| 1. |
- Aghajani, Moji, et al.
(författare)
-
Neural processing of socioemotional content in conduct-disordered offenders with limited prosocial emotions
- 2021
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 105
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Reflecting evidence on Callous-Unemotional (CU) traits (e.g., lack of empathy and guilt, shallow affect), the DSM-5 added a categorical CU-based specifier for Conduct Disorder (CD), labeled 'with Limited Prosocial Emotions' (LPE). Theory and prior work suggest that CD youths with and without LPE will likely differ in neural processing of negative socioemotional content. This proposition, however, is mainly derived from studies employing related, yet distinct, operationalizations of CU traits (e.g., dimensional measure/median split/top quartile), thus precluding direct examination of LPE-specific neurocognitive deficits.METHODS: Employing a DSM-5 informed LPE proxy, neural processing of recognizing and resonating negative socioemotional content (angry and fearful faces) was therefore examined here among CD offenders with LPE (CD/LPE+; N = 19), relative to CD offenders without LPE (CD/LPE-; N = 31) and healthy controls (HC; N = 31).RESULTS: Relative to HC and CD/LPE- youths and according to a linearly increasing trend (CD/LPE- < HC < CD/LPE+), CD/LPE+ youths exhibited hyperactivity within dorsolateral, dorsomedial, and ventromedial prefrontal regions during both emotion recognition and resonance. During emotion resonance, CD/LPE+ youths additionally showed increased activity within the posterior cingulate and precuneal cortices in comparison to HC and CD/LPE- youths, which again followed a linearly increasing trend (CD/LPE- < HC < CD/LPE+). These effects moreover seemed specific to the LPE specifier, when compared to a commonly employed method for CU-based grouping in CD (i.e., median split on CU scores).CONCLUSIONS: These data cautiously suggest that CD/LPE+ youths may exhibit an over-reliance on cortical neurocognitive systems when explicitly processing negative socioemotional information, which could have adverse downstream effects on relevant socioemotional functions. The findings thus seem to provide novel, yet preliminary, clues on the neurocognitive profile of CD/LPE+, and additionally highlight the potential scientific utility of the LPE specifier.
|
|
| 2. |
- Akkermann, Kirsti, et al.
(författare)
-
Serotonin transporter gene promoter polymorphism affects the severity of binge eating in general population
- 2010
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 34:1, s. 111-114
-
Forskningsöversikt (refereegranskat)abstract
- Objective: The s-allele of the 5-HTTLPR has been suggested to lead to the development of less efficient and less flexible 5-HT system and has been associated to different forms of psychopathology. It has also been shown that alterations in serotonergic activity contribute to the pathophysiology of binge eating but it is not clear which changes in 5-HT function observed in eating disorder patients represent trait vs state effect. We investigated the association between the 5-HTTLPR and binge eating in a population-representative sample of women, and tested whether the 5-HTTLPR genotype influences the severity of binge eating. Methods: The sample was based on women participating in the third wave of the Estonian Children Personality, Behaviour and Health Study. EDI-2 subscales - drive for thinness and bulimia - were used to assess eating behaviour and attitudes. Barratt Impulsiveness Scale (BIS-11) and State and Trait Anxiety Inventory (STAI) were used to measure impulsivity and anxiety. Participants were genotyped for the 5-HTTLPR. Results: There was no 5-HTTLPR genotype effect on binge eating even after the covarying effect of impulsivity and anxiety was controlled for. However, women prone to binge eating and carrying the s-allele showed significantly higher levels of bulimia scores, and among them, women with s/s genotype had also higher levels of state anxiety and tendency for higher impulsivity. Conclusions: While the 5-HTTLPR genotype does not predict symptoms of eating disorder in general population, the s-allele, and especially the s/s genotype increases the risk for affective instability and symptom severity.
|
|
| 3. |
- Azocar, V.H., et al.
