Adolf Meyer (1866-1950) did not see schizophrenia as a discrete disorder with a specific etiology but, rather, as a reaction to a wide variety of biopsychosocial factors. He may have been right. Today, we have evidence that gene mutations, brain injury, drug use (cocaine, amphetamine, marijuana, phencyclidine, and steroids), prenatal infection and malnutrition, social isolation and marginalizat...

Patients with schizophrenia are more likely than the general population to develop diabetes, which contributes to a high risk of cardiovascular complications; individuals with schizophrenia are two to three times more likely to die from cardiovascular disease than the general population. The risk of diabetes, and hence cardiovascular disease, is particularly increased by some of the new atypica...

Prepulse inhibition (PPI) of acoustic startle response is impaired in patients with schizophrenia and in animals acutely treated with dopamine agonists and NMDA antagonists. In this study, we investigated the time course of PPI disruption induced by repeated amphetamine, quinpirole, phencyclidine (PCP), and dizocilpine (MK-801) treatment. We focused on how PPI disruption development was influen...

A disruption of dopaminergic transmission in the amygdala of subjects with schizophrenia was proposed as a main contributor to pathophysiological and clinical manifestations of this disorder. We tested the hypothesis that the expression of the dopamine transporter (DAT) is decreased in the amygdala of subjects with schizophrenia. In normal control, schizophrenic subjects and bipolar disorder su...

Clinical Utility Dopamine, a key neurotransmitter that controls cognition, emotion, locomotor activity, and other endocrine functions, exerts its action by binding to five different receptors, including the dopamine D2 receptor (DRD2). Dysregulation of dopaminergic signal transmission is found in many pathological conditions such as Parkinson's disease and schizophrenia, and compounds that act ...

The dopamine hypothesis of schizophrenia and psychosis originated from observations of the dopamine-blocking actions of early neuroleptic drugs. These results support the dopamine hypothesis, however, only on the assumption that the drugs act by reversing an underlying disease mechanism (or part of it). An alternative explanation is that the drugs work by inducing a state of neurological suppre...

The pharmacologic management of schizophrenia has dramatically improved over the past 50 years. While the first-generation, or conventional, antipsychotic medications were found to be helpful in reducing the positive symptoms of the disorder, they had little effect on negative and cognitive symptoms. Additionally, the first-generation agents were associated with the troubling neurologic side ef...

Individuals with schizophrenia are often treated with medications that block dopamine (DA) neurotransmission. Chronic administration of many DA antagonists alters dopaminergic function, causing a supersensitivity to DA agonists. Because the DA agonist properties of cocaine seem to be involved in its behavioral effects, chronic DA antagonist treatments may enhance these effects of cocaine. This ...

“Breakthrough” of psychosis despite good compliance antipsychotics medication for a long time is major obstacle to the treatment schizophrenia, whether mechanism caused by dopamine hypersensitivity or insufficient dose antipsychotics. Researchers advocating “Dopamine Supersensitivity Psychosis” (DSP) emphasize avoid excessive inhibition 2 receptors from beginning treatment. On other hand, resea...

SIGNIFICANCE Schizophrenia is a complex neuropsychiatric disorder affecting around 1% of the population worldwide. Its mode of inheritance suggests a multigenic neurodevelopmental disorder with symptoms appearing during late adolescence/early adulthood, with its onset strongly influenced by environmental stimuli. Many neurotransmitter systems, including dopamine, glutamate, and gamma-aminobutyr...