bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged Exposure Therapy for Chronic Combat-Related PTSD: A Case Report of Five Veterans
Authors: Nacasch Nitsa , Foa Edna B. , Fostick Leah , Polliack Miki , Dinstein Yula , Tzur Dana , Levy Pnina , Zohar Joseph
Published: August 2016

Prolonged exposure (PE) therapy has been found efficient in reducing posttraumatic stress disorder (PTSD) symptoms mostly among rape victims, but has not been explored in combat-related PTSD. Five patients with severe chronic PTSD, unresponsive to previous treatment (medication and supportive therapy) are described. Patients were evaluated with the PTSD Symptom Scale–Interview, and Beck Depression Inventory, before and after 10–15 sessions of PE therapy. All five patients showed marked improvement with PE, with a mean decrease of 48% in PTSD Symptom Scale–Interview score and 69% in Beck Depression Inventory score. Moreover, four patients maintained treatment gains or kept improving 6–18 months after the treatment. The results suggest that PE was effective in reducing combat-related chronic PTSD symptoms.
The Neuropsychiatry of Adrenomyeloneuropathy
Authors: Walterfang Mark A. , O'Donovan John , Fahey Michael C. , Velakoulis Dennis
Published: August 2016

Background: While the adult form of adrenoleukodystrophy (ALD) has been associated with an elevated rate of affective disturbance, the myeloneuropathic form of the disease known as adrenomyeloneuropathy (AMN) has been associated with only occasional cases of major mental illness. Given that cerebral involvement occurs in up to half of AMN sufferers, we hypothesized that rates of mental illness may match those with adult ALD.

Objective: To describe the psychiatric, cognitive, and disability variables in a sample of Australian AMN sufferers.

Methods: Ten genetically confirmed AMN sufferers underwent diagnostic psychiatric interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders), rating scales of psychiatric disturbance (Brief Psychiatric Rating Scale, Hospital Anxiety and Depression Scale, Beck Depression and Anxiety Inventories, and Short-Form 36), and cognitive function (the Neuropsychiatry Unit Cognitive Assessment Tool and Mini-Mental State Examination).

Results: While the group as a whole was generally cognitively intact, it demonstrated a higher than expected prevalence of lifetime and current major affective illness. Current symptom levels were low at the time of study participation. Psychopathology did not relate to adrenal status, nor to level of physical or functional impairment.

Conclusion: This small sample suggests that the level of psychiatric morbidity in AMN patients is elevated, and the rate of affective disturbance approaches those of adult ALD sufferers. This may reflect that AMN is not a “pure” myeloneuropathy, and that mild cerebral involvement may be associated with affective illness.
Analysis of the Rate of Improvement of Specific Psychic and Somatic Symptoms of General Anxiety Disorder During Long-Term Treatment with Venlafaxine ER
Authors: Stahl Stephen M. , Ahmed Saeeduddin , Haudiquet Vincent
Published: August 2016

Introduction: Generalized anxiety disorder (GAD) is a chronic illness with psychic and somatic symptoms that do not respond uniformly in the first weeks of treatment.

Methods: A post-hoc analysis of pooled data from five placebo-controlled, double-blind, randomized studies in non-depressed GAD patients treated with venlafaxine extended release (ER) or placebo was performed to determine the temporal response of psychic and somatic symptoms to treatment over 8 weeks. Two of the studies included extension phases of up to 6 months, the results of which were also analyzed here.

Results: The earliest symptoms to respond included both psychic symptoms (anxious mood, tension, behavior at interview) and somatic muscular, cardiovascular, and respiratory symptoms. The last symptoms to respond included the psychic symptoms of insomnia and fear and the somatic sensory, gastrointestinal and autonomic symptoms, perhaps in part because of drug-related side effects. Continuing treatment beyond 8 weeks in venlafaxine ER responders for up to 6 months of total treatment results not only in additional improvement in early-responding symptoms, but also in the improvement of late-responding symptoms, perhaps due in part to the development of tolerance to antidepressant side effects.

Conclusion: Serious consideration should be given to maintaining partial responders to venlafaxine ER treatment on the same treatment for ≥3–6 months.
Psychotic Symptoms in Posttraumatic Stress Disorder
Authors: Lindley Steven E. , Carlson Eve , Sheikh Javaid
Published: August 2016

Recent data suggest that the presence of psychotic symptoms in patients suffering from posttraumatic stress disorder (PTSD) may represent an underrecognized and unique subtype of PTSD. Among combat veterans with PTSD, 30% to 40% report auditory or visual hallucinations and/or delusions. The presence of psychotic symptoms in PTSD is associated with a more severe level of psychopathology, similar to that of chronic schizophrenia. In this review, the differential diagnosis of psychotic symptoms in PTSD is discussed, including possible comorbid schizophrenia, psychotic depression, substance-induced psychosis, and personality disorder. A recent biologic study supporting the existence of a unique subtype of PTSD with psychotic features is also addressed, as are the similarities between PTSD with psychotic features and psychotic depression disorder. Finally, data on the treatment implications of psychotic symptoms in PTSD are presented. The intriguing recent findings on psychotic symptoms in PTSD need further investigation in noncombat-related PTSD populations before findings can be generalized to all individuals with PTSD.
Raising the Bar From Response to Remission in the Treatment of Generalized Anxiety Disorder
Authors: Ninan Philip T. , Christensen Daniel D. , Gorman Jack M. , Ginsberg David L.
Published: August 2016