(författare)
-
Differential phase-amplitude coupling in nucleus accumbens and orbitofrontal cortex reflects decision-making during a delay discounting task
- 2024
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 134
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The impulsive choice is characterized by the preference for a small immediate reward over a bigger delayed one. The mechanisms underlying impulsive choices are linked to the activity in the Nucleus Accumbens (NAc), the orbitofrontal cortex (OFC), and the dorsolateral striatum (DLS). While the study of functional connectivity between brain areas has been key to understanding a variety of cognitive processes, it remains unclear whether functional connectivity differentiates impulsive-control decisions.Methods: To study the functional connectivity both between and within NAc, OFC, and DLS during a delay discounting task, we concurrently recorded local field potential in NAc, OFC, and DLS in rats. We then quantified the degree of phase-amplitude coupling (PAC), coherence, and Granger Causality between oscillatory activities in animals exhibiting either a high (HI) or low (LI) tendency for impulsive choices.Results: Our results showed a differential pattern of PAC during decision-making in OFC and NAc, but not in DLS. While theta-gamma PAC in OFC was associated with self-control decisions, a higher delta-gamma PAC in both OFC and NAc biased decisions toward impulsive choices in both HI and LI groups. Furthermore, during the reward event, Granger Causality analysis indicated a stronger NAc➔OFC gamma contribution in the HI group, while the LI group showed a higher OFC➔NAc gamma contribution.Conclusions: The overactivity in NAc during reward in the HI group suggests that exacerbated contribution of NAcCore can lead to an overvaluation of reward that biases the behavior toward the impulsive choice.
|
|
| 4. |
|
|
| 5. |
- Bergman, Olle, 1978, et al.
(författare)
-
Preliminary evidence that polymorphisms in dopamine-related transcription factors LMX1A, LMX1B and PITX3 are associated with schizophrenia
- 2010
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 34:6, s. 1094-1097
-
Tidskriftsartikel (refereegranskat)abstract
- The early development of dopaminergic pathways has been attributed importance for the aetiology of schizophrenia. Several transcription factors are involved in the survival and maturation of dopamine neurons, including LMX1A, LMX1B and PITX3. The possibility that polymorphisms in these genes may influence the development and/or the maintenance of dopaminergic neurons prompted us to investigate if five single nucleotide polymorphisms (SNPs) previously linked to Parkinson's disease are associated with this disorder. Preliminary evidence that genetic variation in LMX1A (rs6668493, rs4657411), LMX1B (rs10987386) and PITX3 (rs4919621) may increase the risk of developing schizophrenia is presented.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Ciralli, Barbara, et al.
(författare)
-
Unraveling the role of Slc10a4 in auditory processing and sensory motor gating : Implications for neuropsychiatric disorders?
- 2024
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 131
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundPsychiatric disorders, such as schizophrenia, are complex and challenging to study, partly due to the lack of suitable animal models. However, the absence of the Slc10a4 gene, which codes for a monoaminergic and cholinergic associated vesicular transporter protein, in knockout mice (Slc10a4−/−), leads to the accumulation of extracellular dopamine. A major challenge for studying schizophrenia is the lack of suitable animal models that accurately represent the disorder. We sought to overcome this challenge by using Slc10a4−/− mice as a potential model, considering their altered dopamine levels. This makes them a potential animal model for schizophrenia, a disorder known to be associated with altered dopamine signaling in the brain.MethodsThe locomotion, auditory sensory filtering and prepulse inhibition (PPI) of Slc10a4−/− mice were quantified and compared to wildtype (WT) littermates. Intrahippocampal electrodes were used to record auditory event-related potentials (aERPs) for quantifying sensory filtering in response to paired-clicks. The channel above aERPs phase reversal was chosen for reliably comparing results between animals, and aERPs amplitude and latency of click responses were quantified. WT and Slc10a4−/− mice were also administered subanesthetic doses of ketamine to provoke psychomimetic behavior.ResultsBaseline locomotion during auditory stimulation was similar between Slc10a4−/− mice and WT littermates. In WT animals, normal auditory processing was observed after i.p saline injections, and it was maintained under the influence of 5 mg/kg ketamine, but disrupted by 20 mg/kg ketamine. On the other hand, Slc10a4−/− mice did not show significant differences between N40 S1 and S2 amplitude responses in saline or low dose ketamine treatment. Auditory gating was considered preserved since the second N40 peak was consistently suppressed, but with increased latency. The P80 component showed higher amplitude, with shorter S2 latency under saline and 5 mg/kg ketamine treatment in Slc10a4−/− mice, which was not observed in WT littermates. Prepulse inhibition was also decreased in Slc10a4−/− mice when the longer interstimulus interval of 100 ms was applied, compared to WT littermates.ConclusionThe Slc10a4−/− mice responses indicate that cholinergic and monoaminergic systems participate in the PPI magnitude, in the temporal coding (response latency) of the auditory sensory gating component N40, and in the amplitude of aERPs P80 component. These results suggest that Slc10a4−/− mice can be considered as potential models for neuropsychiatric conditions.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Harro, Jaanus, et al.
