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1.
Syst Rev ; 11(1): 44, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35292116

ABSTRACT

BACKGROUND: The hippocampus has for long been known for its ability to form new, declarative memory. However, emerging findings across conditions in the psychosis spectrum also implicate its role in emotional regulation. Systematic reviews have demonstrated consistent volume atrophic changes in the hippocampus. The aim of the systematic review and metanalysis which will follow from this protocol will be to investigate the volume-based neuroimaging findings across each of the subfields of the hippocampus in psychosis independent of diagnosis. METHODS: Volume changes across subfields of the hippocampus in psychotic illnesses will be assessed by systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). MRI neuroimaging studies of patients with a definitive diagnosis of psychosis (including brief pre-diagnostic states) will be included. Studies lacking adequate controls, illicit drug use, medical psychosis, history of other significant psychiatric comorbidities, or emphasis on age groups above 65 or below 16 will be excluded. Subfields investigated will include the CA1, CA2/3, CA4, subiculum, presubiculum, parasubiculum, dentate gyrus, stratum, molecular layer, granular cell layer, entorhinal cortex, and fimbria. Two people will independently screen abstracts from the output of the search to select suitable studies. This will be followed by the two reviewers performing a full-text review of the studies which were selected based on suitable abstracts. One reviewer will independently perform all the data extraction, and another reviewer will then systemically check all the extracted information using the original articles to ensure accuracy. Statistical analysis will be performed using the metafor and meta-packages in R Studio with the application of the random-effects model. DISCUSSION: This study will provide insight into the volumetric changes in psychosis of the subfields of the hippocampus, independent of diagnosis. This may shed light on the intricate neural pathology which encompasses psychosis and will open avenues for further exploration of the structures identified as potential drivers of volume change. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020199558.


Subject(s)
Psychotic Disorders , Hippocampus/diagnostic imaging , Hippocampus/pathology , Humans , Magnetic Resonance Imaging/methods , Meta-Analysis as Topic , Psychotic Disorders/diagnostic imaging , Systematic Reviews as Topic
2.
Schizophr Res ; 215: 378-384, 2020 01.
Article in English | MEDLINE | ID: mdl-31495700

ABSTRACT

Around 1 in 5 children under 13 years old experience sub-clinical psychotic experiences (PEs) like hallucinations and delusions. While PEs in childhood are a significant risk factor for adult psychotic disorders, the majority of those experiencing childhood PEs do not develop a psychotic disorder. Individual differences in regional brain maturation rates may be responsible for this age-related and often transient emergence of PEs. Fronto-temporal association tracts undergo extensive maturation and myelination throughout childhood and adolescence, thus we focus on individual differences in one such tract, the arcuate fasciculus. A normative population-based sample of children (aged 11-13) attended a clinical interview and MRI (n = 100), 25 of whom were identified as reporting strong PEs. This group had reduced mean and radial diffusivity in the arcuate fasciculus compared with a group of matched controls (n = 25) who reported no PEs. The group difference was greater in the left hemisphere than the right. Mediation analyses showed that this group difference was driven predominantly by perceptual disturbances and an along-tract analysis showed that the group difference was greatest approximately halfway between the frontal and temporal termination points of the tract (adjacent to the left lateral ventricle). This study is the first to investigate links between arcuate fasciculus diffusivity and psychotic experiences in a population sample of children.


Subject(s)
Delusions/pathology , Frontal Lobe/pathology , Hallucinations/pathology , Psychotic Disorders/pathology , Temporal Lobe/pathology , White Matter/pathology , Adolescent , Case-Control Studies , Child , Delusions/diagnostic imaging , Delusions/physiopathology , Diffusion Tensor Imaging , Female , Frontal Lobe/diagnostic imaging , Hallucinations/diagnostic imaging , Hallucinations/physiopathology , Humans , Male , Neural Pathways/diagnostic imaging , Neural Pathways/pathology , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/physiopathology , Temporal Lobe/diagnostic imaging , White Matter/diagnostic imaging
3.
Brain Res ; 1125(1): 171-5, 2006 Dec 13.
Article in English | MEDLINE | ID: mdl-17101120

ABSTRACT

Neonatal (postnatal days 8-21) exposure of rats to the selective serotonin reuptake inhibitor (SSRI), citalopram, results in persistent changes in behavior including decreased sexual activity in adult animals. We hypothesized that this effect was a consequence of abnormal stimulation of 5-HT(1A) and/or 5-HT(1B) receptors as a result of increased synaptic availability of serotonin during a critical period of development. We examined whether neonatal exposure to a 5-HT(1A) (8OH-DPAT) or a 5-HT(1B) (CGS 12066B) receptor agonist can mimic the effect of neonatal exposure to citalopram on adult sexual behavior. Results showed that neonatal treatment with 5-HT(1B) receptor agonist robustly impaired sexual behavior similar to the effect of citalopram, whereas exposure to 5-HT(1A) receptor agonist only moderately influenced male sexual activity in adult animals. These data support the hypothesis that stimulation of serotonin autoreceptors during development contributes to the adult sexual deficit in rats neonatally exposed to citalopram.


