Major depression is a multidimensional disorder producing emotional dysregulation, cognitive impairment, and neuro-vegetative symptoms. A pathophysiological model of depression needs to explain how these dimensions interact to produce specific clinical phenotypes and how these interactions may predict remission to specific treatments. It is unlikely that major depression results from discrete brain lesions. Here we propose to define major depression as a disorder of neural networks. We review evidence suggesting that the dynamics of neural networks involved in allocation of attention resources to the internal and external world contribute to cognitive impairment, increased self-focus, and dysfunctional saliency detection in depression. We describe cognitive and emotional tasks that reveal abnormal cooperation between the Central Executive Network and the Default Mode Network. Finally we suggest that depression is associated with increased social rejection sensitivity. Studies on social rejection will shed light on how attachment relates to impairment in allocation of attention resources to produce depressive symptoms such as rumination and cognitive problems.

Brain imaging techniques, especially those based on magnetic resonance imaging (MRI) and magnetoencephalography (MEG), have been increasingly applied to study multiple large-scale distributed brain networks in healthy people and neurological patients. With regard to neurodegenerative disorders, amyotrophic lateral sclerosis (ALS), clinically characterized by the predominant loss of motor neurons and progressive weakness of voluntary muscles, and frontotemporal lobar degeneration (FTLD), the second most common early-onset dementia, have been proven to share several clinical, neuropathological, genetic, and neuroimaging features. Specifically, overlapping or mildly diverging brain structural and functional connectivity patterns, mostly evaluated by advanced MRI techniques—such as diffusion tensor and resting-state functional MRI (DT–MRI, RS–fMRI)—have been described comparing several ALS and FTLD populations. Moreover, though only pioneering, promising clues on connectivity patterns in the ALS–FTLD continuum may derive from MEG investigations. We will herein overview the current state of knowledge concerning the most advanced neuroimaging findings associated with clinical and genetic patterns of neurodegeneration across the ALS–FTLD continuum, underlying the possibility that network-based approaches may be useful to develop novel biomarkers of disease for adequately designing and monitoring more appropriate treatment strategies.

Secondary mania develops in as many as 9% of persons with traumatic brain injuries.The treatment of posttraumatic mania is not well defined, and agents traditionally used for the treatment of idiopathic manic episodes may not be well suited for use among individuals with traumatic brain injuries. Atypical antipsychotics are indicated for the treatment of idiopathic bipolar disorder, and have been used for other purposes among individuals with posttraumatic neuropsychiatric disturbances. This article offers the first description of the treatment of posttraumatic mania using the atypical antipsychotic quetiapine. Beneficial effects of this agent on posttraumatic mania, cognitive impairments, and functional disability in the subacute post-injury period are described. Possible mechanisms of action are discussed and the need for additional investigation of quetiapine for posttraumatic mania is highlighted.

In this article, data are presented from Parts A and B of the Trail Making Test, which examined the effects of haloperidol vs risperidone on cognitive function in treatment-resistant scxhizophrenic patients. This report focuses on findings from the Trail Making Test. Overall, risperidone had a positive effect on Trail Making Part B performance following 4 weeks of treatment. These effects were due, at least in part, to the direct effects of risperidone. The possibility that an antipsychotic agent can enhance executive functioning through direct mechanisms, perhaps mediated by frontal cortex neurochemistry, indicates that the evaluation of antipsychotic medications in the treatment of schizophrenia should be expanded to include cognition.

Trichotillomania (TTM) is increasingly being recognized as a prevalent disorder. Nevertheless, few data are available regarding the effects of TTM on quality of life or the economic costs associated with this disorder. Two hundred members of the Obsessive-Compulsive Disorder Association of South Africa were surveyed in this pilot study, using a detailed self-report questionnaire. Of the 75 respondents, 27 reported hair pulling as a symptom. Results from this investigation indicate that hair pulling may be associated with substantial morbidity, including significant effects on occupational, academic, social, and family functioning. Additional costs may be incurred by delays in seeking treatment and incorrect diagnoses. While further work in a larger sample of patients is clearly needed, psychoeducation of practitioners and the public on TTM may result in earlier referral, diagnosis, treatment, and greater cost savings in the long term.

Distinguishing dependent from recreational drug use can be a surprisingly difficult task, and the current means for identifying substance abuse can be inadequate or even misleading. In subjective self-reports, those who are most at risk may downplay their consumption, not admitting to the full extent of their habit, and measures purely of quantity of use rarely capture the true nature of an individual's relationship to the drug, such as a psychological dependence on the substance. This trend is particularly true for heavy stimulant use, which is absent of the physical withdrawal symptoms that can help identify opiate or alcohol dependence. As such, a simple objective measure to help identify substance abuse, particularly in individuals who might not otherwise raise suspicion, would be a valuable tool in both clinical and experimental settings. We propose that the drug-word Stroop task, an objective assessment of attentional bias and distraction to salient drug-related stimuli, would be a valuable tool in helping to make these categorizations. This measure has been shown to correlate with drug craving, as well as to successfully distinguish dependent from recreational stimulant users and to help to predict outcomes in treatment-seeking individuals. Here, we survey prior literature on the drug-word Stroop task and provide a perspective on using the assessment as a potential diagnostic for drug use severity.