(författare)
-
The role of MAO in personality and drug use
- 2016
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 69, s. 101-111
-
Tidskriftsartikel (refereegranskat)abstract
- Monoamine oxidases, both MAO-A and MAO-B, have been implicated in personality traits and complex behaviour, including drug use. Findings supporting the involvement of MAO-A and MAO-B in shaping personality and in the development of strategies of making behavioural choices come from a variety of studies that have examined either prevalence of gene variants in clinical groups or population-derived samples, estimates of enzyme activity in blood or, by positron emission tomography, in the brain and, most recently, measurement of methylation of the gene. Most of the studies converge in associating MAO-A and MAO-B with impulsive, aggressive or antisocial personality traits or behaviours, including alcohol-related problems, and for MAO-A available evidence strongly supports interaction with adverse environmental exposures in childhood. What is known about genotype effects, and on expression and activity of the enzyme in the brain and in blood has not yet been possible to unite into a mechanistic model of the role of monoamine systems, but the reason for this low degree of generalization is likely caused by the cross-sectional nature of investigation that has not incorporated the developmental effects of MAO-s in critical time windows, including the foetal period. The "risk variants" of both MAO-s appear to increase behavioural plasticity, as supportive environments may particularly well enhance the hidden potential of their carriers. Importantly, male and female brain and behaviours have been found very different with regard to MAO x life events interaction. Future studies need to take into consideration these developmental aspects and sex/gender, as well as to specify the role of different types of environmental factors.
|
|
| 19. |
|
|
| 20. |
- Haukvik, Unn Kristin, et al.
(författare)
-
An exploratory model for G x E interaction on hippocampal volume in schizophrenia; obstetric complications and hypoxia-related genes
- 2010
-
Ingår i: Progress in Neuro-Psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 34:7, s. 1259-1265
-
Forskningsöversikt (refereegranskat)abstract
- Background Smaller hippocampal volume has repeatedly been reported in schizophrenia patients Obstetric complications (OCs) and single nucleotide polymorphism (SNP) variation in schizophrenia susceptibility genes have independently been related to hippocampal volume We investigated putative independent and interaction effects of severe hypoxia-related OCs and variation in four hypoxia-regulated schizophrenia susceptibility genes (BDNF, DTNBP1, GRM3 and NRG1) on hippocampal volume in schizophrenia patients and healthy controls. Methods Clinical assessment, structural MRI scans, and blood samples for genotyping of 32 SNPs were obtained from 54 schizophrenia patients and 53 control subjects Information on obstetric complications was collected from original birth records Results Severe OCs were related to hippocampal volume in both patients with schizophrenia and healthy control subjects Of the 32 SNPs studied, effects of severe OCs on hippocampal volume were associated with allele variation in GRM3 rs13242038, but the interaction effect was not specific for schizophrenia. SNP variation in any of the four investigated genes alone did not significantly affect hippocampal volume. Conclusions. The findings suggest a gene-environment (G x E) interaction between GRM3 gene variants and severe obstetric complications on hippocampus volume, independent of a diagnosis of schizophrenia Due to the modest sample size, the results must be considered preliminary and require replication in independent samples. (C) 2010 Elsevier Inc All rights reserved
|
|
| 21. |
- Haukvik, Unn Kristin, et al.
