Pregnancy is a period of substantial neuroendocrine changes. These changes are not limited to the hypothalamic-pituitary-gonadal hormones, but also involve the placenta and its secreted hormones, especially the corticotropin releasing hormone that is a major component of the stress axis. These hormonal changes are also associated with changes in the immune/inflammatory and cardiovascular systems. The cumulative evidence that dysregulation in this multifactorial interactional field may cause deleterious effects on the fetus and its future development emphasizes the importance and clinical relevance of this line of research. When vulnerability and genetic predisposition to gestational stress and its adverse effects are added to the equation, the importance of adequate treatments and possible preventive interventions is underscored.

Pregnancy is usually perceived as a happy period. However, as demonstrated by Uriel Halbreich, MD, severe mood, behavior, and cognitive symptoms are quite prevalent during pregnancy. The magnitude of the problem is probably not reflected by the reported prevalence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition or International Classification of Diseases, Ninth Edition major mental disorders. A closer evaluation and treatment of symptoms, especially when they are associated with impairment, stress, and distress, may improve the mental health of the mother and the expected baby.

Bipolar disorder, particularly bipolar type I disorder, is at least as highly comorbid with other psychiatric and behavioral disorders as any Axis I medical disorder (Slide 1). Two iterations of the National Comorbidity Survey study, which is epidemio-logic-based and not anecdotal evidence from clinical offices and hospital emergency rooms, have shown that these data are reflective of the overall population in the United States and potentially for all other countries across the world.

In particular, if the prevalence rates of all anxiety disorders are grouped together, they are almost as prevalent as bipolar disorder itself, and clinicians rarely see a patient with bipolar disorder who does not have an anxiety disorder. This finding raises the question that anxiety may not be a separate entity, but an additional fundamental component of bipolar symptomatology, at least for a substantial number of patients. Regardless, the role of anxiety in bipolar disorder is unique. Perugi and colleagues studied the time sequence of different anxiety disorders in relation to first presence and clinical recognition of bipolar disorder (Slide 2). In contrast to panic disorder/agoraphobia and obsessive-compulsive disorder (OCD), social anxiety or social phobia was shown to be prevalent in 94.7% of patients prior to onset of hypomania and the clinically recognizable problematic school and home situations before the diagnosis of the bipolar disorder. This finding suggests that there may be some fundamental aspect of social anxiety and other anxiety disorders that is a ties. These patients tend to be more unstable symptomatically and have multiple comorbidities.

Treatment of attention-deficit/hyperactivity disorder (ADHD) may positively impact the neurobiology of adult patients with ADHD. Treatment may also minimize impairment from core symptoms and may alter the course of co-morbid disorders such as depression and substance use disorder. However, much of the information on stimulant use in adult ADHD comes from studies conducted in children, and it remains unclear whether there is a difference between children and adults when it comes to the side effects and tolerability of ADHD treatments. It is known that clinical presentation differs between adults and children, with adults demonstrating a higher percentage of mood disorders. Current treatments for adult ADHD include psychosocial therapies and pharmacologic therapies, the latter of which include the stimulants d-methylphenidate extended release (XR), OROS methylphenidate, lisdexamfetamine, and mixed amphetamine salts XR; and the nonstimulant atomoxetine, a selective norepinephrine reuptake inhibitor. There is need for additional study of treatment strategies for adult ADHD. Although all classes of ADHD medications are approved in adults, there are fewer approved formulations for adults than for children. Efficacy in adults is more subjective than in children, which may affect how efficacy rates for adult treatments are calculated. Adults also present a greater diversion risk than children. In addition, there are several new and emerging medication treatments worth considering.

This Expert Roundtable Supplement represents part 2 of a 3-part supplement series on adult ADHD led by Lenard A. Adler, MD. In this activity, Thomas J. Spencer, MD, discusses the neurobiology and genetics of adult ADHD; Mark A. Stein, PhD, discusses stimulant therapy; and Jeffrey H. Newcorn, MD, reviews nonstimulants and psychosocial treatments.

A 14-year-old girl with anorexia nervosa (AN) was found to have an intracranial neoplasm. Atypical psychological symptoms prompted further evaluation, including electroencephalogram and neuroimaging, which revealed a sellar and suprasellar mass.This patient had an eating disorder and a brain tumor, which appear to be two unrelated conditions. However, it remains unclear how each affected the other. The diagnosis of AN, like all other psychiatric disorders, requires that possible medical etiologies and coexisting medical problems be excluded. AN and other eating disorders are particularly difficult to diagnose in children and adolescents because they often do not present in the manner typical of adults. Perceptual and cognitive disturbances associated with AN are difficult to evaluate because children and adolescents normally change over time as they progress through different stages of development. Therefore, It is particularly important to evaluate for the presence of medical conditions when a diagnosis of an eating disorder is made in a child or adolescent.

