommended by depression guidelines, and nearly 50% of depressed patients referred from primary care to specialty care treatment fail to complete the referral. Patients with chronic or treatment-resistant depression often require multiple trials using an algorithm-based approach involving more than one treatment strategy. Under conditions of usual care, 40% to 44% of patients with MDD treated with antidepressants in the primary care setting show a >or=50% improvement in depression scores at 4-month follow-up, compared with 70% to 75% of those treated using collaborative care models. This demonstrates the importance of factors other than antidepressant medication per se for achieving treatment effectiveness. Additional research is needed to evaluate longer-term outcomes of algorithm-based, stepped, collaborative care models that incorporate patient self-management in conjunction with usual care. Furthermore, the health care system must undergo major transformation to effectively treat depression, along with other chronic illnesses. The use of evidence-based treatment algorithms are discussed and recommendations are provided for patients and physicians based on collaborative care interventions that may be useful for improving the current management of depressive disorders.

111 citations


Journal ArticleDOI
TL;DR: It is suggested that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled.
Abstract: Anxiety disorders are commonly treated with exposure-based therapies that rely on extinction of conditioned fear. Persistent fear and anxiety following exposure therapy could reflect a deficit in the recall of extinction learning. Animal models of fear learning have elucidated a neural circuit for extinction learning and recall that includes the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus. Whereas the amygdala is important for extinction learning, the vmPFC is a site of neural plasticity that allows for the inhibition of fear during extinction recall. We suggest that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled. Imaging studies of human fear conditioning and extinction lend credence to this extinction network. Understanding the neural circuitry underlying extinction recall will lead to more effective therapies for disorders of fear and anxiety.

104 citations


Journal ArticleDOI
TL;DR: In this article, a review examines potential classifications of OCD among the wider spectrum of affective disorders and at the interface between affective disorder and addiction, and its implications for diagnosis, treatment, and research are discussed.
Abstract: Although obsessive-compulsive disorder (OCD) is classified as an anxiety disorder in the DSM-IV, recent considerations for a reclassification into an obsessive-compulsive spectrum disorders (OCSDs) cluster are gaining prominence. Similarities in symptomatology, course of illness, patient population, and neurocircuitry of OCD and OCSD are supported by comorbidity, family, and neurological studies, which also offer a critical re-evaluation of the relationship between OCD and anxiety disorders. This review examines potential classifications of OCD among the wider spectrum of affective disorders and at the interface between affective disorders and addiction. In addition, it has been suggested that the categorical diagnostic approach would be enhanced by an additional dimensional approach, including parameters such as stability of mood and ability to sustain attention. With further studies, it is ultimately the goal to define OCD and related disorders based on endophenotypes. Despite efforts in this field, there are several fundamental unresolved issues, including the question of which disorders should be grouped together in this category and which characteristics to include as their shared common features. A reclassification of OCD among the OCSDs would allow for better scrutiny of distinct obsessive-compulsive symptoms, as currently this disorder often goes undetected in patients who complain of a broad symptom of anxiety. Advantages and disadvantages of establishing OCSDs and its implications for diagnosis, treatment, and research are discussed.

