Cognitive impairment has emerged as a key treatment priority in neuropsychiatric disorders. However, there is a lack of treatments with solid and lasting efficacy on cognition. A neurocircuitry-based biomarker model of pro-cognitive effects is critically needed to select among new candidate treatments. In a recent review of functional magnetic resonance imaging (fMRI) studies in mood disorders, we found that cognitive impairments are consistently accompanied by aberrant (hypo- and hyper-) activity in the dorsal prefrontal cortex (PFC) and the default mode network (DMN), and that activity change in these regions commonly occurs with cognitive improvements. Here, we (i) review the putative model from our recent review article, which explains the discrepant findings regarding the direction of aberrant dorsal PFC activity and treatment-related activity change in mood disorders. Inspired by the Research Domain Criteria project, we do this in order to (ii) examine whether a similar pattern of activity change occurs across distinct neuropsychiatric disorders and thereby provides a common biomarker for pro-cognitive effects. Lastly, we (iii) discuss whether dorsal PFC and DMN target engagement is a putative transdiagnostic neurocircuitry-based biomarker model for pro-cognitive effects, and (iv) outline the necessary next steps to address this question.

This article provides an overview of cognitive-behavioral therapy (CBT) for panic disorder. CBT is currently considered a first-line treatment for panic disorder. It offers benefit after short-term intervention, typically consisting of 12–15 sessions conducted in either an individual or a group format. The treatment focuses on the elimination of the patterns that underlie and perpetuate the disorder. Through CBT, patients learn about the nature of the disorder and acquire a set of strategies that counter the fears of panic attacks themselves, and break the recurring cycle of anticipatory anxiety, panic, and agoraphobic avoidance. The collaborative format of treatment, and a focus on elimination of core fears may be factors in enhancing longer-term outcome. In this article, we review the efficacy of CBT as a first-line treatment, a strategy for medication nonresponders, a replacement strategy for patients who wish to discontinue pharmacotherapy, and a potential preventive strategy for at-risk individuals. We also discuss some of the complex issues involved with combination-treatment strategies.

Reduction of core body temperature has been proposed to contribute to the increased lifespan and the anti-aging effects conferred by caloric restriction in mice and higher primates. Cooler biologically compatible core body temperatures have also been hypothesized to combat neurodegenerative disorders. Yet, validation of these hypotheses has been difficult until recently, when it demonstrated that transgenic mice engineered to have chronic low core body temperature have longer lifespan independent of alteration in diet or caloric restriction. This article reviews the literature and highlights the potential influence of core body temperature's governing role on aging and in the pathophysiology of neurodegenerative disorders in humans. What makes recent findings more significant for humans is the existence of several methods to lower and maintain low core body temperatures in human subjects. The therapeutic potential of “cooler people” may also raise the possibility that this could reverse the adverse-health consequences of elevations in core body temperature.

Clozapine is a prototype atypical antipsychotic drug and displays efficacy in 30% to 60% of schizophrenia patients who do not respond to traditional antipsychotics. There is considerable evidence supporting a concentration-response relationship for clozapine. A plasma clozapine concentration >200 to 420 ng/mL increases the probability of antipsychotic effects. Approximately 70% to 80% of variability in clozapine plasma concentration can be attributed to variability in cytochrome P450 1A2 activity. Measurement of caffeine metabolites in plasma or urine can be used as an in vivo index of cytochrome P450 1A2 activity, since caffeine is primarily eliminated by oxidative metabolism through this cytochrome P450 enzyme. Caffeine-based tests may contribute to individualization of clozapine dosages and optimization of its antipsychotic effects in schizophrenia patieents There are several lines of evidence suggesting the potential involvement of the dopamine D4 receptor in pharmacodynamic effects of clozapine. Clozapine has a 10-fold higher affinity for the dopamine D4 receptor in comparison to the D2 and the D3 receptors. Moreover, the free plasma fluid concentration of clozapine is comparable to its binding affinity for the D4 receptor in vitro. Blockade of the D4 receptor in the mesocorticolimbic region, a brain area implicated in the pathogenesis of schizophrenia, may contribute to efficacy of clozapine in negative symptoms. Moreover, the dopamine D4 receptor gene (DRD4) displays an unusual degree of genetic variation (polymorphism). In a recent preliminary study, investigated the (G)n mononucleotide repeat polymorphism within the first intron of the D4 gene in 50 schizophrenia patients refractory to traditional antipsychotics. These patients were prospectively followed for antipsychotic response during clozapine treatment. Analysis of variance found significant differences in antipsychotic response as demonstrated by mean change in Brief Psychiatric Rating Scale scores among the genotype panels for this polymorphism F[3,49]=4.1 (P=0.01). Future studies investigating the mechanistic basis of variability in response to clozapine should focus on both pharmacokinetic and pharmacodynamic factors.

There are few clinical or biologic predictors of response to treatments for depression. This article reviews growing evidence that electrophysiologic and neurocognitive measures of brain function may be of value as predictors of therapeutic response to antidepressants. Initial studies using dichotic listening, quantitative electroencephalography, or event-related brain potential measures have found differences between treatment responsive and nonresponsive subgroups of depressed patients. The neurophysiologic basis for these differences and the potential clinical utility of electrophysiologic and dichotic predictors of treatment out come remain to be determined in future studies.

The distinction between Alzheimer's disease and vascular dementia, the two most common types of dementia, has been undermined by recent advances in epidemiologic, clinical, imaging, and neuropathological studies. Cardiovascular risk factors, traditionally regarded as distinguishing criteria between the two entities, have been shown to be associated with both AD and vascular dementia. In this article, we propose mechanisms of action of cardiovascular risk factors in AD, suggest possible explanations for the overlap with vascular dementia and discuss the implications this might have on future differential diagnosis, research, and treatment strategies.

