Dopaminergic Blockade Research Articles

Delirium and Pseudoparkinsonism in a Bipolar Patient: Case Report

Background Bipolar patients are at higher risk of delirium, in comparison to other psychiatric patients, regardless of being under lithium treatment. Indeed, lithium and antipsychotics are the mainstay drugs in the management of bipolar disorder. In clinical practice, the combinations of these drugs are commonly used in the management of acute phase of mania. Despite rare previous cases of olanzapine-associated delirium and cases of delirium with extrapyramidal signs due to a lithium-olanzapine combination therapy, these are mainly reported in elderly or severely ill patients. Case Presentation This case report illustrates a complex neuropsychiatric syndrome characterized by olanzapine-associated delirium alongside parkinsonism induced by aripiprazole, during a severe manic episode, in an antipsychotic-naïve young adult bipolar patient, under lithium maintenance treatment. Conclusions This case highlights the need for caution regarding delirium and extrapyramidal symptoms when treating antipsychotic-naïve bipolar patients under lithium maintenance therapy. The risk factors and the underlying physiopathology of this iatrogenic neuropsychiatric syndrome are discussed. We hypothesise a central cholinergic antagonism in the pathophysiology for delirium, and both pharmacokinetic and pharmacodynamic mechanisms for Parkinsonism, namely a putative flaw functioning of CYP2D6 or CYP3A4 cytochromes, bringing about a failure in metabolising aripiprazole at a normal rate, and a synergistic effect of lithium and antipsychotics on dopaminergic blockade.

The dangers of neuroleptic use in Parkinsonian-spectrum illnesses - management of emergent hypodopaminergic syndromes and catatonia

IntroductionIn Parkinson disease (PD), the incidence of psychotic symptoms has an estimated rate of 25-30%, a cumulative long term prevalence rate of 60%, with visual hallucinations being the most common type of sensory hallucination. The use of high and low potency, antidopaminergic, antipsychotic medications (AP) have the potential to exacerbate motor symptoms of PD and precipitate neuroleptic malignant syndrome (NMS), neuroleptic malignant-like syndrome in PD known as Parkinson hyperpyrexia syndrome (PHS), and catatonia in at risk population. MethodsHere, we present a clinical case and a review of the current treatment modalities available for movement disorder emergencies in parkinsonian-spectrum illnesses (PSI). Patient was assessed by a multidisciplinary team, including neurology and a geriatric consult-liaison psychiatry service. ResultsThis is a case report of a 79-year-old man with no previous psychiatric history, an initial diagnosis of PD due to early emergence of tremors and motor symptoms responsive to levodopa-carbidopa (LC). This was followed by progressive cognitive impairments, delusional jealousy, and formed visual hallucinations, which prompted concern for cortical lewy body involvement. Pimavanserin was initiated for presumed diagnosis of Parkinson disease psychosis and ameliorated the frequency of visual hallucinations. Patient presented to the hospital for agitation and was positive for COVID-19 on admission; prior to this, he had missed doses of LC and was febrile per family. He received intramuscular haloperidol and ziprasidone for behavioral disturbances and subsequently developed delirium, severe VH's, elevated serum CK, diffuse rigidity, and hyperactive non-purposeful activity, raising concern for NMS.Emergent treatment included bromocriptine, lorazepam, and supportive measures; home dose of LC and pimavanserin were resumed after significant reductions in CK levels. Unfortunately, rigidity and delirium persisted leading to a prolonged hospitalization and requirement of a nasogastric tube for malnutrition. Neurology was concerned for PHS due to clinical overlap with NMS. Psychiatry consult-liaison service suspected protracted delirium and catatonia secondary to recent COVID-19 infection and neuroleptic use.Initial Bush Francis Catatonia Rating Score (BFCRS) was 22. Treatment trials of benzodiazepines, amantadine and memantine were unsuccessful due to adverse effects of excessive sedation, myoclonus, and increase aggression, respectively. Ultimately, bilateral, brief wave, electroconvulsive therapy (ECT) was initiated. Patient had improvements in increased alertness, executive speech, verbal comprehension, appetite, with BFCRS 6 by ninth ECT session, and was more attuned to his surroundings. After twelve ECT sessions and successful treatment of catatonia, despite some residual delirium, family felt comfortable caring for patient at their own home with supportive services. ConclusionThis case demonstrates the nebulous presentation of overlapping syndromes of delirium and catatonia - with NMS and PHS also in the differential - in the setting of acute COVID-19 infection and iatrogenic neuroleptic use in a patient with PSI. NMS and catatonia can be precipitated by dopaminergic blockade, while PHS is most encountered during dopaminergic withdrawal and intercurrent infections. Theorized pathophysiology is due to central dopamine hypofunction, leading to clinical features of altered consciousness, fevers, elevated serum CK, and parkinsonian exacerbation – all of which can be indistinguishable from the above-mentioned diagnoses. These syndromic illnesses appear to occur on an NMS-like spectrum, are a neurological emergency and necessitate prompt treatment with supportive measures, intensive care level monitoring, and restoration of the dopaminergic balance with LC, bromocriptine, and dantrolene. ECT has shown to improve both motor and psychotic symptoms in PD, should be first line in NMS, malignant and benzodiazepine-refractory catatonia, and has even demonstrated effectiveness in a case report of PHS. ECT could be the ideal next step in exacerbated movement disorder emergencies following medication trials and supportive measures. However, the evidence is limited and the logistical nuances of conducting a randomized controlled trial in the geriatric population would be ethically challenging.

