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Article: New directions in therapeutics for Huntington disease.

Potkin, Katya T / Potkin, Steven G

Future neurology

2018 Volume 13, Issue 2, Page(s) 101–121

Abstract: Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disease that affects motor, cognitive and psychiatric functions, and ultimately leads to death. The pathology of the disease is based on an expansion of CAG repeats in exon 1 ... ...

Abstract	Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disease that affects motor, cognitive and psychiatric functions, and ultimately leads to death. The pathology of the disease is based on an expansion of CAG repeats in exon 1 of the
Language	English
Publishing date	2018-05-29
Publishing country	England
Document type	Journal Article ; Review
ISSN	1479-6708
ISSN	1479-6708
DOI	10.2217/fnl-2017-0035
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Article ; Online: Asenapine: a clinical overview.

Potkin, Steven G

The Journal of clinical psychiatry

2011 Volume 72 Suppl 1, Page(s) 14–18

Abstract: Asenapine is a new, second-generation (atypical) antipsychotic medication with demonstrated efficacy for the acute and maintenance treatment of schizophrenia. It is administered as sublingual tablets in doses of 5 or 10 mg bid. It is well tolerated, with ...

Abstract	Asenapine is a new, second-generation (atypical) antipsychotic medication with demonstrated efficacy for the acute and maintenance treatment of schizophrenia. It is administered as sublingual tablets in doses of 5 or 10 mg bid. It is well tolerated, with a dropout rate for adverse events similar to that of placebo. Asenapine is associated with a mean weight gain of less than 1 kg over a year and a relatively neutral effect on lipid and glucose levels. It can cause sedation and mild extrapyramidal side effects. Asenapine has a broad receptor affinity profile for most serotonergic, dopaminergic, and adrenergic receptors, with no appreciable affinity for muscarinic receptors. Asenapine may be a helpful treatment option for patients with schizophrenia when weight gain, dyslipidemia, and endocrine abnormalities are a concern.
MeSH term(s)	Antipsychotic Agents/administration & dosage ; Antipsychotic Agents/adverse effects ; Blood Glucose/drug effects ; Dyslipidemias/chemically induced ; Heterocyclic Compounds, 4 or More Rings/administration & dosage ; Heterocyclic Compounds, 4 or More Rings/adverse effects ; Humans ; Schizophrenia/drug therapy ; Treatment Outcome ; Weight Gain/drug effects
Chemical Substances	Antipsychotic Agents ; Blood Glucose ; Heterocyclic Compounds, 4 or More Rings ; Asenapine (JKZ19V908O)
Language	English
Publishing date	2011
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	716287-x
ISSN	1555-2101 ; 0160-6689
ISSN (online)	1555-2101
ISSN	0160-6689
DOI	10.4088/JCP.10075su1.03
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Article ; Online: Aripiprazole once-monthly long-acting injectable for the treatment of schizophrenia.

Potkin, Steven G / Preda, Adrian

Expert opinion on pharmacotherapy

2016 Volume 17, Issue 3, Page(s) 395–407

Abstract: Introduction: Patient non-adherence increases the risk for relapse and the long-term care of schizophrenia. Long-acting injectable (LAI) antipsychotics can decrease this risk by ensuring adherence. An extended formulation, aripiprazole 400 mg once- ... ...

Abstract	Introduction: Patient non-adherence increases the risk for relapse and the long-term care of schizophrenia. Long-acting injectable (LAI) antipsychotics can decrease this risk by ensuring adherence. An extended formulation, aripiprazole 400 mg once-monthly (AOM 400) LAI (AOM LAI), received regulatory approval in the year 2013 for the treatment of schizophrenia. AOM LAI is the first dopamine D2 partial agonist available in a long-acting formulation for the treatment of schizophrenia. Areas covered: This review covers data on the efficacy and tolerability/safety of AOM LAI. AOM LAI is a lyophilized powder of aripiprazole, with an elimination half-life of 29.9 - 46.5 days, allowing for a 4-week injection interval. Antipsychotic efficacy was documented in a 12-week double-blind trial (n = 340) and in two maintenance-of-effect trials: a 38-week trial (n = 662) and a 52-week trial (n = 403). The side effect profile is similar to that of oral aripiprazole. Adverse events (≥5% and at least twice that for placebo) were typically mild or moderate and did not lead to discontinuation: increased weight, akathisia, injection site pain and sedation. The 400 mg dose is tolerated by >90% of patients. Injection does not require additional training of health personnel or post-injection observation. Expert opinion: AOM LAI is an efficacious and well-tolerated antipsychotic treatment for schizophrenia.
MeSH term(s)	Antipsychotic Agents/pharmacokinetics ; Antipsychotic Agents/therapeutic use ; Aripiprazole/pharmacokinetics ; Aripiprazole/therapeutic use ; Delayed-Action Preparations ; Drug Administration Schedule ; Drug Partial Agonism ; Humans ; Injections, Intramuscular ; Randomized Controlled Trials as Topic ; Receptors, Dopamine D2/agonists ; Schizophrenia/drug therapy
Chemical Substances	Antipsychotic Agents ; Delayed-Action Preparations ; Receptors, Dopamine D2 ; Aripiprazole (82VFR53I78)
Language	English
Publishing date	2016
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1517/14656566.2015.1114100
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Zs.A 5130: Show issues