How can clinicians diagnosis generalized anxiety disorder (GAD) earlier and treat it more effectively? The most successful treatment is often determined through the remission of psychic and somatic symptoms, an increase in functional capacity at work and in relationships, and how the patient handles their daily responsibilities. This monograph attempts to:

—Define GAD

—Explore psychotherapeutic and pharmacologic treatment modalities

—Identify comorbidities associated with GAD

—Understand the importance of dual uptake mechanisms in gaining remission
SSRI Reduction of Nonparaphilic Sexual Addiction
Authors: Elmore James L.
Published: August 2016

The author presents two cases of nonparaphilic sexual addiction (NPSA) with comorbid depression and other psychiatric disorders in which symptoms were relieved during treatment with selective serotonin reuptake inhibitors. NPSA is defined and comorbid disorders, the neurotransmitter hypothesis of sexual function, treatment considerations, and evidence for an obsessive-compulsive disorder vs mood/affect dysregulation disorder etiology for these sexual symptoms are discussed.
New Developments in the Treatment of Epilepsy
Authors: Stahl Stephen M. , Klitgaard Henrik , Ginsberg David L.
Published: August 2016

Various agents have been used for the treatment of epilepsy. Standard antiepileptics (AEDs) have been available in the United States for many years and although they continue to play an important role in the treatment of epilepsy, these agents have limitations. Many have a lack of efficacy, side effects or toxicities, or potentially cause interactions with other agents. While the mechanism of action for AEDs is still not entirely clear, most experts agree that it is related to ion channels and ultimately to the balance between neural inhibition and excitation. The ultimate goal of all AEDs is to either reduce excitation or promote inhibition. There is an opportunity for newer AEDs to be developed and marketed; these newer agents have the promise of fewer adverse effects and greater efficacy. A challenge for the new AEDs is to actually prevent the initiation of epileptiform activity and prophylactically suppress seizure induction.
The Syndrome of Traumatic Grief
Authors: Shear M. Katherine , Zuckoff Allan , Frank Ellen
Published: August 2016

Traumatic grief is a common and debilitating syndrome whose clinical presentation is well recognized but whose diagnostic criteria have only recently been delineated. Though it shares features with major depressive disorder, adjustment disorder, and posttraumatic stress disorder, none of these subsume the criteria set for traumatic grief, and the diagnostic overlap is limited in community samples. Furthermore, diagnosis of traumatic grief appears to have prognostic value for clinical course and treatment response among bereaved individuals. In the absence of empirically supported treatments of pathological grief, a new, manualized treatment for traumatic grief symptoms has been developed and is currently undergoing testing in a randomized controlled trial. The conceptual basis for Traumatic Grief Treatment (TGT) is presented, the structure of the treatment is outlined, and the primary clinical strategies employed are described.
Low Heart Rate Variability Is Not Caused by Typical Neuroleptics in Schizophrenia Patients
Authors: Malaspina Dolores , Dalack Gregory , Leitman David , Corcoran Cheryl , Amador Xavier F. , Yale Scott , Glassman Alexander , Gorman Jack M.
Published: August 2016

Both elevated cardiovascular mortality and low cardiovagal (parasympathetic) heart rate variability (HRV)—a risk factor for postmyocardial infarction—are reported in schizophrenia (SZ). Since a number of medications have strong effects of cardiac conductivity, we thought it important to examine if typical neuroleptic medications might also affect HRV. We examined cardiac vagal activity during both neuroleptic treatment and a drug-free condition in seven SZ patients who were participating in a pilot double-blind, crossover study of placebo and haloperidol treatment. Twenty-four–hour Holter electrocardiograms were analyzed for high frequency HRV, quantitated as the percent of successive normal interbeat intervals greater than 50 milliseconds (PNN50), which is a good index of parasympathetic cardiac modulation. The patients showed unchanged PNN50 (8.4±9.5 versus 8.3±10.5; t=.22, df=6, P=.5) between the haloperidol treatment and drug-free conditions. Despite the elapsed time, change in medication, and altered clinical state, the PNN50s were highly correlated (Spearman r=.98, P=.000). SAPS positive symptom scores declined with treatment from 12.8±6.5 to 8.5±3.5; paired t=3.26: df=6; P=.01. PNN50s were significantly associated with positive (r=-.86, df=6, P=.012) and negative symptom scores (r=-.87, df=6, P=.01). We found low cardiovagal modulation in medication-free SZ patients that was associated with core SZ symptoms and was unchanged by haloperidol and benztropine treatment. The reduced HRV in SZ patients at baseline may render them at greater cardiovascular risk than healthy subjects when treated with medications having strong cardiovascular effects.
Neurocognitive Manifestations of Human Immunodeficiency Virus
Authors: Paul Robert H. , Cohen Ronald A. , Stern Robert A.
Published: August 2016

