Animal models are considered essential in research ensuing elucidation of human disease processes and subsequently, testing of potential therapeutic strategies. This is especially true for neurodegenerative disorders, in which the first steps in pathogenesis are often not accessible in human patients. Alzheimer's disease is vastly becoming a major medical and socioeconomic problem in our aging society. Valid animal models for this uniquely human condition should exhibit histopathological, biochemical, cognitive, and behavioral alterations observed in Alzheimer's disease patients. Major progress has been made since the understanding of the genetic basis of Alzheimer's disease and the development and improvement of transgenic mouse models. All present Alzheimer's disease models developed are partial but nevertheless essential in further unraveling the nature and spatial and temporal development of the complex molecular pathology underlying this condition. One of the more recent transgenic attempts to mode Alzheimer's disease is the APP23 transgenic mouse. This article describes the development and assessment of this human amyloid precursor protein overexpression model. We summarize histopathological and biochemical, cognitive and behavioral observations made in heterozygous APP23 mice, thereby emphasizing the model's contribution to clarification of neurodegenerative disease mechanisms. In addition, the first therapeutic interventions in the APP23 model are included.

All three serotonin norepinephrine reuptake inhibitors (SNRIs) inhibit the reuptake of both serotonin and norepinephrine but they do so with differing affinity ratios. Venlafaxine has a 30-fold higher affinity for serotonin than for norepinephrine while duloxetine has a 10-fold selectivity for serotonin. Milnacipran has a balanced (1:1) ratio of potency for inhibition of reuptake of the two neurotransmitters. The most frequent adverse event with SNRIs is nausea. Not unexpectedly, adverse effects related to a noradrenergic stimulation, such as dry mouth, sweating, and constipation, are found more frequently with SNRIs than with selective serotonin reuptake inhibitors. At true SNRI doses, venlafaxine is associated with dose-dependent cardiovascular phenomena (principally increased blood pressure), an effect which is less frequent with duloxetine and rare with milnacipran. Serious and potentially fatal hepatotoxity has been reported with duloxetine. This problem appears to be unique to duloxetine and not a characteristic of the SNRI class. There are differences in overdose toxicity between venlafaxine and the other SNRIs, possibly related to its increased cardiotoxicity.

Posttraumatic stress disorder (PTSD) is a prevalent anxiety disorder marked by behavioral, physiologic, and hormonal alterations. PTSD is disabling and commonly follows a chronic course. The etiology of PTSD is unknown, although exposure to a traumatic event constitutes a necessary, but not sufficient, factor. A twin study of Vietnam veterans has shown significant genetic contribution to PTSD. The fact that PTSD's underlying genotypic vulnerability is only expressed following trauma exposure limits the usefulness of family-based linkage approaches. In contrast to the other major psychiatric disorders, large studies for the search of underlying genes have not been described in PTSD to date. Complementary approaches for locating involved genes include association-based studies employing case-control or parental genotypes for transmission dysequilibrium analysis and quantitative trait loci studies in animal models. Identification of susceptibility genes will increase our understanding of traumatic stress disorders and help to elucidate their molecular basis. The current review provides an up-to-date outline of progress in the field of PTSD.

Introduction: The co-occurrence of obsessive-compulsive disorder (OCD) in patients with schizophrenia and related disorders has been increasingly recognized. However, the rate of psychosis comorbidity in OCD patients has yet to be systematically evaluated.

Methods: The prevalence of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition psychotic disorders was evaluated in 757 subjects consecutively referred to a specialised diagnostic and treatment facility for OCD. Demographic and clinical characteristics were assessed.

Results: Thirteen OCD patients (1.7%) also met the DSM-IV criteria for a psychotic disorder. We found no significant differences in clinical characteristic between OCD patients with and without a psychotic disorder, although patients with OCD and a psychotic disorder more likely used illicit substances and more likely were male.

Conclusion: Relatively few patients referred to a specialized treatment OCD center suffer from a psychotic disorder.

Learning Objective: Discuss the theory of modulation of receptor activity or the blockade of the reuptake of multiple neurotransmitter systems for the future treatment of MDD.

Major depressive disorder (MDD) is a serious and often crippling psychiatric illness with a high risk of relapse and treatment resistance. In this article, we discuss the role of the serotonergic system in MDD including our current understanding of how various serotonin (5HT) receptors modulate monoamine neurotransmission and behavior. We also discuss how pharmacologic interventions, including novel and existing antidepressants and atypical antipsychotics, may be utilized to adjust serotonergic neurotransmission and provide more effective treatments for patients with MDD.