101 citations


Journal ArticleDOI
TL;DR: Brain-damaged patients with lesion or dysfunction involving the parietal cortex may show a variety of neuropsychological impairments involving spatial cognition, including the syndrome of unilateral spatial neglect, which is typically associated with bilateral posterior parietal and occipital damage.
Abstract: Brain-damaged patients with lesion or dysfunction involving the parietal cortex may show a variety of neuropsychological impairments involving spatial cognition. The more frequent and disabling deficit is the syndrome of unilateral spatial neglect that, in a nutshell, consists in a bias of spatial representation and attention ipsilateral to of extrapersonal, personal (ie, the body) space, or both, toward the side of the hemispheric lesion. The deficit is more frequent and severe after damage to the right hemisphere, involving particularly the posterior-inferior parietal cortex at the temporo-parietal junction. Damage to these posterior parietal regions may also impair visuospatial short-term memory, which may be associated with and worsen spatial neglect. The neural network supporting spatial representation, attention and short-term memory is, however, more extensive, including the right premotor cortex. Also disorders of drawing and building objects (traditionally termed constructional apraxia) are a frequent indicator of posterior parietal damage in the left and in the right hemispheres. Other less frequent deficits, which, however, have a relevant localizing value, include optic ataxia (namely, the defective reaching of visual objects, in the absence of elementary visuo-motor impairments), which is typically brought about by damage to the superior parietal lobule. Optic ataxia, together with deficits of visual attention, of estimating distances and depth, and with apraxia of gaze, constitutes the severely disabling Balint-Holmes' syndrome, which is typically associated with bilateral posterior parietal and occipital damage. Finally, lesions of the posterior parietal lobule (angular gyrus) in the left hemisphere may bring about a tetrad of symptoms (left-right disorientation, acalculia, finger agnosia, and agraphia) termed Gerstmann's syndrome, that also exists in a developmental form.

Journal ArticleDOI
TL;DR: Available data suggests that oral CoQ10 seems to be relatively safe and tolerated across the range of 300–2,400 mg/day, and Randomized controlled trials are warranted to confirm Co Q10's safety and promise as a clinically effective neuroprotectant.
Abstract: Coenzyme Q10 (CoQ10) is a powerful antioxidant that buffers the potential adverse consequences of free radicals produced during oxidative phosphorylation in the inner mitochondrial membrane. Oxidative stress, resulting in glutathione loss and oxidative DNA and protein damage, has been implicated in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Experimental studies in animal models suggest that CoQ10 may protect against neuronal damage that is produced by ischemia, atherosclerosis and toxic injury. Though most have tended to be pilot studies, there are published preliminary clinical trials showing that CoQ10 may offer promise in many brain disorders. For example, a 16-month randomized, placebo-controlled pilot trial in 80 subjects with mild Parkinson's disease found significant benefits for oral CoQ10 1,200 mg/day to slow functional deterioration. However, to date, there are no published clinical trials of CoQ10 in Alzheimer's disease. Available data suggests that oral CoQ10 seems to be relatively safe and tolerated across the range of 300-2,400 mg/day. Randomized controlled trials are warranted to confirm CoQ10's safety and promise as a clinically effective neuroprotectant.

Journal ArticleDOI
TL;DR: Clinicians can improve psychiatric and physical health by selecting medications carefully, routinely screening and monitoring for reversible cardiovascular risk factors, and playing an active role in the prevention and interdisciplinary management of cardiovascular risk Factors and medical illness in the vulnerable mentally ill.
Abstract: Balancing efficacy with tolerability and safety of prescribed treatments is critical to optimizing antipsychotic treatment outcomes in the mentally ill. Symptom control, symptom remission, and functional recovery are only realistic goals when treatments are both effective and well tolerated. The consideration of predictable differences in antipsychotic adverse-effect profiles is central to successful illness management. Minimizing adverse effects on alertness, motivation, cognition, sexual/reproductive functioning, and physical health enhances mental health outcomes, partly through improving treatment adherence. Neuroendocrine and metabolic side effects of antipsychotics for cardiovascular morbidity and mortality need to be addressed proactively and aggressively. In view of the widespread lack of primary care engagement and the adverse effects of psychotropic medications on cardiovascular health, psychiatric care providers should function as key facilitators of an integrated mental and physical health management approach. In addition to psychoeducation and healthy lifestyle counseling, clinicians can improve psychiatric and physical health by selecting medications carefully, routinely screening and monitoring for reversible cardiovascular risk factors, and playing an active role in the prevention and interdisciplinary management of cardiovascular risk factors and medical illness in the vulnerable mentally ill.