Is human immunodeficiency virus still a terminal condition? Recent advances in treatment have significantly reduced both mortality and morbidity associated with HIV, but these treatments have not been successful in eradicating the virus itself. As such, HIV has evolved into a chronic condition that is complicated by neurocognitive factors. Cognitive difficulties associated with HIV are characterized by a subcortical pattern with primary deficits in information processing speed and psychomotor speed. These deficits interfere with the ability of patients to complete important instrumental activities of daily living even in the absence of dementia. Treatment of HIV improves neurocognitive functioning, but the regimens are complex and patient adherence is critical. Cognitive factors can negatively impact treatment adherence, which in turn results in poorer immunological, cognitive, and psychiatric outcome. This cycle emphasizes the important interrelationships between symptom expression and treatment outcome in patients with HIV. The nature of these relationships will change with further developments in treatment regimens such as once-daily dosing. Less complex treatment approaches should improve health outcome as well as provide additional opportunities to further understand the impact of HIV on brain function.
Substance P and Human Immunodeficiency Virus Infection: Psychoneuroimmunology
Authors: Ho Wen-Zhe , Evans Dwight L. , Douglas Steven D.
Published: August 2016

Effects on the immune system caused by changes in behavioral state or brain activity are mediated, at least in part, through neuroendocrine-immune pathways. Life stress and depression may be associated with altered blood levels of central nervous system-released neuropeptides, including substance P (SP). SP acts as a neuroregulator or neurotransmitter in the conduction of nociceptive stimuli, and is a modulator of neuroimmunoregulation. This review summarizes current knowledge regarding the role of the neuropeptide, SP, in psychoneuroimmunology, in particular as it relates to human immunodeficiency virus infection and acquired immunodeficiency disease syndrome. The association between depression, anxiety, and stress in HIV-disease progression suggests that neurobiologic and neurophysiologic factors play a role in modulating HIV infection and responses to antiretroviral therapy. Individuals with HIV or AIDS may experience stressful life circumstances that can result in increased symptoms of anxiety, stress, and/or depression. Furthermore, psychological and psychiatric symptoms, which occur in individuals with HIV and AIDS, may be related to the progression of AIDS disease. This review presents evidence from the literature, as well as findings from basic investigations conducted in the authors' laboratories, demonstrating that SP may play an important role in HIV pathophysiology. SP can impact the susceptibility of immune cells to HIV infection and modulate immune cell functions in ways that may affect the course of HIV in infected individuals. Moreover, modulation of SP activity and SP receptor is being explored for its potential as a novel therapeutic approach to the treatment of some psychological and psychiatric disorders and to the design of new anti-HIV therapy.
Descriptive Epidemiology of Affective Disorders in Multiple Sclerosis
Authors: Patten Scott B. , Svenson Lawrence W. , Metz Luanne M.
Published: August 2016

Background: Affective disorders present an important clinical challenge in multiple sclerosis (MS). Due to prohibitive sample size requirements, population-based studies have not yet provided an adequate description of the underlying epidemiology of this association.

Objective: To describe the epidemiology of affective disorders in MS in a general population sample.

Methods: The study presented here accessed administrative data from a universal healthcare insurance plan in the Canadian province of Alberta. Physician billing data recorded in the Alberta Health Care Insurance Plan was used to identify members of the population ≥15 years of age with and without MS. Crude and stratified estimates of the association between affective disorders and MS were made. Logistic regression analysis was used to evaluate statistical interactions and to provide adjusted estimates of the association.

Results: The estimated prevalence of MS in the population within the targeted age range (2.3 million individuals) was 386/100,000 and that of affective disorders was 7.7%. As expected, an association between MS and affective disorders was identified (crude relative prevalence: 2.2). The association varied in strength over age-sex categories. Although the prevalence of affective disorder was higher in women with MS than men with MS, the association of MS with affective disorders was stronger in men. The strength of association declined with age in both men and women. Affective disorder prevalence in people with MS becomes similar to that of the general population in older age groups.

Conclusion: Affective disorders occur with an increased frequency in MS. This is true in men and women and across all relevant age groups, although the association gets weaker with advancing age. Higher frequencies of affective disorder occur in women with MS than in men with MS. The frequency of affective disorder in people with MS is highest in the 25–44 age group, and declines in older age categories.
Suicide: Clinical/Risk Management Issues for Psychiatrists
Authors: Jacobs Douglas G. , Jamison Kay Redfield , Baldessarini Ross J. , Fawcett Jan A. , Hendin Herbert , Gutheil Thomas G.
Published: August 2016

The materials in the following section are speaker comments from an educational symposium entitled Suicide: Clinical/Risk Management Issues for Psychiatrists sponsored by the American Psychiatric Association, May 16, 1999. The program chairpersons were Drs. Douglas Jacobs and Ross J. Baldessarini. The symposium was supported by an unrestricted educational grant from Solvay Pharmaceuticals.