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Article: Alterations in grey matter structure linked to frequency-specific cortico-subcortical connectivity in schizophrenia via multimodal data fusion.

Duda, Marlena / Faghiri, Ashkan / Belger, Aysenil / Bustillo, Juan R / Ford, Judith M / Mathalon, Daniel H / Mueller, Bryon A / Pearlson, Godfrey D / Potkin, Steven G / Preda, Adrian / Sui, Jing / Van Erp, Theo G M / Calhoun, Vince D

bioRxiv : the preprint server for biology

2023

Abstract: Schizophrenia (SZ) is a complex psychiatric disorder that is currently defined by symptomatic and behavioral, rather than biological, criteria. Neuroimaging is an appealing avenue for SZ biomarker development, as several neuroimaging-based studies ... ...

Abstract	Schizophrenia (SZ) is a complex psychiatric disorder that is currently defined by symptomatic and behavioral, rather than biological, criteria. Neuroimaging is an appealing avenue for SZ biomarker development, as several neuroimaging-based studies comparing individuals with SZ to healthy controls (HC) have shown measurable group differences in brain structure, as well as functional brain alterations in both static and dynamic functional network connectivity (sFNC and dFNC, respectively). The recently proposed filter-banked connectivity (FBC) method extends the standard dFNC sliding-window approach to estimate FNC within an arbitrary number of distinct frequency bands. The initial implementation used a set of filters spanning the full connectivity spectral range, providing a unified approach to examine both sFNC and dFNC in a single analysis. Initial FBC results found that individuals with SZ spend more time in a less structured, more disconnected low-frequency (i.e., static) FNC state than HC, as well as preferential SZ occupancy in high-frequency connectivity states, suggesting a frequency-specific component underpinning the functional dysconnectivity observed in SZ. Building on these findings, we sought to link such frequency-specific patterns of FNC to covarying data-driven structural brain networks in the context of SZ. Specifically, we employ a multi-set canonical correlation analysis + joint independent components analysis (mCCA + jICA) data fusion framework to study the connection between grey matter volume (GMV) maps and FBC states across the full connectivity frequency spectrum. Our multimodal analysis identified two joint sources that captured co-varying patterns of frequency-specific functional connectivity and alterations in GMV with significant group differences in loading parameters between the SZ group and HC. The first joint source linked frequency-modulated connections between the subcortical and sensorimotor networks and GMV alterations in the frontal and temporal lobes, while the second joint source identified a relationship between low-frequency cerebellar-sensorimotor connectivity and structural changes in both the cerebellum and motor cortex. Together, these results show a strong connection between cortico-subcortical functional connectivity at both high and low frequencies and alterations in cortical GMV that may be relevant to the pathogenesis and pathophysiology of SZ.
Language	English
Publishing date	2023-07-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.05.547840
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Article ; Online: Reliability and clinical utility of spatially constrained estimates of intrinsic functional networks from very short fMRI scans.

Duda, Marlena / Iraji, Armin / Ford, Judith M / Lim, Kelvin O / Mathalon, Daniel H / Mueller, Bryon A / Potkin, Steven G / Preda, Adrian / Van Erp, Theo G M / Calhoun, Vince D

Human brain mapping

2023 Volume 44, Issue 6, Page(s) 2620–2635

Abstract: Resting-state functional network connectivity (rsFNC) has shown utility for identifying characteristic functional brain patterns in individuals with psychiatric and mood disorders, providing a promising avenue for biomarker development. However, several ... ...