Treatment resistance, along with its sibling partial response, remains a common phenomenon in schizophrenia, complicating the disability burden inherent in the disease. Antipsychotic medications are the mainstay of treatment, and treatment resistance has mainly been defined in terms of poor response to antipsychotic medication. At the same time, clozapine, the most effective antipsychotic, remains underutilized at the expense of exposing patients to polypharmacy. We review known causes of disability in schizophrenia, how they impact various areas of everyday functioning, and discuss potential treatment options including but not limited to pharmacological approaches aimed at maximizing treatment response and reducing treatment resistance.

NMU of prescription stimulant medications (RxStim) intended for treatment of attention deficit/hyperactivity disorder (ADHD) is a growing public health concern, particularly when used via non-oral routes of administration. However, the role of non-oral routes of administration for RxStim NMU in the larger substance abuse pathway is less well studied. The purpose of this study was to characterize RxStim NMU and investigate substance use trajectories among adults who reported non-oral RxStim NMU recruited from Reddit.

Eligible participants must have been located in the US, English speaking, age 18 y, and have reported RxStim NMU via a non-oral route (any route other than ingestion) within the past 5 y. Participants were recruited from Feb-Sep 2019 using banner ads on Reddit, the 5th most visited website in the US. Participants completed an online survey which captured demographics, lifetime RxStim NMU and illicit substance use; they were compensated for their time. For purposes of this study, NMU included ANY of the following: (1) use for any reason, even once, without their own prescription, (2) use in ways other than prescribed, and (3) use for the feeling or experience the medication caused.

Respondents (n=225) were primarily male (86.2%), 18–24 (48.0%) or 25–34 (43.1%) years of age, and Caucasian (78.2%), Black (7.1%) or Hispanic (5.3%). Lifetime diagnosis of ADHD was reported by 27.6%, with 53.2% diagnosed at age 11–19 and 35.5% at age 20+ years. RxStim NMU via snorting was reported by 99.1%, smoking 3.6% and injecting 6.2% (multiple routes could be reported). Almost all (n=222; 98.7%) also reported lifetime illicit drug use, among whom 182 (82.0%) initiated substance use by using an illicit drug (77.9% marijuana, 1.8% cocaine/crack, 0.9% inhalants, 0.9% hallucinogens, 0.5% methamphetamine/amphetamines) prior to RxStim NMU. Forty (18.0%) respondents initiated with RxStim NMU; 14.4% then initiated marijuana use, 0.9% initiated cocaine/crack use, 0.9% initiated barbiturate use, and 0.5% initiated heroin, inhalant, methamphetamine/amphetamine, and hallucinogen use. Average age of initial RxStim NMU was 18.7 (SD 3.7) years and most often was via swallowing (89.1%) followed by snorting (10.9%). Respondents began using marijuana at age 15.9 (SD 2.5), cocaine or crack at 19.7 (SD 3.3), and heroin at 20.9 (SD 5.5).

Engagement in RxStim NMU via a non-oral route of administration is most often preceded by marijuana use. Among this Reddit-recruited population of non-oral RxStim nonmedical users, only 1 in 4 reported an ADHD diagnosis and <1 in 5 reported RxStim NMU as their first substance use experience; most of these then added marijuana and few moved toward cocaine/crack or methamphetamine. RxStim NMU via non-oral routes is associated with a larger pattern of risky substance use behaviors. Nearly all non-oral RxStim NMU is associated with concomitant drug use, especially marijuana.

Funding. Arbor Pharmaceuticals, LLC

The new diagnosis of disruptive mood dysregulation disorder (DMDD) was introduced in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, to address the overdiagnosis of bipolar disorder in children and adolescents. However, there are ongoing debates about its nosology given chronic persistent irritability in children and adolescents has contextual valence. Those meeting the criteria for DMDD may, in fact, have an oppositional defiant disorder, attention deficit hyperactivity disorder, or other behavioral disorders. Similarly, in the last few years, there are many different types of treatment studies that have also yielded mixed results. These counterintuitive findings need a meticulous review for a wider debate given its clinical utility for patients, families, and practicing clinicians.

The treatment of major depression remains problematic for several reasons. In particular, the therapeutic response to medications usually does not manifest itself until a week after administration has begun, and more than half the patients will not experience a full recovery with the first antidepressant drug administration. There are, however, some pharmacologic strategies that can accelerate antidepressant response. When facing a treatment-resistant depression, combination therapy offers a more time-efficient approach to achieve remission than drug substitution. These interventions have been devised on a better understanding of the basis for the therapeutic response obtained with the first- and second-generation antidepressants, and evidence derived from controlled clinical trials of their superior effectiveness is growing. The rationale for such approaches will be described in this article, as well as their advantages and potential inconveniences. Ongoing research in this field continues to fuel the development of novel, better-tolerated, and more effective pharmacotherapies for depression.