(författare)
-
No effect of obstetric complications on basal ganglia volumes in schizophrenia
- 2010
-
Ingår i: Progress in Neuro-Psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 34:4, s. 619-623
-
Forskningsöversikt (refereegranskat)abstract
- Background: Heterogeneous findings have been reported in studies of basal ganglia volumes in schizophrenia patients as compared to healthy controls. The basal ganglia contain dopamine receptors that are known to be involved in schizophrenia pathology and to be vulnerable to pre- and perinatal hypoxic insults. Altered volumes of other brain structures (e.g. hippocampus and lateral ventricles) have been reported in schizophrenia patients with a history of obstetric complications (005). This is the first study to explore if there is a relationship between OCs and basal ganglia volume in schizophrenia. Methods: Thorough clinical investigation (including information on medication) of 54 schizophrenia patients and 54 healthy control subjects was undertaken. MR images were obtained on a 1.5T scanner, and volumes of nucleus caudatus, globus pallidum, putamen, and nucleus accumbens were quantified automatically. Information on OCs was blindly collected from original birth records. Results: Unadjusted estimates demonstrated a relationship between increasing number of OCs and larger volume of nucleus accumbens in schizophrenia patients and healthy controls. No statistically significant relationships were found between OCs and the basal ganglia volumes when controlled for intracranial volume, age, and multiple comparisons. There were no effects of typical versus atypical medication on the basal ganglia volumes. The patients with schizophrenia had larger globus pallidum volumes as compared to healthy controls, but there were no case-control differences for accumbens, putamen, or caudate volumes. Conclusion: The present results do not support the hypothesis that OCs are related to alterations in basal ganglia volume in chronic schizophrenia. (C) 2010 Elsevier Inc. All rights reserved.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Kindlundh, Anna MS, et al.
(författare)
-
Dopaminergic effects after chronic treatment with nandrolone visualized in rat brain by positron emission tomography
- 2002
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - 0278-5846 .- 1878-4216. ; 26:7-8, s. 1303-1308
-
Tidskriftsartikel (refereegranskat)abstract
- Anabolic-androgenic steroids (AAS) have recently been shown to induce neurochemical alterations in areas of the male rat CNS related to behavioural changes that have been observed among AAS misusers. In the present study, positron emission tomography (PET) is suggested as a suitable in vivo method in order to visualize the density of the dopamine transporter ([11C]-FE-beta-CIT) as well as the dopamine D1-like ([11C]-(+)-SCH23390) and the D2-like receptors ([11C]-raclopride) in the male rat brain. Chronic treatment with the AAS nandrolone decanoate (15 mg/kg/day for 14 days) caused an up-regulation of the binding potential of the dopamine transporter in the striatum.
|
|
| 25. |
- Knott, Verner, et al.
(författare)
-
Effects of acute cholecystokinin infusion on hemispheric EEG asymmetry and coherence in healthy volunteers
- 2003
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - 0278-5846 .- 1878-4216. ; 27:1, s. 179-184
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effects of continuous slow infusion of cholecystokinin tetrapeptide (CCK-4), a neuropeptide with panicogenic properties, on functional hemispheric differences, as indexed by quantitative electroencephalographic (EEG) asymmetry and coherence measures. Twenty-four adult volunteers (15 females and 9 males) were assigned to infusion with either placebo or CCK-4 in a randomized, double-blind, parallel-group design, with EEG being recorded before and during (10 and 40 min) a 60-min infusion period. No significant treatment differences were observed for absolute EEG power but, compared to placebo, CCK-4 infusion increased asymmetry and reduced coherence of slow-wave activity at midtemporal recording sites. These findings support the contention that functional imbalance of the temporal cortex, perhaps mediated by CCK-4, is involved in panic disorder (PD).
|
|
| 26. |
- Koch, Elise, et al.
