bluuebunny/crossref_metadata_2025 huggingface dataset:
HF-rTMS Treatment in Medication-Resistant Melancholic Depression:Results from18FDG-PET Brain Imaging
Authors: Baeken Chris , De Raedt Rudi , Van Hove Christian , Clerinx Peter , De Mey Johan , Bossuyt Axel
Published: August 2016

Introduction:High frequency repetitive transcranial magnetic stimulation (HF-rTMS) of the left dorsolateral prefrontal cortex (DLPFC) might be a promising strategy to treat depression, but not all patients show a positive outcome.

Objective:In this open study, we evaluate whether a favorable HF-rTMS treatment outcome could be predicted by baseline prefrontal brain glucose metabolism (CMRglc), measured by18fluorodeoxyglucose positron emission tomography (18FDG-PET).

Methods:A sample of 21 antidepressant-free, treatment-resistant depression (TRD) patients of the melancholic subtype received 10 sessions of HF-rTMS delivered on the left DLPFC. Patients underwent a static18FDG-PET before and after HF-rTMS treatment.

Results:Forty-three percent of the patients showed a reduction of at least 50% on their Hamilton Rating Scale for Depression scores. Higher baseline metabolic activities in the DLPFC and the anterior cingulate cortex (ACC) were associated with better clinical outcome. Successful HF-rTMS treatment was related to metabolic changes in subdivisions of the ACC (Brodmann areas 24 and 32).

Conclusion:This biological impact of HF-rTMS on regional brain CMRglc explains to some extent how HF-rTMS may improve moods in TRD patients. Larger sham-controlled HF-rTMS treatment studies are needed to confirm these results.
Functional Magnetic Resonance Imaging Studies in Bipolar Disorder
Authors: Yurgelun-Todd Deborah A. , Ross Amy J.
Published: August 2016

Abnormalities in brain activation using functional magnetic resonance imaging (fMRI) during cognitive and emotional tasks have been identified in bipolar disorder patients, in frontal, subcortical and limbic regions. Several studies also indicate that mood state may be differentiated by lateralization of brain activation in fronto-limbic regions. The interpretation of fMRI studies in bipolar disorder is limited by the choice of regions of interest, medication effects, comorbidity, and task performance. These studies suggest that there is a complex alteration in regions important for neural networks underlying cognition and emotional processing in bipolar disorder. However, measuring changes in specific brain regions does not identify how these neural networks are affected. New analytical techniques of fMRI data are needed in order to resolve some of these issues and identify how changes in neural networks relate to cognitive and emotional processing in bipolar disorder.
Retrospective Case Review of Lamotrigine Use for Affective Instability of Borderline Personality Disorder
Authors: Weinstein Wendy , Jamison Katrina L.
Published: August 2016

Introduction: The diagnosis of borderline personality disorder is complex as is its pharmacologic treatment. Lamotrigine may offer promise in the treatment of this condition.

Objective: To assess the use of lamotrigine to treat symptoms of affective instability in patients with borderline personality disorder.

Methods: Charts of patients treated with lamotrigine in a private practice during the period of 2003–2004 were reviewed. Patients were included in the analysis if they had been given a clinical diagnosis of borderline personality disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision, had continued to display affective instability while taking their previous medications before being treated with lamotrigine; had received a Clinical Global Impression-Severity score before and after lamotrigine therapy; had been treated with lamotrigine, as monotherapy or adjunctive therapy, at a dose ranging from 50–200 mg/day; and continued to take lamotrigine for at least 3 months.

Results: The charts of 13 patients were reviewed and included in the analysis. All patients were female, 19–43 years of age, and had reported continuing symptoms of affective instability despite treatment with two to seven psychotropic drugs, including, but not limited to, fluoxetine, paroxetine, escitalopram, buproprion, and clonazepan. The duration of lamotrigine treatment, before the end of the period covered by the chart review was 3–15 months. The patients had initial Clinical Global Impression-Severity scores of 5 or 6 and a final scores of 1 or 2, except for one patient with an initial score of 3 and a final score of 1 and one patient with an initial score of 6 and a final score of 7.

Conclusion: Lamotrigine seems to be a safe and effective option for the treatment of patients with symptoms of affective instability associated with borderline personality disorder.
Modulation of Fear and Anxiety by the Endogenous Cannabinoid System
Authors: Chhatwal Jasmeer P. , Ressler Kerry J.
Published: August 2016

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.
Serotonin Syndrome Associated with the Use of Escitalopram
Authors: Huska Matthew T. , Catalano Glenn , Catalano Maria C.
Published: August 2016