Low continuation of antipsychotic therapy in Parkinson disease \u2013 intolerance, ineffectiveness, or inertia?

BackgroundAntipsychotics are used in Parkinson disease (PD) to treat psychosis, mood, and behavioral disturbances. Commonly used antipsychotics differ substantially in their potential to worsen motor symptoms through dopaminergic receptor blockade. Recent real-world data on the use and continuation of antipsychotic therapy in PD are lacking. The objectives of this study are to (1) examine the continuation of overall and initial antipsychotic therapy in individuals with PD and (2) determine whether continuation varies by drug dopamine receptor blocking activity.MethodsWe conducted a retrospective cohort study using U.S. commercially insured individuals in Optum 2001–2019. Adults aged 40 years or older with PD initiating antipsychotic therapy, with continuous insurance coverage for at least 6 months following drug initiation, were included. Exposure to pimavanserin, quetiapine, clozapine, aripiprazole, risperidone, or olanzapine was identified based on pharmacy claims. Six-month continuation of overall and initial antipsychotic therapy was estimated by time to complete discontinuation or switching to a different antipsychotic. Cox proportional hazards models evaluated factors associated with discontinuation.ResultsOverall, 38.6% of 3566 PD patients in our sample discontinued antipsychotic therapy after the first prescription, 61.4% continued with overall treatment within 6 months of initiation. Clozapine use was too rare to include in statistical analyses. Overall therapy discontinuation was more likely for those who initiated medications with known dopamine-receptor blocking activity (adjusted hazard ratios 1.76 [95% confidence interval 1.40–2.20] for quetiapine, 2.15 [1.61–2.86] for aripiprazole, 2.12 [1.66–2.72] for risperidone, and 2.07 [1.60–2.67] for olanzapine), compared with serotonin receptor-specific pimavanserin. Initial antipsychotic therapy discontinuation also associated with greater dopamine-receptor blocking activity medication use – adjusted hazard ratios 1.57 (1.28–1.94), 1.88 (1.43–2.46), 2.00 (1.59–2.52) and 2.03 (1.60–2.58) for quetiapine, aripiprazole, risperidone, and olanzapine, respectively, compared with pimavanserin. Similar results were observed in sensitivity analyses.ConclusionsOver one-third of individuals with PD discontinued antipsychotic therapy, especially if the initial drug has greater dopamine-receptor blocking activity. Understanding the drivers of antipsychotic discontinuation, including ineffectiveness, potentially inappropriate use, clinician inertia, patient adherence and adverse effects, is needed to inform clinical management of psychosis in PD and appropriate antipsychotic use in this population.

Transmodulation of Dopaminergic Signaling to Mitigate Hypodopminergia and Pharmaceutical Opioid-Induced Hyperalgesia.