(författare)
-
Candidates for Drug Repurposing to Address the Cognitive Symptoms in Schizophrenia
- 2023
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 20
-
Tidskriftsartikel (refereegranskat)abstract
- In the protein-protein interactome, we have previously identified a significant overlap between schizophrenia risk genes and genes associated with cognitive performance. Here, we further studied this overlap to identify potential candidate drugs for repurposing to treat the cognitive symptoms in schizophrenia. We first defined a cognition-related schizophrenia interactome from network propagation analyses, and identified drugs known to target more than one protein within this network. Thereafter, we used gene expression data to further select drugs that could counteract schizophrenia-associated gene expression perturbations. Additionally, we stratified these analyses by sex to identify sex-specific pharmacological treatment options for the cognitive symptoms in schizophrenia. After excluding drugs contraindicated in schizophrenia, we identified 12 drug repurposing candidates, most of which have anti-inflammatory and neuroprotective effects. Sex-stratified analyses showed that out of these 12 drugs, four were identified in females only, three were identified in males only, and five were identified in both sexes. Based on our bioinformatics analyses of disease genetics, we suggest 12 candidate drugs that warrant further examination for repurposing to treat the cognitive symptoms in schizophrenia, and suggest that these symptoms could be addressed by sex-specific pharmacological treatment options.
|
|
| 27. |
- Kotsovolou, Olga, et al.
(författare)
-
Hepatic drug metabolizing profile of Flinders Sensitive Line rat model of depression
- 2010
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 34:6, s. 1075-1084
-
Forskningsöversikt (refereegranskat)abstract
- The Flinders Sensitive Line (FSL) rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed patients and has been very effective in screening antidepressants. Major factor that determines the effectiveness and toxicity of a drug is the drug metabolizing capacity of the liver. Therefore, in order to discriminate possible differentiation in the hepatic drug metabolism between FSL rats and Sprague Dawley (SD) controls, their hepatic metabolic profile was investigated in this study. The data showed decreased glutathione (GSH) content and glutathione S-transferase (GST) activity and lower expression of certain major CYP enzymes, including the CYP2B1, CYP2C11 and CYP2D1 in FSL rats compared to SD controls. In contrast, p-nitrophenol hydroxylase (PNP), 7ethoxyresorufin-O-dealkylase (EROD) and 16 alpha-testosterone hydroxylase activities were higher in FSL rats. Interestingly, the wide spread environmental pollutant benzo(alpha)pyrene (B(alpha)P) induced CYP1A1, CYP1A2, CYP2B1/2 and ALDH3c at a lesser extend in FSL than in SD rats, whereas the antidepressant mirtazapine (MIRT) up-regulated CYP1A1/2, CYP2C11, CYP2D1, CYP2E1 and CYP3A1/2, mainly, in FSL rats. The drug also further increased ALDH3c whereas suppressed GSH content in B(a)P-exposed FSL rats. In conclusion, several key enzymes of the hepatic biotransformation machinery are differentially expressed in FSL than in SD rats, a condition that may influence the outcome of drug therapy. The MIRT-induced up-regulation of several drug-metabolizing enzymes indicates the critical role of antidepressant treatment that should be always taken into account in the designing of treatment and interpretation of insufficient pharmacotherapy or drug toxicity.
|
|
| 28. |
|
|
| 29. |
- Lindholm, Sara, et al.
(författare)
-
Nociceptin/orphanin FQ tissue concentration in the rat brain : Effects of repeated ethanol administration at various post-treatment intervals
- 2002
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - 0278-5846 .- 1878-4216. ; 26:2, s. 303-306
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to study short- and long-term effects of repeated ethanol administration on nociceptin/orphanin FQ (N/OFQ) tissue concentrations in rat brain with radioimmunoassay. Animals were given either ethanol (intraperitoneal) or saline for 13 consecutive days. N/OFQ levels were examined at 30 min, 5 days and 21 days after the last dose on day 13. Ethanol-treated rats had significantly decreased N/OFQ tissue concentration in the hippocampus at 30 min after the last dose. N/OFQ levels were decreased in the cingulate cortex at 5 days after cessation of ethanol administration whereas no significant changes were found at 21 days. There were no significant changes in N/OFQ tissue concentrations at any time point studied in the mesolimbic dopamine (DA) system, a brain area associated with ethanol-induced activation. However, the results indicate that repeated ethanol administration may induce short- and long-term changes in N/OFQ tissue concentrations in other brain regions innervated with dopaminergic neurons.
|
|
| 30. |
|
|
| 31. |
- Lonsdorf, Tina B, et al.