Since their introduction 50 years ago, antidepressants have been used in a wide variety of settings involving gastrointestinal (GI) disease. In the 1950s, antidepressants were shown to have some efficacy for the treatment of peptic ulcer disease. This is most likely due to their antihistaminic and anticholinergic effects. Since then, more efficacious and more disease-specific treatments have become available. In the last 20 years, antidepressants have been increasingly used for the treatment of functional gastrointestinal disorders such as irritable bowel syndrome, noncardiac chest pain, and other functional GI disorders. This article will review the rationale for the use of antidepressant drugs for the treatment of functional GI disorders. The role of psychiatric comorbidity in functional GI disorders, the impact of antidepressants on GI motility and visceral sensation, and the ability of these agents to produce improvements in the global well-being and overall quality of life will be reviewed. Finally, guidelines for prescribing and barriers to a patient's acceptance of these agents will be discussed.

Bipolar disorders are prevalent, disabling, and costly diseases that often pursue an inexorable course. Underdetection, misdiagnosis, and diagnostic delay frequently and unnecessarily interfere with appropriate treatment of the disorder. Mortality studies in bipolar disorder underscore the relevance of both unnatural and natural causes of death, inviting the need for improved preventative and primary health care for bipolar patients. The treatment framework for bipolar disorder must recognize and anticipate the multidirnensionality and comorbidity of this illness. Pharmacotherapy is necessary, with multiple concomitant medications required for most patients, In addition, adjunctive psychosocial interventions offer enhanced compliance and may beneficially influence psychopathological and functional outcomes. This article emphasizes the public health concern of bipolr disorder, and provides tactics to enhance detection of cryptic bipolar states, underscore the clinical and pathophysiological relevance of comorbidity in bipolar disorder, and provide a framework for multimodality therapy for this condition.

It has long been considered that psychosocial stress plays a role in the expression of symptoms in schizophrenia (SZ), as it interacts with latent neural vulnerability that stems from genetic liability and early environmental insult. Advances in the understanding of the neurobiology of the stress cascade in both animal and human studies lead to a plausible model by which this interaction may occur: through neurotoxic effects on the hippocampus that may involve synaptic remodeling. Of late, the neurodevelopmental model of SZ etiology has been favored. But an elaboration of this schema that credits the impact of postnatal events and considers a role for neurodegenerative changes may be more plausible, given the evidence for gene-environment interaction in SZ expression and progressive structural changes observed with magnetic resonance imaging. Furthermore, new insights into nongliotic neurotoxic effects such as apoptosis, failure of neurogenesis, and changes in circuitry lead to an expansion of the time frame in which environmental effects may mediate expression of SZ symptoms.

The authors assessed the ability of lorazepam and other benzodiazepines to affect the course of neuroleptic malignant syndrome (NMS). Records of inpatients who met both stringent research criteria and criteria under the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) (n=11) or DSM-IV criteria alone (n=5)for NMS were identified. All received lorazepam or related benzodiazepines within 24 hours of NMS onset or hospital admission. The records were reviewed for resolution of clinical signs NMS. Rigidity and fever abated within 24—48 hours, while secondary features of NMS were relieved within 64 hours. These results compared favorably with prior reports of 5-day to 10-day recovery periods. Benzodiazepine administration appeared to be well tolerated. Lorazepam and related benzodiazepines may reduce recovery time in NMS.

The present paper aims at reviewing and commenting on the relationships between sleep and circadian phasing alterations and neurodegenerative/neuroprogressive processes in mood disorder. We carried out a systematic review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, in PubMed, PsycINFO, and Embase electronic databases for literature related to mood disorders, sleep disturbances, and neurodegenerative/neuroprogressive processes in relation to (1) neuroinflammation, (2) activation of the stress system, (3) oxidative stress, (4) accumulation of neurotoxic proteins, and (5) neuroprotection deficit. Seventy articles were collectively selected and analyzed. Experimental and clinical studies revealed that insomnia, conditions of sleep loss, and altered circadian sleep may favor neurodegeneration and neuroprogression in mood disorders. These sleep disturbances may induce a state of chronic inflammation by enhancing neuroinflammation, both directly and indirectly, via microglia and astrocytes activation. They may act as neurobiological stressors that by over-activating the stress system may negatively influence neural plasticity causing neuronal damage. In addition, sleep disturbances may favor the accumulation of neurotoxic proteins, favor oxidative stress, and a deficit in neuroprotection hence contributing to neurodegeneration and neuroprogression. Targeting sleep disturbances in the clinical practice may hold a neuroprotective value for mood disorders.

The worldwide economic crisis of the last decade, and still unresolved, led to a great recession involving all major economies. Since economic factors may influence mental wellbeing, not surprisingly a rise in poor mental health was observed in different countries, while representing a great challenge to psychiatric interventions. This paper aims at reviewing the available English literature focusing on the impact of the current economic crisis on mental health, with a special focus on depression and suicide. Available studies indicate that consequences of economic crisis, such as unemployment, increased workload or work reorganization, and reduced staff and wages, may constitute important stressing factors with a negative impact on mental health. Although data are not easily comparable in different countries, depression seems to be the most common psychiatric disorders especially in middle-aged men. Even suicide rates seem to be increased in men, mainly in countries with no public welfare or poor family relationships. All these findings require a careful attention from both governments that cut resources on public health instead of investing in it, and psychiatric associations that should implement appropriate strategies to face and to manage this sort of depression epidemic driven by economic crisis. Again, as available data suggest that the impact of the crisis might have been attenuated in countries with higher spending in social protection, they clearly urge policy makers to take into account possible health externalities associated to inadequate social protection systems.

