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.

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.

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.

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.

This review aims to shed light on the symptoms of obsessive–compulsive disorder (OCD) with a focus on contamination fears. In addition, we will briefly review the current therapies for OCD and detail what their limitations are. A key focus will be on discussing how smartphone solutions may provide approaches to novel treatments, especially when considering global mental health and the challenges imposed by rural environments and limited resources; as well as restrictions imposed by world-wide pandemics such as COVID-19. In brief, research that questions this review will seek to address include: (1) What are the symptoms of contamination-related OCD? (2) How effective are current OCD therapies and what are their limitations? (3) How can novel technologies help mitigate challenges imposed by global mental health and pandemics/COVID-19.

Genetic factors are known to contribute to the development of schizophrenia and related psychoses. Cytogenetic abnormalities have been occasionally found in patients with psychotic disorders and, thus, have helped identify candidate gene contributors for these conditions. The individual described here first presented with mental retardation and anxiety disorder in his mid-childhood. In his early 20s, the patient started exhibiting various psychotic manifestations, including delusions and hallucinations. His psychotic symptoms were difficult to control with psychotropic medications. The family history was negative for psychiatric disorders. This patient was found to have a 6.2 megabase deletion of the terminal portion of the short arm of chromosome 12 that was characterized using fluorescence in situ hybridization and microarray comparative genomic hybridization analysis. The maternal chromosomes were normal, but the paternal chromosomes could not be tested. To date such a chromosomal abnormality has not been described in association with schizophrenia/psychosis. This case suggests that psychosis-associated gene(s) may be located in the terminal region of the short arm of chromosome 12.

Both obsessive-compulsive disorder (OCD) and social phobia are common in community and clinical settings, and it should be expected that a proportion of patients with one of these conditions will also fulfill either current or lifetime criteria for the other condition. However, comorbid social phobia is more common among patients with a primary diagnosis of OCD than is comorbid OCD in patients with a primary diagnosis of social phobia. This article explores the extent of the association of OCD and social phobia in epidemiological studies, and examines the possible role of underlying depression and other disorders in mediating the appearance of the comorbid condition. Although there have been no published randomized controlled trials in patients with this particular pattern of co-morbidity, it seems sensible to adopt pharmacologic and psychologic treatment approaches which have been found efficacious in both OCD and social phobia. Pharmacologic management therefore centers on first-line treatment with a selective serotonin reuptake inhibitor. Psychologic intervention should draw on the range of cognitive and behavioral approaches required for optimal outcomes in OCD and social phobia, as discrete conditions.

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.

Anxiety disorders are currently one of the most common health concerns in the United States. Overall, they are the single largest cost to the healthcare system. They are also underdiagnosed and undertreated. Selective serotonin reuptake inhibitors and benzodiazepines appear to be the most common pharmacologic treatment approaches. Unfortunately, not all patients respond to these treatments. Many augmentation strategies have been tried in the past with varying levels of success or safety. This article describes a safe and highly effective augmentation technique in patients suffering from some of the most serious and debilitating forms of anxiety disorders, namely obsessive-compulsive disorder and panic disorder.

Our knowledge and understanding of the underlying neurobiology and symptomatic expression of ADHD has advanced dramatically over the past decade. Associated with these advances has been a similar explosion of new treatment options to individualize treatment for our patients.

This article will:

• ∙ review strategies to measure ADHD symptoms and functional difficulties while seeking to achieve full symptomatic remission throughout the day

• ∙ summarize recent findings regarding the management and prioritization of ADHD and comorbid conditions and

• ∙ discuss the various pharmacologic treatment options with a focus on recently developed molecules and novel delivery systems

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.

Schizophrenia is a complex syndrome of unknown etiology and difficult to manage. Unconjugated bilirubin has been researched as a potential biological marker of this syndrome. The objective of this review article was to gather the studies published to date on the relationship between this molecule and schizophrenia. Broad inclusion criteria have been used (PRISMA) to include as many relevant studies as possible. Fourteen studies were selected: 3 analyzed the effects of unconjugated hyperbilirubinemia in animal models; 6 demonstrated an increased incidence of schizophrenia in patients with increased unconjugated bilirubin; 2 reported an increased incidence of the disease in patients with decreased unconjugated bilirubin; and 3 linked an increased incidence of schizophrenia with an increased excretion of the oxidative product of bilirubin, the so-called biopyrrins. Because of apparently contradictory reported results, the hypothesis that the relationship between schizophrenia and unconjugated bilirubin was not linear and that there was an inflammatory dysfunction explaining this was considered. The 2 most accepted models for the pathophysiology of schizophrenia are described, and the possible role of the molecule in each is clarified. The bilirubin buffer system and its role in antioxidant defense was explored. The average levels of unconjugated bilirubin in patients with schizophrenia, schizoaffective disorder, and bipolar disorder were also compared, having been hypothesized that these diseases could be different points of a same pathological spectrum. Finally, it was concluded that unconjugated bilirubin is a promising molecule that could be used as a possible biological marker for schizophrenia, and the necessity of subsequent efforts for its research was considered.