Escitalopram is the newest selective serotonin reuptake inhibitor (SSRI) available for use in the United States. It has been approved for the treatment of major depression and generalized anxiety disorder. It is the S-enantiomer of the SSRI citalopram and is highly serotonin specific as it has minimal effect on the reuptake of dopamine or norepinephrine. It is also a well-tolerated medication, with a side-effect profile comparable to the other SSRIs. While a number of side effects have been seen during escitalopram therapy, such as insomnia, nausea, and increased sweating, there are no reported cases of serotonin syndrome associated with escitalopram therapy to date. We present the case of a 24-year-old woman who developed serotonin syndrome after an increase in her escitalopram to 30 mg/day. We will review the diagnostic criteria of serotonin syndrome and the clinical scenarios in which serotonin syndrome can develop. We will also discuss the proposed treatments and role that polypharmacology may play in the development of this clinical entity.
Suicidal Ideation Versus Suicidal Obsession: A Case Report
Authors: Wetzler Alzbeta Juven , Elias Rachela , Fostick Leah , Zohar Joseph
Published: August 2016

This case report illustrates the relationship between stress and obsessive-compulsive disorder (OCD) by describing an unusual case of OCD sequelae following a suicide attempt. The patient is a 29-year-old married woman who suffered a major depressive episode without OCD and tried to commit suicide by drinking household cleaner. Following the attempt, violent obsessive thoughts of harming herself and others emerged along with avoidance behavior. After exposure therapy, there was a decrease in her obsessive thoughts, less anxiety, and no avoidance behavior. This report highlights not only the existence of “posttraumatic obsession” but also the importance of accurate interpretation of suicidal preoccupation, leading to the diagnosis of OCD rather then suicidal ideation secondary to depression.
Rasmussen's Syndrome: Intractable Epilepsy and Progressive Neurological Deterioration From a Unilateral Central Nervous System Disease
Authors: Carney Paul R.
Published: August 2016

Rasmussen's syndrome (chronic encephalitis with epilepsy) is a rare neurological disorder of unknown cause characterized by severe epilepsy, hemiplegia, dementia, and inflammation of the brain, and progressive functional and structural destruction of a single cerebral hemisphere. While one mechanism underlying the pathogenesis of Rasmussens encephalitis has been hypothesized to be mediated by production of excitotoxic GluR3 autoantibodies to the a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor, other neuropathological etiologies have also been indicated. Proposed therapies have included antiepileptics, steroids, antiviral agents, alpha-interferon, and immunoglobulin. The mainstay of therapy is surgical hemispherectomy. To date, no medical therapies have permanently halted neurologic deterioration.
If We Had Known Then What We Know Now: A Review of Local and National Surveys Following September 11, 2001
Authors: Marshall Randall D.
Published: August 2016

There is little research on the consequences of large-scale violent disasters in a community despite their unfortunate prevalence over many decades. The primary source of epidemiological data for the greater New York community in dealing with the September 11, 2001, attacks was the Oklahoma City bombing. In the latter event, 45% of directly exposed adults met criteria for a major psychiatric disorder 6 months later, including 34% with posttraumatic stress disorder (PTSD). The first survey after the World Trade Center and Pentagon attacks, conducted within one week, revealed a remarkable degree of symptomatology across the nation in both adults and children. Forty-four percent of adults reported at least 1 of 5 PTSD screening symptoms in the 3–5 days after the attacks; 35% of parents reported children who had at least one symptom, and 47% of children worried about their own or someone else's safety. Coping behaviors were consistent with a community mental health model and included turning to open discussion (98%), religion (90%), and community activities (60%) in order to cope with their reactions.

Rates of disorder were also high in a survey conducted 5–8 weeks later in Manhattan below 110th Street, with 38% saying they directly witnessed the World Trade Center attack. The current prevalence of new-onset PTSD was 7.5%, and of new-onset major depressive disorder, 9.7%. This translates into 67,000 persons with PTSD and 87,000 persons with major depression. This survey also found a significant increase in tobacco, alcohol, and marijuana use, but primarily among adults already using these substances. All surveys found strong associations between media exposure and symptomatology. The greatest need at this point in the literature is therapeutics research after such traumatic events.
Optimizing Treatment in Social Phobia: A Review of Treatment Resistance
Authors: Van Ameringen Michael , Mancini Catherine , Pipe Beth , Bennett Mark
Published: August 2016

Over the last 25 years, there has been a rapid expansion of our knowledge base of social phobia (SP). Although there are a number of well-validated treatment modalities, including pharmacotherapy and cognitive-behavioral therapy, significant gaps remain in our ability to achieve full remission in most patients. Despite advances in the neurobiology of SP, the etiology has yet to be determined. Investigations examining potential predictors of response have provided little guidance in selecting an appropriate treatment modality. These gaps in our knowledge have pushed us to examine issues related to treatment resistance. This paper presents a review of the current literature and issues related to treatment-resistant SP, including a discussion of the functional impairment associated with SP, definitions of treatment response and remission, as well as outcome measures that have been used in clinical investigations of SP. In addition, criteria for a standard treatment trial, predictors of treatment response, a review of treatment resistance studies, and potential directions for future research are examined. The most promising strategies to attain remission, will likely involve augmenting selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors with agents such as anticonvulsants, benzodiazepines, and antipsychotics as well as combining pharmacotherapy with cognitive-behavioral therapy. Our current treatment target of simply attaining a response needs to be refocused, so that an asymptomatic state and high end state functioning become the final goal of treatment.
Literary Factitious Epilepsy Syndromes
Authors: Jones Jeffrey M.
Published: August 2016