Problems with memory are a very common complaint in the elderly and are not synonymous with dementia. Some degree of cognitive decline, manifested as greater difficulty in learning and retrieving new information for instance, develops with normal aging. Thus many older patients do not perform at the same level they did when they were younger but they do perform well when compared to their peers. For many, cognitive change ends at this stage and they proceed to lead normal, healthy, dementia-free lives.

The cohort that has cognitive changes beyond what is expected in normal aging but does not yet meet criteria for dementia concerns clinicians greatly as many of these patients eventually become demented. These patients usually go through a latent stage in which neurodegenerative pathology silently spreads in the brain. Once there is enough pathological burden, cognitive decline beyond what is expected for normal aging can be detected by formal neuropsychological testing. Frequently such patients go through a state called mild cognitive impairment (MCI). In this state patients are still functionally intact and live independently, but show cognitive impairment relative to the age- and education-adjusted norms.

The MCI state in itself is a prominent risk factor for developing dementia. Most patients with amnestic MCI develop Alzheimer’s disease (AD) dementia over time. At six years, as many as 80% progress to AD. Thus, MCI is a very important topic of research and an increasingly important topic of clinical care.

Although anxiety disorders are the most prevalent group of disorders in the United States, little is known about the efficacy of treatments for these disorders in elderly patients. Anxiety disorders, especially generalized anxiety disorder and phobias, are highly prevalent in older people. Anxiety symptoms and disorders are associated with increased mortality and disability in older people. Risk factors for anxiety disorders include chronic medical illness, disability, low education, low social network, and poor social support. The newer antidepressant medications, in particular the selective serotonin reuptake inhibitors and venlafaxine-extended relief, are recommended as first-line pharmacotherapy of these disorders in elderly. Cognitive-behavioral therapy is recommended as first-line psychotherapy for these disorders. However, these recommendations are based on extrapolation of data from younger adults or retrospective analysis of datasets, the results need to be confirmed with controlled studies in an elderly age group.

A 27-year-old woman presented to the emergency room after having witnessed generalized tonic clonic seizure while asleep. Birth and development were normal. She had suffered a single febrile seizure at 13 months of age, but had no other seizure risk factors. She was otherwise well except for a history of depression for which she was taking sertraline. Depressive symptoms had been well controlled over the past 3 months, but she had been under increased stress working to finish a doctoral thesis. Neurological examination was normal. Magnetic resonance imaging (MRI) showed modest asymmetry of the hippocampi, slightly smaller on the right, but no abnormal signal and well-preserved laminar anatomy. An electroencephalogram was negative. She was discharged from the emergency room with no treatment. Three weeks later, the patient's boyfriend witnessed an episode of behavioral arrest with lip smacking and swallowing automatisms lasting 45 seconds, after which the patient was confused for 20–30 minutes. The next morning she and her boyfriend kept a previously scheduled appointment with a neurologist.

For most patients with major depressive disorder (MDD) the first-line treatment is one of the selective serotonin reuptake inhibitors (SSRIs). However, some practitioners prefer to utilize a serotonin norepinephrine reuptake inhibitor (SNRI) or the norepinephrine-dopamine reuptake inhibitor bupropion as their first-line antidepressant treatments (Slide 1). Differences of opinion regarding first, second, or third choice of antidepressant often stem from regional practices or individual training.

A basic standard of practice in MDD treatment is to initiate monotherapy trials with several first-line choices of antidepressants before moving on to alternate strategies. This basic strategy was evaluated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Only approximately one third of the patients remitted after being treated with the study's first-line treatment, a 12-week trial of citalopram in doses up to 60 mg/day. As in other contemporary treatment studies, remission was defined as virtually complete relief of depressive symptoms. This is defined as a Hamilton Rating Scale for Depression score of ≤7 or a score of ≤5 on the self-report version of the Quick Inventory of Depressive Symptomatology.

For those who did not obtain an adequate response to the initial course of citalopram therapy, the STAR*D study compared several alternate treatments, including switching to another antidepressant, adjunctive therapy with another type of medication (ie, a medication that is not an antidepressant), or combination treatment (ie, adding another antidepressant). At the end of four sequential treatment trials, only approximately two thirds of the patients remitted. Of those, 40% to 70% relapsed within the next year despite continued therapy.

Panic disorder (PD) is a complex, multidimensional psychiatric disorder characterized by the presence of panic attacks as well as anticipatory anxiety and panic-related phobias (eg, agoraphobia). Although the etiology of this disabling disorder remains unclear, advances in basic neuroscience and in imaging studies have led to a greater understanding of the neurocircuitry and neurochemistry that are involved in modulating fear and anxiety and that are relevant to understanding PD. A preliminary integrated model can be outlined, but there is a need for additional research that cuts across genetic investigation, provocation studies, neuroimaging techniques, and treatment trials. As research continues and greater insight into the mechanisms underlying PD is achieved, additional treatment strategies may emerge.