The habenula, which in humans is a small nuclear complex within the epithalamus, plays an essential role in regulating the intensity of reward-seeking and adversity-avoiding behavior in all vertebrate ancestors by regulating the activity of ascending midbrain monoaminergic tracts. In lampreys, considered to possess a brain comparable to humans’ earliest evolutionary vertebrate ancestor, the activity of the lateral habenula is controlled by a subset of glutamatergic neurons of the animal’s pallidum (habenula-projecting globus pallidus) that inhibit reward-seeking behavior when this conduct is not successful enough. The pathophysiological roles of the habenula and habenula-projecting globus pallidus in humans have hardly been studied, which is probably due to insufficient resolution of common neuroimaging techniques. Their dysregulation may, however, play an essential role in the pathogenesis of mood and stress disorders and addiction.

Brain stimulation methods in the treatment of affective disorder are electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS). Clinically, ECT is considered the strongest remedy in the treatment of severe depression, especially depression with psychotic features, and in the elderly. TMS, despite positive reports, is somewhat more controversial. VNS has, so far, only been used in treatment-resistant depression with limited results. DBS may be of potential use in rare cases of treatment-resistant cases of affective disorder. This article highlights the similarities and differences between the four stimulation methods. The main difference is the seizures necessary in ECT. A stronger involvement of the hippocampus following experimental seizures compared with effects in that region induced by TMS and VNS might explain the consistent findings of the superiority of ECT in the most severe cases of affective disorder.

Sleep problems, day somnolence, and fatigue as a result of psychotropic drugs are very common. Psychiatrists usually consider these effects a result of insomnia and treat them by prescribing sleeping pills or other benzodiazepine agents.

We describe here 10 cases of circadian rhythm sleep disorders (CRSD)—and not merely insomnia—as a possible side effect of fluvoxamine (FVA). Two other serotonin reuptake inhibitors, fluoxetine and clomipramine, did not induce CRSD in any of these 10 patients. We speculate that FVA-induced CRSD is caused by the effect of FVA on serotonin and melatonin levels in the central nervous system.

CRSD as a side effect of FVA can be treated by replacing the suspected FVA or adding melatonin to a beneficial FVA treatment. Thus, it is important to be aware of possible iatrogenic CRSD in order to treat appropriately. Prospective studies are needed to confirm our observation and to study the influence of other psychotropic drugs on sleep-wake schedule.

In this article, we present rationales for using complex combination therapy in treatment-refractory bipolar patients and discuss the agents available for use in this therapeutic approach. We review a case example of successful remission that was achievable only with complex combination therapy, and examine its theoretical implications. Practical approaches to devising the optimal complex combination treatment for individual patients are explained, and we look to the development of new methodologies and a more systematic database for decision making in the future.

This paper describes a model of psychopathology termed the panic-agoraphobic spectrum. The model has been constructed by identifying different psychopathologic and clinical domains that incorporate and extend the diagnosis of panic disorder as described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).

Categorical classifications do not take into account the subthreshold, atypical, and often enduring symptoms that accompany the core manifestations of full-blown mental disorders. These often-neglected spectrums of symptoms, however, may be as distressing and debilitating as the full-blown disorders and can have unrecognized importance in selection of and response to treatment. At the Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnology, Institute of Psychiatry of the University of Pisa, Italy, a spectrum approach to mental disorders (eg, bipolar, obsessive-compulsive, eating, and panic disorders) has been used extensively and has proven effective in clinical practice.

The need for systematic identification and assessment of a broad array of symptoms and behavioral features has led, as a first step, to the conceptualization of the panic-agoraphobic spectrum model. In collaboration with researchers from the University of Pittsburgh, PA, and elsewhere, the University of Pisa scientists have further refined the panic-agoraphobic spectrum model and have developed a structured interview for this spectrum called the Structured Clinical Interview for Panic-Agoraphobic Spectrum. The rationale, clinical usefulness, and heuristic significance of the panic-agoraphobic spectrum model are discussed below.

Although Parkinson's disease is defined by its motor symptoms, the symptoms that are most devastating to patients and caregivers are dementia and psychosis. In addition, sleep has a tremendous impact on patient well being and quality of life. Eighty percent to 90% of Parkinson's disease patients have a sleep disorder affecting their ability to fall asleep, ability to stay asleep, dreams, motor activity during sleep, post-sleep behavior, or day-time somnolence. Treatment plans for patients with Parkinson's disease who experience sleep disorders aim to improve nighttime sleep or daytime wakefulness, and treatment options vary by sleep disorder.

