Device-Based Modulation of Neurocircuits as a Therapeutic for Psychiatric Disorders.
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ABSTRACT:
SUBMITTER: Deng ZD
PROVIDER: S-EPMC8100981 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDeep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders.Objective/Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field.MethodsWe implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators.ResultsIntraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°).ConclusionThis novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders.
| S-EPMC10787578 | biostudies-literature
Project description:BackgroundConnectomic modeling studies are expanding understanding of the brain networks that are modulated by deep brain stimulation (DBS) therapies. However, explicit integration of these modeling results into prospective neurosurgical planning is only beginning to evolve. One challenge of employing connectomic models in patient-specific surgical planning is the inherent 3D nature of the results, which can make clinically useful data integration and visualization difficult.MethodsWe developed a holographic stereotactic neurosurgery research tool (HoloSNS) that integrates patient-specific brain models into a group-based visualization environment for interactive surgical planning using connectomic hypotheses. HoloSNS currently runs on the HoloLens 2 platform and it enables remote networking between headsets. This allowed us to perform surgical planning group meetings with study co-investigators distributed across the country.ResultsWe used HoloSNS to plan stereo-EEG and DBS electrode placements for each patient participating in a clinical trial (NCT03437928) that is targeting both the subcallosal cingulate and ventral capsule for the treatment of depression. Each patient model consisted of multiple components of scientific data and anatomical reconstructions of the head and brain (both patient-specific and atlas-based), which far exceed the data integration capabilities of traditional neurosurgical planning workstations. This allowed us to prospectively discuss and evaluate the positioning of the electrodes based on novel connectomic hypotheses.ConclusionsThe 3D nature of the surgical procedure, brain imaging data, and connectomic modeling results all highlighted the utility of employing holographic visualization to support the design of unique clinical experiments to explore brain network modulation with DBS.
| S-EPMC10784872 | biostudies-literature
Project description:Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the essential role creatine, a natural regulator of energy homeostasis, plays in brain function and development. Creatine supplementation has shown promise as a safe, effective, and tolerable adjunct to medication for the treatment of brain-related disorders linked with dysfunctional energy metabolism, such as Huntington's Disease and Parkinson's Disease. Impairments in creatine metabolism have also been implicated in the pathogenesis of psychiatric disorders, leaving clinicians, researchers and patients alike wondering if dietary creatine has therapeutic value for treating mental illness. The present review summarizes the neurobiology of the creatine-phosphocreatine circuit and its relation to psychological stress, schizophrenia, mood and anxiety disorders. While present knowledge of the role of creatine in cognitive and emotional processing is in its infancy, further research on this endogenous metabolite has the potential to advance our understanding of the biological bases of psychopathology and improve current therapeutic strategies.
| S-EPMC3340488 | biostudies-literature
Project description:Medicinal chemistry has produced small-molecule agents with drug-like character that potently and safely modulate the activity of discrete endocannabinoid system components as potential treatments for medical disorders, including various psychiatric conditions. Two cannabinoid (CB) receptors (CB1 and CB2) currently represent prime endocannabinoid-system therapeutic targets for ligands that either mimic endocannabinoid signalling processes and/or potentiate endocannabinoid-system activity (agonists) or attenuate pathologically heightened endocannabinoid-system transmission (antagonists). Two endocannabinoid deactivating enzymes, fatty acid amide hydrolase (FAAH) and soluble monoacylglycerol lipase (MGL), are increasingly prominent targets for inhibitors that indirectly potentiate endocannabinoid-system signalling. Continued profiling of drug candidates in relevant disease models, identification of additional cannabinoid-related therapeutic targets, and validation of new pharmacological modes of endocannabinoid system modulation will undoubtedly invite further translational efforts in the cannabinoid field for treating psychiatric disorders and other medical conditions.
| S-EPMC5531754 | biostudies-other
Project description:The conventional antihypertensive therapies including renin-angiotensin-aldosterone system antagonists (converting enzyme inhibitors, receptor blockers, renin inhibitors, and mineralocorticoid receptor blockers), diuretics, ?-blockers, and calcium channel blockers are variably successful in achieving the challenging target blood pressure values in hypertensive patients. Difficult to treat hypertension is still a commonly observed problem world-wide. A number of drugs are considered to be used as novel therapies for hypertension. Renalase supplementation, vasopeptidase inhibitors, endothelin antagonists, and especially aldosterone antagonists (aldosterone synthase inhibitors and novel selective mineralocorticoid receptor blockers) are considered an option in resistant hypertension. In addition, the aldosterone antagonists as well as (pro)renin receptor blockers or AT(2) receptor agonists might attenuate end-organ damage. This array of medications has now been complemented by a number of new approaches of non-pharmacological strategies including vaccination, genomic interference, controlled breathing, baroreflex activation, and probably most successfully renal denervation techniques. However, the progress on innovative therapies seems to be slow and the problem of resistant hypertension and proper blood pressure control appears to be still persisting. Therefore the regimens of currently available drugs are being fine-tuned, resulting in the establishment of several novel fixed-dose combinations including triple combinations with the aim to facilitate proper blood pressure control. It remains an exciting question which approach will confer the best blood pressure control and risk reduction in this tricky disease.