The symposium focused on critical clinical and risk management issues about suicide as they impact clinical practice. Dr. Douglas G. Jacobs presented a suicide assessment protocol with suggestions on how to include current understanding about suicide in treatment planning. Dr. Kay Redfield Jamison reviewed bipolar disorder with an emphasis on early diagnosis, aggressive treatment, and the phenomenology of suicidal behavior. Dr. Ross J. Baldessarini discussed the lethality of bipolar depression and the effectiveness of lithium maintenance therapy to limit bipolar depression and reduce suicide risk. Dr. Jan A. Fawcett presented four clinical profiles of completed suicide and reviewed suggested treatment approaches appropriate for each that may help psychiatrists reduce the risk of suicide among their patients. Dr. Herbert Hendin explored the role psychiatrists play in performing comprehensive assessments of patients who request assisted suicide. Finally, Dr. Thomas G. Gutheil reviewed the basis for malpractice litigation and provided guidelines for preventing liability following a patient's suicide.
The Mouse Who Couldn't Stop Washing: Pathologic Grooming in Animals and Humans
Authors: Feusner Jamie D. , Hembacher Emily , Phillips Katharine A.
Published: August 2016

The basic science literature is replete with descriptions of naturally occurring or experimentally induced pathological grooming behaviors in animals, which are widely considered animal models of obsessive-compulsive disorder (OCD). These animal models rely largely on observed similarities between animal behaviors and human OCD behaviors, and on studies of animal pathological grooming disorders that respond to serotonin enhancing drugs. However, current limitations in assessment of complex cognition and affect in animals precludes the field's ability to match the driving primary processes behind observable phenomenology in animal “OCD” with human behavioral disorders. We propose that excessive grooming behaviors in animals may eventually prove to be equally, or possibly more relevant to, other conditions in humans that involve pathological grooming or grooming-like behaviors, such as trichotillomania, body dysmorphic disorder, olfactory reference syndrome, compulsive skin-picking, and onychophagia. Research is needed to better understand pathological grooming behaviors in both humans and animals, as animal models have the potential to elucidate pathogenic mechanisms and inform the treatment of these psychiatric conditions in humans.
Current Treatments of Attention-Deficit/Hyperactivity Disorder
Authors: Pliszka Steven , Dodson William W. , Spencer Thomas J.
Published: August 2016

Attention-deficit/hyperactivity disorder (ADHD) is a genetic disorder that affects both children and adults. Genetic studies have shown the heritability of ADHD to be higher than other psychiatric disorders. In addition, imaging studies have revealed various structural anomalies in the brain.

Often ADHD persists into adulthood. The presentation of ADHD into adulthood most often results from childhood onset of ADHD. Symptoms of inattention and functional behavior tend to persist. These symptoms may often be less obvious, with less overt hyperactivity and impulsiveness.

Stimulant medications remain the predominant choice for the treatment of ADHD. They are safe and offer good response. Common adverse reactions can usually be removed by changing the dose and the timing of medication administration. Of the second-line agents for treating ADHD, the tricyclic antidepressants have generated the most studies and have proved fairly efficacious.
The Neurobiology of Moral Behavior:Review and Neuropsychiatric Implications
Authors: Mendez Mario F.
Published: August 2016

Morality may be innate to the human brain. This review examines the neurobiological evidence from research involving functional magnetic resonance imaging of normal subjects, developmental sociopathy, acquired sociopathy from brain lesions, and frontotemporal dementia. These studies indicate a “neuromoral” network for responding to moral dilemmas centered in the ventromedial prefrontal cortex and its connections, particularly on the right. The neurobiological evidence indicates the existence of automatic “prosocial” mechanisms for identification with others that are part of the moral brain. Patients with disorders involving this moral network have attenuated emotional reactions to the possibility of harming others and may perform sociopathic acts. The existence of this neuromoral system has major clinical implications for the management of patients with dysmoral behavior from brain disorders and for forensic neuropsychiatry.
Simulated Driving and Brain Imaging: Combining Behavior, Brain Activity, and Virtual Reality
Authors: Carvalho Kara N. , Pearlson Godfrey D. , Astur Robert S. , Calhoun Vince D.
Published: August 2016

Introduction:

Virtual reality in the form of simulated driving is a useful tool for studying the brain. Various clinical questions can be addressed, including both the role of alcohol as a modulator of brain function and regional brain activation related to elements of driving.

Objective:

We reviewed a study of the neural correlates of alcohol intoxication through the use of a simulated-driving paradigm and wished to demonstrate the utility of recording continuous-driving behavior through a new study using a programmable driving simulator developed at our center.

Methods:

Functional magnetic resonance imaging data was collected from subjects while operating a driving simulator. Independent component analysis (ICA) was used to analyze the data. Specific brain regions modulated by alcohol, and relationships between behavior, brain function, and alcohol blood levels were examined with aggregate behavioral measures. Fifteen driving epochs taken from two subjects while also recording continuously recorded driving variables were analyzed with ICA.