Several factitious epileptic syndromes have been associated with famous literary characters. While these syndromes include symptoms other than pseudoseizures, and while pseudoseizures can occur in other syndromes, a review of these disorders provides insights into factitious seizures and epilepsy.
Understanding Neuropathic Pain
Authors: Zieglgänsberger Walter , Berthele Achim , Tölle Thomas R.
Published: August 2016

Neuropathic pain is defined as a chronic pain condition that occurs or persists after a primary lesion or dysfunction of the peripheral or central nervous system. Traumatic injury of peripheral nerves also increases the excitability of nociceptors in and around nerve trunks and involves components released from nerve terminals (neurogenic inflammation) and immunological and vascular components from cells resident within or recruited into the affected area. Action potentials generated in nociceptors and injured nerve fibers release excitatory neurotransmitters at their synaptic terminals such as L-glutamate and substance P and trigger cellular events in the central nervous system that extend over different time frames. Short-term alterations of neuronal excitability, reflected for example in rapid changes of neuronal discharge activity, are sensitive to conventional analgesics, and do not commonly involve alterations in activity-dependent gene expression. Novel compounds and new regimens for drug treatment to influence activity-dependent long-term changes in pain transducing and suppressive systems (pain matrix) are emerging.
A Case of Alcohol Withdrawal Requiring 1,600 mg of Lorazepam in 24 Hours
Authors: Kahn Debra R. , Barnhorst Amy V. , Bourgeois James A.
Published: August 2016

Alcohol withdrawal continues to present significant morbidity and mortality in hospitalized medical/surgical patients. The authors present a case of a patient with delirium tremens requiring up to 1,600 mg/day of lorazepam and discuss alternative treatments for alcohol withdrawal.
Endocrinology of Menopausal Transition and Its Brain Implications
Authors: Genazzani Andrea Riccardo , Bernardi Francesca , Pluchino Nicola , Begliuomini Silvia , Lenzi Elena , Casarosa Elena , Luisi Michele
Published: August 2016

The central nervous system is one of the main target tissues for sex steroid hormones, which act on both through genomic mechanisms, modulating synthesis, release, and metabolism of many neuropeptides and neurotransmitters, and through non-genomic mechanisms, influencing electrical excitability, synaptic function, morphological features, and neuron-glia interactions. During the climacteric period, sex steroid deficiency causes many neuroendocrine changes. At the hypothalamic level, estrogen withdrawal gives rise to vasomotor symptoms, to eating behavior disorders, and altered blood pressure control. On the other hand, at the limbic level, the changes in serotoninergic, noradrenergic, and opioidergic tones contribute to the modifications in mood, behavior, and nociception. Hormone replacement therapy (HRT) positively affects climateric depression throughout a direct effect on neural activity and on the modulation of adrenergic and serotoninergic tones and may modulate the decrease in cognitive efficiency observed in climaterium. The identification of the brain as a de novo source of neurosteroids, suggests that the modifications in mood and cognitive performances occurring in postmenopausal women may also be related to a change in the levels of neurosteroids. These findings open new perspectives in the study of the effects of sex steroids on the central nervous system and on the possible use of alternative and/or auxiliary HRT.
The Association of Perimenopausal Mood Disorders with Other Reproductive-Related Disorders
Authors: Feld Judith , Halbreich Uriel , Karkun Sandhya
Published: August 2016

Data regarding the increased incidence of psychiatric illness during midlife in women are still conflicting. However, there is a growing consensus that certain groups of women may in fact be at higher risk for mood symptoms and psychiatric disorders during the perimenopausal transition. Mood symptoms during the perimenopause may be related to mood disorders during other periods of hormonal fluctuation throughout a woman's reproductive lifecycle. Elucidating these associations may advance the understanding of mood disorders during the perimenopausal transition. The epidemiology and treatment of perimenopausal mood symptoms compared with the epidemiology and treatment of mood disorders during the late luteal phase of the menstrual cycle, pregnancy, and postpartum. Common risk factors associated with mood disorders during these periods of hormonal changes or instability include poor lifestyle habits, a history of hormonally related mood disorders, stress and negative life events, ethnicity, and comorbidity. Reproductive-related mood disorders also are subject to an improvement in symptoms in response to treatment with selective serotonin reuptake inhibitors. As the morbidity associated with mood disorders during midlife may be quite significant, and as life expectancy continues to increase, recognition, prevention, and treatment of perimenopausal affective illness is becoming increasingly essential.
Lithium Plus Valproate as Maintenance Polypharmacy for Patients With Bipolar I Disorder: A Review
Authors: Solomon David A. , Keitner Gabor I. , Ryan Christine E. , Miller Ivan W.
Published: August 2016