Neuroscientists and psychiatrists working in the areas of "pain and addiction" are asked in this perspective article to reconsider the current use of dopaminergic blockade (like chronic opioid agonist therapy), and instead to consider induction of dopamine homeostasis by putative pro-dopamine regulation. Pro-dopamine regulation could help pharmaceutical opioid analgesic agents to mitigate hypodopaminergia-induced hyperalgesia by inducing transmodulation of dopaminergic signaling. An optimistic view is that early predisposition to diagnosis based on genetic testing, (pharmacogenetic/pharmacogenomic monitoring), combined with appropriate urine drug screening, and treatment with pro-dopamine regulators, could conceivably reduce stress, craving, and relapse, enhance well-being and attenuate unwanted hyperalgesia. These concepts require intensive investigation. However, based on the rationale provided herein, there is a good chance that combining opioid analgesics with genetically directed pro-dopamine-regulation using KB220 (supported by 43 clinical studies). This may become a front-line technology with the potential to overcome, in part, the current heightened rates of chronic opioid-induced hyperalgesia and concomitant Reward Deficiency Syndrome (RDS) behaviors. Current research does support the hypothesis that low or hypodopaminergic function in the brain may predispose individuals to low pain tolerance or hyperalgesia.

The longitudinal effect of antipsychotic burden on psychosocial functioning in first-episode psychosis patients: the role of verbal memory.

Previous literature supports antipsychotics' (AP) efficacy in acute first-episode psychosis (FEP) in terms of symptomatology and functioning but also a cognitive detrimental effect. However, regarding functional recovery in stabilised patients, these effects are not clear. Therefore, the main aim of this study is to investigate dopaminergic/anticholinergic burden of (AP) on psychosocial functioning in FEP. We also examined whether cognitive impairment may mediate these effects on functioning. A total of 157 FEP participants were assessed at study entry, and at 2 months and 2 years after remission of the acute episode. The primary outcomes were social functioning as measured by the functioning assessment short test (FAST). Cognitive domains were assessed as potential mediators. Dopaminergic and anticholinergic AP burden on 2-year psychosocial functioning [measured with chlorpromazine (CPZ) and drug burden index] were independent variables. Secondary outcomes were clinical and socio-demographic variables. Mediation analysis found a statistical but not meaningful contribution of dopaminergic receptor blockade burden to worse functioning mediated by cognition (for every 600 CPZ equivalent points, 2-year FAST score increased 1.38 points). Regarding verbal memory and attention, there was an indirect effect of CPZ burden on FAST (b = 0.0045, 95% CI 0.0011-0.0091) and (b = 0.0026, 95% CI 0.0001-0.0006) respectively. However, only verbal memory post hoc analyses showed a significant indirect effect (b = 0.009, 95% CI 0.033-0.0151) adding premorbid IQ as covariate. We did not find significant results for anticholinergic burden. CPZ dose effect over functioning is mediated by verbal memory but this association appears barely relevant.

Clinical Course, Neurobiology and Therapeutic Approaches to Treatment Resistant Schizophrenia. Toward an Integrated View.

Despite considerable psychotherapeutic advancement since the discovery of chlorpromazine, almost one third of patients with schizophrenia remain resistant to dopamine-blocking antipsychotics, and continue to be exposed to unwanted and often disabling side effects, but little if any clinical benefit. Even clozapine, the superior antipsychotic treatment, is ineffective in approximately half of these patients. Thus treatment resistant schizophrenia (TRS), continues to present a major therapeutic challenge to psychiatry. The main impediment to finding novel treatments is the lack of understanding of precise molecular mechanisms leading to TRS. Not only has the neurobiology been enigmatic for decades, but accurate and early detection of patients who are at risk of not responding to dopaminergic blockade remains elusive. Fortunately, recent work has started to unravel some of the neurobiological mechanisms underlying treatment resistance, providing long awaited answers, at least to some extent. Here we focus on the scientific advances in the field, from the clinical course of TRS to neurobiology and available treatment options. We specifically emphasize emerging evidence from TRS imaging and genetic literature that implicates dysregulation in several neurotransmitters, particularly dopamine and glutamate, and in addition genetic and neural alterations that concertedly may lead to the formation of TRS. Finally, we integrate available findings into a putative model of TRS, which may provide a platform for future studies in a bid to open the avenues for subsequent development of effective therapeutics.

Influence of Dopaminergic Blockade on Stress Responses, Motivation and Emotional Reactivity in Humans.

Influence of Dopaminergic Blockade on Stress Responses, Motivation and Emotional Reactivity in Humans.

