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Book: The new view of self

Siever, Larry J. / Frucht, William

how genes and neurotransmitters shape your mind, your personality, and your mental health

1997

Author's details	Larry J. Siever with William Frucht
Keywords	Neurotic Disorders / etiology ; Brain / physiology ; Personality / physiology ; Behavior / physiology ; Psychiatry / trends
Language	English
Size	XIII, 257 S.
Publisher	Macmillan
Publishing place	New York u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT008402648
ISBN	0-02-861544-1 ; 978-0-02-861544-8
Database	Catalogue ZB MED Medicine, Health

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Article: The neurobiology of aggression and violence.

Rosell, Daniel R / Siever, Larry J

CNS spectrums

2015 Volume 20, Issue 3, Page(s) 254–279

Abstract: Aggression and violence represent a significant public health concern and a clinical challenge for the mental healthcare provider. A great deal has been revealed regarding the neurobiology of violence and aggression, and an integration of this body of ... ...

Abstract	Aggression and violence represent a significant public health concern and a clinical challenge for the mental healthcare provider. A great deal has been revealed regarding the neurobiology of violence and aggression, and an integration of this body of knowledge will ultimately serve to advance clinical diagnostics and therapeutic interventions. We will review here the latest findings regarding the neurobiology of aggression and violence. First, we will introduce the construct of aggression, with a focus on issues related to its heterogeneity, as well as the importance of refining the aggression phenotype in order to reduce pathophysiologic variability. Next we will examine the neuroanatomy of aggression and violence, focusing on regional volumes, functional studies, and interregional connectivity. Significant emphasis will be on the amygdala, as well as amygdala-frontal circuitry. Then we will turn our attention to the neurochemistry and molecular genetics of aggression and violence, examining the extensive findings on the serotonergic system, as well as the growing literature on the dopaminergic and vasopressinergic systems. We will also address the contribution of steroid hormones, namely, cortisol and testosterone. Finally, we will summarize these findings with a focus on reconciling inconsistencies and potential clinical implications; and, then we will suggest areas of focus for future directions in the field.
MeSH term(s)	Aggression/psychology ; Brain Chemistry ; Disruptive, Impulse Control, and Conduct Disorders/drug therapy ; Disruptive, Impulse Control, and Conduct Disorders/physiopathology ; Disruptive, Impulse Control, and Conduct Disorders/psychology ; Humans ; Neurobiology ; Serotonin Agents/therapeutic use ; Violence/psychology
Chemical Substances	Serotonin Agents
Language	English
Publishing date	2015-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2008418-3
ISSN	2165-6509 ; 1092-8529
ISSN (online)	2165-6509
ISSN	1092-8529
DOI	10.1017/S109285291500019X
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Article: Neurobiology of aggression and violence.

Siever, Larry J

The American journal of psychiatry

2008 Volume 165, Issue 4, Page(s) 429–442

Abstract: Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are ... ...

Abstract	Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are grounded in an underlying neurobiological susceptibility that is just beginning to be understood. The failure of "top-down" control systems in the prefrontal cortex to modulate aggressive acts that are triggered by anger provoking stimuli appears to play an important role. An imbalance between prefrontal regulatory influences and hyper-responsivity of the amygdala and other limbic regions involved in affective evaluation are implicated. Insufficient serotonergic facilitation of "top-down" control, excessive catecholaminergic stimulation, and subcortical imbalances of glutamatergic/gabaminergic systems as well as pathology in neuropeptide systems involved in the regulation of affiliative behavior may contribute to abnormalities in this circuitry. Thus, pharmacological interventions such as mood stabilizers, which dampen limbic irritability, or selective serotonin reuptake inhibitors (SSRIs), which may enhance "top-down" control, as well as psychosocial interventions to develop alternative coping skills and reinforce reflective delays may be therapeutic.
MeSH term(s)	Aggression/classification ; Aggression/physiology ; Aggression/psychology ; Amygdala/physiopathology ; Brain/physiopathology ; Cognition Disorders/physiopathology ; Disease Susceptibility/physiopathology ; Kindling, Neurologic/physiology ; Limbic System/physiopathology ; Models, Neurological ; Models, Psychological ; Neurotransmitter Agents/physiology ; Prefrontal Cortex/physiopathology ; Terminology as Topic ; Violence/psychology ; Violence/statistics & numerical data
Chemical Substances	Neurotransmitter Agents
Language	English
Publishing date	2008-03-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	280045-7
ISSN	1535-7228 ; 0002-953X
ISSN (online)	1535-7228
ISSN	0002-953X
DOI	10.1176/appi.ajp.2008.07111774
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Article: Endophenotypes in the personality disorders.