Jealousy is a complex emotion characterized by the perception of a threat of loss of something that the person values, particularly in reference to a relationship with a loved one, which includes affective, cognitive, and behavioral components. Neural systems and cognitive processes underlying jealousy are relatively unclear, and only a few neuroimaging studies have investigated them. The current article discusses recent empirical findings on delusional jealousy, which is the most severe form of this feeling, in neurodegenerative diseases. After reviewing empirical findings on neurological and psychiatric disorders with delusional jealousy, and after considering its high prevalence in patients with Parkinson's disease under dopamine agonist treatment, we propose a core neural network and core cognitive processes at the basis of (delusional) jealousy, characterizing this symptom as possible endophenotype. In any case, empirical investigation of the neural bases of jealousy is just beginning, and further studies are strongly needed to elucidate the biological roots of this complex emotion.

This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Psychopathic individuals account for substantial predatory and impulsive violence. To the present, the principal intervention used to decrease the harm inflicted by psychopaths has been confinement. Nevertheless, most confined psychopathic persons return to the community. Recent advances in the understanding of the neurobiology of psychopathy hold promise for new research directions and more effective treatments. In this article, we will explore recent advances in genetics, electrophysiology, brain imaging, and psychopharmacology, as well as, in brief, their implications for new directions in research and treatment.

This paper critically examines the literature on face recognition in autism, including a discussion of the neural correlates of this ability. The authors begin by selectively reviewing the behavioral and cognitive neuroscience research on whether faces are represented by a “special” behavioral and neural system—one distinct from object processing. The authors then offer a neuroconstructivist model that attempts to account for the robust finding that certain regions in the inferior temporal cortex are recruited in the service of face recognition. This is followed by a review of the evidence supporting the view that face recognition is atypical in individuals with autism. This face-recognition deficit may indicate a continued risk for the further development of social impairments. The authors conclude by speculating on the role of experience in contributing to this atypical developmental pattern and its implications for normal development of face processing.

Serotonin (5-hydroxytryptamine, 5-HT) has long been suspected to play a role in the etiology of depression, and modern neurochemical techniques have confirmed this suspicion. Furthermore, all drugs known to be selective (a relative term) serotonin transporter (SERT) inhibitors are effective antidepressants. Of the selective serotonin reuptake inhibitors (SSRIs) approved in a number of countries for use in depression, panic disorder, and obsessive-compulsive disorder, citalopram is the most selective. Citalopram has been used worldwide to treat an estimated 35 million patients, with an excellent safety record. Citalopram is a racemic drug, and its effects on serotonin transport are thought to reside in the S-enantiomer, known as (S)-citalopram or escitalopram. Escitalopram is the most selective SSRI yet developed. Its receptor binding properties and activity in preclinical animal models of depression predict that escitalopram would be effective in the treatment of depression, with approximately twice the potency of the racemate. The pivotal clinical trials of escitalopram not only support this conclusion, but also suggest escitalopram possesses advantages over citalopram in terms of both efficacy and safety. In conclusion, escitalopram is a promising candidate for use as a first-line antidepressant.

Introduction: A wealth of evidence indicates that neurocognitive deficits are evident in patients with schizophrenia at both illness onset and after many years of treatment. Little is known regarding if or how these deficits change during the lifespan. The goal of the study was to evaluate changes in full-scale intelligence quotient and neurocognitive test performance over a 10-year interval in patients with schizophrenia.

Methods: Twelve patients were administered the Wechsler Adult Intelligence Scale-Revised as a measure of intellectual function and a neuropsycshological test battery including measures of attention, verbal and nonverbal memory, language, visuospatial function, problem-solving, and motor function at entry to the study and at a 10-year follow-up.

Results: With the exception of performance on a measure of speeded motor sequencing, there was no significant decline in any of the measures at 10-year follow-up. Results from a measure of sustained auditory attention showed improvement at follow-up.

Discussion: These data support a neurodevelopmental model of schizophrenia for young adult to middle-age patients by suggesting that neurocognitive deficits that emerge either before disease onset or early in the course of the illness remain stable as the patient ages.

Conclusion: Overall, measures of intelligence quotient as well as specific neurocognitive skills, do not decline over a 10-year period in at least a subgroup of patients with schizophrenia.