The neuroanatomical pattern of sex and gender in cis/transgender individuals revealed by machine learning-based pattern recognition with NeuroMiner

The medial prefrontal cortex (mPFC) has reciprocal projections with many cerebral structures that are crucial in the control of food ingestion behavior and reward processing; Thus the mPFC has an important function in taste memory recognition. Previous results indicate that long-term consumption of sugar produces changes in appetitive re-learning and suggest that this could trigger an escalating consumption due to the inability to learn new negative consequences related to the same taste. Further evidence suggests that general identity reward value could be encoded in the mPFC. Therefore, the purpose of this study was to evaluate in rats whether after 21 days of sugar consumption the increase in sweet taste preference and latent inhibition of conditioned taste aversion (CTA) were affected differentially by pharmacological activation or blockage of dopaminergic and β-adrenergic receptors, in the mPFC, during CTA acquisition. Results showed that after long-term sugar exposure, mPFC activation of β-adrenergic receptors with clenbuterol delayed aversive memory extinction, but the blockade with propranolol or activation of dopaminergic receptors with apomorphine increased CTA latent inhibition and accelerated aversive memory extinction only after acute sugar exposure. Only dopaminergic blockade with haloperidol prevented sweet taste preference expression after long-term sugar consumption, increased CTA latent inhibition and accelerated extinction after acute sugar exposure. Taken together, the present data provide evidence that catecholaminergic receptors in the mPFC after prolonged sugar consumption underwent functional changes related to re-learning and new aversive taste learning.

Introducing Precision Addiction Management of Reward Deficiency Syndrome, the Construct That Underpins All Addictive Behaviors.

These basic concepts underpin translational addiction-related research that can help the multitude of victims of genetically induced RDS become the recipients of better therapeutic relapse-preventive tactics. Finally, as neuroscientists and psychiatrists, working in the “addiction space” we encourage the global scientific community to take heed and reconsider the current utilization of dopaminergic blockade and instead adopt the goal of regaining dopamine homeostasis. Optimistically, early predisposition diagnosis through genetic testing; including pharmacogenetic and pharmacogenomic monitoring, with appropriate urine drug screening, and treatment with pro-dopamine regulators could conceivably reduce stress, craving, and relapse and enhance well-being in the recovery community. Following required basic and clinically directed research, the notion of genetically guided therapy may become a front-line technology with the potential to overcome, in part, the current heightened rates of substance abuse.

The acute efficacy of antipsychotics in schizophrenia: a review of recent meta-analyses.

Schizophrenia is the eighth leading cause of disability worldwide in people aged 15-44 years. Before antidopaminergic antipsychotics were introduced in the 1950s, no effective medications existed for the treatment of schizophrenia. This review summarizes key meta-analytic findings regarding antipsychotic efficacy in the acute treatment of schizophrenia, including clozapine in treatment-resistant patients. In the most comprehensive meta-analysis of randomized controlled trials conducted in multi-episode schizophrenia, antipsychotics outperformed placebo regarding total symptoms, positive symptoms, negative symptoms, depressive symptoms, quality of life and social functioning. Amongst these outcomes, the standardized mean difference for overall symptoms was largest, that is, 0.47 (95% credible interval = 0.42-0.51), approaching a medium effect size, being reduced to 0.38 when publication bias and small-trial effects were accounted for. A comparison of two meta-analyses indicated that first-episode patients, compared with multi-episode patients, were more likely to have at least minimal treatment response [⩾20% Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) score reduction: 81% versus 51%] and good response (⩾50% PANSS/BPRS score reduction: 52% versus 23%). In multi-episode schizophrenia, no response or worsening after 2 weeks of a therapeutic antipsychotic dose was highly predictive of not achieving a good response at endpoint (median treatment = 6 weeks: specificity = 86%; positive predictive value = 90%), suggesting a change in treatment should be considered in such cases. In first-episode psychosis, adequately dosed antipsychotic treatment trials for more than 2 weeks are recommended before using no response or worsening as a decision point for aborting a given antipsychotic. In clearly defined treatment-resistant schizophrenia, clozapine generally outperformed other antipsychotics, especially when dosed appropriately (target = 3-6 months' duration; trough clozapine level ⩾350-400 μg/L) with a response rate (⩾20% PANSS/BPRS) of 33% by 3 months of treatment. High antipsychotic doses and psychotropic combinations are unlikely to be superior to standard doses of antipsychotic monotherapy. Acute antipsychotic efficacy in schizophrenia depends on the targeted symptom domain (greater efficacy: total and positive symptoms, lesser efficacy: negative symptoms, depressive symptoms, social functioning and quality of life). Greater antipsychotic efficacy is associated with higher total baseline symptom severity, treatment-naïveté/first-episode status, shorter illness duration, and trials that are nonindustry sponsored and that have a lower placebo effect. The heterogeneity of antipsychotic response across individuals and key symptom domains, the considerable degree of nonresponse/treatment resistance in multi-episode patients, and the adverse effect potential of antipsychotics are major limitations, underscoring the need to develop new medications for the treatment of schizophrenia. Drug development should include matching patient subgroups, which are identified by means of clinical and biomarker variables, to mechanisms of action of novel medications, targeting specific symptom domains, and investigating mechanisms of action other than dopaminergic blockade.

