While monoaminergic hypotheses of psychopathology remain popular, there has been growing interest in the role of neurotrophins in neuropsychiatric disorders. Basic laboratory work has documented the importance of neurotrophins in neuronal survival and synaptic plasticity, and a range of clinical studies has provided analogous evidence of their role in neuropathology. Work on gene variants in brain-derived neurotrophic factor, and associated changes in structural and function brain imaging, have further contributed to our understanding of this area. Much remains to be done to delineate fully the relevant mechanisms by which brain-derived neurotrophic factor and other neurotrophins contribute to psychopathology, and to develop targeted therapeutic interventions. Nevertheless, the neurotrophin hypothesis has already given impetus to a range of valuable research.

Fibromyalgia pain is frequent in the general population, but its pathogenesis is only partially understood. Patients with fibromyalgia lack consistent tissue abnormalities but display features of hyperalgesia (increased sensitivity to painful stimuli) and allodynia (lowered pain threshold). Many recent fibromyalgia studies have demonstrated central nervous system (CNS) pain processing abnormalities, including abnormal temporal summation of pain. In the CNS, persistent nociceptive input from peripheral tissues can lead to neuroplastic changes resulting in central sensitization and pain. This mechanism appears to represent a hallmark of fibromyalgia and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain. Importantly, after central sensitization has been established, only minimal peripheral input is required for the maintenance of the chronic pain state. Additional factors, including pain-related negative affect and poor sleep have been shown to significantly contribute to clinical fibromyalgia pain. Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of fibromyalgia and other chronic pain syndromes.

Quality of life (QoL) is increasingly recognized as a pivotal outcome parameter in research on obsessive-compulsive disorder (OCD). While the concept remains somewhat ill-defined, there is now little dispute that the patients’ personal goals deserve foremost consideration during the course of treatment as the primary aim of treatment should be relief from individual despair, which is related but by no means synonymous to symptom reduction. Studies using generic (ie, illness-unspecific) instruments have confirmed poor QoL in OCD patients across a wide range of domains, especially with respect to social, work role functioning, and mental health aspects. Scores are sometimes as low as those obtained by patients with schizophrenia. Depression and obsessions are the symptom clusters that most strongly contribute to low QoL. Findings from a novel survey of 105 OCD participants point to multiple daily life problems, poor work status, and tense social networks in these patients. In order to achieve therapeutic success and improve QoL, functional problems at work and comorbid disorders such as secondary depression and physical impairments should be targeted. While successful treatment sometimes positively impacts well-being, in some studies symptom decline did not translate into improved QoL.

Co-occurring psychiatric and alcohol use disorders can have devastating personal and societal effects, yet little evidence exists to guide clinical treatment. In the face of scant data, individual practitioners must rely instead on professional experience and those limited practice guidelines that currently exist. The American Psychiatric Association (APA) advises that failure to treat a concurrent psychiatric disorder reduces the likelihood that the treatment for a substance use disorder (SUD) will be effective. Indeed, the effects of nontreatment were demonstrated in a prospective study assessing alcohol-dependent patients for 1 year following hospitalization for alcohol dependence, in which untreated depression was directly associated with a shorter time to first drink. The results also showed that among those patients with depression (Slide 1), taking antidepressants at the time of discharge increased the likelihood of an individual remaining abstinent during the follow-up period.

Computer-based measures to evaluate cognition have been used with growing frequency in recent years. These batteries are shown to be useful for identifying mild cognitive impairment (MCI) and dementia. There are few requirements to administer these tests. All that is typically needed is a computer, a response pad for patients to input their answers, and an examiner. In many cases, the examiner does not need to be a trained neuropsychologist. These computer-based assessments should yield a score report detailing the patient’s cognitive profile.