Results:

Preliminary findings reveal that four independent components correlate with various aspects of behavior. An increase in braking while driving was found to increase activation in motor areas, while cerebellar areas showed signal increases during steering maintenance, yet signal decreases during steering changes. Additional components and significant findings are further outlined.

Conclusion:

In summary, continuous behavioral variables conjoined with ICA may offer new insight into the neural correlates of complex human behavior.
Studies of Carbamazepine Extended-Release Capsules in Bipolar Disorder
Authors: Weisler Richard H.
Published: August 2016

This discussion reviews data from two 3-week, double-blind, placebo-controlled pivotal trials of carbamazepine extended release capsules (CBZ ERC; SPD417.301 and SPD417.304); pooled results from these trials; data from a 3-week, double-blind, placebo-controlled trial in lithium non-responders or non-tolerators (SPD417.302); and additional supportive data from a 6-month, open-label, extension trial (SPD417.303). In addition, information on a retrospective chart review of 600 adolescent and adult bipolar patients on CBZ ERC is presented.

In the first large double-blind, placebo-controlled study assessing CBZ ERC in acute mania, manic and mixed bipolar patients from multiple centers were hospitalized and all medications were discontinued. After reaching a stable baseline 2–5 days later, the patients were randomized to CBZ ERC (n=101; 59% with mixed states) or placebo (n=103; 47% with mixed states) for 3 weeks. An aggressive initial titration schedule was implemented, beginning with 200 mg BID and increased by 200 mg/day until good clinical response was achieved or the patient could not tolerate the dosage. Many patients were taking 1,200–1,600 mg/day by the end of week 1. Efficacy was assessed using the Young Mania Rating Scale (YMRS). The Clinical Global Impressions (CGI) scale and the Hamilton Rating Scale for Depression (HAM-D) were also followed.
A Guide to Diagnosis of Alzheimer's Disease
Authors: Sano Mary
Published: August 2016

A major challenge in the management of Alzheimer's disease (AD) is accurate diagnosis of the condition. Aging itself is associated with cognitive change, and physicians must first distinguish between age-associated complaints and true memory impairment as in AD before optimal management can begin. This article reviews tools used to assess and diagnose AD patients in both the primary care and clinical trial setting. AD assessment instruments commonly used in research may be too cumbersome for use in primary care. Tools specifically designed to meet the needs of busy practitioners that can accurately assess function, cognition, and global change will be reviewed. The issues of cognitive screening in old age and age-associated memory impairment will be discussed. Similarly, the pitfalls and advantages of routine cognitive screening in daily practice will be addressed.
Bipolar Disorder and ADHD: Clinical Concerns
Authors: McIntyre Roger
Published: August 2016

During the past decade, a similar composite has emerged for both bipolar disorder and adult attention-deficit/hyperactive disorder (ADHD). First, both conditions have a relatively high prevalence, a low case detection, a protracted illness course, a high rate of comorbidity, multifactorial ideology, substantial heritable liability, and tremendous burden of illness in economic cost as well as interpersonal and vocational maladjustments. What has also been interesting along with these reports is that there has been emerging scientific studies implicating common brain regions and neural circuits subserving essential features of both conditions.
Obsessive-Compulsive Disorder and Anxiety Spectrum in Children
Authors: Thomsen Per Hove , Leckman James
Published: August 2016

Obsessive-compulsive disorder (OCD) is now recognized as a frequent and disabling disorder among children and adolescents. The phenomenology is similar to adult OCD, but several reports have indicated that compulsions are more prominent in children and that children are more inclined than adults to include their family surroundings in ritualistic behavior. It is also clear that young children engage in a significant amount of repetitive, ritualistic compulsive activity that appears to be a normal part of their behavioral repertoire.

Although the cause of childhood-onset OCD is unknown, many factors are likely to contribute to the heterogenous clinical phenotypes, including both genetic and environmental factors. The neurobiological circuitry involved in childhood-onset OCD is likely to involve alterations to the same cortico-striatothalamic circuitry implicated in adult OCD, but the develop-mental differences have yet to be fully delineated. The treatment response patterns of adults and children are generally inconsis-tent with each other, and specific OCD subtypes may also respond differentially.

Phenotypic characterization can be undertaken either categorically, as seen with traditional diagnostic categories, or dimensionally. Extended phenotypes can be defined in terms of symptoms and course of the illness, or neuroimaging and neurobiologic study findings, or treatment responses. Phenotypic characterization must also reflect an understanding of the rituals and repetitive behaviors that are associated with normal development. (A proposed categorization of OCD subtypes appears in the “Table library.”)
Pharmacologic Differences Among the SSRIs: Focus on Monoamine Transporters and the HPA Axis
Authors: Nemeroff Charles B. , Owens Michael J.
Published: August 2016