Differential function of medial prefrontal cortex catecholaminergic receptors after long-term sugar consumption

The medial prefrontal cortex (mPFC) has reciprocal projections with many cerebral structures that are crucial in the control of food ingestion behavior and reward processing; Thus the mPFC has an important function in taste memory recognition. Previous results indicate that long-term consumption of sugar produces changes in appetitive re-learning and suggest that this could trigger an escalating consumption due to the inability to learn new negative consequences related to the same taste. Further evidence suggests that general identity reward value could be encoded in the mPFC. Therefore, the purpose of this study was to evaluate in rats whether after 21 days of sugar consumption the increase in sweet taste preference and latent inhibition of conditioned taste aversion (CTA) were affected differentially by pharmacological activation or blockage of dopaminergic and β-adrenergic receptors, in the mPFC, during CTA acquisition. Results showed that after long-term sugar exposure, mPFC activation of β-adrenergic receptors with clenbuterol delayed aversive memory extinction, but the blockade with propranolol or activation of dopaminergic receptors with apomorphine increased CTA latent inhibition and accelerated aversive memory extinction only after acute sugar exposure. Only dopaminergic blockade with haloperidol prevented sweet taste preference expression after long-term sugar consumption, increased CTA latent inhibition and accelerated extinction after acute sugar exposure. Taken together, the present data provide evidence that catecholaminergic receptors in the mPFC after prolonged sugar consumption underwent functional changes related to re-learning and new aversive taste learning.

Neuroleptic Malignant Syndrome and Elevated CSF Protein with Quetiapine: Case Report and Review of Literature

Neuroleptic malignant syndrome (NMS) is a well-known complication of dopaminergic blockade. While there have been many case reports on Quetiapine-induced NMS, cerebrospinal fluid (CSF) abnormalities have never been documented. We report this case of bipolar affective disorder who had a previous history of Risperidone-induced parkinsonian rigidity. He presented to us 20 days after increasing lithium dose and starting Quetiapine and lamotrigine for an acute episode of mania. He had coarse tremors at rest, hyperthermia, altered sensorium and elevated creatine phosphokinase (CPK). CSF analysis showed elevated protein with no cells. A provisional diagnosis NMS was made and he was given bromocriptine. Patient’s hyperthermia resolved and CPK normalized with this treatment. He was subsequently discharged and is in follow up for his bipolar disorder.

Two subgroups of antipsychotic-naive, first-episode schizophrenia patients identified with a Gaussian mixture model on cognition and electrophysiology

Deficits in information processing and cognition are among the most robust findings in schizophrenia patients. Previous efforts to translate group-level deficits into clinically relevant and individualized information have, however, been non-successful, which is possibly explained by biologically different disease subgroups. We applied machine learning algorithms on measures of electrophysiology and cognition to identify potential subgroups of schizophrenia. Next, we explored subgroup differences regarding treatment response. Sixty-six antipsychotic-naive first-episode schizophrenia patients and sixty-five healthy controls underwent extensive electrophysiological and neurocognitive test batteries. Patients were assessed on the Positive and Negative Syndrome Scale (PANSS) before and after 6 weeks of monotherapy with the relatively selective D2 receptor antagonist, amisulpride (280.3±159 mg per day). A reduced principal component space based on 19 electrophysiological variables and 26 cognitive variables was used as input for a Gaussian mixture model to identify subgroups of patients. With support vector machines, we explored the relation between PANSS subscores and the identified subgroups. We identified two statistically distinct subgroups of patients. We found no significant baseline psychopathological differences between these subgroups, but the effect of treatment in the groups was predicted with an accuracy of 74.3% (P=0.003). In conclusion, electrophysiology and cognition data may be used to classify subgroups of schizophrenia patients. The two distinct subgroups, which we identified, were psychopathologically inseparable before treatment, yet their response to dopaminergic blockade was predicted with significant accuracy. This proof of principle encourages further endeavors to apply data-driven, multivariate and multimodal models to facilitate progress from symptom-based psychiatry toward individualized treatment regimens.

