It is challenging to treat symptoms of autism spectrum disorder (ASD), comorbid psychiatric disorders and ASD-associated symptoms. Some of the commonly used medications to treat these can, and frequently do have serious adverse side effects. Therefore, it is important to identify medications that are effective and with fewer side effects and negative outcomes. In this review, we looked at current evidence available for using the serotonin and norepinephrine reuptake inhibitors (SNRIs) class of medications in treating some of these often difficult to treat symptoms and behaviors. An extensive literature search was conducted using EBSCO.host. Our search algorithm identified 130 articles, 6 of which were deemed to meet criteria for the purpose of this review. Each of these six articles was independently reviewed and critically appraised. As a prototype of the SNRIs family, venlafaxine was found to be a useful adjuvant in children and adults with ASD for the treatment of self-injurious behaviors, aggression, and ADHD symptoms when used in doses lower than its antidepressant dosage. However, duloxetine was not found to show any added benefit in treatment of any of the comorbid symptoms and behaviors in ASD when compared to other antidepressants. On the other hand, milnacipran was reported to produce improvements in impulsivity, hyperactivity symptoms, and social functioning through reduction of inattention of ADHD when comorbid with ASD. Overall, SNRIs were shown variable effectiveness in treatment of these comorbid symptoms and behaviors in ASD.

Anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis is a relatively recent autoimmune entity, as it was first described in 2007. Given that it is a condition with neuropsychiatric symptoms, its initial symptom is frequently psychiatric in nature. Hence, psychiatrists are often the first physicians to assess these patients and, as so, must recognize this type of encephalitis as a possible cause. Catatonia may be inaugural or develop throughout the course of the disease. Management of patients with anti-NMDAr encephalitis is based on etiologic treatment with immunotherapy and removal of the associated tumor, if any. However, these catatonic patients may have variable responses to etiologic treatment, sometimes with refractory catatonic symptoms, which attests to the necessary urgency to know how to manage these patients. In the clinical setting, physicians appear to be using guidelines originally created to the management of catatonia due to primary psychiatric conditions. In this literature review, catatonia was historically contextualized and anti-NMDAr encephalitis overall described. Finally, catatonia secondary to this type of encephalitis was discussed.

Although adverse environments are well known to be a risk factor for psychopathology, many individuals respond adaptively to such environments. There is growing interest in the underlying mechanisms involved in such resilience. Several cognitive-affective processes may be involved, and these may be mediated by particular neuronal circuits and neurochemical systems. This article summarizes some of the relevant work on the role of fear conditioning, reward processing, and social behavior in resilience. There is a growing body of data on how particular gene-environment interactions affect these processes, and thus underpin resilience. Ultimately, a better understanding of the mechanisms underpinning resilience may lead to novel interventions.

While obsessive-compulsive (OC) symptoms in schizophrenia have been reported for many years, they have achieved only limited recognition and, perhaps for this reason, few studies their pharmacological treatment have been carried out. One suggested treatment approach is the use of different agents for different symptoms. In this article, we review the small number of published studies and case reports regarding this multi-pharmacological method of treatment for OC symptoms in schizophrenia. While each study used a somewhat different patient population and provided varying and limited information concerning patient sample, study design, and results, some tentative conclusions and treatment recommendations may be drawn from their findings.

In this study, we attempt to demonstrate an association between low platelet monoamine oxidase (MAO) activity, as assessed by isotopic methods, and the stable behavioral pattern of sensation- and risk-seeking of professional bull-fighters. Sixteen professional bullfighters were studied and compared with a control group of 46 healthy control subjects who did not engage in risky jobs or activities. The group of bullfighters had significantly reduced platelet MAO activity compared with the control group (P<0.05). Bullfighters were shown to be significantly more extroverted and sensation-seeking than controls on various temperament scales. A predisposition to engage in risky activities (eg, bullfighting) and sensation-seeking could be partly conditioned by the presence of biological components of personality manifested by a significantly decreased platelet MAO activity.

