Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

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Biological insights from 108 schizophrenia-associated genetic loci

background The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. methods A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. results Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. conclusions The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.

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Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia

Dementia prevention, intervention, and care

Objective: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of ≤5 on the Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR 16 ) (equivalent to ≤7 on the 17-item Hamilton Rating Scale for Depression [HRSD 17 ]) defined remission; a QIDS-SR 16 total score of ≥11 (HRSD 17 ≥14) defined relapse. Results: The QIDS-SR 16 remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, t...

https://ajp.psychiatryonline.org/doi/pdf/10.1176/ajp.2006.163.11.1905

Acute and Longer- Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report

Although several psychological theories predict that members of stigmatized groups should have low global self-esteem, empirical research typically does not support this prediction. It is proposed here that this discrepancy may be explained by considering the ways in which membership in a stigmatized group may protect the self-concept It is proposed that members of stigmatized groups may (a) attribute negative feedback to prejudice against their group, (b) compare their outcomes with those of the ingroup, rather than with the relatively advantaged outgroup, and (c) selectively devalue those dimensions on which their group fares poorly and value those dimensions on which their group excels. Evidence for each of these processes and their consequences for self-esteem and motivation is reviewed. Factors that moderate the use of these strategies and implications of this analysis for treatment of stigmas are also discussed. For more than three decades, social psychological research on prejudice, stereotyping, and discrimination has examined both the content of stereotypes about a variety of social groups

Social stigma and self-esteem: The self-protective properties of stigma.

The objective of the present study was to examine the relationship between serum folate, vitamin B12, and homocysteine levels and the timing of clinical improvement to fluoxetine in major depressive disorder (MDD) patients A total of 110 outpatients with MDD who responded to an 8-wk trial of fluoxetine had serum folate, B12, and homocysteine measurements at baseline (prior to fluoxetine initiation) Onset of clinical improvement was defined as a 30% decrease in Hamilton Depression Scale scores that led to a 50% decrease by week 8 Patients with low folate levels ( 005) In conclusion, low serum folate levels were found to be associated with a delayed onset of clinical improvement during treatment with fluoxetine in MDD by, on average, 15 wk

/pdf/the-relationship-between-serum-folate-vitamin-b12-and-3zk6omsus5.pdf

The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine

With the aging of most Western populations, there is growing research attention to the social and behavioral aspects of age-related chronic diseases and disabilities. Research is just beginning to focus on how families and other social supports affect and are affected by Alzheimer's Disease and related disorders. This article reviews the current state of knowledge in this area and suggests a future research agenda.

Families, informal supports, and Alzheimer's disease: Current research and future agendas.

Clinical correlates of the worsening or emergence of suicidal ideation during SSRI treatment of depression: an examination of citalopram in the STAR*D study.

Socialization to Old Age

Publisher Summary Like aging, mental health is a multifaceted concept that refers more clearly to a field of research and clinical activity than to a unitary theoretical entity. Mental health phenomena emerge from the interplay of multiple contributing subsystems and require multisystemic thinking to be understood. The chapter discusses some concepts in mental health and aging. There are five major themes that combine to create a unique characterization of the subject matter of mental health and aging. These are the gerontological revolution, the geriatric revolution, senescence or normal processes of development and change in biological, psychological, cognitive, and behavioral systems, and comorbidity of physical illness and mental disorder. Each of these features combines with the well-established heterogeneity of the population by age, gender, race, and ethnicity to complete the overall background prospective on the area of aging and mental health. These five characteristics combine to influence the presentation, course, response to treatment, and outcome of major mental disorders and combine as well to influence psychological development and the promotion of positive mental health. The chapter further discusses the issues in mental health and aging. Each of these issues is a piece of the overall picture, and even a brief overview shows the interlocking nature of the concerns.

Barry D. Lebowitz

Papers

The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine

Families, informal supports, and Alzheimer's disease: Current research and future agendas.

Clinical correlates of the worsening or emergence of suicidal ideation during SSRI treatment of depression: an examination of citalopram in the STAR*D study.

Socialization to Old Age

Concepts and Issues in Mental Health and Aging