Aim: To assess the degree of compliance and adherence to treatment during the follow-up of schizophrenic outpatients after a new therapeutic strategy had been initiated.

Methods: A multicenter, retrospective, prospective, observational study of 1,848 outpatients with schizophrenia or schizoaffective disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) was conducted. Patients were treated either with oral or injectable conventional or second generation antipsychotics, and were followed up for 3 months at mental health centers. Patient compliance with the pharmacological treatment was assessed by the use of questionnaires, scales, medication accountability, and the Medication Event Monitoring System. Patients were considered compliant if they reported a high compliance rate (≥80%).

Results: At baseline only 29% of patients on oral medication were compliant compared with 79% of patients on injectable medication (injection counting) (OR= 9.11; 95% CI 6.02-13.77; P<.0001). At the 3 month visit, 84% of patients had changed their treatment and in these, the compliance rate of those on injectable medication was 94% versus 87% of patients taking oral medication (OR= 2.47; 95% CI 1.21-5.05; P=.022).

Conclusion: The use of long-acting injectable antipsychotics, which improves compliance rates and patient follow-up, should facilitate the management of Spanish patients with schizophrenia in mental health centers.

Introduction: The clinical and self-report versions of the Quick Inventory of Depressive Symptomatology (QIDS-C16 and QIDS-SR16) have been well studied in patients with major depressive disorder and in one recent study using patients with bipolar disorder. This article examines these measures in a second sample of 141 outpatients with bipolar disorder in different phases of the illness.

Methods: At baseline, 61 patients were depressed and 30 were euthymic; at exit, 50 were depressed and 52 were euthymic. The remaining patients (at baseline or exit) were in either a manic or mixed phase and were pooled for statistical reasons.

Results: Similar results were found for the QIDS-C16 and QIDS-SR16. Scores were reasonably reliable to the extent that variability within groups permitted. As expected, euthymic patients showed less depressive symptomatology than depressed patients. Sad mood and general interest were tne most discriminating symptoms between depressed and euthymic phases. Changes in illness phase (baseline to exit) were associated with substantial changes in scores. The relation of individual depressive symptoms to the overall level of depression was consistent across phases.

Conclusion: Both the QIDS-SR16 and QIDS-C16 are suitable measures of depressive symptoms in patients with bipolar disorder.

The present paper examines the role of cognitive-behavioral therapy (CBT) in the treatment of social anxiety disorder (SAD). A cognitive-behavioral model of SAD is first presented. Different modalities of CBT for SAD are then described, including exposure, cognitive restructuring, relaxation training, and social skills training, and evidence supporting their efficacy is reviewed. The comparative and combined impact of CBT and pharmacotherapeutic interventions is also explored. CBT appears to be an efficacious treatment for SAD. However, the overall efficacy CBT may be increased by closer examination of the active ingredients of treatment. Such analyses may also enable more successful integration of the different CBT techniques and of CBT and pharmacotherapy in the treatment of SAD.

Obsessive-compulsive disorder (OCD) has been recently drawn apart from anxiety disorder by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and clustered together with related disorders (eg, hoarding, hair pulling disorder, skin picking), which with it seems to share clinical and neurophysiological similarities. Recent literature has mainly explored brain circuitries (eg, orbitofrontal cortex, striatum), molecular pathways, and genes (eg, Hoxb8, Slitrk5, Sapap3) that represent the new target of the treatments; they also lead the development of new probes and compounds. In the therapeutic field, monotherapy with cognitive behavioral therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs) is recommendable, but combination or augmentation with a dopaminergic or glutamatergic agent is often adopted. A promising therapy for OCD is represented by repetitive transcranial magnetic stimulation (rTMS), which is suitable to treat compulsivity and impulsivity depending on the protocol of stimulation and the brain circuitries targeted.

There is increased recognition that bipolar disorder has an early age of onset. The prevalence of bipolar disorder in prepubertal children has not been determined, however the prevalence in adolescence is ˜1%. Bipolar disorder in children poses a diagnostic challenge since the symptoms may differ from those in late adolescence and adulthood. Comorbid disorders, such as attention-deficit/hyperactivity disorder, further complicate both the diagnosis and course of the disorder. There is increasing evidence of the chronicity and severity of this disorder in youths. Bipolar disorder significantly disrupts a child's psychosocial development including impairments in academic functioning, family functioning, and relationship with peers. Although this disorder has significant morbidity in children and adolescents, there is a paucity of controlled studies to assess the efficacy and safety of mood stabilizers in the treatment of this disorder in youths. The treatment literature consists largely of case studies, retrospective chart reviews, and open-label studies. There is a compelling need for double-blind, placebo-controlled trials to determine whether commonly used medications to treat this disorder are significantly superior to placebo. Since many children in clinical practice require more than one psychotropic medication to adequately manage this disorder, studies of combination treatments are warranted. This review will provide an overview of the literature of bipolar disorder in children and adolescents, including discussion of the prevalence, diagnosis, epidemiology, course of the illness, and treatment issues.

The association between obsessive-compulsive (OC) symptoms and schizophrenia has been discussed in the literature for many decades. Recent studies, which have been more systematic than earlier reports and benefited from more rigorous diagnostic criteria, have generated results that contradict earlier findings. The current consensus is that OC symptoms are seen in a significant number of patients with schizophrenia, and indicate a poor prognosis. These recent studies also suggest that OC symptoms are more than just expressions of persistent schizophrenic psychosis, and that they share characteristics with obsessive-compulsive disorder (OCD). This article discusses the arguments supporting the possibility that OC symptoms are either manifestations of comorbid OCD, or are characteristics of a distinct subtype of schizophrenia.