Journal ArticleDOI
TL;DR: Nonadherence to medication is a frequent cause of exacerbations in psychopathology, psychotic relapse, and rehospitalization, and a number of strategies have been developed to assess and facilitate adherence.
Abstract: The successful management of schizophrenia is an enormous public health issue. Although antipsychotic medications can be very helpful in reducing rates of relapse and rehospitalization, nonadherence to medication is a frequent cause of exacerbations in psychopathology, psychotic relapse, and rehospitalization. Relapses can have devastating consequences in a variety of clinical and functional domains. Nonadherence can result from a variety of factors that vary from patient to patient and vary over time in individual patients. A number of strategies have been developed to assess and facilitate adherence. The first critical step is clinician awareness of the scope of the problem and consideration of appropriate strategies to address it.

Journal ArticleDOI
TL;DR: The dopamine hypothesis has dominated theories of schizophrenia, based initially upon observations that drugs that increase dopamine, such as amphetamine and cocaine, can cause psychosis, whereas antipsychotic drugs that decrease dopamine by blocking dopamine D2 receptors can treat psychosis.
Abstract: NEW TREND IN PSYCHOPHARMACOLOGY Hypotheses of schizophrenia have progressed beyond the dopamine hypothesis of overactive mesolimbic dopamine neurons, causing the positive symptoms of psychosis and underactive mesocortical dopamine neurons, causing the negative, cognitive and affective symptoms of schizophrenia. A major hypothesis of schizophrenia proposes that numerous genetic risk factors converge on the A/-methyl-D-aspartate (NMDA) receptor for the neurotransmitter glutamate. Theoretically, neurodevelopmental abnormalities in glutamate synapse formation result in the hypofunction of NMDA receptors. Since NMDA receptors regulate dopamine neurons, the hypofunction of NMDA receptors may be responsible for the abnormal dopamine activity associated with the symptoms of schizophrenia. For more than 30 years, the dopamine hypothesis has dominated theories of schizophrenia, based initially upon observations that drugs that increase dopamine, such as amphetamine and cocaine, can cause psychosis, whereas antipsychotic drugs that decrease dopamine by blocking dopamine D2 receptors can treat psychosis. 1

Journal ArticleDOI
TL;DR: Although the understanding of the dimensional structure of obsessive-compulsive symptoms (OCS) is still imperfect, this quantitative approach to phenotypic traits has the potential to advance the authors' understanding of OCD and may aid in the identification of more robust endophenotypes.
Abstract: In the absence of definitive etiological markers of vulnerability or a unitary profile of pathophysiology for obsessive-compulsive disorder (OCD), obsessive-compulsive (OC) symptom dimensions seem to offer a fruitful point of orientation. The complex clinical presentation of OCD can be summarized using a few consistent and temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping features that are likely to be continuous with "normal" worries and extend beyond the traditional nosological boundaries of OCD. Although the understanding of the dimensional structure of obsessive-compulsive symptoms (OCS) is still imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. Preliminary data suggest that these dimensional phenotypes may be useful in studies of the natural history, genetics, neurobiology, and treatment outcome of OCD. A dimensional approach is not mutually exclusive of other methods to parse the larger spectrum of disorders related to OCD. Thus far, age-of-onset of OCS and the individual's "tic-related" status seem to be particularly useful categorical distinctions. Finally, existing assessment methods are inadequate and new dimensional scales are needed to take full advantage of a dimensional approach in clinical and population-based studies.