Standard pharmacotherapy for the maintenance of treatment of patients with bipolar I disorder consists of lithium, valproate, or carbamazepine. However, many patients fail to respond to monotherapy with any of these agents, and as a result, psychiatrists often resort to polypharmacy. Findings from some open-label trials and retrospective chart reviews suggest this approach may be useful, but in the few controlled trials that have been conducted, the results have been negative. One drug combination that warrants further study as maintenance therapy is lithium plus valproate. Each is approved by the U.S. Food and Drug Administration for treatment of acute mania, and lithium has demonstrated efficacy for maintenance treatment as well. Some preliminary evidence suggests that the combination can be effective for patients who do not respond to monotherapy, and it seems to be no more dangerous than monotherapy. Concomitant administration of lithium plus valproate does not significantly alter lithium pharmacokinetics, and statistically significant changes that arise in valproate pharmacokinetics are not clinically significant. Although it is not known whether the drugs interact to augment response, many of their effects in the central nervous system do differ, and there is no indication of pharmacodynamic interactions that oppose each other. Finally, some evidence suggests that lithium and valproate may differ with regard to clinical variables that predict response to treatment. (J Clin Psychopharmacol 1998;18:38–49)

Bipolar I disorder afflicts approximately 1% of the U.S. adult population, with a median age at onset of 19 years. In many respects, it is a disabling disease. Acute episodes of mania and depression are often protracted with 24% of patients still acutely ill after 1 year has elapsed, 16% after 2 years, and 9% after 5 years. Subsyndromal symptoms, which impose significant morbidity that falls short of meeting full criteria for a mood episode, may occur frequently. Patients with bipolar I disorder are more likely than not to be unemployed or underemployed, less likely to marry and more likely to divorce than matched control subjects, and almost every family perceives the illness as a burden. Even remitted patients manifest poor psychosocial functioning, Ultimately, nearly 19% of patients die from suicide.
The Effects of Stressful Life Events, Coping, and Cortisol on HIV Infection
Authors: Leserman Jane
Published: August 2016

What is the role of stress and coping in changes in immunologic and clinical indicators of human immunodeficiency virus disease progression? There is substantial evidence that stressful life events and passive coping strategies, such as denial, may have a detrimental effect on HIV disease progression. Given the harmful effects of stress and passive coping, the author reviews the limited research testing the efficacy of interventions, such as cognitive-behavioral therapies for HIV-infected persons. Finally, in trying to understand psychoimmune relationships in HIV, the evidence is examined for the mediating and direct effects of cortisol, a hormone associated with stress, on HIV disease progression. Delineating the role of psychosocial factors and cortisol on HIV disease progression may aid in the development of new interventions for this devastating disease.
Stress Management and Psychoneuroimmunology in HIV Infection
Authors: Antoni Michael H.
Published: August 2016

Does stress management affect psychological and immune functioning in persons with human immunodeficiency virus infections? Stress-management techniques, such as relaxation training and imagery, cognitive restructuring, coping-skills training, and interpersonal-skills training, may reduce anxiety, depression, and social isolation in HIV-infected persons by lowering physical tension and increasing a sense of control and self-efficacy. A psychoneuroimmunologic model is proposed wherein these psychological changes are hypothesized to be accompanied by an improved ability to regulate neuroendocrine functioning, which in turn may be associated with a partial normalization of immune system functions such as lymphocyte proliferation and cytotoxicity, providing more efficient surveillance of latent viruses that may contribute directly to increased HIV replication and generate opportunistic infections or cancer if left unchecked. Such a normalization of stress-associated immune system decrements are hypothesized to forestall or minimize increases in viral load and expression of clinical symptoms. This model is useful for testing the factors contributing to the health effects of stress-management interventions in HIV-infected persons. In this context, one general research strategy for testing the effects of stress-management interventions is to target them toward the more prevalent psychosocial challenges that HIV-infected people face at various points in the disease process; enroll an HIV-infected population (eg, HIV-positive homosexual and bisexual men) into a randomized trial; and monitor changes in cognitive, affective, behavioral, and social factors in parallel with hormonal, immunologic, viral, and clinical changes over the course of time. This article will review the major psychoneuroimmunologic findings that have emerged using this paradigm and suggest future research directions and clinical applications.
Ziprasidone in Black Patients with Schizophrenia: Analysis of Four Short-term, Double-blind Studies
Authors: Lawson William B. , Herman Barry K. , Loebel Antony , Lazariciu Irina , Malik Mansoor
Published: August 2016

Objective: To better understand the efficacy and tolerability of atypical antipsychotics among racial groups, we reviewed data from four short-term (4–6 weeks), fixed-dose, placebo-controlled trials of ziprasidone for black, white, and overall populations of patients with schizophrenia.

