Childhood trauma and psychosis - what is the evidence?

In the last decade, a substantial number of population-based studies have suggested that childhood trauma is a risk factor for psychosis. In several studies, the effects held after adjusting for a wide range of potentially confounding variables, including genetic liability for psychosis. Less is known about the mechanisms underlying the association between childhood trauma and psychosis. Possible pathways include relationships between negative perceptions of the self, negative affect, and psychotic symptoms, as well as biological mechanisms such as dysregulated cortisol and increased sensitivity to stress. Psychotic patients with a history of childhood trauma tend to present with a variety of additional problems, including post-traumatic stress disorder, greater substance abuse, higher levels of depression and anxiety, and more frequent suicide attempts. Initial studies suggest that trauma-specific treatments are as beneficial for these patients as for other diagnostic groups.     

Current research in child and adolescent bipolar disorder

Although recently more research has considered children with bipolar disorder than in the past, much controversy still surrounds the validity of the diagnosis. Furthermore, questions remain as to whether or not childhood expressions of bipolarity are continuous with adult manifestations of the illness. In order to advance current knowledge of bipolar disorders in children, researchers have begun to conduct phenomenological, longitudinal, treatment, and neuroimaging studies in youths who exhibit symptoms of bipolar illness, as well as offspring of parents with bipolar disorders. Regardless of the differences between research groups regarding how bipolar disorder in children is defined, it is agreed that pediatric bipolarity is a serious and pernicious illness. With early intervention during the period of time in which youths are exhibiting subsyndromal symptoms of pediatric bipolarity, it appears that the progression of the illness to the more malignant manifestation of the disorder may be avoided. This paper will review what is currently known and what still is left to learn about clinically salient topics that pertain to bipolar disorder in children and adolescents.     

Conceptualization of the liability for schizophrenia: clinical implications

Historically, the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for schizophrenia have emphasized several features, including symptoms of psychosis, a dissociation of symptoms from their etiology, a reliance on clinical symptoms, and a categorical approach to classifying the disorder. Although these emphases are quite useful, they have limitations. We review these here, and stress the importance of incorporating recent data on the genetic /biological and neurodevelopmental origins of schizophrenia into current conceptions of the disorder. We also review "schizotaxia, " which is a concept thai embodies this point of view, occurs before the onset of psychosis, and is hypothesized to represent the liability for schizophrenia. If our hypothesis on this point is correct, the identification of schizotaxic individuals will eventually facilitate the development of prevention strategies by identifying a premorbid (but clinically significant) condition for schizophrenia. Moreover, the identification of biological or neuropsychological components of schizotaxia will provide more specific bases for developing novel treatment interventions. Our initial attempts to develop protocols for the assessment and treatment of schizotaxia are encouraging, and will be reviewed.     

Effects of different antidepressant treatments on the core of depression

Core symptoms of depression are a combination of psychological and somatic symptoms, often combined with psychomotor and cognitive disturbances. Diagnostic classification of depression including the concepts of melancholic, endogenous, or severe depression describe severely depressed patients suffering from most of the core symptoms, together with clinical characteristics of a cyclic unipolar or bipolar course, lower placebo response rates, higher response rates to electroconvulsive therapy, to antidepressant treatments with dually or mixed modes of action, or to lithium augmentation. Higher rates of hypothalamic-pituitary-adrenal axis hyperactivity and specific electroencephalographic patterns have also been shown in this patient group. Summarizing the symptomatology of depression in these patients, a broad overlap between the abovementioned subgroups can be suggested. Because the positive diagnosis of those core symptoms of depression may include clinical consequences, it would be of use to integrate all the mentioned concepts in the upcoming new versions of the diagnostic systems DSM-V and ICD-11.     

Treatment-refractory schizophrenia

Between one-third and one-half of the individuals who meet diagnostic criteria for schizophrenia remain actively ill despite optimal pharmacological treatment. These individuals tend to progressively deteriorate in terms of social and vocational functioning despite major public and private investments in their rehabilitation. For patients who do not respond to the first prescribed antipsychotic drug, current clinical practice is to switch to a second and a third drug, and eventually to clozapine, the only antipsychotic drug proven to be effective in treatment-refractory schizophrenia (TRS). Occasionally, two antipsychotics are given concomitantly or psychotropic drugs are added to antipsychotic drugs; however, very few empirical data exist to support this practice. Although there are many exceptions, patients who do not benefit from the first prescribed drug will not benefit from any pharmacological intervention. Therefore, efforts are under way to determine the reason for lack of response to available treatments and devise novel, more effective treatments. To be successful these efforts must result in a more specific definition of TRS, as well as in a better understanding of the illness pathophysiology and the mechanism of action of the drugs.     