Hyperprolactinemia is increasingly prevalent in patients with common psychiatric disorders due to increasing prescriptions of antipsychotics, particularly newer atypical neuroleptics, in these patients. However, measurement of prolactin levels is indicated only in symptomatic patients. When hyperprolactinemia is diagnosed, work-up should include exclusion of other causes of hyperprolactinemia, particularly those that might require treatment. Once such causes have been ruled out, a minority of patients with antipsychotic medication-induced hyperprolactinemia, including those with clinically significant signs and symptoms, will require treatment. When treatment is indicated, specifically when hyperprolactinemia results in amenorrhea in women or testosterone deficiency in men, dopamine agonist therapy is generally not advisable. Hormone-replacement therapy, which involves estrogen/progestogen in women and testosterone in men, can often prevent modification and interruption of successful psychiatric medication regimens.

Chronic aggression and violence in schizophrenia are rare, but receive disproportionate negative media coverage. This contributes to the stigma of mental illness and reduces accessibility to mental health services. Substance Use Disorders (SUD), antisocial behavior, non-adherence and recidivism are known risk factors for violence. Treatment with antipsychotic medication can reduce violence. Aside from clozapine, long-acting injectable antipsychotics (LAI) appear to be superior to oral antipsychotics for preventing violence, addressing adherence and recidivism. LAI also facilitate the implementation of functional skills training. For the high-risk recidivist target population with schizophrenia, better life skills have the potential to also reduce the risk for contact with the legal system, including an improved ability to live independently in supported environments and interact appropriately with others. High-risk patients who are resistant to treatment with other antipsychotics should receive treatment with clozapine due to its direct positive effects on impulsive violence, along with a reduction in comorbid risk factors such as SUDs.

We tested 28 individuals with schizophrenia (SZ) and 16 healthy individuals on a test of logical reasoning and “cognitive gating,” defined as the ability to discriminate between relevant and irrelevant information in confirming or disconfirming a given belief. The Logical Reasoning and Cognitive Gating Task tests both processes under neutral and affect-laden conditions. This is done by presenting formally identical constructs using benign and emotionally arousing language. When separated by symptom profiles, we found statistically significant differences for performance and arousal response between patients with delusions, patients with formal thought disorder, and patients with neither delusions nor formal thought disorder, as well as between patients and healthy controls. When analyzed by error type, we found that nearly all errors by delusional patients were caused by overly restrictive information choice, a pattern that may be related to a delusional patient's tendency to “jump to conclusions” on Bayesian probabilistic tasks. This is in contrast to patients with formal thought disorder, whose low performance resulted also from overly extensive information choice. The tendencies towards restriction were exacerbated by arousal, which is consistent with studies on cognition and arousal in healthy individuals. After briefly examining research on emotional arousal and SZ, and the interaction between emotional arousal and restriction of perceptual cues in healthy individuals, we conclude by suggesting a model which accounts for the distinctive cognitive characteristics of delusional patients by their possessing distinct vulnerabilities to emotional arousal. Specifically, these results suggest the possibility that delusional patients process information in a manner that is essentially intact. However, delusional patients may possess an acute vulnerability to emotional arousal that might cause delusional individuals to behave cognitively as if they were healthy individuals under significantly more severe forms of stress.

Cognitive impairment in schizophrenia is present in almost all persons with the disorder and can be a substantial obstacle to efforts in the recovery process. In clinical research, cognition is assessed through neuropsychological testing as well as by different types of structured instruments focusing on function. Although nonpharmacological interventions such as cognitive remediation have been therapeutic, particularly in combination with vocational rehabilitation and supported employment, these modalities are not always easy to access. Pharmacological interventions are in development and have principally focused on the dopamine, glutamate, and acetylcholine neurotransmitter systems, aiming to target the dorsolateral prefrontal cortex and its interactions with other brain regions.

Alzheimer's disease (AD) is an urgent public health challenge that is rapidly approaching epidemic proportions. New therapies that defer or prevent the onset, delay the decline, or improve the symptoms are urgently needed. All phase 3 drug development programs for disease-modifying agents have failed thus far. New approaches to drug development are needed. Translational neuroscience focuses on the linkages between basic neuroscience and the development of new diagnostic and therapeutic products that will improve the lives of patients or prevent the occurrence of brain disorders. Translational neuroscience includes new preclinical models that may better predict human efficacy and safety, improved clinical trial designs and outcomes that will accelerate drug development, and the use of biomarkers to more rapidly provide information regarding the effects of drugs on the underlying disease biology. Early translational research is complemented by later stage translational approaches regarding how best to use evidence to impact clinical practice and to assess the influence of new treatments on the public health. Funding of translational research is evolving with an increased emphasis on academic and NIH involvement in drug development. Translational neuroscience provides a framework for advancing development of new therapies for AD patients.