Abstract	Resting-state functional network connectivity (rsFNC) has shown utility for identifying characteristic functional brain patterns in individuals with psychiatric and mood disorders, providing a promising avenue for biomarker development. However, several factors have precluded widespread clinical adoption of rsFNC diagnostics, namely a lack of standardized approaches for capturing comparable and reproducible imaging markers across individuals, as well as the disagreement on the amount of data required to robustly detect intrinsic connectivity networks (ICNs) and diagnostically relevant patterns of rsFNC at the individual subject level. Recently, spatially constrained independent component analysis (scICA) has been proposed as an automated method for extracting ICNs standardized to a chosen network template while still preserving individual variation. Leveraging the scICA methodology, which solves the former challenge of standardized neuroimaging markers, we investigate the latter challenge of identifying a minimally sufficient data length for clinical applications of resting-state fMRI (rsfMRI). Using a dataset containing rsfMRI scans of individuals with schizophrenia and controls (M = 310) as well as simulated rsfMRI, we evaluated the robustness of ICN and rsFNC estimates at both the subject- and group-level, as well as the performance of diagnostic classification, with respect to the length of the rsfMRI time course. We found individual estimates of ICNs and rsFNC from the full-length (5 min) reference time course were sufficiently approximated with just 3-3.5 min of data (r = 0.85, 0.88, respectively), and significant differences in group-average rsFNC could be sufficiently approximated with even less data, just 2 min (r = 0.86). These results from the shorter clinical data were largely consistent with the results from validation experiments using longer time series from both simulated (30 min) and real-world (14 min) datasets, in which estimates of subject-level FNC were reliably estimated with 3-5 min of data. Moreover, in the real-world data we found rsFNC and ICN estimates generated across the full range of data lengths (0.5-14 min) more reliably matched those generated from the first 5 min of scan time than those generated from the last 5 min, suggesting increased influence of "late scan" noise factors such as fatigue or drowsiness may limit the reliability of FNC from data collected after 10+ min of scan time, further supporting the notion of shorter scans. Lastly, a diagnostic classification model trained on just 2 min of data retained 97%-98% classification accuracy relative to that of the full-length reference model. Our results suggest that, when decomposed with scICA, rsfMRI scans of just 2-5 min show good clinical utility without significant loss of individual FNC information of longer scan lengths.
MeSH term(s)	Humans ; Magnetic Resonance Imaging/methods ; Reproducibility of Results ; Brain/diagnostic imaging ; Neuroimaging ; Mood Disorders ; Brain Mapping/methods
Language	English
Publishing date	2023-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	1197207-5
ISSN	1097-0193 ; 1065-9471
ISSN (online)	1097-0193
ISSN	1065-9471
DOI	10.1002/hbm.26234
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Article: New advances in the treatment of schizophrenia. Introduction.

Potkin, Steven G

Journal of clinical psychopharmacology

2008 Volume 28, Issue 2 Suppl 1, Page(s) S1–3

MeSH term(s)	Antipsychotic Agents/adverse effects ; Antipsychotic Agents/therapeutic use ; Humans ; Isoxazoles/adverse effects ; Isoxazoles/therapeutic use ; Piperidines/adverse effects ; Piperidines/therapeutic use ; Schizophrenia/drug therapy
Chemical Substances	Antipsychotic Agents ; Isoxazoles ; Piperidines ; iloperidone (VPO7KJ050N)
Language	English
Publishing date	2008-04
Publishing country	United States
Document type	Introductory Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604631-9
ISSN	1533-712X ; 0271-0749
ISSN (online)	1533-712X
ISSN	0271-0749
DOI	10.1097/JCP.0b013e318168f758
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Zs.A 1664: Show issues

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Article ; Online: Multi-model order spatially constrained ICA reveals highly replicable group differences and consistent predictive results from resting data: A large N fMRI schizophrenia study.

Meng, Xing / Iraji, Armin / Fu, Zening / Kochunov, Peter / Belger, Aysenil / Ford, Judy M / McEwen, Sara / Mathalon, Daniel H / Mueller, Bryon A / Pearlson, Godfrey / Potkin, Steven G / Preda, Adrian / Turner, Jessica / van Erp, Theo G M / Sui, Jing / Calhoun, Vince D

NeuroImage. Clinical

2023 Volume 38, Page(s) 103434

Abstract: Brain functional networks identified from resting functional magnetic resonance imaging (fMRI) data have the potential to reveal biomarkers for brain disorders, but studies of complex mental illnesses such as schizophrenia (SZ) often yield mixed results ... ...