(författare)
-
The symptomatic profile of panic disorder is shaped by the 5-HTTLPR polymorphism
- 2009
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 33:8, s. 1479-1483
-
Forskningsöversikt (refereegranskat)abstract
- The short allele of a functional polymorphism (5-HTTLPR) in the serotonin transporter (5-HTT) promoter is associated with reduced serotonin transporter expression, lower in vivo 5-HTT binding, higher neuroticism and amygdala reactivity as well as facilitated fear conditioning and is a candidate variant for panic disorder. However, case-control studies have consistently failed to show an association between 5-HTTLPR and panic disorder. As psychiatric disorders are broadly defined phenotypes merging different symptoms to syndromes, they may not be very well suited for genetic association studies. An alternative approach is to measure symptoms along continuous symptom dimensions which may more appropriately reflect their biological underpinnings and may reveal subpopulations within clinical diagnostic groups. We recorded the symptomatic profile in 73 in panic disorder patients using observer-rated instruments (Panic Disorder Severity Scale, PDSS; Montgomery-Asberg Depression Rating Scale, MADRS) and hypothesized more severe symptoms in patients carrying the 5-HTTLPR s-allele. We observed a strong association between bi- and triallelic 5-HTTLPR polymorphisms and the symptomatic profile. Carriers of the 5-HTTLPR s-allele suffered from most severe panic and depressive symptoms. Our data highlight the importance of defining appropriate phenotypes for psychiatric genetic studies and demonstrate that the 5-HTTLPR genotype may be related to the symptomatic profiles rather than to the vulnerability to develop panic disorder.
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Owe-Larsson, Björn, et al.
(författare)
-
Increased plasma levels of thioredoxin-1 in patients with first episode psychosis and long-term schizophrenia.
- 2011
-
Ingår i: Progress in neuro-psychopharmacology & biological psychiatry. - : Elsevier BV. - 1878-4216 .- 0278-5846. ; 35:4, s. 1117-21
-
Tidskriftsartikel (refereegranskat)abstract
- Excessive level of radicals and/or dysfunctional antioxidant response, oxidative stress, is implicated in the pathogenesis of schizophrenia. A condition of oxidative stress has been detected in the brain, peripheral tissues and fluids including plasma. Plasma thioredoxin-1 (Trx1) is well characterized and a putative marker for oxidative stress and recently shown to be increased in plasma at the onset of schizophrenia. The present study aimed to explore whether Trx1 can be used as a marker to identify schizophrenic patients at the time-point when patients have their first episode of psychosis as compared to patients with long-term schizophrenia and mentally healthy patients, respectively. Plasma samples obtained from 18 patients at first episode of psychosis, from 49 long-term schizophrenic patients and from 20 mentally healthy controls (admitted with minor physical injury to the general ward) where analyzed by ELISA for Trx1. The patients with first episode of psychosis were diagnosed at least 6months later and shown to constitute various psychotic syndromes, including schizophrenia, or affective disorder. The concentration of Trx1 in the patients with first episode of psychosis was 1.5±1.0ng/ml and 0.8±0.6ng/ml in controls. In the long-term schizophrenic patients the plasma concentration was 1.5±0.7. The differences between the groups of acute psychotic or long-term schizophrenia patients to controls were significant (p<0.016 and p<0.001, respectively). Our data indicate that Trx1 may not be used as an early marker to identify schizophrenic patients in a mixed population of first episode psychotic patients. Further, Trx1 did not discriminate with reliable accuracy patients with psychotic disorder from mentally healthy controls on an individual basis due to overlap in levels of Trx1. However, our observations show that psychotic patients in general are in a significant long-term condition of oxidative stress, with possible implications for the profound morbidity and mortality found in this patient population.
|
|
| 37. |
- Paaver, Marika, et al.