This is the first case report of a patient who received long-term (69-month) adjunctive vagus nerve stimulation (VNS) therapy for treatment-resistant depression (TRD) and reached VNS battery end-of-service (EOS).The patient is a 41-year-old female with depression who entered a study of adjunctive VNS therapy for TRD. Her Hamilton Rating Scale for Depression (HAM-D) scores dropped from a mean of 33.5 (pre-implantation baseline period) to 16 at the end of the 12-week acute-phase treatment period, and then fluctuated from <7 (normal range) to scores in the moderately depressed range (∼20) during long-term follow-up. Three and one-half years after VNS implantation, the patient's HAM-D scores began to increase from a score of 18 to a peak score of 27 ∼ 16 months later (5-years post-implantation). The patient subsequently reported that she could no longer feel stimulation from the device and device interrogation 2 weeks later indicated battery EOS. The patient was hospitalized due to worsened depression, the pulse generator was replaced, and medication adjusted. HAM-D scores through the subsequent 9 months of followup returned to a pattern of fluctuations within the range noted during the long-term follow-up period prior to VNS battery EOS.

Unlike the other articles in this series on rTMS, this paper will not include clinical research or magnetic stimulation experiments. Instead, we will focus on an animal model of epilepsy called kindling and a procedure that we have recently developed to inhibit kindled seizures called quenching. Both procedures involve direct intracerebral electrical stimulation of the brain. We demonstrate that low-frequency stimulation, which does not disrupt ongoing behavior, can have profound and long-lasting effects on both seizure development and fully kindled seizures.

At this point, we do not know how well these models relate, either mechanistically or phenomenologically, to the effects of repeated transcranial magnetic stimulation (rTMS); however, we believe that at the very least, some of the principles emerging from studying these phenomena may be relevant to our thinking about rTMS and its potential treatment utility. Specifically, we discuss the possible relationship between quenching and rTMS with regards to parameters of induction, possible common mechanisms, and potential treatment implications.

Alzheimer's disease is a degenerative neurological condition characterized by the presence of β-amyloid plaques and neurofibrillary tangles in the limbic and neocortical regions of the brain. Pittsburgh Compound-B (PIB), a benzothiazole analog, has recently been found to specifically label amyloid deposits in positron emission tomography (PET) studies of the brain, opening the door for a wide range of applications related to Alzheimer's disease. In this article, data demonstrating the specificity of PIB as a PET tracer for β-amyloid lesions are reviewed, and the potential clinical applications of PIB PET imaging is discussed. Because amyloid plaques are common even in elderly individuals who are not suffering from dementia, the primary diagnostic function of PIB PET imaging presumably would be to rule out, rather than definitively confirm, Alzheimer's diagnoses in elderly patients. Other possible uses include monitoring plaque loads in patients receiving anti-amyloid therapy for Alzheimer's disease, as well as assessing plaque formation in unaffected individuals as a means of evaluating future Alzheimer's disease.

In this article, the authors examine the growth of the discipline of psychiatric surgery from the earliest lesioning procedures to the neuroaugmentative strategies used today. Special attention is paid to the neural circuitry that underlies psychiatric disorders and how surgical manipulation of these circuits might result in the amelioration of the disease state. Also examined is the effect that the technology curve has had on psychiatric surgery with regard to functional imaging and neurosurgical equipment. Finally, the authors use the current state of psychiatric surgery to speculate on some of the future directions that psychiatric neurosurgical procedures might take.

Mixed features specifier (MFS) is a new nosological entity defined and operationalized in the Diagnostic and Statistical Manual of Mental Disorders (DSM), 5th Edition. The impetus to introduce the MFS and supplant mixed states was protean, including the lack of ecological validity, high rates of misdiagnosis, and guideline discordant treatment for mixed states. Mixed features specifier identifies a phenotype in psychiatry with greater illness burden, as evidenced by earlier age at onset, higher episode frequency and chronicity, psychiatric and medical comorbidity, suicidality, and suboptimal response to conventional antidepressants. Mixed features in psychiatry have historical, conceptual, and nosological relevance; MFS according to DSM-5, is inherently neo-Kraepelinian insofar as individuals with either Major Depressive Disorder (MDD) or Bipolar Disorder (BD) may be affected by MFS. Clinicians are encouraged to screen all patients presenting with a major depressive episode (or hypomanic episode) for MFS. Although “overlapping symptoms” were excluded from the diagnostic criteria (eg, agitation, anxiety, irritability, insomnia), clinicians are encouraged to probe for these nonspecific symptoms as a possible proxy of co-existing MFS. In addition to conventional antidepressants, second generation antipsychotics and/or conventional mood stabilizers (eg, lithium) may be considered as first-line therapies for individuals with a depressive episode as part of MDD or BD with mixed features.

There is a great unmet need for new medications with novel mechanisms of action that can effectively treat patients who do not benefit from standard antidepressant therapies. After a period in which it seemed as if the pharmaceutical pipeline for new antidepressants was going dry, the past decade has witnessed renewed interest, beginning with discovery of the antidepressant effects of ketamine. This article briefly highlights more recent research on ketamine and other investigational antidepressants.