Journal ArticleDOI
TL;DR: Identifying the functional neuroanatomical profile of brain systems involved in the regulation of emotion and behavior in the postpartum period will increase the understanding of the affective disorder spectrum, shed additional light on the possible mechanism(s) responsible for PPD and provide a necessary foundation for the development of more targeted, biologically based diagnostic and therapeutic strategies for P PD.
Abstract: Introduction With approximately 4 million births each year in the United States, an estimated 760,000 women annually suffer from a clinically significant postpartum depressive illness. Yet even though the relationship between psychiatric disorders and the postpartum period has been documented since the time of Hippocrates, fewer than half of all these cases are recognized. Objective Because postpartum depression (PPD), the most common complication of childbearing, remains poorly characterized, and its etiology remains unclear, we attempted to address a critical gap in the mechanistic understanding of PPD by probing its systems-level neuropathophysiology, in the context of a specific neurobiological model of fronto-limbic-striatal function. Methods Using emotionally valenced word probes, with linguistic semantic specificity within an integrated functional magnetic resonance imaging (fMRI) protocol, we investigated emotional processing, behavioral regulation, and their interaction (functions of clinical relevance to PPD), in the context of fronto-limbic-striatal function. Results We observed attenuated activity in posterior orbitofrontal cortex for negative versus neutral stimuli with greater PPD symptomatology, increased amygdala activity in response to negative words in those without PPD symptomotology, and attenuated striatum activation to positive word conditions with greater PPD symptomotology. Conclusion Identifying the functional neuroanatomical profile of brain systems involved in the regulation of emotion and behavior in the postpartum period will not only assist in determining whether the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition psychiatric diagnostic specifier of PPD has an associated, unique, functional neuroanatomical profile, but a neurobiological characterization in relation to asymptomatic (postpartum non-depressed) control subjects, will also increase our understanding of the affective disorder spectrum, shed additional light on the possible mechanism(s) responsible for PPD and provide a necessary foundation for the development of more targeted, biologically based diagnostic and therapeutic strategies for PPD.

Journal ArticleDOI
TL;DR: The clinician is provided with a summary of risk factors for youth suicide, as well as providing standardized terminology to enhance assessment of suicidal ideation and behavior.
Abstract: Suicide remains a leading cause of death among youth, and suicide ideation and behavior are relatively common in both normal and clinical populations. Clinicians working with young people must assess for the presence of suicidal ideation, suicidal behavior, and other risk factors, in order to determine the level of risk. This paper provides the clinician with a summary of risk factors for youth suicide, as well as providing standardized terminology to enhance assessment of suicidal ideation and behavior.

Journal ArticleDOI
TL;DR: Open-label aripiprazole treatment was beneficial in the treatment of mania in youth with bipolar disorder and future placebo-controlled, double blind studies are warranted.
Abstract: INTRODUCTION Aripiprazole is a novel second-generation antipsychotic approved for the treatment of bipolar disorder in adults but there is no systematic data available in pediatric bipolar disorder. METHODS This was an 8-week, open-label, prospective study of aripiprazole 9.4+/-4.2 mg/day monotherapy to assess the efficacy and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale, Clinical Global Impressions-Improvement scale, and Brief Psychiatric Rating Scale. Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. RESULTS Fifteen of the 19 bipolar youth (79%) completed the study. Aripiprazole treatment was associated with clinically and statistically significant improvement in mean Young Mania Rating Scale scores (-18.0+/-6.9, P<.0001). With the important exception of two cases of extrapyramidal symptoms that precipitated dropout, aripiprazole was well tolerated with no statistically significant increase in body weight (1.8+/-1.7 kg, P=.2). CONCLUSION Open-label aripiprazole treatment was beneficial in the treatment of mania in youth with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.

Journal ArticleDOI
TL;DR: The putative mechanism of action of MTHF as an augmenting agent to antidepressants is that it acts as a trimonoamine modulator (TMM), enhancing the synthesis of the three monoamines: dopamine (DA), norepinephrine (NE), and serotonin (5-HT), resulting in a boost to the efficacy of antidepressants.
Abstract: Folate deficiency may increase the risk of depression and reduce the action of antidepressants. Individuals with an inherited polymorphism that reduces the efficiency of folate formation may be at high risk for folate deficiency and for major depression. Antidepressant effects have been reported when antidepressants are augmented with folic acid, folinic acid, or the centrally active L-methylfolate (known formally as (6(S)-5-methyltetrahydrofolate [MTHF]), particularly in depressed patients with folate deficiency whose major depressive episodes have failed to respond to antidepressants. The putative mechanism of action of MTHF as an augmenting agent to antidepressants is that it acts as a trimonoamine modulator (TMM), enhancing the synthesis of the three monoamines: dopamine (DA), norepinephrine (NE), and serotonin (5-HT), resulting in a boost to the efficacy of antidepressants.