Dopaminergic contributions to working memory-related brain activation in postmenopausal women.

The current study examined the effects of pharmacologic dopaminergic manipulations on working memory-related brain activation in postmenopausal women to further understand the neurochemistry underlying cognition after menopause. Eighteen healthy postmenopausal women, mean age 55.21 years, completed three study days with dopaminergic drug challenges during which they performed a functional magnetic resonance imaging visual verbal N-back test of working memory. Acute stimulation with 1.25 mg oral D2 agonist bromocriptine, acute blockade with 1.5 mg oral haloperidol, and matching placebo were administered randomly and blindly on three study days. We found that dopaminergic stimulation increased activation primarily in the posterior regions of the working memory network compared with dopaminergic blockade using a whole brain cluster-level corrected analysis. The dopaminergic medications did not affect working memory performance. Patterns of increased blood-oxygen-level dependent signal activation after dopaminergic stimulation were found in this study in posterior brain regions with no effect on working memory performance. Further studies should examine specific dopaminergic contributions to brain functioning in healthy postmenopausal women to determine the effects of the increased brain activation on cognition and behavior.

Positive changes in the severity of residual psychotic symptoms in schizophrenic patients switched to treatment with risperidone

To evaluate the effect of changing therapy from typical antipsychotics to the atypical antipsychotic risperidone in the treatment of difficult-to-treat residual psychotic symptoms. The study included 15 patients, 8 men and 7 women, mean age 49.1±10.25 years, diagnosed with paranoid schizophrenia, partial remission (ICD-10 F20.04). At the beginning all participants received regular maintenance antipsychotic therapy with typical antipsychotics. The patient assessment with the PANSS, CGI scale and GAF scale was performed at the beginning (before the change of antipsychotics to risperidone) and in the end of the study. The primary efficacy endpoint was a reduction in scores on the PANSS items P1 'delusions' and P3 'hallucinatory behavior' to 1 (no such symptom) or 2 (minimal residual symptom). Secondary criteria were positive changes in the severity of other psychopathological symptoms and an increase in the social functioning level. The average dose of risperidone was 4.62±1.35 mg. The duration of treatment was 2 month. After switching from typical antipsychotics to risperidone and two months monotherapy, there were significant positive changes in the total PANSS score as well as in positive subscale score and CGI-S score. The small, but statistically significant, changes were detected in the overall functioning of the patients (the increase in the GAF score). The dynamics of residual psychotic symptoms was unequal: the severity of hallucinatory symptoms decreased significantly while the delusional symptoms remained unchanged. The authors suggest that excessive dopaminergic blockade might play a significant role in the pathogenesis of residual symptoms. This fact may explain the positive effect of treatment in the cases with the less degree of dopaminergic blockade. If it is true, the treatment strategy in the maintenance phase should not be a direct continuation of acute phase therapy and switching to other drugs and changing of the dose are needed.

Dopaminergic receptor blockade changes a functional connectivity network centred on the amygdala.

Resting-state connectivity has become an increasingly important measure in characterizing the functional integrity of brain circuits in neuro-psychiatric conditions. One approach that has recently gained prominence in this regard-and which we use in this study-is to investigate how resting-state connectivity depends on the integrity of certain neuromodulator systems. Here, we use a pharmacological challenge in combination with functional magnetic resonance imaging to investigate the impact of dopaminergic receptor blockade on whole brain functional connectivity in twenty healthy human subjects. Administration of the D2-receptor antagonist haloperidol led to a profound change in functional integration in network nodes linked to the amygdala. Compared to placebo and baseline measurements, network-based statistics and pairwise connectivity analyses revealed reduced connectivity and decreased link strength between the amygdala and the bilateral posterior cingulate cortex and other cortical areas. This was complemented by less extensive but very circumscribed enhanced connectivity between the amygdala and the right putamen during D2-receptor blockade. It will be interesting to investigate whether these pharmacologically induced shifts in resting-state connectivity will similarly be evident in clinical conditions that involve a dysfunction of the dopaminergic system. Our findings might also aid in interpreting alterations in more complex states, such as those seen psychiatric conditions and their treatment. Hum Brain Mapp 37:4148-4157, 2016. © 2016 Wiley Periodicals, Inc.