Depression is a widespread and serious disorder that afflicts an estimated 13.1 to 14.2 million adults in the United States each year. Even more compellingly, the lifetime prevalence rate of depression in the US has recently been estimated to include 16.2% of adults (21% women, 13% men), or >32.6 million people. There are multiple putative “causes” of depression, with approximately one-third of an individual's propensity for unipolar depression due to genetic vulnerability, while the remaining two-thirds is due to environmental factors. Although the selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to mainly act by selectively binding to the serotonin (5-HT) transporter to block reuptake of 5-HT from the synapse into the presynaptic nerve terminal, thereby increasing synaptic serotonin concentrations, some of the SSRIs also exhibit other neuropharmacologic effects. One such example is the high affinity for paroxetine in blocking norepinephrine reuptake. Another is the inhibition of dopamine reuptake by sertraline. In depression, hyperactivity of corticotropin-releasing factor (CRF)-producing neurons contribute to the well-characterized hypothalamic-pituitary-adrenal axis hyperactivity of depression. Increased activity of extrahypothalamic CRF circuits are believed to contribute to several depressive symptoms. Treatment and certain SSRIs have been shown to reduce the activity of CRF neurons and may contribute to their therapeutic action. Each SSRI apparently has its own unique pharmacologic properties that likely underlie their observed differences in clinical use.
Understanding the Neurobiology of Comorbidity in Anxiety Disorders
Authors: Nutt David J. , Stein Dan J.
Published: August 2016

Anxiety and depression are common disorders that frequently co-exist. Both disorders show good response to antidepressants, especially the selective serotonin reuptake inhibitors. Some suggest that these disorders are variants of the same underlying brain pathology. This review examines the similarities and differences between anxiety and depression in terms of the known neurobiological etiologic mechanisms as well as their biological underpinnings and response to treatment. Sufficient and significant differences between these disorders support the view that they are independent entities. Shared abnormalities in the 5HT1A receptor function, for example, may help explain some of the comorbidity.
Defining Response and Remission in Anxiety Disorders: Toward an Integrated Approach
Authors: Bandelow Borwin
Published: August 2016

Response and remission rates are commonly used to evaluate the efficacy of treatments for anxiety disorders and other psychiatric illnesses. Response is generally regarded as a clinically meaningful improvement in symptoms, while remission, the goal of treatment, is generally thought of as the absence or near absence of symptoms following illness, accompanied by a return to premorbid levels of functioning. Response and remission are often defined using psychiatric rating scales, based on score cutoffs or the magnitude of score changes from baseline. While no universally accepted criteria exist, a commonly used threshold for response is a >50% improvement in the total score, while for remission, various cutoff points have been used. Comparison of cutoffs or change scores for disease-specific scales with Clinical Global Impressions ratings is a useful way of evaluating response and remission criteria across disorders. To illustrate the use of disease-specific and global measures, this article summarizes data from randomized, placebo-controlled studies of adult patients with generalized anxiety disorder, social anxiety disorder, or panic disorder treated with the serotonin norepinephrine reuptake inhibitor venlafaxine extended release, for which acute-phase data are available (a total of 13 trials).
History and Prevalence of Involuntary Emotional Expression Disorder
Authors: Duda John E.
Published: August 2016

The syndrome now known as involuntary emotional expression disorder (IEED) is a condition characterized by uncontrollable episodes of laughing and/or crying. It has been known for more than a century, but confusing and conflicting terminology may have hampered the progress of physicians in recognizing this condition. IEED is associated with various neurological disorders and neurodegenerative diseases, including amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease and other dementias, and neurological injuries such as stroke and traumatic brain injury. It is hoped that better defined terminology for IEED may help in the future diagnosis of this debilitating condition, the establishment of accurate prevalence rates for IEED in the varying underlying conditions, and also in removing blame and stigma from sufferers by providing reassurance about the nature of their condition.
Involuntary Emotional Expression Disorder: Definition, Diagnosis, and Measurement Scales
Authors: Cummings Jeffrey L.
Published: August 2016

Involuntary emotional expression disorder (IEED) is a syndrome in which emotional or affective motor control becomes dysregulated as a result of brain damage from neurological disease or as a result of brain injury. A debilitating disorder with persistent symptoms, IEED has a significant impact upon the lives of patients and caregivers, but is often overlooked or misdiagnosed. IEED is a clinically well-defined disorder, and specific criteria may be used when making a diagnosis. It must be distinguished from depression or other psychological and neurological conditions. Several assessment scales have been validated for use in IEED, in order to evaluate the baseline severity and to track the course of the disorder and response to treatment.
Pathophysiology of Involuntary Emotional Expression Disorder
Authors: Rabins Peter V. , Arciniegas David B.
Published: August 2016

Extensive clinical experience and research suggest that a cortico-limbic-subcortico-thalamic-ponto-cerebellar network plays a significant role in the expression of human emotions. This network includes specific cerebral, cerebellar, and brainstem areas and their multiple projections/pathways, with activity modulated through serotonergic, dopaminergic, glutamatergic, and possibly sigma receptor neurotransmitter systems. Disruptions of regulatory and inhibitory mechanisms in the structure and function of this network likely constitute a pathophysiological basis for the crying and laughing episodes characteristic of involuntary emotional expression disorder. Pharmacologic interventions targeting the neurochemical modulators of the emotional expression systems may afford opportunities for symptom control among persons affected by this disorder.
Non-Stimulant Trials of Adult ADHD
Authors: Adler Lenard A.
Published: August 2016