Journal ArticleDOI
TL;DR: Preclinical studies suggest that the neural circuitry and pharmacology of the cannabinoid system as it relates to the acquisition, expression, and extinction of conditioned fear as a model of human anxiety may provide important emerging targets for new treatments of anxiety disorders.
Abstract: The last decade has witnessed remarkable progress in the understanding of the mammalian cannabinoid system, from the cloning of the endogenous cannabinoid receptor to the discovery of new pharmacologic compounds acting on this receptor. Current and planned studies in humans include compounds with effects ranging from direct antagonists to inhibitors of reuptake and breakdown. This progress has been accompanied by a much greater understanding of the role of the cannabinoid system in modulating the neural circuitry that mediates anxiety and fear responses. This review focuses on the neural circuitry and pharmacology of the cannabinoid system as it relates to the acquisition, expression, and extinction of conditioned fear as a model of human anxiety. Preclinical studies suggest that these may provide important emerging targets for new treatments of anxiety disorders.

Journal ArticleDOI
TL;DR: Schizophrenia is a neurodevelopmental disorder associated with persistent symptomatology, severe functional disability, and residual morbidity characteristic of neurodegenerative brain diseases as discussed by the authors, however, identifying and treating patients in the earliest disease states presents methodological challenges as there is no consensus on the best methods of intervention and differences in atrisk children are not readily detectable or substantial enough to predict which ones will develop schizophrenia.
Abstract: Schizophrenia is a neurodevelopmental disorder associated with persistent symptomatology, severe functional disability, and residual morbidity characteristic of neurodegenerative brain diseases. The illness begins with genetic susceptibility and generally expresses itself after puberty through subtle changes that begin during the prodromal stage. Symptoms get progressively worse and tend to become more resistant to treatment with each relapse. Evidence for a neuroprotective effect of some forms of early treatment is beginning to emerge. While the underlying mechanisms remain uncertain, atypical antipsychotics may counteract some of the progressive deteriorative effects by enhancing synaptic plasticity and cellular resilience. However, identifying and treating patients in the earliest disease states presents methodological challenges as there is no consensus on the best methods of intervention and differences in at-risk children are not readily detectable or substantial enough to predict which ones will develop schizophrenia. In this expert roundtable supplement, Jeffrey A. Lieberman, MD, reviews the historical context of progressive deterioration in schizophrenia. Next, Diana O. Perkins, MD, MPH, reviews some of the challenges to early identification of illness as well as the impact of early versus delayed treatment. Finally, L. Fredrik Jarskog, MD, focuses on the neurobiology of functional progression in schizophrenia as well as pharmacology and the potential for neuroprotection.

Journal ArticleDOI
TL;DR: An expert roundtable supplement will address the diagnosis, pathophysiology, phenomenology, classification, and history of akathisia as well as discuss screening tools and treatment options for the condition.
Abstract: Akathisia is a neurological side effect of antipsychotic medications, which are used to treat various psychiatric disorders, and is characterized by physical restlessness and a subjective urge to move. Although side effects, such as akathisia, dystonia, and dyskinesia, are common for conventional medications, these effects occur in reduced frequency with the use of new-generation antipsychotics. Despite a lowered incidence profile, akathisia and similar conditions continue to affect patients. Neuroleptic-induced akathisia can present as fidgety movements while seated, rocking in place while standing, pacing, or the inability to sit or stand still for an extended period of time as well as the overwhelming urge to move, which can cause severe distress and an increased risk of suicide for affected patients. First-line treatment of akathisia includes benzodiazepines or beta-blockers for patients who do not have symptoms of Parkinson's disease and anticholinergics for patients with Parkinson's symptoms. Clinicians should ensure that an accurate diagnosis of akathisia is made and target symptoms are decreasing due to treatment, which does not negatively affect the mental health of the patient. This expert roundtable supplement will address the diagnosis, pathophysiology, phenomenology, classification, and history of akathisia as well as provide screening tools and treatment options for the condition.