Abstract	Brain functional networks identified from resting functional magnetic resonance imaging (fMRI) data have the potential to reveal biomarkers for brain disorders, but studies of complex mental illnesses such as schizophrenia (SZ) often yield mixed results across replication studies. This is likely due in part to the complexity of the disorder, the short data acquisition time, and the limited ability of the approaches for brain imaging data mining. Therefore, the use of analytic approaches which can both capture individual variability while offering comparability across analyses is highly preferred. Fully blind data-driven approaches such as independent component analysis (ICA) are hard to compare across studies, and approaches that use fixed atlas-based regions can have limited sensitivity to individual sensitivity. By contrast, spatially constrained ICA (scICA) provides a hybrid, fully automated solution that can incorporate spatial network priors while also adapting to new subjects. However, scICA has thus far only been used with a single spatial scale (ICA dimensionality, i.e., ICA model order). In this work, we present an approach using multi-objective optimization scICA with reference algorithm (MOO-ICAR) to extract subject-specific intrinsic connectivity networks (ICNs) from fMRI data at multiple spatial scales, which also enables us to study interactions across spatial scales. We evaluate this approach using a large N (N > 1,600) study of schizophrenia divided into separate validation and replication sets. A multi-scale ICN template was estimated and labeled, then used as input into scICA which was computed on an individual subject level. We then performed a subsequent analysis of multiscale functional network connectivity (msFNC) to evaluate the patient data, including group differences and classification. Results showed highly consistent group differences in msFNC in regions including cerebellum, thalamus, and motor/auditory networks. Importantly, multiple msFNC pairs linking different spatial scales were implicated. The classification model built on the msFNC features obtained up to 85% F1 score, 83% precision, and 88% recall, indicating the strength of the proposed framework in detecting group differences between schizophrenia and the control group. Finally, we evaluated the relationship of the identified patterns to positive symptoms and found consistent results across datasets. The results verified the robustness of our framework in evaluating brain functional connectivity of schizophrenia at multiple spatial scales, implicated consistent and replicable brain networks, and highlighted a promising approach for leveraging resting fMRI data for brain biomarker development.
MeSH term(s)	Humans ; Schizophrenia/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Brain Mapping/methods ; Brain/diagnostic imaging ; Cerebellum ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-05-17
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2023.103434
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Article ; Online: Switching patients with schizophrenia from paliperidone palmitate to aripiprazole lauroxil: A 6-month, prospective, open-label study.

Miller, Brian J / Claxton, Amy / Du, Yangchun / Weiden, Peter J / Potkin, Steven G

Schizophrenia research

2019 Volume 208, Page(s) 44–48

Abstract: We assessed the effectiveness of switching from paliperidone palmitate (PP) or risperidone long-acting injection (RLAI) to aripiprazole lauroxil (AL). Prospective, 6-month study in patients with schizophrenia with residual symptoms or intolerance with PP/ ...

Abstract	We assessed the effectiveness of switching from paliperidone palmitate (PP) or risperidone long-acting injection (RLAI) to aripiprazole lauroxil (AL). Prospective, 6-month study in patients with schizophrenia with residual symptoms or intolerance with PP/RLAI. Effectiveness assessed via all-cause and medication-related discontinuation; CGI-S/BPRS and adverse event monitoring assessed efficacy/tolerability, respectively. Fifty-one patients (n = 50 PP; n = 1 RLAI) enrolled; 35 completed the study. All-cause and medication-related discontinuation was 30% and 9% over 6 months, respectively. CGI-S/BPRS improved significantly in those continuing treatment. Adverse events were generally mild to moderate. Patients with efficacy or tolerability concerns with PP/RLAI can be switched to AL.
MeSH term(s)	Adult ; Antipsychotic Agents/administration & dosage ; Antipsychotic Agents/adverse effects ; Aripiprazole/administration & dosage ; Aripiprazole/adverse effects ; Delayed-Action Preparations ; Drug Substitution ; Female ; Humans ; Injections ; Male ; Middle Aged ; Outcome Assessment, Health Care ; Paliperidone Palmitate/administration & dosage ; Paliperidone Palmitate/adverse effects ; Prospective Studies ; Schizophrenia
Chemical Substances	Antipsychotic Agents ; Delayed-Action Preparations ; Aripiprazole (82VFR53I78) ; aripiprazole lauroxil (B786J7A343) ; Paliperidone Palmitate (R8P8USM8FR)
Language	English
Publishing date	2019-02-07
Publishing country	Netherlands
Document type	Clinical Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639422-x
ISSN	1573-2509 ; 0920-9964
ISSN (online)	1573-2509
ISSN	0920-9964
DOI	10.1016/j.schres.2019.01.038
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Zs.A 2351: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 543: Show issues

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Article: The Neurobiology of Treatment-Resistant Schizophrenia: Paths to Antipsychotic Resistance and A Roadmap for Future Research.

