Progress in biological psychiatry is contingent upon progress in neurobiology and progress in research of proper characterization and assessment of abnormal behavior. Advances in neurobiology are rapid and steady; however, advances are few and far between in psychopathology. In many ways, developments over the past two decades run counter to what I believe to be diagnostic pre-requisites for fruitful biological research in psychiatry. I presume this to be a major reason why thus far biology has made no significant contributions to the diagnoses of mental disorders.

For progress to occur in biological psychiatry, the traditional diagnostic philosophies and attitudes must be reevaluated and alternative diagnostic approaches put into practice. This and the diagnostic method of functional psychopathology are reviewed in this article, with a focus on how the functional psychopathological approach could contribute to the advancement of the diagnostic process in psychiatry, and the opportunities it provides for biological psychiatric research.

Optimal treatment for patients with mental health illness depends upon accurate diagnosis, individualized treatment, patient adherence to effective agents, and an intact family support system. Healthcare system (eg, limited access to certain medications), provider (eg, bias and discrimination), and patient factors (eg, biologic and cultural) greatly influence the level of mental health care given, especially to minority populations. Furthermore, limited data in African Americans, Hispanics, and Asians suggest that there are racial, ethnic, and cultural variations in responsiveness to antipsychotic medications, as well as potential differences in the types, rates, and severity of adverse events. Non-Caucasian patients tend to receive older, less-expensive agents, sometimes at higher doses (African Americans, leading to potentially intolerable side effects and early withdrawal of therapy or a less than optimal therapeutic response, respectively. Differences in response may have a biologic, pharmacokinetic, or pharmacodynamic basis and may also be influenced by lifestyle factors (eg, diet, smoking). Variations in dopamine receptor occupancy and cytochrome P450 polymorphism may explain some racial/ethnic differences in antipsychotic effects and adverse-event profiles, suggesting that dosing may need to be individualized based on ethnicity. The newer atypical antipsychotics, while seemingly better tolerated compared with conventional antipsychotics, may not be totally devoid of bothersome side effects (eg, extrapyramidal side effects) in minorities. While further research is needed, recognition of potential interracial/ethnic pharmacogenetic differences may help minimize intolerable side effects and achieve optimal psychosis management.

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.

In the last 20 years, research on substance addictions has changed its focus from the social foundations to the neurobiological foundations. Hence, some behaviors have begun to be considered as equivalent to addiction based on proposed criteria: salience, withdrawal symptoms, tolerance, conflicts, relapse, and mood modifications.

New knowledge about the brain's reward system suggests that “as far as the brain is concerned a reward is a reward, regardless of whether it comes from a chemical stimulus or an experience.”

Pathological gambling was the prototypical addiction disorder, sharing some hallmarks with substance addictions: a high rate of comorbidity and treatment response to pharmacotherapies, such as opioid antagonist. However, compulsive sexual behavior, compulsive exercise, food starving, binge eating, and, most recently, Internet addiction have been gradually conceptualized as non-substance addictions with overlapping features with substance dependence. Several definitions” have been adopted regarding these behaviors: natural addiction, non-chemical addiction, and negative dependence are only some examples. This issue of CNS Spectrums focuses on behavioral addictions.

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.

Tourette syndrome (TS) is a complex neurobehavioral disorder principally characterized by motor and vocal tics. However, features of obsessive-compulsive and attention-deficit/hyperactivity disorders are often present. The basal ganglia and associated brain structures have been implicated in the pathophysiology of TS, as well as in these related conditions. Specifically, it is believed that the neuroanatomically and functionally defined basal ganglia thalamocortical loops are involved in TS. These loops are composed of a sequence of connections originating in the cortex and passing in series through the striatum (caudate and putamen), globus pallidus, and thalamus before returning to the cortical areas of origin. This review concentrates on the neuroimaging findings in Ts, particularly as they relate to alterations in components of the basal ganglia thalamocortical circuits. These neuroimaging data suggest that the major abnormalities in TS involve striatal or cortical dysfunction, as well as dysfunction of dopaminergic systems that regulate basas ganglia neurotransmission.

Infection with human immunodeficiency virus type 1 (HIV-1 ) leads rapidly to infection of the brain and subsequent neuropsychological impairment, including subclinical impairment, minor cognitive-motor disorder, and HIV-1–associated dementia (HAD). This article reviews HAD and the factors involved in its pathogenesis; the effectiveness of antiretroviral therapy; the prevalence of HIV-1 and subtypes; and the role of chemokines and cytokines as the capstones associated with neuropathology due to inflammation.

Bipolar disorder is a prevalent psychiatric disorder with a high rate of misdiagnosis and evidence of degenerative progression. Research indicates that the interval between bipolar episodes decreases steadily until the patient settles into a relatively frequent course of mania and depression. Various imaging techniques have been used in the understanding of the brain pathology underlying bipolar disorder through identification of patterns consistent with disruption of the normal brain activity in bipolar patients. These techniques have demonstrated evidence of abnormalities in the structure and function of the prefrontal cortex. In addition, the cerebellar vermis, which serves as an error-detection function to modulate the iterative network, appears to shrink with recurrent episodes. Functional imaging demonstrates that the anterior limbic network is overactivated and overresponsive in patients with bipolar disorder. In many patients, those deficits are often compensated for by activation of other brain areas. Ultimately, when the compensation fails, expression of bipolar symptoms arise. Using magnetic resonance spectroscopy, simple models can be constructed based on the hypothesis that mitochondrial function may be impaired in bipolar disorder. There is also increasing evidence that psychotropic medications can affect specific brain regions that are thought to be involved in the pathogenesis of psychiatric disorders. Glutamate levels appear to be elevated in untreated patients with bipolar disorder, which may cause glutamatergic neurotoxicity and negative therapeutic implications. Further advances in brain imaging may contribute to the improvement of available therapies and the understanding which treatments will be most suitable for specific patients.

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.

Unraveling the significant complexity of brain-immune interactions could provide essential new insights and potential treatment considerations for the clinical neurosciences. Despite considerable research relating immunological changes to major neuropsychiatric disorders, it has been difficult to establish that immunological processes are involved in the development of central nervous system pathology associated with these disorders. This brief article highlights some of the landmark basic studies and seeks to convey essential principles guiding research in brain-immune interactions. Research in this area often incorporates several disciplines, ranging from psychology and neuroscience to immunology and molecular genetics. The clinical implications of this area of research are discussed, with emphasis on the challenge of disentangling pathogenic factors and valid markers of disease from epiphenomena.

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.