Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intraindividual variability (IIV) reflects lawful but transient within-person changes in performance. Increased IIV in cognition shares systematic associations with numerous conditions characterized by alterations in dopamine (DA) neuromodulation (e.g., old age, ADHD, schizophrenia, and Parkinson's disease). In a group of normal middle-aged adults, we examined links between PET-derived measures of D2 receptor binding in striatum, orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus (HC) and IIV for tasks assessing recognition memory and executive functioning. An index of IIV, the intraindividual standard deviation (ISD), was computed across successful response latency trials for each cognitive outcome. Lower D2 binding in OC, ACC, and HC, but not striatum, was associated with increasing ISDs for the memory and executive measures. Consistent with neurocomputational models, the present findings suggest a role for extrastriatal DA neurotransmission in modulating variability in cognitive functioning.
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PMID:Extrastriatal dopamine D2 receptor binding modulates intraindividual variability in episodic recognition and executive functioning. 1952 93

Serotonin (5-HT) is involved in many developmental processes and influences behaviors including anxiety, aggression, and cognition. Disruption of the serotonergic system has been implicated in human disorders including autism, depression, schizophrenia, and ADHD. Although pharmacological, neurotoxin, and dietary manipulation of 5-HT and tryptophan hydroxylase has added to our understanding of the serotonergic system, the results are complicated by multiple factors. A newly identified ETS domain transcription factor, Pet-1, has direct control of major aspects of 5-HT neuronal development. Pet-1 is the only known factor that is restricted in the brain to 5-HT neurons during development and adulthood and exerts dominant control over 5-HT neuronal phenotype. Disruption of Pet-1 produces an approximately 80% loss of 5-HT neurons and content and results in increased aggression in male Pet-1(-/-) mice [Hendricks TJ, Fyodorov DV, Wegman LJ, Lelutiu NB, Pehek EA, Yamamoto B, Silver J, Weeber EJ, Sweatt JD, Deneris ES (2003) Neuron 37:233-247]. We hypothesized that Pet-1(-/-) mice would also exhibit changes in anxiety and cognition. Pet-1(-/-) mice were hypoactive which may have affected the observed lack of anxious behavior in the elevated zero maze and light-dark test. Pet-1(-/-) mice, however, were more defensive during marble burying and showed acoustic startle hyper-reactivity. No deficits in spatial, egocentric, or novel object recognition learning were found in Pet-1(-/-) mice. These findings were unexpected given that 5-HT depleting drugs given to adult or developing animals result in learning deficits [Mazer C, Muneyyirci J, Taheny K, Raio N, Borella A, Whitaker-Azmitia P (1997) Brain Res 760:68-73; Morford LL, Inman-Wood SL, Gudelsky GA, Williams MT, Vorhees CV (2002) Eur J Neurosci 16:491-500; Vorhees CV, Schaefer TL, Williams MT (2007) Synapse 61:488-499]. Lack of differences may be the result of compensatory mechanisms in reaction to a constitutive knock out of Pet-1 or 5-HT may not be as important in learning and memory as previously suspected.
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PMID:Mouse plasmacytoma-expressed transcript 1 knock out induced 5-HT disruption results in a lack of cognitive deficits and an anxiety phenotype complicated by hypoactivity and defensiveness. 1978 75

ADHD (Attention Deficit Hyperactivity Disorder) has a complex, heterogeneous phenotype only partially captured by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. In this report, latent class analyses (LCA) are used to identify ADHD phenotypes using K-SADS-IVR (Schedule for Affective Disorders & Schizophrenia for School Age Children-IV-Revised) symptoms and symptom severity data from a clinical sample of 500 ADHD subjects, ages 6-18, participating in an ADHD genetic study. Results show that LCA identified six separate ADHD clusters, some corresponding to specific DSM-IV subtypes while others included several subtypes. DSM-IV comorbid anxiety and mood disorders were generally similar across all clusters, and subjects without comorbidity did not aggregate within any one cluster. Age and gender composition also varied. These results support findings from population-based LCA studies. The six clusters provide additional homogenous groups that can be used to define ADHD phenotypes in genetic association studies. The limited age ranges aggregating in the different clusters may prove to be a particular advantage in genetic studies where candidate gene expression may vary during developmental phases. DSM-IV comorbid mood and anxiety disorders also do not appear to increase cluster heterogeneity; however, longitudinal studies that cover period of risk are needed to support this finding.
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PMID:ADHD latent class clusters: DSM-IV subtypes and comorbidity. 1990 Jul 17

Modafinil is a psychostimulant approved for treating excessive sleepiness in adults; off-label uses (e.g., treatment of cognitive impairment in schizophrenia, ADHD and age-related dementias) are currently being explored. The effects and mechanisms of action of modafinil have not been fully established. In the present study, the effects of modafinil were examined in young adult (7-month-old) and middle-aged (21-22-month-old) rats, using the acoustic startle response (ASR) and prepulse inhibition (PPI). In the control condition, middle-aged rats showed lower activity levels, significantly lower ASR amplitudes and significantly longer ASR latencies compared to young adult rats. The effects of modafinil differed by age: activity levels and ASR amplitudes were significantly increased in middle-aged rats, whereas activity levels were lower and ASR amplitude was significantly decreased in young adult rats. Modafinil did not significantly alter PPI or startle latencies relative to the control condition. Amphetamine, used as a positive control, significantly decreased ASR amplitude in young adult rats and significantly impaired PPI for both age groups. Amphetamine-induced PPI impairment was greater for young adult rats (34% reduction in ASR amplitude) than for middle-aged rats (24% reduction). The results offer new insights into the effects of modafinil and its mechanism of action, and are consistent with the idea that modafinil enhances vigilance and cognitive functioning in individuals with deficits but not in normal, healthy individuals.
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PMID:Age-dependent effects of modafinil on acoustic startle and prepulse inhibition in rats. 1991 96