The risks of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage are not increased in the 9 months of gestation except for a high risk in the 2 days prior and 1 day postpartum. The remaining 6 weeks postpartum also have an increased risk of ischemic stroke and intracerebral hemorrhage, though less than the peripartum period. Although there are some rare causes of stroke specific to pregnancy and the postpartum period, eclampsia, cardiomyopathy, postpartum cerebral venous thrombosis, and, possibly, paradoxical embolism warrant special consideration. The diagnostic and therapeutic approaches to stroke during pregnancy and the postpartum period are similar to the approaches in the nonpregnant woman with some minor modifications based on consideration of the welfare of the fetus. There is a theoretical risk of magnetic resonance imaging exposure during the first and second trimester but the benefit to the mother of obtaining the information may outweigh the risk. Available evidence suggests that low-dose aspirin (<150 mg/day) during the second and third trimesters is safe for both mother and fetus. Postpartum use of low-dose aspirin by breast-feeding mother is also safe for infant. While proper counseling is imperative, a history of pregnancy-related stroke should not be a contraindication for subsequent pregnancy.

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacotherapy treatments for obsessive-compulsive disorder (OCD). Clomipramine is effective in OCD but associated with more adverse events. Typically, higher doses of antidepressants are required for OCD. Up to 50% of patients do not respond to initial treatment of OCD. Treatment options for nonresponders include augmentation of antidepressants with atypical antipsychotics, among other strategies. First-line treatments for anxiety disorders include SSRIs, serotonin norepinephrine reuptake inhibitors, and pregabalin. Tricyclic antidepressants are equally effective as SSRIs, but are less well tolerated. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of dependency and tolerance. Other treatment options include irreversible and reversible monoamine oxidase inhibitors, the atypical antipsychotic quetiapine, and other medications. Cognitive-behavioral therapy has been sufficiently investigated in controlled studies of OCD and anxiety disorders and is recommended alone or in combination with the above medications.

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial was an effectiveness/”pragmatic” clinical trial designed to compare the efficacy, tolerability, and cost-effectiveness of four atypical antipsychotics (olanzapine, quetiapine, risperidone and ziprasidone) and a conventional antipsychotic (perphenazine) for an 18-month period in patients with schizophrenia. The study randomized 1,460 patients with fewer exclusion criteria than in most trials in hopes that this would allow for a more representative sample of outpatients in “real world” practice. Olanzapine demonstrated significant superiority in time to discontinuation for all cause and for lack of efficacy, as well as likelihood of hospitalization for relapse; however, it was associated with a significantly higher rate of metabolic side effects. Perphenazine exhibited comparable effectiveness with quetiapine, risperidone, and ziprasidone, and appeared to be as well tolerated as the atypicals. However, it had the highest rate of drop out due to extrapyramidal symptoms and was restricted to patients who did not have tardive dyskinesia (TD). This article examines the phase 1 CATIE results to guide the clinician in understanding how to interpret the findings, which were intended to be a guide for clinical practice. The nature of the patient population, the doses of drugs relative to one another, inclusion of patients who were treatment resistant, and exclusion of patients with TD from randomization to perphenazine were potential sources of bias in the study. In particular, the use of a higher-than-usual peak dose of olanzapine may have led to the superior results achieved with it. Practical suggestions are given for choice of antipsychotic medication in patients with chronic schizophrenia.

Posttraumatic stress disorder (PTSD) is a common and disabling condition. In addition to combat-related PTSD, the disorder occurs in civilians exposed to severe traumatic events, with the community prevalence rate for the combined populations reaching as high as 12%. If left untreated, PTSD may continue for years after the stressor event, resulting in severe functional and emotional impairment and a dramatic reduction in quality of life, with negative economic consequences for both the sufferer and society as a whole. Although PTSD is often overlooked, diagnosis is relatively straight-forward once a triggering stressor event and the triad of persistent symptoms—reexperiencing the traumatic event, avoiding stimuli associated with the trauma, and hyperarousal—have been identified. However, comorbid conditions of anxiety and depression frequently hamper accurate diagnosis. Treatment for PTSD includes psychotherapy and pharmacotherapy. The latter includes selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and monoamine oxidase inhibitors. Only SSRls have been proven effective and safe in long-term randomized controlled trials. Current guidelines from the Expert Consensus Panel for PTSD recommend treatment of chronic PTSD for a minimum of 12–24 months.