ISSUE:A paradigm shift is afoot in which the “last shall be first,” namely, use of long-acting injectable (LAI) antipsychotics, rather than being reserved for use only at the last stages of schizophrenia, may be shifting to first-line treatment of early episodes of this illness.

Background: Attention-deficit/hyperactivity disorder (ADHD) occurs in as many as 4% of adults yet it is often not recognized in clinical settings because the presenting symptoms may resemble those seen in other disorders or because symptoms may be masked by commonly comorbid conditions such as anxiety and depression.

Objective: The purpose of this study was to examine the diagnostic utility of instruments commonly used in the assessment of adults presenting with symptoms of ADHD.

Methods: We reviewed several widely used self-report and laboratory measures and empirically examined the utility of the Brown Attention-Deficit Disorder Scale for Adults (Brown ADD Scale) and the Conners Continuous Performance Test (CPT) in differentially identifying adults with ADHD and those with other Axis I disorders.

Results:Ninety-three adults who self-referred to the ADHD program for adults at a university medical center participated in the study. Of these, 44 had ADHD combined subtype (ADHD-CB), and 26 had ADHD, predominantly inattentive subtype (ADHD-IA). Thirty-three non-ADHD adults diagnosed with Axis I mood or anxiety disorders comprised an “Other Psychiatric” group. Rates of comorbid disorders, including substance abuse, in the ADHD groups were typical of those reported in the adult ADHD literature. Data on the Brown ADD Scale and on the CPT were available for subsets of 61 and 46 participants, respectively. Analyses showed that the ADHD-CB, ADHD-IA, and Other Psychiatric groups all received mean scores in the clinical range on the Brown ADD Scale, with a trend toward even higher elevations in the two ADHD groups. Among 12 CPT variables assessed for the three groups, the mean scores on only two variables for the ADHD-IA group were clinically elevated. Neither the Brown ADD Scale nor CPT scores evinced sufficient sensitivity and specificity to qualify them to assist in differential diagnosis of ADHD vis-a-vis other, predominantly internalizing, psychiatric disorders.

Conclusion: The results indicate a need for closer examination of executive and adaptive functioning in adults with ADHD compared with those with internalizing disorders in order to identify features that could assist in differential diagnosis.

Pimavanserin, a novel agent approved for the treatment of Parkinson’s disease psychosis, has potent actions as an antagonist/inverse agonist at serotonin 5HT2A receptors and less potent antagonist/inverse agonist actions at 5HT2C receptors.

Previous reports concerning the cerebrospinal fluid (CSF) of pathologic gamblers have described disturbed norepinephrine and dopamine (but not serotonin) functioning in the central nervous system. We analyzed neurotransmitter metabolites in two consecutive 6-mL samples of CSF obtained from 10 pathologic male gamblers punctured at the L4-5 level following 8 hours of fasting along with strict bed rest. Data were compared with those for healthy male controls. In conformity with findings in healthy male controls, we found gradients in CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), but not 4-hydroxy-3-methoxyphenyl glycol (HMPG). Expressing the CSF concentrations as nmol x L-1 x min-1 of tapping time (an estimate of the mass flow through the needle), the levels of 5-HIAA and HMPG (but not HVA) were found to be significantly lower in gamblers. Levels of 5-HIAA and HVA showed a significant correlation in gamblers but not in healthy controls. Taking tapping time into account, the CSF levels of HMPG and 5-HIAA were significantly lower in gamblers. We concluded that, in light of previous CSF findings of disturbed norepinephrine and dopamine function, altered indolamine function cannot be fully ruled out.