Anorexia nervosa: an increasing problem in children and adolescents

Information from eating disorder clinics across five continents suggests that anorexia nervosa is becoming an increasing problem in children and young adolescents. There is some indication that anxiety disorders in childhood may be a major risk factor for the development of anorexia nervosa. Early recognition and family treatment for this disorder are essential to prevent chronic impairment.     

Evolution of diagnostic criteria in psychoses

The term psychosis was first introduced in the mid-19th century for the separation of psychiatric disorders from neurological disorders within the neuroses. The concept of psychosis has become gradually restricted from a generic term for psychiatric disorders to one of the major classes of mental illness, which was assumed to be the result of a disease process, and, more recently, to a symptom present in many psychiatric disorders. In the course of this development, the díagnostic criteria for psychosis shifted from the severity of the clinical manifestations and the degree of impairment in social functioning to the presence of one or more symptoms in a set of psychopathological symptoms, which include hallucinations, formal thought disorder manifest in disorganized or odd speech, delusions, flat/inappropriate affect, avolition/apathy disorganized behavior, catatonic motor behavior, and depersonalization/derealization. The changes in the conceptualization of psychosis and in the diagnostic criteria for psychosis are documented in the various editions of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Assocíation (from DSM-I to DSM-IV] and the International Classification of Diseases of the World Health Organization (from ICD-9 to ICD-10].     

Cognitive behavioral therapy of obsessive-compulsive disorder

Until the mid-1960s, obsessive-compulsive disorder (OCD) was considered to be treatment-resistant, as both psychodynamic psychotherapy and medication had been unsuccessful in significantly reducing OCD symptoms. The first real breakthrough came in 1966 with the introduction of exposure and ritual prevention. This paper will discuss the cognitive behavioral conceptualizations that influenced the development of cognitive behavioral treatments for OCD. There will be a brief discussion of the use of psychodynamic psychotherapy and early behavioral therapy, neither of which produced successful outcomes with OCD. The main part of the paper will be devoted to current cognitive behavioral therapy (CBT) with an emphasis on variants of exposure and ritual or response prevention (EX/RP) treatments, the therapy that has shown the most empirical evidence of its efficacy.     

Neurobiologically informed treatment for adults with anorexia nervosa: a novel approach to a chronic disorder

Anorexia nervosa (AN) is a severe and debilitating disorder with significant medical and psychological sequelae. To date, there are no effective treatments for adults, resulting in high rates of chronicity, morbidity, and mortality. Recent advances in brain imaging research have led to an improved understanding of etiology and specific neurobiological mechanisms underlying symptoms. Despite this, there are no treatments focused on targeting symptoms using this empirically supported mechanistic understanding of the illness. Updated treatment approaches focused on targeting neurobiological mechanisms underlying core AN symptomatology are necessary to improve treatment out-comes for this population. Neurobiologically Enhanced With Family Eating Disorder Trait Response Treatment (NEW FED TR) is a neurobiologically informed treatment targeting key temperament constructs associated with the illness through the delivery of psychoeducation and skills training to patients and nominated carers.     

Clinical impact of recently detected susceptibility genes for schizophrenia

After years of frustration, the search for genes impacting on schizophrenia is now undergoing some exciting developments. Several proposals of susceptibility genes have been able to be supported by replications. Thus, there are now at least three very strong candidates: the gene for dysbindin (DTNBP1), the gene for neuregulin-1 (NRG1), and a less well-understood gene locus, G72/G30, which are likely to influence manifestations of schizophrenia. Other "hot" candidates such as the disrupted-in-schizophrenia 1 gene (DISC1) and the gene coding for protein kinase B (AKT1) might also prove to be susceptibility genes in the next future. The clinical implications of these findings are not yet fully visible. However, some first insights are possible: most of the genetic findings lack diagnostic specificity, and are also reproduced in bipolar disorder. Strong associations are also obtained on a symptomatic level, not only on a diagnostic level. The pathophysiological role of these hot candidate genes is currently under intensive study.     

Characteristics,correlates, and outcomes of childhood and adolescent depressive disorders

Depressive illness beginning early in life can have serious developmental and functional consequences. Therefore, understanding the disorder during this developmental stage is critical for determining its etiology and course, as well as for deveiopinq effective intervention straieqies. This paper summarizes current knoviedqe reqardinq the etiology, phenomenoiogy, correlates, natural course, and consequences of unipolar depression in children and adolescents. Using adult depression as a framevork, the unique aspects of childhood and adolescence are considered in order to better understand depression within a developmental context. The data suggest that the clinical presentation, correlates, and natural course of depression are remarkably similar across the lifespan. There are, however, important developmental differences. Specifically, the familial and psychological context in which depression develops in youngsters is associated with variability in the frequency and nature of depressive symptoms and comorbid conditions among children and adolescents. Maturational differences have also been identified in the neurobiological correlates of depression. These developmental differences may be associated with the observed variability in clinical response to treatment and longitudinal course. Characterization of the developmental differences will be helpful in developing more specific and effective interventions for youngsters, thereby allowing them to reach their full potential as adults.     

