Accurate comparisons of the prevalence of psychiatric disorders across Eastern and Western cultures are difficult and limited by methodological problems. Nevertheless, using standardized diagnostic and evaluation techniques, recent surveys have suggested that depression and anxiety disorders exist in all countries and cultures examined thus far, although variations in the prevalence rates and symptomatology may exist. This article discusses the influence and impact that culture can have on recognizing and treating mood and anxiety disorders, with a particular focus on Japan. Over the last 20 years, studies have consistently reported an increase in mental illness in Japan, especially symptoms of depression and anxiety. While such symptoms have had an adaptive cultural role in the past, current social and economic changes in Japan have turned any adaptive advantage into a potentially significant disadvantage, with a major impact on the capacity of individuals to function adequately. The situation is compounded by the fact that Japanese patients are reluctant to openly discuss disturbances of mood, since these are considered to be indicative of personal weakness rather than treatable medical conditions. Reluctance to discuss personal mental health hinders timely recognition and appropriate treatment.

Clinical experience and systematic inquiry demonstrate that many patients with mood and anxiety disorders remain symptomatic despite standard interventions. These observations have prompted the search for alternative pharmacotherapeutic treatment options. Anticonvulsants, including valproic acid and carbamazepine, have demonstrated benefit for a number of psychiatric conditions. Recently, clinical and research attention has focused on the use of the new anticonvulsants gabapentin and lamotrigine as alternatives to standard pharmacotherapies for the treatment of mood and anxiety disorders. This paper reviews the experience to date with these agents in the treatment of psychiatric conditions. Gabapentin demonstrates promise for the treatment of panic and generalized anxiety, while both gabapentin and lamotrigine appear useful as mood stabilizers in the treatment of bipolar disorder.

How can functional neuroimaging be applied to clinical neurology and psychiatry? This article reviews selected contributions of functional neuroimaging to the clinical neurosciences. We review selected technical aspects of positron emission tomography, single photon emission tomography, and functional magnetic resonance imaging with a focus on the relative strengths and weaknesses of these techniques. Consumers of functional neuroimaging research are encouraged to consider the limitations of imaging techniques and theoretical pitfalls of cognitive task design when interpreting results of functional imaging studies. Then, we selectively review the contributions of functional neuroimaging to neurology and psychiatry, including the areas of epilepsy, stroke, chronic pain, schizophrenia, depression, and obsessive-compulsive disorder. Future directions of functional neuroimaging research are offered, with the emphasis that the best conclusions are informed by a convergence of research from functional neuroimaging, neurophysiological, and lesion studies.

Emerging therapies for Alzheimer's disease offer hope to patients and their caregivers. Future treatments will probably include combination approaches with agents that modify amyloid processing, deposition, and clearance. One example, the AD vaccine, reduced amyloid burden and changed behavior in animal models of AD, but the human trial was halted when several subjects developed brain inflammation. Anti-inflammatory agents have epidemiologic support, but clinical trials have been disappointing, possibly related to inadequate study with anti-inflammatory agents that modify amyloid processing. Agents that target known cardiovascular risk factors, such as hypercholesterolemia, hypertension, and insulin resistance, have epidemiologic, preclinical, and clinical evidence to warrant further investigation. Heavymetal chelators, antioxidants, neurotrophic factors, glutaminergic modulators, and agents that modify hyper-phosphorylation of Tau are other approaches in research and development.

Past research has established that traditional neuroleptic treatment improves attentional functioning in schizophrenic (SZ) patients. The present investigation expands on this finding by examining attentional improvement in nine acute SZ patients treated with either the novel neuroleptic ziprasidone or aripiprazole over a 4-week inpatient period. Twelve SZ in patients receiving typical neuroleptic treatment over the same time period served as controls. The results revealed that while all patients showed marked attentional improvement from medication-free baseline to week 4 of treatment, the SZ patients who received novel antipsychotics showed significant improvement on immediate recall and reaction time measures. These results suggest that novel neuroleptic treatment, perhaps through preferential activation of the prefrontal cortical pathways, improves SZ patients' information processing speed and efficiency.

The need for long-term management of bipolar disorder is evident. Bipolar patients spend more time depressed than manic; however, few agents used for maintenance therapy of bipolar disorder have demonstrated good efficacy in delaying relapse into depression. This article provides a comprehensive review of open-label and randomized, controlled studies examining prophylactic efficacy in bipolar disorder, especially bipolar depression. Lithium, considered the gold standard for bipolar disorder maintenance therapy may be more effective in delaying manic relapse than in delaying depressive relapse. Evidence for the efficacy of divalproex and carbamazepine in delaying depressive relapse is yet to be fully elucidated. Lamotrigine has demonstrated efficacy in delaying time to depressive relapse. Unpublished studies show ohnzapine's efficacy in preventing manic recurrence, while its efficacy in preventing depressive recunence is yet to be proven. As patients with bipohr disorder are prone to experiencing depressive episodes, more attention needs to be focused on preventing depressive relapse. To date, three agents—lithium, lamotrigine, and olanzapine—have been shown to have prophylactic benefits in treating this highly recunent disorder.

Anticonvulsants are being used clinically as monotherapy and adjuncts in mental illnesses other than affective disorders. This review focuses on the literature for anticonvulsants and lithium in substance use disorders, anxiety disorders, and schizophrenia. Given the abuse potential and other difficulties with prescribing benzodiazepines for alcohol and benzodiazepine withdrawal, anticonvulsants have been considered as an alternative. Promising therapeutic effects have been demonstrated in many of the anxiety disorders, with the greatest number of trials and positive results in posttraumatic stress disorder. Although anticonvulsant and lithium augmentation for schizophrenia is common in practice and has been studied in double-blind, randomized, controlled trials, the sum of the evidence has been inconclusive.