(författare)
-
The effect of 5-HTT gene promoter polymorphism on impulsivity depends on family relations in girls
- 2008
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 32:5, s. 1263-1268
-
Forskningsöversikt (refereegranskat)abstract
- The short (S) allele of the 5-HTT gene promoter region polymorphism (5-HTTLPR), in combination with adverse environmental influence, leads to higher likelihood of depression. Impulsivity has been related to low serotonin turnover, poor regulation of affect, and problems in the family, including child maltreatment. The current study explored the effect of the 5-HTTLPR polymorphism in the serotonin transporter gene and adverse family environment on impulsivity in adolescents. Healthy adolescents participating in the Estonian Children Personality Behaviour and Health Study (n=483) filled the Adaptive and Maladaptive Impulsivity Scale (AMIS), Barratt Impulsiveness Scale (BIS-11), a scale measuring family relations, and were genotyped. While genotype alone was not associated with thoughtlessness, BIS-11 impulsiveness, fast decision-making or excitement seeking, 5-HTTLPR S allele carriers, however, had higher scores of disinhibition. In girls carrying the S allele, scores of thoughtlessness and disinhibition depended on family relations, being higher with less warmth in the family. Adverse family relations had no effect on impulsivity in girls with LL genotype. In boys, the effects of family relations on maladaptive impulsivity did not depend on genotype. However, the S allele and high maltreatment in the family both independently increased disinhibition and the BIS-11 score in boys. Family environment and the 5-HTTLPR genotype had no interactive effect on excitement seeking or fast decision-making. In summary, carrying the S allele may lead to high maladaptive impulsivity due to higher sensitivity to environmental adversity, which is more significantly expressed in girls.
|
|
| 38. |
- Paola Carlini, Valeria, et al.
(författare)
-
Differential effects of fluoxetine and venlafaxine on memory recognition : Possible mechanisms of action
- 2012
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 38:2, s. 159-167
-
Tidskriftsartikel (refereegranskat)abstract
- Serotonin-specific reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are antidepressant drugs commonly used to treat a wide spectrum of mood disorders (Wong and Licinio, 2001). Although they have been clinically used for more than 50 years, the molecular and cellular basis for the action of SSRIs and SNRIs is not clear. Considering that the changes in gene expression involved in the action of antidepressant drugs on memory have not been identified, in this study we investigated the impact of chronic treatment with a SSRI (fluoxetine) and a SNRI (venlafaxine) on the mRNA expression of genes related to memory cascade in the mouse hippocampus, namely, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), nitric oxide synthase 1 (NOS1), neurotrophic tyrosine kinase receptor type 2 (TrKB), mitogen-activated protein kinases (MAPK/ERK) and serotonin transporter (SERT). Animals treated with fluoxetine 10 mg/Kg/day for 28 days showed a significant decrease in the percentage of time spent in the novel object recognition test (p <= 0.005) and induced MAPK1/ERK2 down-regulation (p = 0.005). Our results suggest that the effect on cognition could probably be explained by fluoxetine interference in the MAPK/ERK memory pathway. In contrast, chronic treatment with venlafaxine did not reduce MAPK1/ERK2 expression, suggesting that MAPK1/ERK2 down-regulation is not a common effect of all antidepressant drugs. Further studies are needed to examine the effect of chronic fluoxetine treatment on the ERK-CREB system, and to determine whether there is a causal relationship between the disruption of the ERK-CREB system and the effect of this antidepressant on memory performance. (c) 2012 Elsevier Inc. All rights reserved.
|
|
| 39. |
|
|
| 40. |
- Pickering, Chris, et al.