Behavioral and psychological signs and symptoms of dementia: a practicing psychiatrist's viewpoint

Alzheimer's disease typically presents with two often overlapping syndromes, one cognitive, the other behavioral. The behavioral syndrome is characterized by psychosis, aggression, depression, anxiety, agitation, and other common if less well-defined symptoms subsumed under the umbrella entity "behavioral and psychological symptoms of dementia" (BPSD), itself divided into a number of subsyndromes: psychosis, circadian rhythm (sleepwake) disturbance, depression, anxiety, and agitation, it is BPSD with its impact on care providers that ultimately precipitates the chain of events resulting in long-term institutional care. The treatment challenge involves eliminating unmet medical needs (undiagnosed hip fracture and asymptomatic urinary tract infection or pneumonia). Pharmacologic intervention relies on risperidone and, increasingly cholinesterase inhibitors for the control of psychosis (but with response rates of only 65% at tolerable doses), olanzapine and risperidone for anxiety, and carbamazepine and valproic acid for agitation. However, evidence increasingly favors nonpharmacologic interventions, to the extent that these should now be considered as the foundation of BPSD treatment. Problem behaviors are viewed as meaningful responses to unmet needs in the therapeutic milieu. Because the progression and impact of BPSD varies between patients, interventions must be explored, designed, implemented, and assessed on an individual basis. They include: family support and education, psychotherapy reality orientation, validation therapy, reminiscence and life review, behavioral interventions, therapeutic activities and creative arts therapies, environmental considerations (including restraint-free facilities), behavioral intensive care units, and workplace design and practices that aid the ongoing management of professional caregiver stress.     

Attention deficit-hyperactivity disorder and early-onset bipolar disorder: two facets of one entity?

Early-onset bipolar disorder (BD) and attention-deficithyperactivity disorder (ADHD) have recently been the subject of highly controversial debate, due to theories regarding underlying pathophysiological processes and a clinical overlap of symptoms. Epidemiological data, clinical aspect, neuroimaging, neurochemical, and genetic studies suggest that there may be a possible relationship between biological factors and clinical characteristic in the development of symptoms. However, longitudinal data supporting the hypothesis of a diagnostic shift from BD to ADHD symptoms and vice versa are currently not available. These would be essential to enable further investigations into whether these two disorders possibly represent two different aspects of an underlying common psychopathophysioiogical entity.     

The epidemiology of anxiety disorders: a review

Epidemiological studies show that anxiety disorders are highly prevalent and an important cause of functional impairment; they constitute the most frequent menial disorders in the community. Phobias are the most common with the highest rates for simple phobia and agoraphobia. Panic disorder (PD) and obsessive-compulsive disorder (OCD) are less frequent (2% lifetime prevalence), and there are discordant results for social phobia (SP) (2%-16%) and generalized anxiety disorder (GAD) (3%-30%). These studies underline the importance of an accurate definition of disorders using unambiguous diagnostic and assessment criteria. The boundaries between anxiety disorders are often ill defined and cases may vary widely according to the definition applied. Simple phobia, agoraphobia, and GAD are more common in vmrnen, while there is no gender différence for SP, PD, and OCD, Anxiety disorders are more common in separated, divorced, and widowed subjects; their prevalence is highest in subjects aged 25 to 44 years and lowest in subjects aged >65 years. The age of onset of the different types of anxiety disorders varies widely: phobic disorders begin early in life, whereas PD occurs in young adulthood. Clinical - rather than epidemiological - studies have examined risk factors such as life events, childhood experiences, and familial factors. Anxiety disorders have a chronic and persistent course, and are frequently comorbid with other anxiety disorders, depressive disorders, and substance abuse. Anxiety disorders most frequently precede depressive disorders or substance abuse, Comorbid diagnoses may influence risk factors like functional impairment and quality of life. It remains unclear whether certain anxiety disorders (eg, PD) are risk factors for suicide. The comorbidity of anxiety disorders has important implications for assessment and treatment and the risk factors should be explored. The etiology, natural history, and outcome of these disorders need to be further addressed in epidemiological studies.     