Attention-deficit/hyperactivity disorder (ADHD) and conditions involving excessive eating (eg, obesity, binge/loss of control eating) are increasingly prevalent within pediatric populations, and correlational and some longitudinal studies have suggested inter-relationships between these disorders. In addition, a number of common neural correlates are emerging across conditions, eg, functional abnormalities within circuits subserving reward processing and executive functioning. To explore this potential cross-condition overlap in neurobehavioral underpinnings, we selectively review relevant functional neuroimaging literature, specifically focusing on studies probing (i) reward processing, (ii) response inhibition, and (iii) emotional processing and regulation, and we outline 3 specific shared neurobehavioral circuits. Based on our review, we also identify gaps within the literature that would benefit from further research.

Alzheimer’s disease (AD) has long been recognized as a heterogeneous illness, with a common clinical presentation of progressive amnesia and less common “atypical” clinical presentations, including syndromes dominated by visual, aphasic, “frontal,” or apraxic symptoms. Our knowledge of atypical clinical phenotypes of AD comes from clinicopathologic studies, but with the growing use of in vivo molecular biomarkers of amyloid and tau pathology, we are beginning to recognize that these syndromes may not be as rare as once thought. When a clinician is evaluating a patient whose clinical phenotype is dominated by progressive aphasia, complex visual impairment, or other neuropsychiatric symptoms with relative sparing of memory, the differential diagnosis may be broader and a confident diagnosis of an atypical form of AD may require the use of molecular biomarkers. Despite the evolving sophistication in our diagnostic tools, and the acknowledgment of atypical AD syndromes in the 2011 revised diagnostic criteria for AD, the assessment of such patients still poses substantial challenges. We use a case-based approach to review the clinical and imaging phenotypes of a series of patients with typical and atypical AD, and discuss our current approach to their evaluation. One day, we hope that regardless of whether a patient exhibits typical or atypical symptoms of AD pathology, we will be able to identify the condition at a prodromal phase and institute a combination of symptomatic and disease-modifying therapies to support cognitive processes, function, and behavior, and slow or halt progression to dementia.

The management of patients with compulsive sexual behavior requires an understanding of the profile of the sexually compulsive or addicted patient. This article summarizes patient characteristics and their implications for treatment. Data from a study of the recovery of 957 patients who had problematic, sexually excessive behavior are presented. Spanning 5 years, the study shows six distinct stages patients experienced and the clinical activities that were most useful to them. A trajectory of a typical diagnosis and treatment path is provided, as well as important resources for physicians and patients.

In the absence of definitive etiological markers of vulnerability or a unitary profile of pathophysiology for obsessive-compulsive disorder (OCD), obsessive-compulsive (OC) symptom dimensions seem to offer a fruitful point of orientation.The complex clinical presentation of OCD can be summarized using a few consistent and temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping features that are likely to be continuous with “normal” worries and extend beyond the traditional nosological boundaries of OCD. Although the understanding of the dimensional structure of obsessive-compulsive symptoms (OCS) is still imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. Preliminary data suggest that these dimensional phenotypes may be useful in studies of the natural history, genetics, neurobiology, and treatment outcome of OCD. A dimensional approach is not mutually exclusive of other methods to parse the larger spectrum of disorders related to OCD. Thus far, age-of-onset of OCS and the individual's “tic-related” status seem to be particularly useful categorical distinctions. Finally, existing assessment methods are inadequate and new dimensional scales are needed to take full advantage of a dimensional approach in clinical and population-based studies.

This article provides an overview of the etiology, epidemiology, and first-line treatment options for obsessive-compulsive disorder (OCD). The subject of treatment-resistant and treatment-refractory OCD is the discussed, including a definition of these often-debated terms, and the latest treatment options delineated. This includes a review of the latest research concerning the pharmacological agents that have been studied as monotherapy or augmenting agents for the treatment of OCD, the use of experimental medications and procedures, treatment with reversible, minimally invasive procedure, such as vagal nerve stimulation and transcranial magnetic stimulation, invasive but the potentially reversible deep brain stimulation, and irreversible lesioning with ablative psychosurgery. A discussion of the role of psychotherapy in the treatment of OCD is also included.

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.