Attention-deficit/hyperactivity disorder (ADHD) is a lifelong condition that begins in childhood and continues with adult manifestations related to the core symptoms. Approximately 50% to 75% of children with ADHD continue to meet criteria for the disorder as adolescents and adults. Adults with the disorder increasingly present to primary care physicians, psychiatrists, and other practitioners for diagnosis and treatment. Understanding the diagnosis of ADHD in adults requires knowledge of age-dependent decline of symptoms over time. Retrospective recall of symptoms and impairment are valid methods of diagnosing the disorder. ADHD is also a brain disorder with a strong neurobiologic basis, complex etiology, and genetic component. Genetic and environmental vulnerabilities give rise to abnormalities in the brain and subsequent behavioral and cognitive deficits, which may produce the symptoms associated with ADHD. Magnetic resonance imaging studies of ADHD have provided evidence that abnormalities in the brain are caused by the disorder itself rather than treatment of the disorder. Psychiatric comorbidity is common among patients with ADHD and tends to complicate treatment. Acute and long-term use of long-acting stimulant formulations (methylphenidate and amphetamine compounds) have shown robust efficacy and tolerability consistent with the treatment response established in children with ADHD. Non-stimulant medications have demonstrated efficacy as well, and may be preferred in patients with tic and substance use disorders.

In this expert roundtable supplement, Timothy E. Wilens, MD, reviews the epidemiology and clinical presentation of adult ADHD. Next, Joseph Biederman, MD, provides an overview of recent advances in the neurobiology of ADHD. Thomas J. Spencer, MD, reviews stimulant treatment of adult ADHD, and Lenard A. Adler concludes with a discussion of non-stimulant trials in adult ADHD.
The Treatment of Acute Agitation in Schizophrenia
Authors: Battaglia Joseph , Robinson Delbert G. , Citrome Leslie
Published: August 2016

Acute agitation is a nonspecific term applied to an array of syndromes and behaviors. It is frequently defined as an increase in psychomotor activity, aggression, disinhibition/impulsivity, and irritable or labile mood. Etiologies of acute agitation include medical disorders, delirium, substance intoxication or withdrawal, psychiatric disorders, and medication side effects. Treatment of acute agitation requires both environmental and pharmacologic intervention. Patients should be calmed with sedating agents early in the course of treatment, allowing for diagnostic tests to take place. Failure to correctly diagnose causes of agitation may lead to delayed treatment for serious conditions, and can even exacerbate agitation.The most common cause of agitation in patients with schizophrenia is psychotic relapse due to medication nonadherence. Pharmacologic treatment options for these patients include lorazepam and antipsychotic agents. Lorazepam causes nonspecific sedation and treats some substance withdrawal, but has little effect on psychosis. First-generation antipsychotics treat psychosis and, at high enough doses, cause sedation, but may induce extrapyramidal side effects (EPS). Some second-generation antipsychotics have been approved for the treatment of agitation in schizophrenia. These agents treat psychosis with a favorable EPS profile, but are comparatively expensive and cause risks such as hypotension. However, avoiding EPS may reduce patients' resistance to antipsychotic treatment.

In this expert roundtable supplement, Joseph Battaglia, MD, provides an overview of the definition of acute agitation. Next, Delbert, G. Robinson, MD, outlines evaluation methods for actue agitation. Finally, Leslie Citrome, MD, MPH, reviews interventions for acute and ongoing management of agitation.
The Management of Schizophrenia: Safety, Treatment, and Continuity of Care
Authors: Kane John M.
Published: August 2016

Schizophrenia affects ~1% of the population and is associated with enormous personal suffering, family distress and burden, and tremendous healthcare and societal costs. Although considerable progress has been made in treating this illness enormous challenges remain.

Early detection and treatment are at present a distant goal. There is undue delay between the onset of full-blown psychosis and appropriate diagnosis and treatment. Continuity of care is often spoken about rather than truly implemented. Adverse effects remain a critical challenge, and comorbid medical conditions as well as suicide result in a markedly diminished life expectancy. Substance abuse affects a substantial proportion of patients, creating an impediment to optimum outcome. Nonadherence remains a very common, but inadequately appreciated obstacle to adequate and sustained treatment response and contributes enormously to a high rate of preventable relapse and rehospitalization.