The concept of anxiety as a distinct comorbid disorder in schizophrenia has recently been rediscovered after having been neglected for a long period of time due to both theoretical and clinical approaches adopted from the appearance of the first edition of the Diagnostic and Statistical Manual of Mental Disorders in 1950. This rediscovery was accentuated by the fact that the concept of comorbidity in various psychiatric disorders has recently won widespread favor within the scientific community, and that the use of atypical neuroleptic medication to treat patients with schizophrenia has been reported to lead to the emergence of anxiety symptoms. Of the atypical neuroleptic medications used to treat schizophrenia, clozapine has most frequently been reported to induce anxiety symptoms. In this paper, 12 cases of patients with paranoid schizophrenia who developed social phobia during clozapine treatment are reported, and their response to fluoxetine augmentation is assessed. Premorbid personality disorders were also investigated; patients were assessed using the Structured Clinical Interview for DSM-III-R—Patient Version and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (DSM-III-R=Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). In addition, the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Liebowitz Social Anxiety Scale (LSAS), the Frankfurt Beschwerde Fragebogen (Frankfurt Questionnaire of Complaints), and the Brief Psychiatric Rating Scale were used to rate clinical symptomatology. All patients were reevaluated after 12 weeks of cotreatment with clozapine and fluoxetine. In 8 (66.6%) of the 12 cases, symptoms responded (≥35% LSAS score reduction) to an adjunctive regimen of fluoxetine. Furthermore, in 7 (58.3%) of the 12 cases, an anxious personality disorder (avoidant=33.3%; dependent=25%) was identified, but no significant differences in the prevalence of comorbid personality disorders emerged in comparison with a group of 16 patients with paranoid schizophrenia treated with clozapine who did not show symptoms of social phobia. The clinical relevance of the assessment and treatment of anxiety disorders is discussed in light of a clinical therapeutic approach that overcomes the implicit hierarchy of classification. Considering that the onset of anxiety-spectrum disorders (such as social phobia) can occur during the remission of psychotic symptoms in clozapine-treated patients with schizophrenia, a comprehensive approach to pharmacological therapy for patients with schizophrenia (or, at least for those treated with clozapine) should be adopted.

Schizophrenia and bipolar disorder are two debilitating mental health disorders, both of which manifest early in adulthood and are associated with severe impairment as well as increased suicide risk. In addition, factors affecting disease severity, such as substance abuse, are often prevalent in these patient populations. In the United States, the prevalence of bipolar disorder is believed to be ~3.5%, while the rate for schizophrenia is ~1%. Although each disorder presents with its own symptom profile, the approaches to treatment are similar and include early diagnosis and use of psychosocial therapy. Research initiatives, such as genetic studies, are used in both disorders as well. For schizophrenia, treatment typically includes the combination of an antipsychotic and psychosocial intervention. For bipolar disorder, clinicians commonly prescribe mood-stabilizing drugs (eg, lithium, valproic acid) as first-line treatment. Many of the second-generation antipsychotics have been approved by the US Food and Drug Administration for bipolar disorder treatment in the manic phase. Patients who are affected by either disorder also face the challenges of treatment nonadherence, which can be affected by substance abuse and can hinder symptom remission as well as spur unnecessary medication switches due to nonresponse. Family members play a key role in the treatment of either disorder.

This expert review supplement focuses on treatment options and research strategies being utilized for the management and advanced understanding of schizophrenia and bipolar disorder. Research examining the pharmacology of commonly used medications for the treatment of both disorders is also presented.

Aggressive and violent behavior, including both verbal and physical aggression, have considerable adverse consequences for people with schizophrenia. There are several potential causes of violent behavior on the part of people with severe mental illness, which include intellectual impairments, cognitive and social-cognitive deficits, skills deficits, substance abuse, antisocial features, and specific psychotic features. This review explores the interventions that have been tested to this date. Computerized Cognitive Training (CCT) or Computerized Social-Cognitive Training (CSCT) have been associated with reductions in violence. Combined CCT and CSCT have been found to improve social cognition and neurocognition, as well as everyday functioning when combined with rehabilitation interventions. These interventions have been shown to reduce violence in schizophrenia patients across multiple environments, including forensic settings. The reductions in violence and aggression have manifested in various ways, including reduced violent thinking and behavior, reduced physical and violent assaults, and reduced disruptive and aggressive behaviors. Effects of cognitive training may be associated with improvements in problem-solving and the increased ability to deploy alternative strategies. The effect of social cognition training on violence reduction appears to be direct, with improvements in violence related to the extent of improvement in social cognition. There are still remaining issues to be addressed in the use of CCT and CSCT, and the benefits should not be overstated; however, the results of these interventions are very promising.