Methods: Efficacy of ziprasidone in the black, white, and overall schizophrenic populations was compared to placebo using standard efficacy measures (Positive and Negative Syndrome Scale [PANSS] total, PANSS negative, Brief Psychiatric Rating Scale [BPRS], Clinical Global Impression-Severity [CGI-S], CGI-Improvement [CGI-I]).

Results: Black patients receiving ziprasidone demonstrated statistically significant improvements from baseline in PANSS total, PANSS negative, and BPRS, and improvements in CGI-S and CGI-I (n=99–149) compared with placebo (n=41–66); improvements were comparable to those observed in the overall population (n=451–639) and the white population (n=310–430). Interaction effect (treatment by race) was not significant for any efficacy variables. Ziprasidone was well-tolerated among black patients (n=175). Adjusted mean (least squares mean) overall weight gain in black patients receiving ziprasidone (n=124) was 1.8 kg. There were no increases in total cholesterol, triglycerides, or random glucose in the black population.

Conclusion: Ziprasidone has similar efficacy and safety in black patients with schizophrenia compared with patients in the white and overall populations.
Factors Associated with Concomitant Psychotropic Drug Use in the Treatment of Major Depression: A STAR*D Report
Authors: Shelton Richard C. , Hollon Steve D. , Wisniewski Stephen R. , Alpert Jonathan E. , Balasubramani G.K. , Friedman Edward S. , Rush A. John , Trivedi Madhukar H. , Preskorn Sheldon H.
Published: August 2016

Introduction: Concomitant psychotropic medication (CPM) treatment is common in persons with major depression (MDD). However, relationships with patient characteristics and response to treatment are unclear.

Methods: Participants with nonpsychotic MDD (N=2682) were treated with citalopram, 20–60 mg/day. Sociodemographic, clinical, and treatment outcome characteristics were compared between those using CPMs at study entry or during up to 14 weeks of citalopram treatment, and non-users.

Results: About 35% of participants used a CPM. Insomnia was the predominant indication (70.3%). CPM users were more likely to be seen in primary care settings (69.3% versus 30.7%), be white, of non-Hispanic ethnicity, married, and have a higher income, private insurance, and certain comorbid disorders. CPM users had greater depressive severity, poorer physical and mental functioning, and poorer quality of life than non-users. Response and remission rates were also lower. CPM users were more likely to achieve ≥50 mg/day of citalopram, to report greater side effect intensity, and to have serious adverse events, but less likely to be intolerant of citalopram.

Conclusion: CPMs are associated with greater illness burden, more Axis I comorbidities (especially anxiety disorders), and lower treatment effectiveness. This suggests that CPM use may identify a more difficult to treat population that needs more aggressive treatment.
New Developments in the Treatment of Epilepsy
Authors: Pellock John M. , Montouris Georgia D. , Ramsay R. Eugene
Published: August 2016

Epilepsy is a medical disorder that presents with single or clustered seizures. There are several new drugs that effectively treat epilepsy with few side effects, and treatments of children, women, and the elderly are discussed. In the special population of children, there is a strong emphasis on the cognitive and behavioral benefits of specific therapies.

In the population of epileptic women, seizures most often occur at the start of puberty and menarche, and worsen periodically with each menstrual cycle. Relief of symptoms often occurs at menopause, but a possibility of exacerbation also exists. Women with epilepsy often battle a fear of becoming pregnant. This is a fallacy which must be widely dispelled, as the risk is less than supposed.

Among the elderly, epilepsy often presents after trauma, particularly stroke, and the incidence is three times greater for those over 60 years of age than the general population. Due to various conditions specific to the elderly, misdiagnosis is common. The greatest challenge in treating the elderly is adverse side effects.
A Clinical Pathway Including Psychotherapy Approaches for Managing Emotional Difficulties After Acquired Brain Injury
Authors: Coetzer Rudi
Published: August 2016

Emotional difficulties, such as anxiety and depression, are common after acquired brain injury in adults and can influence long-term outcome. Diagnosis in a brain injury context can be difficult. Ideally, rehabilitation approaches should consider the specific treatment of anxiety and depression as well and may include pharmacotherapy, individual psychotherapy, and family interventions. Psychotherapy, especially in regards to longer-term adjustment to brain injury, may have an important adjunctive role in treatment approaches, but adaptations of techniques may be needed. A clinical pathway is described which can help to raise clinicians' awareness, as well as increase detection rates and consideration of the specific role of individual psychotherapy in this clinical population. However, an important caveat is that clinical pathways should not serve as a substitute, but rather a facilitator, for the process of reasoning about individual patients in everyday clinical practice.
Mechanism of Action of Trazodone:a Multifunctional Drug
Authors: Stahl Stephen M.
Published: August 2016