| S-EPMC3214724 | biostudies-literature
Project description:Depression is among the most common psychiatric disorders, and in many patients a disorder for which available medications provide suboptimal or no symptom relief. The most commonly prescribed class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs), are thought to act by increasing extracellular serotonin in brain by blocking its uptake via the high-affinity serotonin transporter (SERT). However, the relative lack of therapeutic efficacy of SSRIs has brought into question the utility of increasing extracellular serotonin for the treatment of depression. In this Viewpoint, we discuss why increasing extracellular serotonin should not be written off as a therapeutic strategy. We describe how "uptake-2" transporters may explain the relative lack of therapeutic efficacy of SSRIs, as well as why "uptake-2" transporters might be useful therapeutic targets.
| S-EPMC3547475 | biostudies-other
Project description:Computerized device use (CDU) is societally ubiquitous but its effects on mental health are unknown. We performed genetic correlation, Mendelian randomization, and latent causal variable analyses to identify shared genetic mechanisms between psychiatric disorders (Psychiatric Genomics Consortium; 14,477 < N < 150,064) and CDU (UK Biobank; N = 361,194 individuals). Using linkage disequilibrium score regression, we detected strong genetic correlations between "weekly usage of mobile phone in last 3 months" (PhoneUse) vs. attention deficit hyperactivity disorder (ADHD; rg = 0.425, p = 4.59 × 10-29) and "plays computer games" (CompGaming) vs. schizophrenia (SCZ; rg = -0.271, p = 7.16 × 10-26). Focusing on these correlations, we used two sample MRs to detect the causal relationships between trait pairs by treating single nucleotide polymorphisms as non-modifiable risk factors underlying both phenotypes. Significant bidirectional associations were detected (PhoneUse→ADHD β = 0.132, p = 1.89 × 10-4 and ADHD→PhoneUse β = 0.084, p = 2.86 × 10-10; CompGaming→SCZ β = -0.02, p = 6.46 × 10-25 and CompGaming→SCZ β = -0.194, p = 0.005) and the latent causal variable analyses did not support a causal relationship independent of the genetic correlations between these traits. This suggests that molecular pathways contribute to the genetic overlap between these traits. Dopamine transport enrichment (Gene Ontology:0015872, pSCZvsCompGaming = 2.74 × 10-10) and DRD2 association (pSCZ = 7.94 × 10-8; pCompGaming = 3.98 × 10-25) were detected in SCZ and CompGaming and support their negative correlative relationship. FOXP2 was significantly associated with ADHD (p = 9.32 × 10-7) and PhoneUse (p = 9.00 × 10-11) with effect directions concordant with their positive genetic correlation. Our study demonstrates that epidemiological associations between psychiatric disorders and CDUs are due, in part, to the molecular mechanisms shared between them rather than a causal relationship. Our findings imply that biological mechanisms underlying CDU contribute to the psychiatric phenotype manifestation.
| S-EPMC6947231 | biostudies-literature
Project description:139 samples from cortex and hipocampus of the mice modeling human CNVs associatted with schizophrenia: Df(h15q13)/+, Df(h15q13)/-, Df(h22q11)/+, and Df(h1q21)/+
2019-05-01 | GSE129891 | GEO
Project description:We conducted proteomic profiling of plasma, identifying both overlapping and unique differential proteins in adolescent patients diagnosed with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Our results showed that the protein signatures of adolescent psychiatric disorders differ significantly from those of adults. We propose potential targets for drug development aimed at the prevention or precision therapy of these psychiatric disorders. These findings enhance our understanding of the molecular etiology of adolescent psychiatric disorders. The specific biomolecular signatures of MDD, BD, and SZ could potentially serve as targets for the development of novel interventions aimed at prevention, early diagnosis, and treatment of these mental health conditions.
2023-09-18 | PXD045434 |
Project description:OBJECTIVE:Postpartum psychiatric disorders are common and morbid complications of pregnancy. The authors sought to evaluate how family history of psychiatric disorders is associated with postpartum psychiatric disorders in proband mothers with and without a prior psychiatric history by assessing degree of relationship, type of disorder, and sex of family members. METHOD:The authors linked Danish birth and psychiatric treatment registers to evaluate familial risk of postpartum psychiatric episodes in a national population-based cohort. Probands were first-time mothers who were born in Denmark in 1970 or later and who gave birth after age 15 and before Dec. 31, 2012 (N=362,462). The primary exposure was a diagnosed psychiatric disorder in a relative. Cox regression models were used to estimate the hazard ratio of postpartum psychiatric disorders in proband mothers. RESULTS:The relative risk of psychiatric disorders in the postpartum period was elevated when first-degree family members had a psychiatric disorder (hazard ratio=1.45, 95% CI=1.28-1.65) and highest when proband mothers had a first-degree family member with bipolar disorder (hazard ratio=2.86, 95% CI=1.88-4.35). Associations were stronger among proband mothers with no previous psychiatric history. There were no notable differences by sex of the family member. CONCLUSIONS:Family history of psychiatric disorders, especially bipolar disorder, is an important risk factor for postpartum psychiatric disorders. To assist in identification of women at risk for postpartum psychiatric disorders, questions related to female and male first-degree relatives with bipolar disorder are of the highest importance and should be added to routine clinical screening guidelines to improve prediction of risk.
| S-EPMC6070397 | biostudies-literature