P.1.g.075 - Psilocybin-induced psychosis in humans and in rats − translational quantitative EEG study

The medial prefrontal cortex (mPFC) has reciprocal projections with many cerebral structures that are crucial in the control of food ingestion behavior and reward processing; Thus the mPFC has an important function in taste memory recognition. Previous results indicate that long-term consumption of sugar produces changes in appetitive re-learning and suggest that this could trigger an escalating consumption due to the inability to learn new negative consequences related to the same taste. Further evidence suggests that general identity reward value could be encoded in the mPFC. Therefore, the purpose of this study was to evaluate in rats whether after 21 days of sugar consumption the increase in sweet taste preference and latent inhibition of conditioned taste aversion (CTA) were affected differentially by pharmacological activation or blockage of dopaminergic and β-adrenergic receptors, in the mPFC, during CTA acquisition. Results showed that after long-term sugar exposure, mPFC activation of β-adrenergic receptors with clenbuterol delayed aversive memory extinction, but the blockade with propranolol or activation of dopaminergic receptors with apomorphine increased CTA latent inhibition and accelerated aversive memory extinction only after acute sugar exposure. Only dopaminergic blockade with haloperidol prevented sweet taste preference expression after long-term sugar consumption, increased CTA latent inhibition and accelerated extinction after acute sugar exposure. Taken together, the present data provide evidence that catecholaminergic receptors in the mPFC after prolonged sugar consumption underwent functional changes related to re-learning and new aversive taste learning.

Is My Son Autistic?

Is My Son Autistic?

Induced Obsessive Compulsive Symptoms (OCS) in schizophrenia patients under Atypical 2 Antipsychotics (AAPs): review and hypotheses.

The prevalence of OCS and OCD is higher in schizophrenic patients than in the general population. These disorders are sometimes induced by AAPs. There is higher frequency of OCS and greater severity in patients treated with antipsychotics with predominant anti-serotoninergic profiles opposed to those with predominant dopaminergic blockade. Induced OCS may be due to complex neuromodulation involving many serotonin, dopamine and glutamate receptors and several subtypes. Concerning connectivity, AAPs differentially influence the BOLD signal, depending on the intensity of D2 receptor blockade. The OFC could play a significant role, on account of its involvement in inhibitory control. There is a paradox: AAPs are efficient as augmentation to SSRI in treatment resistant OCD, some of them such as risperidone or aripiprazole have favourable effects in schizoptypic OCD, but AAPs cause induced OCS in schizophrenic patients. When prescribing AAPs, we should inform patients about this potential side effect and assess systematically OCS with Y-BOCS assessment after 1 month of treatment. Afterwards there are different strategies: Aripiprazole in combination can reduce OCS induced by clozapine, SSRI are slightly effective and CBT shows a few encouraging results. OCS are sometimes dose-dependent, so we also recommend prescribing the minimum effective dose and gradual introduction.

Emotional support, depressive symptoms and age-related alterations in male body composition

The prevalence of OCS and OCD is higher in schizophrenic patients than in the general population. These disorders are sometimes induced by AAPs. There is higher frequency of OCS and greater severity in patients treated with antipsychotics with predominant anti-serotoninergic profiles opposed to those with predominant dopaminergic blockade. Induced OCS may be due to complex neuromodulation involving many serotonin, dopamine and glutamate receptors and several subtypes. Concerning connectivity, AAPs differentially influence the BOLD signal, depending on the intensity of D2 receptor blockade. The OFC could play a significant role, on account of its involvement in inhibitory control. There is a paradox: AAPs are efficient as augmentation to SSRI in treatment resistant OCD, some of them such as risperidone or aripiprazole have favourable effects in schizoptypic OCD, but AAPs cause induced OCS in schizophrenic patients. When prescribing AAPs, we should inform patients about this potential side effect and assess systematically OCS with Y-BOCS assessment after 1 month of treatment. Afterwards there are different strategies: Aripiprazole in combination can reduce OCS induced by clozapine, SSRI are slightly effective and CBT shows a few encouraging results. OCS are sometimes dose-dependent, so we also recommend prescribing the minimum effective dose and gradual introduction.