Although most patients with depression ultimately respond to antidepressant therapy, >50% have inadequate response to an individual antidepressant trial. The desire to avoid adverse drug reactions is common among patients, and is an important determinant of drug selection among psychiatrists. However, since the major classes of antidepressants and antipsychotics appear to be comparable in efficacy, clinicians have little basis for selecting the most effective agent for an individual patient. Pharmacogenetics, often described as the study of genetic variation that explains differential response to medication, represents an important new avenue toward improving treatment outcomes. Genetic variation in drug-metabolizing enzymes has been recognized for decades. The main focus of current psychiatric pharmacogenetic testing is on the cytochrome P450 (CYP) 2D6 and, to a somewhat lesser extent, on the 2C19 genes. Data suggest that poor metabolizer status can be associated with an increased risk of adverse drug reactions with certain medications, and that ultra-rapid metabolizers may require higher-than-usual doses to achieve a therapeutic response. The importance of CYP enzymes in the metabolism of several antidepressant and antipsychotic drugs suggest that genetic variation may aid in medication selection or dosing. Advances in pharmacogenetic research may facilitate the development of personalized medicine in which genetic information can inform drug selection, leading to optimal drug effectiveness and minimal drug toxicity.

Alzheimer's disease (AD) is a complex medical condition involving abnormalities in multiple biological and environmental domains. Current knowledge suggests that simultaneous intervention in these domains may be the most effective way to help AD patients and their families. Treatments for AD are centered on the inhibition of enzymes responsible for the degradation of acetylcholine—a neurotransmitter that is reduced in AD patients. Four cholinesterase inhibitors have been approved by the United States Food and Drug Administration, three of which are routinely used for the symptomatic treatment of mild-to-moderate AD. Strategies will be reviewed with regard to cognitive, functional, and behavioral domains. Providing a different treatment option for patients with AD, memantine is a low-to-moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that has been approved for the treatment of moderate-to-severe AD. The clinical efficacy and tolerability of memantine monotherapy and combination therapy in patients with AD will be presented. Finally, the role of non-pharmacologic intervention will be discussed.

Bipolar disorder is clinically characterized by fluctuating affect, and neuropsychologically by impairment in executive functions. Such phenomena are consistent with the centrality of emotional dysregulation and impulsivity to bipolar disorder. They are also consistent with a key role for prefrontal-subcortical (striatal-thalamic) and associated limbic circuitry in its mediation. Furthermore, there is growing data on the cellular mechanisms contributing to neuronal vulnerability in this mediating circuitry.

Emotional reactivity in infancy and early childhood may play a role in the regulation of brain plasticity and hemispheric organization, which has possible implications vulnerability to psychopathology. Empiric findings demonstrate the role of attachment patterns in emotional reactivity modulation and limbic circuitry shaping.

Recurrent major depressive disorder (MDD) is a common and disabling illness, but few studies have addressed long-term antidepressant treatment of recurrent MDD (ie, beyond 1 year of maintenance therapy) or compared the efficacy and safety of different antidepressant classes in this population. This article describes the rationale and design of a unique multi-phase trial in patients with recurrent MDD. The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study is a large double-blind, randomized, multi-center trial designed to assess the long-term efficacy of venlafaxine extended release (ER) in the prevention of depressive recurrence. Approximately 1,100 adult outpatients with MDD and a history of ≥3 lifetime episodes (with at least two occurring in the past 5 years) were randomized to 10 weeks of acute-phase treatment with either venlafaxine ER 75–300 mg/day or fluoxetine 20–60 mg/day, followed by 6 months of continuation-phase treatment for patients experiencing a satisfactory therapeutic response or remission during the acute phase. Responders and remitters to continuation phase treatment were then entered into a 2-year maintenance phase study, in which those receiving venlafaxine ER were re-randomized to either venlafaxine ER or placebo at the start of two 12-month maintenance periods. Those taking fluoxetine during the acute and continuation phases continued to receive double-blind treatment with fluoxetine. This study will address several unanswered questions about the long-term treatment of recurrent MDD, such as whether extended maintenance treatment (ie, up to 2 years) lessens the risk for developing future depressive episodes; whether fluoxetine and venlafaxine ER are effective for both short- and long-term treatment of MDD; whether rates of tachyphylaxis differ between anti- depressant classes; and whether the likelihood of depressive recurrence differs according to the time point when treatment is discontinued.