Anxiety and depression are common disorders that frequently co-exist. Both disorders show good response to antidepressants, especially the selective serotonin reuptake inhibitors. Some suggest that these disorders are variants of the same underlying brain pathology. This review examines the similarities and differences between anxiety and depression in terms of the known neurobiological etiologic mechanisms as well as their biological underpinnings and response to treatment. Sufficient and significant differences between these disorders support the view that they are independent entities. Shared abnormalities in the 5HT1A receptor function, for example, may help explain some of the comorbidity.

How schizophrenia (SZ) is maintained at roughly 1% of the population despite diminished reproduction is one puzzle currently facing researchers. De novo mutations were first proposed over half a century ago as a source for new SZ genes. Current evidence linking advancing paternal age to SZ risk makes revisiting this hypothesis important. Advancing paternal age is the major source of new mutations in the human population. This article will examine potential mechanisms whereby parental age may impact new mutations, as well as review recent data supporting such a hypothesis.

Binge eating disorder is characterized by excessive, uncontrollable consumption of palatable food within brief periods of time. Excessive intake of palatable food is thought to be driven by hedonic, rather than energy homeostatic, mechanisms. However, reward processing does not only comprise consummatory actions; a key component is represented by the anticipatory phase directed at procuring the reward. This phase is highly influenced by environmental food-associated stimuli, which can robustly enhance the desire to eat even in the absence of physiological needs. The opioid system (endogenous peptides and their receptors) has been strongly linked to the rewarding aspects of palatable food intake, and perhaps represents the key system involved in hedonic overeating. Here we review evidence suggesting that the opioid system can also be regarded as one of the systems that regulates the anticipatory incentive processes preceding binge eating hedonic episodes.

Does narcolepsy, a neurological disease, need to be considered when diagnosing major mental illness? Clinicians have reported cases of narcolepsy with prominent hypnagogic hallucinations that were mistakenly diagnosed as schizophrenia. In some bipolar disorder patients with narcolepsy, the HH resulted in their receiving a more severe diagnosis (ie, bipolar disorder with psychotic features or schizoaffective disorder). The role of narcolepsy in psychiatric patients has remained obscure and problematic, and it may be more prevalent than commonly believed. Classical narcolepsy patients display the clinical “tetrad”—cataplexy, hypnagogic hallucinations, daytime sleep attacks, and sleep paralysis. Over 85% also display the human leukocyte antigen marker DQB10602 (subset of DQ6). Since 1998, discoveries in neuroanatomy and neurophysiology have greatly advanced the understanding of narcolepsy, which involves a nearly total loss of the recently discovered orexin/hypocretin (hypocretin) neurons of the hypothalamus, likely by an autoimmune mechanism. Hypocretin neurons normally supply excitatory signals to brainstem nuclei producing norepinephrine, serotonin, histamine, and dopamine, with resultant suppression of sleep. They also project to basal forebrain areas and cortex. A literature review regarding the differential diagnosis of narcolepsy, affective disorder, and schizophrenia is presented. Furthermore, it is now possible to rule out classical narcolepsy in difficult psychiatric cases. Surprisingly, psychotic patients with narcolepsy will likely require stimulants to fully recover. Many conventional antipsychotic drugs would worsen their symptoms and make them appear to become a “chronic psychotic,” while in fact they can now be properly diagnosed and treated.

Therapeutic nihilism on treating psychopathy is widespread and is largely based on many outdated and poorly designed studies. Important recent advances have been made in assessing psychopathy and recidivism risks, as well as in offender rehabilitation to reduce reoffending, all of which are now well supported by a considerable literature based on credible empirical research. A 2-component model to guide risk reduction treatment of psychopathy has been proposed based on the integration of key points from the 3 bodies of literature. Treatment programs in line with the model have been in operation, and the results of early outcome evaluations are encouraging. Important advances also have been made in understanding the possible etiology of mentally disordered offenders with schizophrenia and history of criminality and violence, some with significant features of psychopathy. This article presents a review of recent research on risk reduction treatment of psychopathy with the additional aim to extend the research to the treatment of mentally disordered offenders with schizophrenia, violence, and psychopathy.

Epidemiological and clinical data from a variety of cultural and geographic settings on obsessive-compulsive disorder (OCD), and many of the obsessive-compulsive spectrum disorders, suggest that this is a group of disorders with a good degree of transcultural homogeneity. However, the content and themes that predominate in patients with these disorders, and the course of illness, can be shaped by cultural, ethnic, and religious experiences. Across cultures, OCD is commonly comorbid with mood, anxiety, and impulse-control disorders. However, little is known about the mechanisms by which culture and ethnicity may affect the expression of OCD and related disorders. Cross-national comparative studies exploring culturally influenced differences in clinical course, treatment outcome, including ethnogenetic differences in drug response, and prognosis are needed.

Major depressive disorder (MDD) is a debilitating illness affecting 7% to 12% of men and 20% to 25% of women. It is usually a recurrent illness, with up to 30% of patients experiencing a depressive episode lasting over 2 years. Depression may also increase the morbidity and mortality of numerous medical conditions, such as cardiac disease, myocardial infarction, chronic pain, diabetes, cerebrovascular events, and respiratory illnesses. The goal of antidepressant therapy is to achieve full remission and functional recovery, and continuing treatment beyond the acute phase is usually necessary to maintain remission. In contrast with full remission, individuals who experience residual symptoms, however mild, have a higher chance of experiencing one or more additional episodes.