Potkin, Steven G / Kane, John M / Correll, Christoph U / Lindenmayer, Jean-Pierre / Agid, Ofer / Marder, Stephen R / Olfson, Mark / Howes, Oliver D

Focus (American Psychiatric Publishing)

2020 Volume 18, Issue 4, Page(s) 456–465

Abstract: Reprinted with permission ... ...

Abstract	(Reprinted with permission from
Language	English
Publishing date	2020-11-05
Publishing country	United States
Document type	Journal Article
ISSN	1541-4094
ISSN	1541-4094
DOI	10.1176/appi.focus.18309
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Article ; Online: Long-Term Remission With Cariprazine Treatment in Patients With Schizophrenia: A Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Relapse Prevention Trial.

Correll, Christoph U / Potkin, Steven G / Zhong, Yan / Harsányi, Judit / Szatmári, Balázs / Earley, Willie

The Journal of clinical psychiatry

2019 Volume 80, Issue 2

Abstract: Background: Long-term remission is an important treatment goal in schizophrenia. Cariprazine, a dopamine D₃/D₂ receptor and serotonin 5-HT1A receptor partial agonist, is approved in the United States and Europe to treat adults with schizophrenia.: ... ...

Abstract	Background: Long-term remission is an important treatment goal in schizophrenia. Cariprazine, a dopamine D₃/D₂ receptor and serotonin 5-HT1A receptor partial agonist, is approved in the United States and Europe to treat adults with schizophrenia. Methods: Post hoc analyses of data from a long-term cariprazine relapse prevention study (NCT01412060; September 27, 2011-September 3, 2014) investigated the efficacy of cariprazine for maintaining remission in clinically stable patients with DSM-IV-TR-defined schizophrenia. Patients were stabilized with open-label cariprazine (20 weeks), then randomized 1:1 to cariprazine (3, 6, or 9 mg/d) or placebo for double-blind treatment (up to 72 weeks). Symptomatic remission was defined as scores ≤ 3 on 8 items from the General, Positive, and Negative Symptoms subscales of the Positive and Negative Syndrome Scale (PANSS). Sustained remission included meeting remission criteria at the current and all prior double-blind visits or for ≥ 6 consecutive months. Results: At randomization, 169/200 patients (84.5%) met symptomatic remission criteria. During double-blind treatment, time to loss of sustained remission was significantly longer (P = .0020) for cariprazine versus placebo (hazard ratio = 0.51); 60.5% of cariprazine-treated and 34.9% of placebo-treated patients sustained remission through the final visit (odds ratio [OR] = 2.85; P = .0012; number needed to treat [NNT] = 4). Almost twice as many cariprazine-treated (39.6%) as placebo-treated (21.2%) patients met symptomatic remission criteria at all visits ≥ 6 consecutive months immediately before/including the final double-blind visit (OR = 2.44; P = .0057; NNT = 6). More cariprazine-treated (41.6%) than placebo-treated (27.3%) patients sustained remission for any ≥ 6 consecutive month period (OR = 1.90, P = .0379; NNT = 7). Conclusions: Cariprazine was associated with significantly longer sustained remission, higher remission rates, and increased likelihood of sustaining remission for ≥ 6 consecutive months versus placebo. Trial registration: ClinicalTrials.gov identifier: NCT01412060.
MeSH term(s)	Adult ; Antipsychotic Agents/therapeutic use ; Double-Blind Method ; Female ; Humans ; Male ; Piperazines/therapeutic use ; Schizophrenia/drug therapy ; Secondary Prevention ; Time Factors ; Treatment Outcome ; Young Adult
Chemical Substances	Antipsychotic Agents ; Piperazines ; cariprazine (F6RJL8B278)
Language	English
Publishing date	2019-01-08
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	716287-x
ISSN	1555-2101 ; 0160-6689
ISSN (online)	1555-2101
ISSN	0160-6689
DOI	10.4088/JCP.18m12495
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