The focus of this CNS Spectrums supplement is to address many of these topics in a clinically relevant manner by reviewing the latest research findings in pharmacologic and behavioral treatments, with an emphasis on evaluating appropriate treatment for each patient while considering the host of issues that should inform our clinical decision-making. Historically, a major focus of treatment has been positive symptom control. Though this is clearly important, negative symptoms, cognitive dysfunction, depression, demoralization, and comorbid substance abuse are also critical targets in enhancing functional outcome. Concepts such as remission and recovery are useful metrics to help establish targets and goals for treatment planning and for creating a framework for assessing outcome.
Balancing Efficacy and Safety in Treatment with Antipsychotics
Authors: Correll Christoph U.
Published: August 2016

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 enhancesmental 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.
The Spectrum of Rapid Cycling
Authors: Suppes Trisha
Published: August 2016

While rapid cycling was first identified by Dunner and Fieve in 1974, there is quite a good historical background on the concept. In the 1800s Falret and colleagues identified what they called a “circular course distinct from alternating.” What they meant by “alternating” was a period of remission following an episode. Currently, all types and ranges of cycling are lumped under one rubric; the spectrum ranges from having >4 cycling episodes, the minimum required for rapid cycling, through ultradian cycling, which is far more severe.

While some patients manifest chronic depression with periodic hypermania, which is known as bipolar II, others have ultradian cycles, which are often seen as pure affective instability. We do not know whether these types represent different stages of a disorder that exists on a spectrum or whether they are actually distinct categories of the disorder: one being patients who experience mania, depression, and then remission; the second being those with more continuous cycling that includes ultradian cycling. Greater understanding of the biological underpinnings of the illness will help to determine whether these conditions exist on a spectrum.

Rapid cycling may become less prevalent with age. In the Depression Collaborative Study, Coryell and colleagues found a diminishment of rapid cycling over the course of 13 years. Studies from the Stanley Bipolar Foundation group suggest that the cycling may accelerate in some, but not others. Over a long observation period in ~100 patients, Koukopoulos and colleagues found that once a pattern of rapid cycling is established in a patient, this pattern may become a hallmark of their illness.
Treatment-Refractory Epilepsy: An Evidence-Based Approach to Antiepileptic Monotherapy
Authors: Harden Cynthia L. , Ginsberg David L. , Kanner Andres M. , Bautista Jocelyn F. , Browne Thomas R.
Published: August 2016

Treatment options for epilepsy have increased in the last decade with the introduction of several new antiepileptic drugs (AEDs). As drug selection becomes more challenging, the use of evidence-based guidelines to aid in treatment decisions has become increasingly valued. The American Academy of Neurology's (AAN) guidelines for the use of new AEDs in refractory epilepsy offers many benefits, including expert panel recommendations based on clinically relevant questions with evidence-based responses. However, lack of evidence from randomized-controlled trials, particularly as they relate to monotherapy, limits the recommendations and their use in practice. The studies of new AEDs as monotherapy in treatment-refractory epilepsy are difficult to incorporate into clinical use because they are driven by Food and Drug Administration requirements to show superiority over placebo or pseudoplacebo (ie, low dose of active drug) rather than by clinical questions. However, based on Class I evidence, the AAN guidelines have granted Level A recommendations (established effectiveness) for oxcarbazepine and topiramate monotherapy, and a Level B recommendation (probable effectiveness) for lamotrigine monotherapy in the use of refractory partial epilepsy. There is insufficient evidence to recommend gabapentin, levetiracetam, tiagabine, or zonisamide monotherapy. No monotherapy AED trials have been conducted in refractory generalized epilepsy. Because no differences in efficacy have been reported for AEDs as initial therapy of partial seizures, differences in adverse events, such as weight gain, tremor, and hair loss, are key in drug selection. More comparative studies between the AEDs are necessary for both monotherapy and add-on therapy for treatment-refractory epilepsy.
Interpreting the Efficacy Findings in the CATIE Study: What Clinicians Should Know
Authors: Meltzer Herbert Y. , Bobo William V.
Published: August 2016

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial was an effectiveness/”pragmatic” clinical trial designed to compare the efficacy, tolerability, and cost-effectiveness of four atypical antipsychotics (olanzapine, quetiapine, risperidone and ziprasidone) and a conventional antipsychotic (perphenazine) for an 18-month period in patients with schizophrenia. The study randomized 1,460 patients with fewer exclusion criteria than in most trials in hopes that this would allow for a more representative sample of outpatients in “real world” practice. Olanzapine demonstrated significant superiority in time to discontinuation for all cause and for lack of efficacy, as well as likelihood of hospitalization for relapse; however, it was associated with a significantly higher rate of metabolic side effects. Perphenazine exhibited comparable effectiveness with quetiapine, risperidone, and ziprasidone, and appeared to be as well tolerated as the atypicals. However, it had the highest rate of drop out due to extrapyramidal symptoms and was restricted to patients who did not have tardive dyskinesia (TD). This article examines the phase 1 CATIE results to guide the clinician in understanding how to interpret the findings, which were intended to be a guide for clinical practice. The nature of the patient population, the doses of drugs relative to one another, inclusion of patients who were treatment resistant, and exclusion of patients with TD from randomization to perphenazine were potential sources of bias in the study. In particular, the use of a higher-than-usual peak dose of olanzapine may have led to the superior results achieved with it. Practical suggestions are given for choice of antipsychotic medication in patients with chronic schizophrenia.