Blood disorders have been implicated in ~5% to 10% of ischemic stroke, with an increased frequency in younger patients. Most disorders are associated with an increased thrombotic tendency and, therefore, an increased risk of ischemic stroke. Less commonly, a bleeding diathesis may predispose a patient to intracranial hemorrhage. While many conditions predisposing to thrombosis have been associated with stroke, there are relatively few prospective, epidemiological studies addressing hypercoagulable states and arterial stroke compared with the number of studies on the genetic thrombophilias, which are predominantly associated with venous thrombosis. When ordering tests of coagulation in stroke patients, one should keep in mind whether the results will influence therapy and/or patient outcome. It is generally not advocated to screen all stroke patients for a “hypercoagulable workup”. Typically, patients to be screened for coagulation defects will have a prior history of one or more unexplained thromboembolic events. The yield for diagnosing a hypercoagulable state is typically greatest for young stroke patients or those with a family history of thrombosis and who have no other explanations for their stroke (cryptogenic stroke). The yield in typically low in unselected ischemic stroke patients and older patients. Treatment of a first stroke with a documented hypercoagulable state is typically long-term or indefinite duration warfarin, although there is a paucity of clinical trial data supporting this clinical approach.

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.

The low prevalence of extrapyramidal symptoms associated with atypical antipsychotics has led to their widespread use during the past decade. Aripiprazole, the newest medication in this class, has been associated with extrapyramidal symptoms (eg, akathisia) and with improvement of tardive dyskinesia (TD), but to date it has not been associated with the development of TD. We report a case of TD associated with the use of aripiprazole 15 mg/day for 18 months for refractory depression. Symptoms of TD resolved within several weeks of discontinuation of aripiprazole.

Introduction: This research compares the efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) versus placebo in treating major depressive disorder.

Methods: In this randomized, double-blind study, outpatients with major depressive disorder ≥18 years of age received desvenlafaxine 200–400 mg/day or placebo for 8 weeks. Efficacy endpoints included (primary) change in 17-item Hamilton Rating Scale for Depression score at the final evaluation (last observation carried forward, analysis of covariance) and (secondary) Clinical Global Impressions—Improvement and—Severity of Illness scales.

Results: The difference between desvenlafaxine (n=117) and placebo (n=118) on the primary endpoint was not significant (−9.1 vs −7.5, P=.078). Week 8 observed cases (desvenlafaxine, n=80; placebo, n=94) results were significant (−10.7 vs −7.9, P=.008). Differences at the final evaluation (last observation carried forward) were significant for Clinical Global Impressions—Improvement (2.9 vs 2.5, P=.037) and Clinical Global Impressions—Severity of Illness (−1.9 vs −1.2, P=.041). Discontinuation rates due to adverse events (AEs) were 12% and 3% for desvenlafaxine and placebo, respectively (P=.008). The most frequently reported AE associated with desvenlafaxine was nausea (36% vs 9% [placebo]).

Conclusion: In this study, the primary analysis did not show significant differences between desvenlafaxine and placebo; discontinuations due to AEs associated with the desvenlafaxine dose range may have contributed to the lack of statistical separation.

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.

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.

Recent data suggest that the presence of psychotic symptoms in patients suffering from posttraumatic stress disorder (PTSD) may represent an underrecognized and unique subtype of PTSD. Among combat veterans with PTSD, 30% to 40% report auditory or visual hallucinations and/or delusions. The presence of psychotic symptoms in PTSD is associated with a more severe level of psychopathology, similar to that of chronic schizophrenia. In this review, the differential diagnosis of psychotic symptoms in PTSD is discussed, including possible comorbid schizophrenia, psychotic depression, substance-induced psychosis, and personality disorder. A recent biologic study supporting the existence of a unique subtype of PTSD with psychotic features is also addressed, as are the similarities between PTSD with psychotic features and psychotic depression disorder. Finally, data on the treatment implications of psychotic symptoms in PTSD are presented. The intriguing recent findings on psychotic symptoms in PTSD need further investigation in noncombat-related PTSD populations before findings can be generalized to all individuals with PTSD.

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.

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.

The goal of psychopharmacohgic research in autism is to provide guidance to clinicians and families on the risks and benefits of specific interventions. Careful subject selection and subject characterization in clinical trials are necessary for replication, to inform clinicians about the sample, and to elucidate the type of patients who might benefit from, the treatment. At minimum, subject characterization includes demographic information, diagnosis (autism, Åsperger's syndrome, or pervasive developmental disorder-not otherwise specified), intellectual functioning, adaptive functioning, symptom severity, general behavioral profile, health status, pertinent clinical laboratory measures, height, weight, current treatments, and educational placements. Subject selection, sample size, and choice of the primary outcome measure are closely interrelated and linked to the study hypothesis. The magnitude of expected improvement on the primary outcome measure, which can be expressed by effect size, has direct implications for sample size. Large sample sizes are required to detect small effect sizes. To facilitate interpretation of study results, research reports should provide descriptive characteristics of the sample as well as the mean change and standard deviation on the primary outcome measure data to permit calculation of the effect size.

We report two cases of serotonin syndrome in elderly patients during treatment of psychotic depression with atypical antipsychotics and antidepressants. The first case is a 69-year-old man who was admitted for depression with psychosis and treated with trazodone, risperidone, and sertraline. Subsequently, he developed myoclonus, tremor, cogwheel rigidity, and diaphoresis. The second case is a 72-year-old female initially admitted to a medical inpatient unit for a change in mental status that presented as increased confusion, lethargy, slurred speech, and a fever of 101.5°. She had been on phenelzine and quetiapine. In both cases, all symptoms resolved within 24 hours of the psychotropics being stopped. In both cases, we believe that serotonin syndrome was produced by a combination of an antidepressant and an atypical antipsychotic. There have been several case reports of serotonin syndrome from similar combinations of antidepressant and atypical antipsychotic treatment. Clinicians treating elderly patients with a combination of serotonergic antidepressants and atypical antipsychotics for psychotic depression should be aware of the potential for serotonin syndrome.

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.

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.

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.