Journal ArticleDOI
TL;DR: The findings indicate that patients with different psychiatric disorders would be characterized by higher scores on both the ECR anxiety and the avoidance scales, as well as by the preoccupied style of attachment.
Abstract: IntroductionRomantic attachment is the establishment of a relationship with a partner and is strongly influenced by the individual's attachment style. While several studies have shown that attachment style may contribute to the development of psychopathology, less information is available for romantic attachment.The aim of the present study was to compare romantic attachment styles among patients with different mood and anxiety disorders and control subjects.MethodThe study sample included a total of 126 outpatients, 62 of whom were affected by bipolar disorders, 22 by major depressive disorder (MDD), 27 by panic disorder, 15 by obsessive-compulsive disorder, and 126 healthy control subjects. Romantic attachment was assessed by means of the Italian version of the “Experiences in Close Relationships” (ECR) questionnaire.ResultsThe results showed that the secure attachment style was more frequent in the control group, while the preoccupied style prevailed among the patients, with no difference among the diagnostic categories.The scores of the ECR anxiety and avoidance scales were significantly higher in the patients than in the control subjects. A trend toward higher ECR anxiety scale scores in women with panic disorder was detected, with the opposite being true for MDD.ConclusionOur findings indicate that patients with different psychiatric disorders would be characterized by higher scores on both the ECR anxiety and the avoidance scales, as well as by the preoccupied style of attachment. In addition, women with panic disorder and MDD seem to be characterized by, respectively, higher and lower scores of the ECR anxiety scale than men.

Journal ArticleDOI
TL;DR: The neurocircuitry and neurochemistry of physical pain would overlap with that involved in complex social emotions, and exposure to trauma as well as a range of gene variants in the opioid system may be associated with alterations in opioid systems function.
Abstract: The opioid systems play an important role in mediating both physical pain and negative affects (eg, the pain of social isolation). From an evolutionary perspective, it is not surprising that the neurocircuitry and neurochemistry of physical pain would overlap with that involved in complex social emotions. Exposure to trauma as well as a range of gene variants in the opioid system may be associated with alterations in opioid systems function, with changes in reward processing, and with vulnerability to substance abuse. A role for interventions with opioid agents in depression and anxiety disorders has been suggested.

Journal ArticleDOI
TL;DR: By viewing OCPD as a candidate member of the obsessive-compulsive spectrum, a fresh approach to understanding its neurobiology, etiology, and potential treatments is gained.
Abstract: It has been proposed that certain Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders share overlapping clinical features, genetic contributions, and treatment response and fall within an "obsessive-compulsive" spectrum. Obsessive-compulsive personality disorder (OCPD) resembles obsessive-compulsive disorder (OCD) and other spectrum disorders in terms of phenomenology, comorbidity, neurocognition, and treatment response. This article critically examines the nosological profile of OCPD with special reference to OCD and related disorders. By viewing OCPD as a candidate member of the obsessive-compulsive spectrum, we gain a fresh approach to understanding its neurobiology, etiology, and potential treatments.

Journal ArticleDOI
TL;DR: Additional research is needed on the relationship of BDD and eating disorders to OCD, including studies that directly compare them to OCD in a variety of domains, including phenomenology, family history, neurobiology, and etiology.
Abstract: Body dysmorphic disorder (BDD) and eating disorders are body image disorders that have long been hypothesized to be related to obsessive-compulsive disorder (OCD). Available data suggest that BDD and eating disorders are often comorbid with OCD. Data from a variety of domains suggest that both BDD and eating disorders have many similarities with OCD and seem related to OCD. However, these disorders also differ from OCD in some ways. Additional research is needed on the relationship of BDD and eating disorders to OCD, including studies that directly compare them to OCD in a variety of domains, including phenomenology, family history, neurobiology, and etiology.