Subject(s)
Citalopram/administration & dosage , Receptors, Serotonin, 5-HT1/physiology , Selective Serotonin Reuptake Inhibitors/administration & dosage , Sexual Behavior, Animal/drug effects , Sexual Dysfunction, Physiological/chemically induced , 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Age Factors , Analysis of Variance , Animals , Animals, Newborn , Behavior, Animal/drug effects , Female , Male , Pregnancy , Quinoxalines/pharmacology , Rats , Rats, Long-Evans , Reaction Time/drug effects , Serotonin Antagonists/pharmacology
4.
Eur J Pharmacol ; 532(3): 265-9, 2006 Feb 27.
Article in English | MEDLINE | ID: mdl-16483567

ABSTRACT

Neonatal exposure to antidepressants, including selective serotonin reuptake inhibitors such as citalopram, induces behavioral disturbances which persist in mature rats. These disturbances have been proposed to model the symptoms of endogenous depression. However, to date there is scant evidence for the predictive validity of any of these behaviors in response to adult antidepressant treatments. In order to directly assess the predictive validity of the early antidepressant exposure paradigm, the present study examined whether the behavioral abnormalities observed in adult animals exposed as neonates to citalopram can be reversed by adult antidepressant treatment with the prototypic antidepressant, imipramine. As noted earlier, neonatal citalopram exposure robustly increased locomotor activity and impaired male sexual behavior in adult rats. These behavioral changes were reversed following chronic adult imipramine treatment. No such reversal was observed in handled, saline treated rats. The present data support the hypothesis that some of the lasting behavioral abnormalities induced by early antidepressant exposure are sensitive to clinically relevant antidepressant treatments thus adding a measure of predictive validity to this paradigm as a model of these depressive symptoms.


Subject(s)
Adrenergic Uptake Inhibitors/pharmacology , Antidepressive Agents, Tricyclic/pharmacology , Behavior, Animal/drug effects , Depression/drug therapy , Imipramine/pharmacology , Adrenergic Uptake Inhibitors/therapeutic use , Animals , Animals, Newborn , Antidepressive Agents, Tricyclic/therapeutic use , Citalopram , Depression/chemically induced , Disease Models, Animal , Drug Evaluation, Preclinical , Imipramine/therapeutic use , Male , Motor Activity/drug effects , Rats , Rats, Long-Evans , Reproducibility of Results , Sexual Behavior, Animal/drug effects
5.
Neuropsychopharmacology ; 31(1): 47-57, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16012532

ABSTRACT

A significant fraction of infants born to mothers taking selective serotonin reuptake inhibitors (SSRIs) during late pregnancy display clear signs of antidepressant withdrawal indicating that these drugs can penetrate fetal brain in utero at biologically significant levels. Previous studies in rodents have demonstrated that early exposure to some antidepressants can result in persistent abnormalities in adult behavior and indices of monoaminergic activity. Here, we show that chronic neonatal (postnatal days 8-21) exposure to citalopram (5 mg/kg, twice daily, s.c.), a potent and highly selective SSRI, results in profound reductions in both the rate-limiting serotonin synthetic enzyme (tryptophan hydroxylase) in dorsal raphe and in serotonin transporter expression in cortex that persist into adulthood. Furthermore, neonatal exposure to citalopram produces selective changes in behavior in adult rats including increased locomotor activity and decreased sexual behavior similar to that previously reported for antidepressants that are nonselective monoamine transport inhibitors. These data indicate that the previously reported neurobehavioral effects of antidepressants are a consequence of their effects on the serotonin transporter. Moreover, these data argue that exposure to SSRIs at an early age can disrupt the normal maturation of the serotonin system and alter serotonin-dependent neuronal processes. It is not known whether this effect of SSRIs is paralleled in humans; however, these data suggest that in utero, exposure to SSRIs may have unforeseen long-term neurobehavioral consequences.


Subject(s)
Animals, Newborn/physiology , Antidepressive Agents/pharmacology , Behavior, Animal/drug effects , Serotonin/physiology , Animals , Antidepressive Agents/blood , Antidepressive Agents, Tricyclic/blood , Antidepressive Agents, Tricyclic/pharmacology , Antigens, Nuclear/metabolism , Body Weight/drug effects , Brain/metabolism , Citalopram/blood , Citalopram/pharmacology , Clomipramine/blood , Clomipramine/pharmacology , Data Interpretation, Statistical , Female , Immunohistochemistry , Motor Activity/drug effects , Nerve Tissue Proteins/metabolism , Pregnancy , Rats , Rats, Long-Evans , Selective Serotonin Reuptake Inhibitors/blood , Selective Serotonin Reuptake Inhibitors/pharmacology , Sexual Behavior, Animal/drug effects , Tryptophan Hydroxylase/metabolism
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