Separation anxiety has long been of interest in psychiatry. The term refers to both a phenomenon of normal psychological development and to the symptoms of a common childhood psychiatric disorder, classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and the International Statistical Classification of Diseases and Related Health Problems, Tenth Edition (ICD 10), as separation anxiety disorder. Available epidemiological studies suggest a prevalence rate of this disorder of about 4%. Treatment studies using cognitive behavioral therapy and/or medication are reported in the literature. There is also evidence that symptoms of separation anxiety may occur in adulthood, though this is far less widely known. We consider childhood and adult separation anxiety to be a component of panic spectrum, described in other papers of this issue.

A small and somewhat confusing literature addresses the question of outcome of childhood separation anxiety disorder, with support for a weak association between childhood separation anxiety and adult panic disorder. We believe there is a suggestion of a stronger association of the childhood condition with persistence of a similar syndrome of adult separation anxiety. Symptoms of adult separation anxiety may be a manifestation of panic spectrum, as we suggest. Such symptoms may represent a separate, specific clinical entity, or symptomatic separation anxiety may occur as a manifestation of a range of Axis I disorders, and may respond to treatment of these disorders. In any case, we urge researchers and clinicians to begin to attend to the possibility that adult psychiatric patients may suffer from clinically significant symptoms of adult separation anxiety.

Social cognition involves automatic and stimulus-driven processes; these may be important in mediating stereotypes in the community and schemas and transference in the clinic setting. Significant differences in self-related processing and other-related processing may also lead to important biases in our view of the other. The psychobiology of social cognition is gradually being delineated, and may be useful in understanding these phenomena, and in responding appropriately. In the clinic, schemas can be rigorously assessed, and schema-focused psychotherapy may be useful in a number of indications.

Stiff-person syndrome (SPS) is a rare disease of severe progressive muscle stiffness in the spine and lower extremities with superimposed muscle spasms triggered by external stimuli. Patients with SPS are often referred for psychiatric evaluation and the psychiatrist may be the first to diagnosis SPS. Psychosocial stressors often precede the first manifestations of the disease; depression, anxiety, and alcohol abuse are comorbid illnesses. The identification of an association with antibodies to glutamic acid decarboxylase (GAD) was invaluable for definitively establishing a pathological basis for the disease; antibodies to amphiphysin and gephyrin are also found in cases of SPS but at much lower frequencies. Whether the antibodies inhibit GAD activity in vivo, target GAD-expressing neurons for immune-mediated destruction, are part of a wider immune process, or are merely a marker for destruction of GAD-expressing neurons by an independent neurodegenerative process is not yet clear. Both electromyography and the detection of GAD antibodies are useful in establishing a diagnosis of SPS. Treatment of SPS includes the use of immunomodulating therapies (plasmapheresis and intravenous immunoglobulins) and symptomatic treatment with benzodiazepines and baclofen. The use of tricyclic antidepressants and rapid withdrawal from therapy should be avoided.

Individuals suffering from drug addiction may also manifest features of bipolar spectrum disorders. Hyperthymic and cyclothymic temperaments may render individuals vulnerable to later development of substance abuse. Bipolar disorders themselves may be altered or precipitated by substance use, most notably by stimulants (amphetamines), alcohol, and cannabinoids.The clinical usefulness of mood stabilizers, particularly antiepileptics, has been established as safe and effective in substance abusers with and without comorbid mood disorders. Most studies on this issue have been of short duration and focused on the resolution of a currently manifest period of illness. Few studies have been conducted on the usefulness of these drugs on the long-term longitudinal course of these diseases, such as frequently encountered recurrent relapses into states of agitation, impulsivity, and/or dissatisfaction. As opposed to the clinical experience with traditional antidepressants and neuroleptics, antiepileptics do not induce counter-polar states (depressed patients abruptly turning manic or hypomanic; nor patients currently hypomanic or manic turning abruptly depressed). Many clinicians consider antiepileptic mood stabilizers to be the preferred category of medications for the treatment of such patients. Valproate appears to be a potentially fruitful medication to study in these dual diagnosis patients due to preliminary evidence demonstrating its anticraving efficacy.

Treatment nonadherence is a concern among patients with bipolar disorder and posttraumatic stress disorder (PTSD). PTSD is common among patients with bipolar disorder and those with this comorbidity often have a more severe course of illness. While many factors have been associated with nonadherence in bipolar disorder patients and in PTSD patients, almost no research has focused on the factors associated with non-adherence in bipolar disorder patients with comorbid PTSD. Studies in primary bipolar disorder samples reveal patient, illness, drug and clinician characteristics associated with nonadherence while studies in primary PTSD samples reveal a significantly shorter list of patient, illness and drug characteristics. Shared risk factors between these two populations and the characteristics that predict noncompliance in only one population but often present in the other, suggest a high likelihood of nonadherence in the bipolar disorder-PTSD population. For bipolar disorder-PTSD patients with early childhood trauma, noncompliance may be related to the trauma-related meanings attributed to interactions with their physicians and their prescribed medications. Given the high side effect burden of bipolar disorder treatments and the importance of lifelong adherence, clinicians should vigilantly monitor for nonadherence in their bipolar disorder-PTSD patients and be particularly aware of patient-physician psychodynamics that might contribute to this behavior.