Multifunctional drugs are those with more than one therapeutic mechanism. Trazodone is a multifunctional drug with dose-dependent pharmacologic actions. That is, it has hypnotic actions at low doses due to blockade of 5-HT2Areceptors, as well as H1histamine receptors and α1 adrenergic receptors. Higher doses recruit the blockade of the serotonin transporter (SERT) and turn trazodone into an antidepressant. Although trazodone has traditionally been used as a low dose hypnotic, a new controlled release formulation that has the potential to improve the tolerability of high doses may provide an opportunity to revisit this multifunctional drug as an antidepressant as well.
Psychiatric Symptoms Associated with Brain Tumors: A Clinical Enigma
Authors: Moise Despina , Madhusoodanan Subramoniam
Published: August 2016

Patients in psychiatric settings may present with medical conditions, such as brain tumors, which may or may not be associated with neurological symptoms. In some cases, patients may only have psychiatric symptoms, such as mood changes (depression or mania), psychotic symptoms, panic attacks, changes in personality, or memory difficulties. Brain tumors may be detected in patients at their first presentation to mental health services or sometimes in patients with well-established psychiatric diagnoses.This article presents the case of a 29-year-old woman who was treated for >4 years for posttraumatic stress disorder and borderline personality traits, who developed depressive symptoms and memory difficulties. However, she did not develop any major neurological signs or symptoms. Brain imaging showed the presence of a left thalamic tumor, later confirmed as glioblastoma multiforme. She underwent surgical treatment and radiation therapy. With this we show that in some cases, brain tumors can be neurologically silent and only present atypical psychiatric symptoms.
Dementia Caregiving: Recent Research on Negative Health Effects and the Efficacy of Caregiver Interventions
Authors: Martire Lynn M. , Hall Martica
Published: August 2016

Provision of care to an older adult with dementia is an important societal resource. This resource may also come at a high cost to informal caregivers, most of whom are family members. In this paper we provide an overview of recent research on dementia caregiving and caregiver interventions. First, we provide background information on the prevalence and costs of Alzheimer's disease and related disorders. Second, we describe the specific stressors and broader mental and physical health outcomes of dementia caregiving. Third, recent evidence of the efficacy of caregiver interventions for both caregiver and patient outcomes is reviewed. Throughout the paper, we describe promising new directions for future research in this area, including assessment and intervention with family caregivers of older patients with comorbid dementia and depression, and the focus on sleep disturbance as a critical health consequence of dementia caregiving.
Assessment of Behavioral and Psychological Symptoms of Dementia
Authors: Bharucha Ashok J. , Rosen Jules , Mulsant Benoit H. , Pollock Bruce G.
Published: August 2016

In spite of their prevalence and persistence, why are behavioral and psychological symptoms of dementia difficult for clinicians to assess and manage? This paper provides an overview of the methodological challenges encountered in measuring behavioral disturbances of dementia. Specifically, conceptual constructs of behavioral and psychological symptoms of dementia, the strengths and weaknesses of the currently existing rating instruments, analytic methodologies, and the utility of technological devices are outlined in the service of formulating future directions in behavioral and psychological symptoms of dementia assessment research.
Reproductive Life Events and Sexual Functioning in Women: Case Reports
Authors: Warnock Julia K. , Biggs C. Faye
Published: August 2016

Are reproductive life events in women associated with an increased risk of sexual dysfunction? Female sexual dysfunction effects up to 40% of women in the United States between 18 and 59 years of age. Sexual dysfunction may be accompanied by fluctuations in gonadal hormone secretion, making women more vulnerable to sexual symptoms, especially during times of reproductive life events. Reproductive life events, such as the use of birth control pills, various phases of the menstrual cycles, postpartum and lactation states, and perimenopause, are highly correlated with changes in sex steroids. As an understanding of the role of sex steroids on sexual functioning is elucidated, clinicians will be able to offer more specific and effective treatment options for women during various phases of reproductive life. Several case studies are presented to illustrate the unique clinical considerations that a clinician must consider when treating the biologic component of female sexual dysfunction.
Adult ADHD and Comorbid Depressive Disorders: Diagnostic Challenges and Treatment Options
Authors: Goodman David
Published: August 2016

Attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) are separately common mental health conditions that can have an adverse effect on a patient's quality of life if left untreated. These disorders frequently cooccur with one another, which can lead to increased patient suffering and diagnostic challenges for the treating clinician. In the United States adult population, epidemiological data show that the prevalence rate for MDD is 6.7%, while the ADHD prevalence rate in US adults is 4.4%. This epidemiological data represents the general population and likely underestimates the prevalence rates in clinic or practice patients. Examining the concurrent comorbid rate, if a patient has MDD, the likelihood of that patient also having ADHD is 18.6%; if the patient has ADHD, the likelihood of that patient having comorbid MDD is 9.4%. If the patient has dysthymia, the comorbid rate of ADHD is 12.8%, while those adults with ADHD have a comorbid rate of dysthymia of 22.6% (Slide 1).