An important advantage of computerized assessments over standard paper-and-pencil testing is that they can provide precise measurement at the millisecond level. This can be a more sensitive measure of cognitive impairment, especially in high-functioning older adults and in patients with milder levels of cognitive deficit. Computer tests also have a shorter assessment time. Many batteries take <1 hour to administer, whereas many standard neuropsychological batteries require >4 hours to complete. The presentation of items in some batteries can be adapted to patients’ performance levels to avoid floor effects (the test restricts how low a patients’ scores can be) and ceiling effects (the test restricts how high scores can be). Computer tests have increased standardization; they are administered the same way every time. Scoring is automatic, meaning the results are available immediately and human scoring error is reduced. Examiner effects are reduced, which is an important advantage because clinicians may differ in how they administer standard tests, which may impact patients’ responses. In addition, the batteries are easily transported, and multiple tasks can be made available on a single computer.

Many efforts are being made to medically manage or eliminate Alzheimer's disease. Millions of family members, friends, and professionals are serving as caregivers for those with the disorder. These two efforts are important, but they are not enough. The public must also be educated in order to reduce the risk for Alzheimer's disease and related dementias in younger generations. These various goals can be accomplished through many different community-focused activities, including care and support for families; public awareness; community, patient, and professional education; research; and advocacy.

Patients with schizophrenia have a markedly reduced lifespan compared with the general population. In the United States today, patients with schizophrenia have an average life expectancy of ∼61 years, about 20% lower than that of the general population, in which life expectancy is ∼76 years.

When performing a diagnostic evaluation for an adult patient with possible adult attention-deficit/hyperactivity disorder (ADHD), clinicians must pay particular attention to possible mimics. ADHD mimics are conditions responsible for the symptoms or impairments that superficially resemble, and may be confused with ADHD. These mimics may produce symptoms and impairments similar to those seen in adults with ADHD, but differ in etiology, course, or response to treatment of ADHD. When evaluating someone for ADHD, clinicians should first rule out the possibility of medical, psychiatric, and social mimics of ADHD.

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

There is evidence that the serotonin norepinephrine reuptake inhibitors (SNRIs) venlafaxine, milnacipran, and duloxetine, have probable superior antidepressant activity to most selective serotonin reuptake inhibitors (SSRIs), especially in more severe depression. Some patients, however, respond better than others to SNRIs. Several factors influencing response to milnacipran have been recently studied. The presence of certain polymorphisms related to noradrenergic neurotransmission has been shown to be related to different degrees or rapidity of response to milnacipran. In addition, patients with low pretreatment levels of plasma 3-methoxy-4-hydroxyphenylglycol have a better response to milnacipran. These recent genomic and neurochemical data confirm that milnacipran, in contrast to SSRIs and venlafaxine, has an impact on the noradrenergic system. Differences in metabolism determined by genetic variables in cytochrome P450 (CYP) 2D6 activity are a major determinant of venlafaxine levels to such an extent that genetically determined decreases in CYP 2D6 activity have been associated increased adverse effects. Milnacipran, which is not metabolized by the enzymes of the CYP system is not influenced by polymorphism of these enzymes. These preliminary data suggest that a patient's biochemical and pharmacogenetic characteristics may be useful in the future to help clinicians chose the most  effective antidepressant medication.

A duodenal levodopa (L-dopa) and carbidopa infusion has been developed to stabilize plasma levels of L-dopa, in order to reduce existing motor response fluctuations. Stable plasma levels have been shown to reduce these fluctuations significantly. A constant duodenal infusion with an L-dopa solution can improve response fluctuations, however L-dopa has very poor solubility. Only in an acidic environment can L-dopa be dissolved in large volumes. To supply 1 day of infusion with the conventional L-dopa solution, ∼4–5 liters are necessary, an inconvenience to most patients. With L-dopa/carbidopa infusion, L-dopa and carbidopa are concentrated in a water-based gel-like suspension to 20 mg/mL, which has reduced the infusion volumes to <100 mL/day.

As a general principle, separate treatments are often needed for attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders. There are few treatments for mood disorders that also treat ADHD, and vice versa. This discussion will review the literature on agents that are effective for both disorders, or that may potentially be combined. Physicians must bear in mind that none of these agents is approved by the Food and Drug Administration for the treatment of comorbid ADHD and depression.