Genetic study holds potential for understanding the etiology of a number of serious psychiatric disorders. In the case of obsessive-compulsive disorder (OCD), many investigators agree that there is a strong genetic component to its development. In this article, we review the scientific evidence gleaned from different types of studies that has led to a better understanding of the nature of the inherited factors in OCD.

Subjective cognitive complaints of women exposed to intimate partner violence (IPV) and nonabused women were examined using the Cognitive Difficulties Scale (CDS). Cognitive complaints were compared among victims of IPV with a lifetime diagnosis of posttraumatic stress disorder (PTSD) (PTSD+; n=20), victims of IPV without lifetime PTSD (PTSD-; n=21), and a nonabused comparison group (n=22). The results indicated that both the PTSD+ and PTSD- groups had significantly higher levels of self-perceived cognitive difficulties than nonabused women. Furthermore, PTSD symptom severity was found to be positively correlated with self-perceived cognitive difficulties (r=.47). Further research is needed to determine whether cognitive complaints are associated with exposure to IPV, with the subsequent development of PTSD, or with other not yet understood factors. Furthermore, additional work is needed to resolve whether cognitive complaints are accompanied by objective evidence of cognitive dysfunction in victims of IPV.

The prevalence of Alzheimer's disease (AD) and dementia continues to rise. However, a significant number of patients are undiagnosed or untreated. Given the complexities of detecting cognitive impairment and the early signs of AD, this review discusses how advances in brain imaging can help assist in improving overall management. Imaging techniques and surrogate markers may provide unique opportunities to diagnose accurately AD in presymptomatic stages with practical consequences for patients, caregivers, and physicians. The possible outcomes for using imaging and surrogate markers as adjuncts to clinical examination and as screening tools for AD, as well as tangible and intangible advantages to early diagnosis and treatment, will be discussed. The specific value of using advanced serial imaging in patients with a genetic disposition to AD will be evaluated. If neurons can be protected from neurodegenerative damage in early stages, this may preserve patient cognition, function, and quality of life, and may confer considerable societal healthcare benefits.

Co-occurring psychiatric and alcohol use disorders can have devastating personal and societal effects, yet little evidence exists to guide clinical treatment. In the face of scant data, individual practitioners must rely instead on professional experience and those limited practice guidelines that currently exist. The American Psychiatric Association (APA) advises that failure to treat a concurrent psychiatric disorder reduces the likelihood that the treatment for a substance use disorder (SUD) will be effective. Indeed, the effects of nontreatment were demonstrated in a prospective study assessing alcohol-dependent patients for 1 year following hospitalization for alcohol dependence, in which untreated depression was directly associated with a shorter time to first drink. The results also showed that among those patients with depression (Slide 1), taking antidepressants at the time of discharge increased the likelihood of an individual remaining abstinent during the follow-up period.

The inconsistency in linkage results that has bedeviled psychiatric genetics has been observed to occur regularly in common diseases with complex inheritance. Nonetheless, in two such instances—noninsulin-dependent diabetes mellitus (NIDDM) and inflammatory bowel disease (IBD)—susceptibility genes have been discovered based on the follow-ups of linkage findings. In bipolar illness disorder (BPD) and schizophrenia (SZ), there are some linkage reports with replication of other studies similar to the situation in NIDDM and IBD before the successful positional cloning efforts. Two of the regions with linkage reports, BPD and SZ, on the long arms of chromosomes 13 and 22, show linkage to the same markers in both diseases. This lends some plausibility to the hypothesis of some shared genetic predispositions for both disorders. Cytogenetic evidence offers another positional approach to susceptibility genes. The velocardiofacial syndrome is associated with deletions very close to the linkage region on chromosome 22, and with psychiatric manifestations of both BPD and SZ. Endophenotypes ofSZ, previously demonstrated to be heritable, have been found to have chromosomal linkage in at least one study. These include eye-tracking abnormalities linked to 6p, and an abnormality of the P50 cortical evoked potential linked to chromosome 15. Variants in specific genes have been associated with susceptibility to the psychiatric illnesses. These genetic findings may contribute to etiologic subcategorization of BPD and SZ, and the development of new treatment approaches. A table of genetic terms is included for review.

Augmentation strategies have become popular in patients with a partial response or residual symptoms. In a survey conducted by the American Society of Consultant Pharmacists, 65% of 169 psychiatrists indicated that they would augment treatment as the next step in a partial responder in contrast to non-responders in whom they would switch to another drug (J.C. Nelson, unpublished data). This decision is based on common sense and practicality rather than empirical evidence. Many clinicians and patients think that if a patient achieves at least a partial response to a medication, it makes sense to continue that drug and add a second. To some extent, the patient preferences for treatment shown in the Systematic Treatment Alternatives to Relieve Depression (STAR*D) study reflect this approach. This discussion will update clinicians on the use of augmentation agents for the treatment of major depressive disorder (MDD).

Lithium augmentation has been used since it was first described by de Montigny and colleagues in 1981. This strategy is based on a rational neurochemical hypothesis that lithium has a synergistic effect when added to a tricyclic antidepressant (TCA). Lithium increases serotonin turnover and the TCA increases postsynaptic serotonin receptor sensitivity. Recent debates have focused on whether lithium is as effective combined with selective serotonin reuptake inhibitors (SSRIs) as it is combined with a TCA. The rapid effects sometimes observed with lithium augmentation of TCAs does not seem to occur with SSRIs, conceivably because SSRIs do not increase postsynaptic serotonin receptor sensitivity.