The diagnostic distinction between ADHD and MDD is a critical aspect of clinical evaluation that often presents challenges and confusion to the treating clinician (Slide 2). There are several factors that clinicians should consider in order to best distinguish these disorders, and ensure an accurate diagnosis—age of symptom onset, presenting symptoms, and family history of either disorder.

Typically, ADHD presents first in children, whereas most mood disorders, specifically MDD, have their index case onset in adolescence. Although MDD and dysthymia is reported in childhood, the peak incidence occurs during the adolescent years. Thus, the age of onset becomes one diagnostic factor that can assist in distinguishing these two conditions.
Substance Use Disorders and ADHD
Authors: Bukstein Oscar
Published: August 2016

In examining the challenges in treating comorbid attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD), there are a number of issues regarding misinformation and misconception that exist for clinicians. Like other ADHD comorbidities, there is a lack of screening, particularly among adult clinical populations who have the psychiatric comorbidity or, for patients with SUDs, there is the issue of prioritization, which condition to treat first, and determining the place of medication management—particularly stimulant medication—paramount in treatment planning.
Love and Attachment: The Psychobiology of Social Bonding
Authors: Stein Dan J. , Vythilingum Bavanisha
Published: August 2016

Basic animal studies and human imaging studies have contributed to our understanding of the psychobiology of love and attachment. There are overlaps and distinctions in the neuronal circuitry of maternal love, romantic love, and long-term attachment. In these circuits, important molecules, which have been demonstrated to play a role in the psychobiology of social bonding include dopamine, serotonin, opioids, oxytocin, and vasopressin. Particular genetic and environmental variations contribute to social-bonding phenotypes, consistent with an evolutionary perspective on the value of these behaviors. Advances in the psychobiology of social bonds have led to hypotheses about the pharmacotherapy of disorders of attachment.
Pathological Love: Impulsivity, Personality, and Romantic Relationship
Authors: Sophia Eglacy C. , Tavares Hermano , Berti Marina P. , Pereira Ana Paula , Lorena Andrea , Mello Cidália , Gorenstein Clarice , Zilberman Monica L.
Published: August 2016

Introduction: Pathological love (PL)–behavior characterized by providing repetitive and uncontrolled care and attention to the partner in a romantic relationship–is a rarely studied condition, despite not being rare and causing suffering. This study aims at investigating impulsivity, personality, and characteristics related to the romantic relationship in this population.

Methods: Eighty-nine individuals (50 with PL; 39 individuals with no psychiatric disorder) were compared regarding impulsivity, personality, type of attachment, satisfaction with romantic relationship, and love style.

Results: Individuals with PL have higher levels of impulsivity (P<.001; Barratt Impulsiveness Scale), higher self-transcendence, that is, are more unconventional and hold sense of communion with a wider reality (P<.001; Temperament and Character Inventory) and keep dissatisfactory romantic relationships (P<.001; Adapted Relationship Assessment Scale).

Conclusion: Individuals with PL present personality traits and relationship aspects that must be taken into account in devising assessment and therapeutic strategies for this population.
The Context of Genetic Testing in Clinical Psychiatric Practice
Authors: Mrazek David A.
Published: August 2016

Although most patients with depression ultimately respond to antidepressant therapy, >50% have inadequate response to an individual antidepressant trial. The desire to avoid adverse drug reactions is common among patients, and is an important determinant of drug selection among psychiatrists. However, since the major classes of antidepressants and antipsychotics appear to be comparable in efficacy, clinicians have little basis for selecting the most effective agent for an individual patient. Pharmacogenetics, often described as the study of genetic variation that explains differential response to medication, represents an important new avenue toward improving treatment outcomes. Genetic variation in drug-metabolizing enzymes has been recognized for decades. The main focus of current psychiatric pharmacogenetic testing is on the cytochrome P450 (CYP) 2D6 and, to a somewhat lesser extent, on the 2C19 genes. Data suggest that poor metabolizer status can be associated with an increased risk of adverse drug reactions with certain medications, and that ultra-rapid metabolizers may require higher-than-usual doses to achieve a therapeutic response. The importance of CYP enzymes in the metabolism of several antidepressant and antipsychotic drugs suggest that genetic variation may aid in medication selection or dosing. Advances in pharmacogenetic research may facilitate the development of personalized medicine in which genetic information can inform drug selection, leading to optimal drug effectiveness and minimal drug toxicity.
History and Pathophysiology of ADHD
Authors: Donnelly Craig L.
Published: August 2016