The histamine H(3) receptor is involved in the central and peripheral regulation of levels of histamine and other neurotransmitters (e.g., acetylcholine, noradrenaline, dopamine, serotonin and GABA), which sets it up as a target in the treatment of various CNS (e.g., depression, schizophrenia, ADHD, dementia, neuropathic pain and sleep disorders), metabolic syndrome (e.g., obesity) and allergic disorders. Novel chemical series from the most recent 2 years of patent literature have been reviewed. While overall structural diversity is moderate, these represent or relate to some of the compounds progressing through clinical trials (e.g., GSK-189254). However, an H(3) receptor drug still has yet to reach the market. Patenting activity is likely to remain high in the near future, bolstered by the commercial promise of potential H(3) receptor drugs.
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PMID:Recent advances in the development of histamine H3 antagonists. 2014 64

In a chart review at a psychiatric out-patient department, latitude 59.3 degrees N, a sample of patients with tests of serum 25-hydroxy-vitamin D (25-OHD) and plasma intact parathyroid hormone (iPTH) was collected, together with demographic data and psychiatric diagnoses. During 19 months, 117 patients were included. Their median 25-OHD was 45 nmol/l; considerably lower than published reports on Swedish healthy populations. Only 14.5% had recommended levels (over 75). In 56.4%, 25-OHD was under 50 nmol/l, which is related to several unfavourable health outcomes. Seasonal variation of 25-OHD was blunted. Patients with ADHD had unexpectedly low iPTH levels. Middle East, South-East Asian or African ethnic origin, being a young male and having a diagnosis of autism spectrum disorder or schizophrenia predicted low 25-OHD levels. Hence, the diagnoses that have been hypothetically linked to developmental (prenatal) vitamin D deficiency, schizophrenia and autism, had the lowest 25-OHD levels in this adult sample, supporting the notion that vitamin D deficiency may not only be a predisposing developmental factor but also relate to the adult patients' psychiatric state. This is further supported by the considerable psychiatric improvement that coincided with vitamin D treatment in some of the patients whose deficiency was treated.
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PMID:Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: relations with season, age, ethnic origin and psychiatric diagnosis. 2021 92

Schizotypy is thought to reflect liability for schizophrenia and involves at least 3 facets: disorganized, positive, and negative. However, it is unclear whether disorganized and positive facets can be discriminated from dissociation. In the current study with college students (N=325), the best-fitting confirmatory factor model included 3 factors: (a) disorganization, (b) positive-dissociation, and (c) negative. In addition, the pattern of associations with the disorganization and the positive-dissociation factors with individual difference variables was very different. Disorganization was associated with (a) poor cognitive estimation and increased ADHD symptoms, (b) increased emotional confusion, and (c) increased neuroticism and decreased conscientiousness. In contrast, the positive-dissociation factor was associated with (a) an increased influence of emotion on thinking, (b) self-reported childhood abuse, and (c) increased openness to experience. Overall, these results suggest that disorganized schizotypy can be discriminated from dissociation but that positive schizotypy may not be easily discriminated from dissociation.
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PMID:Can disorganized and positive schizotypy be discriminated from dissociation? 2054 16

Mental illnesses such as bipolar disorders, ADHD, depression and schizophrenia are a major public health concern worldwide. While several pharmacological agents acting on monoamine neurotransmission are used for the management of these disorders, the ultimate molecular mechanisms responsible for their therapeutic effects and their relationships to disease etiology are still poorly understood. Here we provide an overview of recent advances on the involvement of the signaling molecules Akt and glycogen synthase kinase-3 (GSK3) in the regulation of behavior by the monoamine neurotransmitters dopamine and serotonin (5-HT). We also examine the possible participation of these signaling molecules to the effects of antipsychotics, antidepressant and lithium and their contribution to mental disorders. Regulation of Akt and GSK3 by monoamine neurotransmitters may provide a better understanding of mental illnesses leading to new therapeutic approaches having better efficacy.
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PMID:[Psychotropic drugs and the involvement of the Akt/GSK3 signalling pathway in mental illnesses]. 2061 69

The Psychiatric GWAS Consortium was founded with the aim of conducting statistically rigorous and comprehensive GWAS meta-analyses for five major psychiatric disorders: ADHD, autism, bipolar disorder, major depressive disorder, and schizophrenia. In the era of GWAS and high-throughput genomics, a major trend has been the emergence of collaborative, consortia approaches. Taking advantage of the scale that collaborative consortia approaches can bring to a problem, the PGC has been a major driver in psychiatric genetics and provides a model for how similar approaches may be applied to other disease communities.
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PMID:The psychiatric GWAS consortium: big science comes to psychiatry. 2095 24

PSYCHIATRISTS SHOULD REVISIT THE ISSUE OF HOW TO ASSESS, OBJECTIVELY AND reliably, patients' cognitive status. Cognitive disorders, like ADHD (attention deficit/ hyperactivity disorder), and the various dementias are increasing in importance, and perhaps in number. The modern study of schizophrenia has focused on cognition as an outcome predictor; even the mood disorders can be associated, over time, with cognitive impairment. And with so many perfectly good drug alternatives in every therapeutic category, medications might be differentiated by virtue of their comparative effects on cognition. The best reason, however, is this: in clinical practice, cognitive assessment is either gross and insensitive or arduous and inordinately expensive.
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PMID:Computerized neurocognitive testing and its potential for modern psychiatry. 2119 76


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