This article discusses conceptual issues relevant to the prospective diagnosis of the schizophrenic prodrome. Recent efforts to diagnose these patients with operational criteria based on current symptoms are reviewed. Symptomatic patients so identified appear to be treatment-seeking and to have mild cognitive impairments. In addition to being currently symptomatic, these patients are imminently at risk for progression of illness and development of schizophrenia. Data from three international centers suggest that this risk is approximately 40% over the next year of follow-up if untreated. The implications of the reviewed data for the appropriateness of the term “prodromal” and for treatment/prevention research for these patients are discussed.

Assessment and treatment of acute responses to traumatic stress has received much attention since September 11, 2001. This article elucidates principles of early intervention with adults in the immediate (within 48 hours) and early recovery phase (within the first week). The principles have been drawn from research on risk and recover factors, stress and traumatic stress theory, and expert consensus recommendations. The debriefing model is discussed, and principle interventions of psychological first aid, pharmacology, and mass trauma systems are described. This article concludes with brief guidelines for longer-term interventions and recommendations for future research.

Findings from research on psychiatric epidemiology, disaster effects, discrepancies in service use, and cross-cultural psychology are reviewed to generate guidelines for culturally responsive postdisaster interventions. Ethnicity and culture influence mental health care at various points: on need for help; on availability and accessibility of help; on help-seeking comfort (stigma, mistrust), and on the probability that help is provided appropriately. There are aspects of disaster mental health practice that may ameliorate many of barriers that contribute to ethnic disparities in service use. It is proposed that interventions should give greater attention to socially engaged emotions and functioning. To promote disaster recovery, practitioners are advised to: assess community needs early and often; provide easily accessible services; work collaboratively and proactively to reduce stigma and mistrust and engage minorities in care; validate and normalize distress and help-seeking; value interdependence as well as independence as an appropriate developmental goal; promote community action; and advocate for, facilitate, or conduct treatment and evaluation research. Notwithstanding the pain and stress they cause, disasters create opportunities to de-stigmatize mental health needs and build trust between providers and minority communities.

In order to determine the extent to which depression complicates Huntington's disease (HD), we have analyzed the existing literature on depression in HD in order to report the prevalence, clinical manifestations, and treatment of HD depression. By means of MEDLINE literature searches and reviews of HD articles' bibliographies, we identified for our analysis 16 HD depression studies. Our results indicate that the prevalence of depression is 30% for all HD patients. Clinical manifestations of HD depression include a marked increased risk for suicide. The etiology of HD depression is unclear, but may be due to a number of factors, such as dysfunction in the caudate nucleus, dysfunction in the ventral striatum, and various genetic factors that are discussed in this review. Case reports and case series support the efficacy of standard antidepressant interventions in resolving symptoms of depression. Efficacious treatments reported in the literature include tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and electro-convulsive therapy. In this study, the successful anecdotal treatment of seven consecutive HD depressed patients with sertraline suggests that sertraline may be a safe and efficacious treatment of HD depression.

Obsessive-compulsive disorder (OCD) and related conditions (trichotillomania, pathological skin-picking, pathological nail-biting) are common and disabling. Current treatment approaches fail to help a significant proportion of patients. Multiple tiers of evidence link these conditions with underlying dysregulation of particular cortico-subcortical circuitry and monoamine systems, which represent targets for treatment. Animal models designed to capture aspects of these conditions are critical for several reasons. First, they help in furthering our understanding of neuroanatomical and neurochemical underpinnings of the obsessive-compulsive (OC) spectrum. Second, they help to account for the brain mechanisms by which existing treatments (pharmacotherapy, psychotherapy, deep brain stimulation) exert their beneficial effects on patients. Third, they inform the search for novel treatments. This article provides a critique of key animal models for selected OC spectrum disorders, beginning with initial work relating to anxiety, but moving on to recent developments in domains of genetic, pharmacological, cognitive, and ethological models. We find that there is a burgeoning literature in these areas with important ramifications, which are considered, along with salient future lines of research.