Attention-deficit/hyperactivity disorder (ADHD), once considered to be a childhood disorder, is diagnosed in ~7 million adults in the United States, as reported by The National Comorbidity Study. Although it is now recognized that ADHD often persists into adulthood, the current diagnostic criteria is geared toward symptom identification in children. Symptoms of inattention, impulsivity, and hyperactivity evolve over the life cycle and present differently in adults. Further complicating diagnosis is that ADHD is associated with multiple functional impairments and comorbid psychiatric disorders. The Multi-Modal Treatment Study of ADHD reported that only 32% of the study population had ADHD alone; 29% had ADHD plus oppositional defiant disorder and/or conduct disorder, 14% had ADHD plus anxiety or depression, and 25% had all three disorders. Optimal treatment utilizes a multi-modal approach including behavioral treatments combined with pharmacologic treatment strategies. Food and Drug Administration-approved medications for ADHD include the stimulants and nonstimulants, although tricyclic antidepressants and bupropion are also commonly used.

In this monograph, Craig L. Donnelly, MD, reviews the history of ADHD and discusses the pathophysiologic progression of childhood symptoms into those commonly exhibited by adults. Next, Frederick W. Reimherr, MD, reviews comorbidity of ADHD and describes the Utah Criteria as a method of diagnosing adults through recollection of childhood problems. Finally, Joel L. Young, MD, reviews treatment approaches to adult ADHD and its comorbid conditions.
Resilience: Determinants, Measurement, and Treatment Responsiveness
Authors: Connor Kathryn M. , Zhang Wei
Published: August 2016

In human terms, resilience is an ability to cope with stress and varies with context, time, age, gender, and cultural origin. Resilience shifts the focus of psychological investigation onto increasing the positive rather than reducing the negative. Inquiry into resilience has evolved from descriptions of resilient qualities, to discovery of the process to attain resilience, to uncovering the motivation to reintegrate in a resilient manner. Much of the research on resilience has focused on children in settings such as family violence, extreme poverty, war, and natural disasters. A coherent pattern of characteristics associated with successful adaptation has emerged. Salient characteristics include commitment, dynamism, humor in the face of adversity, patience, optimism, faith, and altruism. As such, resilience may represent an important target of treatment in anxiety, depression, and stress reactions. Resilience can be quantified, but available measures need to be validated transculturally. There exist many possible determinants of resilience, including neurobiologic, genetic, temperament, and environmental influences. Resilience is modifiable on individual and cultural levels. Posttraumatic stress disorder is an example of a serious disorder associated with impaired stress coping that can improve with treatment.
Introduction-Neuroprotection: A Therapeutic Strategy to Prevent Deterioration Associated with Schizophrenia
Authors: Lieberman Jeffrey A.
Published: August 2016

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.
Special Considerations in Diagnosing and Treating Attention-Deficit/Hyperactivity Disorder
Authors: Wigal Sharon B. , Wigal Timothy L.
Published: August 2016

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent chronic condition that affects people of all ages, including young children, school-aged children, adolescents, and adults. Symptoms can be noted as early as preschool age, tend to progress into functional impairment and behavioral problems in later childhood, and typically persist into adulthood. Contrary to previous belief, the disorder does not resolve with puberty for the majority of children; rather, the symptoms are manifested differently throughout the lifecycle. Presentation in adults is heavily biased toward inattentive symptoms, which are less likely to draw notice than hyperactive or impulsive symptoms and may contribute to the underrecognition of ADHD in this patient population. Diagnosis is particularly difficult due in large part to the pronounced comorbidity of psychiatric disorders in this patient population. Identification may be even more difficult in adults than children as the diagnostic criteria are not as clear, adults have difficulty remembering symptoms prior to 7 years of age, and there is a high prevalence of comorbid psychiatric disorders in adults. Early identification and treatment of symptoms of ADHD in preschool-age children is essential to effective long-term management of the disorder. Both medication and behavioral treatments appear to alleviate the symptoms of ADHD, and evidence suggests that discontinuation of treatment leads to the reemergence of the condition. Efforts are currently continuing toward understanding the genetic underpinnings of ADHD.

This expert review supplement will address the prevalence, comorbidity, treatment issues, and special considerations surrounding ADHD management throughout each stage of the lifecycle beginning with ADHD in preschool-aged children, continuing with school-aged children and adolescents, and ending with adulthood.
Factors That Impact Choice of Antidepressant Treatment in Medically Complex Patients
Authors: Dago Pedro Luis
Published: August 2016

In medically complex patients with multiple comorbid illnesses who require concomitant medications, selecting the optimal antidepressant (ie, low risk of adverse effects and/or pharmacokinetic interactions) for an individual patient is critical for positive long-term patient outcomes. The serotonin-norepinephrine reuptake inhibitors (SNRIs) are increasingly being used as first-line treatment for major depressive disorder (MDD) and may prove beneficial for treatment of medically complex patients. Thus, it is key for clinicians to evaluate the differences in the pharmacokinetic and tolerability profiles of the SNRI class of antidepressants, evaluating differences both within the class and compared with other antidepressants used to treat MDD.