(författare)
-
Identification of neurotransmitter receptor genes involved in alcohol self-administration in the rat prefrontal cortex, hippocampus and amygdala
- 2007
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 31:1, s. 53-64
-
Forskningsöversikt (refereegranskat)abstract
- About half of the risk to develop alcoholism is related to genetic background and it is well known that alcohol consumption is highly individualized. In this study, we investigated how individual alcohol consumption behaviour in Wistar rats correlated with mRNA expression of 20 genes in the prefrontal cortex, hippocampus and amygdala. We found that the long-term alcohol consumption of an individual could be estimated by the mean of its consumption on Day 2 and 3. This short exposure minimized changes in gene expression induced by alcohol itself. We found a positive correlation in the prefrontal cortex of GABAA α5 (r = 0.96), GABAB1 (r = 0.96), AMPA GluR1 (r = 0.93), 5-HT3A (r = 0.93) and the α adrenoceptors (α1A r = 1.00, α1B r = 0.93, α2A r = 0.93) with consumption. In the hippocampus, we found negative correlations with the NMDA NR2A subunit (r = − 0.86), the α1A adrenoceptor (r = − 0.89) and the glucocorticoid receptor (r = − 0.86). Finally, in the amygdala there was a negative correlation to NMDA NR2A (r = − 0.79) and a positive correlation with serotonin 5-HT2C (r = 0.79). In conclusion, we have used qPCR to identify specific genes in the brain that correlated to alcohol self-administration of an individual animal. This study suggests that alcohol consumption in the early stages of acquisition depends on the genetic background of the individual and that the prefrontal cortex is particularly important in this behaviour.
|
|
| 41. |
- Pickering, Christopher, 1975, et al.
(författare)
-
Sensitization to nicotine significantly decreases expression of GABA transporter GAT-1 in the medial prefrontal cortex.
- 2008
-
Ingår i: Progress in neuro-psychopharmacology & biological psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 32:6, s. 1521-6
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigated GABA signaling following induction of behavioural sensitization to nicotine. Rats were repeatedly injected with saline, nicotine or hexamethonium for 18 days and gene expression was measured with qPCR. Nicotine upregulated GABAA alpha1 subunit expression in the nucleus accumbens (p<0.05) while no changes were observed for GABAA alpha3, alpha4 or alpha5. In the medial prefrontal cortex, no change in expression of the GABAA subunits was observed. We found that nicotine significantly decreased expression of the transporter GAT-1/SLC6A1 (p<0.05) in the medial prefrontal cortex while the expression of the GAT-3/SLC6A11 (p<0.05) transporter was increased in the nucleus accumbens. This provides the first evidence of neuroadaptive changes in the GABA system after nicotine sensitization and the first demonstration of an effect on GAT-1 or GAT-3 transporters in the addiction field. The GAT-1 findings also provide evidence for an alternative theory of why most schizophrenic individuals also use tobacco products.
|
|
| 42. |
|
|
| 43. |
- Poretti, María Belén, et al.
(författare)
-
Ghrelin effects expression of several genes associated with depression-like behavior
- 2015
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 56, s. 227-234
-
Tidskriftsartikel (refereegranskat)abstract
- Ghrelin (Ghr) is an orexigenic peptide that is being investigated for its potential role in development of anxiety-like behavior and modulation of depressive-like symptoms induced by bilateral olfactory bulbectomy (OB) in rodents. Olfactory bulbectomy is an animal model useful to study of depression and Ghr could be an alternative therapeutic tool in depression therapy. We studied the effects of intracerebroventricular (i.c.v.) Ghr administration on the expression of hypothalamic genes related to depression and mood (delta opioid receptor (DOR), mu opioid receptor (MOR) and kappa opioid receptor (KOR), lutropin-choriogonadotropic hormone receptor (LHCGR), serotonin transporter (SERT), interleukin 1 beta (IL-1b), vasopressin (AVP) and corticotrophin releasing hormone (CRH)) in OB animals, as well as changes in plasma levels of AVP, CRH and adenocorticotropic hormone (ACTH). We found that acute Ghr 0.3nmol/μl administration increases gene expression of DOR, SERT and LHCGR in OB mice and decreased expression of IL-1b, suggesting that these genes could be involved in the antidepressant-like effects of Ghr. In addition, OB animals exhibit high AVP gene expression and elevated plasma concentrations of AVP and ACTH and acute Ghr 0.3nmol/μl administration reduces AVP gene expression and the concentration of these hormones, suggesting that peptide-effects on depressive-like behavior could be mediated at least in part via AVP. In conclusion, this study provides new evidence about genes, receptors and hormones involved in the antidepressant mechanism/s induced by Ghr in OB animals.
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
