Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neonatal lupus is a model of passively acquired autoimmunity whereby anti-SSA/Ro-SSB/La antibodies target the fetal heart and neonatal skin in a minority of cases. Since neuro-psychiatric impairment has been reported in humans and mice exposed prenatally to a variety of maternal autoantibodies including anti-Ro/La, this study was initiated to evaluate the potential neurotoxic effects of these specific autoantibodies and the overall frequency of autoimmune diseases, general health, and somatic growth of children with neonatal lupus and their unaffected siblings. In addition to the general health questionnaires maintained on family members enrolled in the Research Registry for Neonatal Lupus (RRNL), specific questionnaires related to neuro-psychiatric development were sent to all mothers whose children (both affected and unaffected) were older than 5 years of age. Controls consisted of healthy friends. Of 121 anti-Ro exposed children meeting the inclusion criteria, information was returned on 104 (33 cardiac manifestations of neonatal lupus, 20 rash, and 51 unaffected siblings) and 22 of the friend controls. The mean age of all of the children was 14.5 years (range 5-39). In total, 42 (40%) of the 104 anti-Ro exposed children were reported to have a neuro-psychiatric disorder, compared with 6 (27%) of the friend controls (p = 0.34). For 8 (24%) of the congenital heart block (CHB) children (6 boys, 2 girls) the mothers reported attention problems. Four, all boys, were on stimulants. Of the rash children, 4 (20%) (2 boys, 2 girls) had attention problems with one boy on Ritalin. Of the unaffected siblings, 9 (18%) (8 boys and 1 girl) had attention problems with 3 boys on stimulants. One (5%) of the control children (a girl) had attention problems, not requiring therapy. There was no statistical difference in attention problems between the groups (p = 0.120). Behavioral problems were present in all groups with no statistical differences noted. The prevalence of depression, anxiety, developmental delays, learning, hearing, and speech problems were not significantly different between groups. In the CHB children, one boy has nephrotic syndrome and one girl has psoriasis. In the rash children, one girl has juvenile rheumatoid arthritis. In the unaffected group there are five children with autoimmune diseases, two with inflammatory bowel diseases (one boy and one girl), one boy has a spondyloarthropathy, one girl has alopecia areata and one young woman has Antiphospholipid syndrome. In the control group one boy has Henoch Schonlein purpura. There were four cases of hypothyroidism, possibly secondary to Hashimoto's thyroiditis, three in boys with CHB and one in a girl with rash. None of the unaffected siblings or controls had hypothyroidism. Parental reporting of neuro-psychiatric abnormalities was high in anti-Ro exposed children regardless of the neonatal lupus manifestation. However, medication use was limited and although the frequency of this reporting was greater than friend controls, it did not reach significance.
 ...
PMID:Frequency of neuro-psychiatric dysfunction in anti-SSA/SSB exposed children with and without neonatal lupus. 2000 45

The psychostimulant methylphenidate (Ritalin) is used in conjunction with selective serotonin reuptake inhibitors (SSRIs) in the treatment of medical conditions such as attention-deficit hyperactivity disorder with anxiety/depression comorbidity and major depression. Co-exposure also occurs in patients on SSRIs who use psychostimulant 'cognitive enhancers'. Methylphenidate is a dopamine/norepinephrine reuptake inhibitor that produces altered gene expression in the forebrain; these effects partly mimic gene regulation by cocaine (dopamine/norepinephrine/serotonin reuptake inhibitor). We investigated whether the addition of SSRIs (fluoxetine or citalopram; 5 mg/kg) modified gene regulation by methylphenidate (2-5 mg/kg) in the striatum and cortex of adolescent rats. Our results show that SSRIs potentiate methylphenidate-induced expression of the transcription factor genes zif268 and c-fos in the striatum, rendering these molecular changes more cocaine-like. Present throughout most of the striatum, this potentiation was most robust in its sensorimotor parts. The methylphenidate + SSRI combination also enhanced behavioral stereotypies, consistent with dysfunction in sensorimotor striatal circuits. In so far as such gene regulation is implicated in psychostimulant addiction, our findings suggest that SSRIs may enhance the addiction potential of methylphenidate.
 ...
PMID:Selective serotonin reuptake inhibitor antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum. 2070 93

Methylphenidate (Ritalin, MPH) is the most commonly prescribed psychoactive drug for children. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, its cellular mechanisms of action and potential long-term effects are poorly understood. We recently reported that a clinically relevant (1 mg/kg i.p., single injection) dose of MPH significantly decreased neuronal excitability in the juvenile rat prefrontal cortical neurons. Here we further explore the actions of acute treatment with MPH on the level of NMDA receptor subunits and NMDA receptor-mediated short- and long-term synaptic plasticity in the juvenile rat prefrontal cortical neurons. We found that a single dose of MPH treatment (1 mg/kg, intraperitoneal) significantly decreased the surface and total protein levels of NMDA receptor subunits NR1 and NR2B, but not NR2A, in the juvenile prefrontal cortex. In addition, the amplitude, decay time and charge transfer of NMDA receptor-mediated EPSCs were significantly decreased whereas the amplitude and short-term depression of AMPA receptor-mediated EPSCs were significantly increased in the prefrontal neurons. Furthermore, MPH treatment also significantly increased the probability and magnitude of LTP induction, but had only a small effect on LTD induction in juvenile rat prefrontal cortical neurons. Our data thus present a novel mechanism of action of MPH, i.e., changes in glutamatergic receptor-mediated synaptic plasticity following early-life treatment. Furthermore, since a single dosage resulted in significant changes in NMDA receptors, off-label usage by healthy individuals, especially children and adolescents, may result in altered potential for plastic learning.
 ...
PMID:Treatment with a clinically-relevant dose of methylphenidate alters NMDA receptor composition and synaptic plasticity in the juvenile rat prefrontal cortex. 2333 2

Albert Hoffman suggested that low doses of LSD might be an appropriate alternative to Ritalin. Following this possibility, a systematic exploration of the effects of "microdoses," comprising hundreds of lengthy descriptive reports, was undertaken. Based on these reports, using a psychedelic in the microdose range (10 micrograms) every three days was determined to be safe across a wide variety of individuals and conditions. Over 18 months, more than a thousand individuals from 59 countries did a daily evaluation of negative and positive emotional state using the PANAS checklist plus written reports for between one week and four months. Participant reports suggested that spaced but repeated microdoses were followed by improvements in negative moods, especially depression, and increases in positive moods. Increased energy, improved work effectiveness, and improved health habits were observed in clinical and non-clinical populations. Smaller samples described alleviation of symptoms in migraine headaches, pre-menstrual syndromes, traumatic brain injury, shingles, and other conditions not previously associated with psychedelic use.
 ...
PMID:Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. 3092 50


<< Previous 1 2