What are the conceptual and empirical bases for current interventions for acute stress reactions following trauma exposure? This review compares the two major alternatives to managing acute stress reactions, outlines their conceptual bases and critiques the evidence for their efficacy in preventing subsequent stress disorders. The review integrates current evidence for cognitive behavior therapy with recent neuroscience findings that fear reduction learning can be enhanced by modulating glutamaterigc systems. D-cycloserine provides exciting opportunities to enhance the effects of cognitive-behavioral therapy, and points to closer understanding of the biological mechanisms that underpin clinical gains achieved by psychological therapies.

Serotonin (5-HT) modulates numerous processes in the central nervous system that are relevant to neuropsychiatric function and dysfunction. It exerts significant effects on anxiety, mood, impulsivity, sleep, ingestive behaviors, reward systems, and psychosis. Serotonergic dysfunction has been implicated in several neuropsychiatric conditions but efforts to more clearly understand the mechanisms of this influence have been hampered by the complexity of this system at the receptor level. There are at least 14 distinct receptors that mediate the effects of 5-HT as well as several enzymes that control its synthesis and metabolism. Pharmacologic agents that target specific receptors have provided clues regarding the function of these receptors in the adult brain. 5-HT is also an important modulator of neural development and several groups have employed a genetic strategy to ablate specific components of the 5-HT system in order to understand the role of different serotonergic in development of brain systems relevant to behavior. Several inactivation mutations of specific 5-HT receptors have been generated producing interesting behavioral phenotypes related to anxiety, depression, drug abuse, psychosis, and cognition. In many cases, knockout mice have been used to confirm what has already been suspected based on pharmacologic studies. In other instances, mutations have demonstrated new functions of serotonergic genes in development and behavior.

What is the long-term outcome of patients with obsessive-compulsive disorder (OCD) who are treatred with exposure and response (ritual) prevention (EX/RP) alone, serotonergic medications alone, or their combination? How is the long-term outcome of these patients affected by the discontinuation? Follow-up assessments were conducted with 62 patients treated for OCD an average of 17 months posttreatment (range: 6–43 months). Patients received one of three treatments: serotonergic medications (fluvoxamine or clomipramine), intensive behavior therapy involving EX/RP, or intensive EX/RP with concurrent antidepressant medication. At follow-up, no differences in OCD symptom severity were found among the three treatment groups. However, when current medication use was taken into consideration, differences among the three treatment groups emerged. Among patients who were medication-free at the time of follow-up assessment (n=37), those in the EX/RP-alone and EX/RP-with-medication groups had lower symptom severity ratings than those in the medication-only group on 4 out of 6 measures. There were no differences in OCD severity ratings among patients taking medications at follow-up (n=25). Although these findings are interpreted with caution due to the uncontrolled nature of the study, results suggested that long-term outcome may be superior following EX/RP than following serotonergic medications, after discontinuation. For patients who remain on medications, the treatment produced benefits equivalent to EX/RP.

Introduction: The high percentage (between 40% and 60%) of resistance to first-line drugs, such as clomipramine or selective serotonin reuptake inhibitors, is a major problem in the pharmacologic management of obsessive-compulsive disorder (OCD). In these cases, different strategies have been employed with controversial outcomes. The meager information available on the association of two serotonergic drugs prompted us to explore the possible effectiveness and tolerability of citalopram+clomipramine in resistant OCD patients.

Methods: Twenty outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD, who had failed to respond to at least two trials with a selective serotonin reuptake inhibitor and were currently taking clomipramine at different doses, were administered citalopram at a maximum dose of 60 mg/day. The clinical assessment was carried out at baseline (t0) and at the 4th (t1), 12th (t2), 24th (t3), 36th (t4), and 48th (t5) week by means of the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Clinical Global Impression scale, and the Dosage Record and Treatment Emergent Symptom Scale. The response was defined as a 35% decrease of the Yale-Brown Obsessive Compulsive Scale total score.

Results: The results showed that ∼50% of the patients improved significantly after 1 month of this regimen and after 1 year of treatment.

Conclusion: This study, although carried out in a small sample and in an open fashion, represents one of the few experiences with the association of two serotonergic compounds in resistant OCD and confirms its potential usefulness and good tolerability profile. Controlled research on this association in OCD is recommended.

The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that “chronically” implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.

A small but growing neuroimaging literature has begun to examine the neural mechanisms underlying the difficulty that substance-use dependent (SUD) groups have with ignoring salient, drug-related stimuli. Drug-related attentional bias appears to implicate the countermanding forces of cognitive control and reward salience. Basic cognitive neuroscience research suggests that ignoring emotionally evocative stimuli in our environment requires both up-regulation of control networks and down-regulation of processing in emotion and reward regions. Research to date suggests that attentional biases for drug-related stimuli emerge from a failure to sufficiently increase control of attention over salient, but task-irrelevant stimuli. While SUD samples have typically shown increased activity in the cognitive control regions (ie, lateral prefrontal and dorsal anterior cingulate), during attentional bias such increases appear to have been insufficient for the concomitant increases in processing by the emotion/reward regions (ie, amygdala, insula, and striatum). Given the potential contribution of attentional biases to perpetuating drug use and the development of interventions (both pharmaceutical and cognitive-behavioral) to treat biases, understanding the neural basis of successfully reducing bias remains an important, but as yet unanswered, question for our field.