Neural models of schizophrenia

Hallucinations and delusions - two diagnostic features of psychosis shared across the spectrum of heterogeneous schizophrenia constructs - can be described in terms of the pathophysiology of sensory information processing: hallucination is the impaired ability to classify representations as internally or externally generated, while delusion is the immutable linking of representations with each other in the absence of external dependency. The key anatomical systems in higher-order information processing are the cortex, thalamus, basal ganglia, and medial temporal lobe, each of which is modulated by neurotransmitter projection systems. Preliminary evidence, concentrating to date on the dorsolateral prefontal cortex, thalamus, and hippocampal region of the medial temporal lobe, points to neural circuitry dysfunction within and between each system in psychosis. This may account for specific symptoms and associated cognitive deficits such as memory impairment, attention deficit, and language disturbance.     

Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan

This review outlines pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders (ASDs) in children, adolescents, and adults. Symptom domains include repetitive and stereotyped behaviors, irritability and aggression, hyperactivity and inattention, and social impairment. Medications covered include serotonin reuptake inhibitors (SRIs), mirtazapine, antipsychotics, psychostimulants, atomoxetine, α-2 agonists, D-cycloserine, and memantine. Overall, SRIs are less efficacious and more poorly tolerated in children with ASDs than in adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in ASDs, and may be useful in the treatment of other symptoms. Psychostimulants demonstrate some benefit for the treatment of hyperactivity and inattention in individuals with ASDs, but are less efficacious and associated with more adverse effects compared with individuals with ADHD. D-cycloserine and memantine appear helpful in the treatment of social impairment, although further research is needed.     

CSF tau and β-amyloid as biomarkers for mild cognitive impairment

Early diagnosis of Alzheimer s disease (AD) is relevant in order to initiate symptomatic treatment with antidementia drugs. This will be of greater significance if the drugs aimed at slowing down the degenerative process (secondary prevention) prove to affect AD pathology and are clinically effective, such as γ-secretase inhibitors. However, there is currently no clinical assessment to differentiate the patients with mild cognitive impairment (MCI) who will progress to AD from those with a benign form of memory impairment that is part of the normal aging process. Thus, there is great clinical need for diagnostic and predictive biomarkers, as well as biomarkers for classification purposes, to identify incipient AD in MCI subjects. The most promising cerebrospinal fluid (CSF) biomarker candidates are total tau protein (T-tau), phosphorylated tau protein (P-tau), and the 42-andno acid form offi-amyloid (Aβ42), which may, if used in the right clinical context, prove to have sufficient diagnostic accuracy and predictive power to resolve this diagnostic challenge.     

Diagnosis and treatment of sleep disorders: a brief review for clinicians

Sleep disorders encompass a wide spectrum of diseases with significant individual health consequences and high economic costs to society. To facilitate the diagnosis and treatment of sleep disorders, this review provides a framework using the International Classification of Sleep Disorders, Primary and secondary insomnia are differentiated, and pharmacological and nonpharmacological treatments are discussed. Common circadian rhythm disorders are described in conjunction with interventions, including chronotherapy and light therapy. The diagnosis and treatment of restless legs syndrome/periodic limb movement disorder is addressed. Attention is focused on obstructive sleep apnea and upper airway resistance syndrome, and their treatment. The constellation of symptoms and findings in narcolepsy are reviewed together with diagnostic testing and therapy, Parasomnias, including sleep terrors, somnambulism, and rapid eye movement (REM) behavior sleep disorders are described, together with associated laboratory testing results and treatment.     

Cognitive-behavioral therapy for anxiety disorders: an update on the empirical evidence

A large amount of research has accumulated on the efficacy and effectiveness of cognitive-behavioral therapy (CBT) for anxiety disorders including posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, and specific phobia. The purpose of the current article is to provide an overview of two of the most commonly used CBT methods used to treat anxiety disorders (exposure and cognitive therapy) and to summarize and discuss the current empirical research regarding the usefulness of these techniques for each anxiety disorder. Additionally, we discuss the difficulties that arise when comparing active CBT treatments, and we suggest directions for future research. Overall, CBT appears to be both efficacious and effective in the treatment of anxiety disorders, but dismantling studies are needed to determine which specific treatment components lead to beneficial outcomes and which patients are most likely to benefit from these treatment components.     

Treatments for chronic psychosis

Psychosis is a mental condition characterized by hallucinations, delusions, and thought disorder; it spans diagnostic entities that respond to similar therapeutic approaches. Psychosis has no fully described tissue pathology, as vet, but is still identified and assessed symptomatically. The first generation of antipsychotic drugs was developed in the middle of the 20th century. The second generation of drugs arrived in the 1990s. This new group of antipsychotic drugs has potent therapeutic actions on the positive symptoms of psychosis with far fewer side effects, especially motor effects. However, each of the new drugs has its own characteristic clinical and pharmacological features that affect individual patient response. Understanding these individual drug characteristics can promote optimal drug choice and use in conditions of chronic psychosis.