Journal ArticleDOI
TL;DR: This review maps the nosological relationships of OCD to other neuropsychiatric disorders, using OCD as the prototype disorder and endophenotype markers, using cognitive, imaging, and molecular data as well as results from demographic, comorbidity, family, and treatment studies.
Abstract: The boundaries between obsessive-compulsive disorder (OCD) and other neuropsychiatric disorders remain unresolved and may well differ from one disorder to another. Endophenotypes are heritable, quantitative traits hypothesized to more closely represent genetic risk for complex polygenic mental disorders than overt symptoms and behaviors. They may have a role in identifying how closely these disorders are associated with another and with other mental disorders with which they share major comorbidity. This review maps the nosological relationships of OCD to other neuropsychiatric disorders, using OCD as the prototype disorder and endophenotype markers, such as cognitive, imaging, and molecular data as well as results from demographic, comorbidity, family, and treatment studies. Despite high comorbidity rates, emerging evidence suggests substantial endophenotypic differences between OCD and anxiety disorders, depression, schizophrenia, and addictions, though comparative data is lacking and the picture is far from clear. On the other hand, strong relationships between OCD, Tourette syndrome, body dysmorphic disorder, hypochondriasis, grooming disorders, obsessive-compulsive personality disorder, and pediatric autoimmune neuropsychiatric disorders associated with streptococcus are likely. Studies designed to delineate the cause, consequences, and common factors are a challenging but essential goal for future research in this area.

Journal ArticleDOI
TL;DR: An accounting, based on evidence for internal context effects, of current limitations in the combination of antidepressant or benzodiazepine medications with CBT and the advantages of isolated-dosing strategies with DCS relative to these limitations are offered.
Abstract: In a particular success for translational research agendas, characterization of the neuronal circuits underlying fear extinction, and basic research in animal extinction paradigms, has led to intervention studies examining the use of D-cycloserine (DCS) to enhance therapeutic learning from exposure-based cognitive-behavioral therapy (CBT). In this article, we review these intervention studies, and discuss DCS augmentation of CBT relative to more traditional combination-treatment strategies in the treatment of anxiety disorders. We offer an accounting, based on evidence for internal context effects, of current limitations in the combination of antidepressant or benzodiazepine medications with CBT and discuss the advantages of isolated-dosing strategies with DCS relative to these limitations. This strategy is contrasted with the chronic-dosing applications of DCS for schizophrenia and Alzheimer's disease, and future directions for isolated-dosing strategies are discussed.

Journal ArticleDOI
TL;DR: In this expert roundtable supplement, Margaret Weiss, MD, PhD, presents a comprehensive overview of complications surrounding differential diagnosis in adults with ADHD, including evaluation, comorbidity, and development of a treatment plan in this population.
Abstract: Attention-deficit/hyperactivity disorder (ADHD) is an impairing but usually treatable condition. Popular culture propagates the myth that ADHD recedes with age; this is not the case. Although it is common, <20% of adults with ADHD are diagnosed or treated. Adults with ADHD show significant comorbidities with depressive disorders, anxiety disorders, substance use, oppositional defiant disorder, personality disorders, sleep problems, and learning disabilities. However, symptoms that result from ADHD, such as mood symptoms or lability, are often mistaken for comorbid disorders. Comorbidity with ADHD impacts treatment compliance, treatment response, and patient insight. Insufficient data on the interaction between ADHD and comorbidities impedes proper diagnosis and treatment. Better clinical tools for assessing these conditions are needed. Food and Drug Administration-approved pharmacologic treatments for adult ADHD include stimulants, dexmethylphenidate, and the nonstimulant atomoxetine. Effect sizes of approved medicines at approved doses are half those seen in children. Adults may also need longer duration of medication effects than children. Short-acting stimulants are likely to result in poorer adherence and have a higher risk for diversion or abuse. Risk of abuse is a major concern; stimulant treatments are controlled substances, and children with ADHD show increased risk of substance abuse. Psychosocial interventions may be beneficial in treating both ADHD and comorbidities.In this expert roundtable supplement, Margaret Weiss, MD, PhD, presents a comprehensive overview of complications surrounding differential diagnosis in adults with ADHD. Next, Mark A. Stein, PhD, reviews evaluation, comorbidity, and development of a treatment plan in this population. Finally, Jeffrey H. Newcorn, MD, provides a discussion on the pharmacologic options available for adults with ADHD, considering dosages specific to adults and common comorbidities.