Siever, Larry J

Dialogues in clinical neuroscience

2005 Volume 7, Issue 2, Page(s) 139–151

Abstract: The identification of endophenotypes in the personality disorders may provide a basis for the identification of underlying genotypes that influence the traits and dimensions of the personality disorders, as well as susceptibility to major psychiatric ... ...

Abstract	The identification of endophenotypes in the personality disorders may provide a basis for the identification of underlying genotypes that influence the traits and dimensions of the personality disorders, as well as susceptibility to major psychiatric illnesses. Clinical dimensions of personality disorders that lend themselves to the study of corresponding endophenotypes include affective instability, impulsivity, aggression, emotional information processing, cognitive disorganization, social deficits, and psychosis. For example, the propensity to aggression can be evaluated by psychometric measures, interview, laboratory paradigms, neurochemical imaging, and pharmacological studies. These suggest that aggression is a measurable trait that may be related to reduced serotonergic activity. Hyperresponsiveness of amygdala and other limbic structures may be related to affective instability, while structural and functional brain alterations underlie the cognitive disorganization in psychotic-like symptoms of schizotypal personality disorder. Thus, an endophenotypic approach not only provides clues to underlying candidate genes contributing to these behavioral dimensions, but may also point the way to a better understanding of pathophysiological mechanisms.
MeSH term(s)	Genetic Predisposition to Disease ; Humans ; Personality Disorders/genetics ; Personality Disorders/physiopathology ; Phenotype
Language	English
Publishing date	2005
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	2188781-0
ISSN	1294-8322
ISSN	1294-8322
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Hypermentalization in adolescents with borderline personality traits: extending the conceptual framework to younger ages.

Goodman, Marianne / Siever, Larry J

Journal of the American Academy of Child and Adolescent Psychiatry

2011 Volume 50, Issue 6, Page(s) 536–537

MeSH term(s)	Borderline Personality Disorder/diagnosis ; Emotional Intelligence ; Female ; Humans ; Internal-External Control ; Male ; Theory of Mind
Language	English
Publishing date	2011-06
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	392535-3
ISSN	1527-5418 ; 0890-8567
ISSN (online)	1527-5418
ISSN	0890-8567
DOI	10.1016/j.jaac.2011.02.013
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Article: Refining the approaches to personality disorders.

Siever, Larry J

CNS spectrums

2003 Volume 8, Issue 10, Page(s) 724

MeSH term(s)	Adult ; Affect ; Brain/physiopathology ; Child ; Child Abuse/psychology ; Family ; Humans ; Personality Disorders/diagnosis ; Personality Disorders/physiopathology ; Self Disclosure ; Stress Disorders, Post-Traumatic/psychology
Language	English
Publishing date	2003-11-05
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	2008418-3
ISSN	2165-6509 ; 1092-8529
ISSN (online)	2165-6509
ISSN	1092-8529
DOI	10.1017/s1092852900019088
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Article: The neurobiology of personality disorders: implications for psychoanalysis.

Siever, Larry J / Weinstein, Lissa N

Journal of the American Psychoanalytic Association

2009 Volume 57, Issue 2, Page(s) 361–398

Abstract: As advances in neuroscience have furthered our understanding of the role of brain circuitry, genetics, stress, and neuromodulators in the regulation of normal behavior and in the pathogenesis of psychopathology, an increasing appreciation of the role of ... ...

Abstract	As advances in neuroscience have furthered our understanding of the role of brain circuitry, genetics, stress, and neuromodulators in the regulation of normal behavior and in the pathogenesis of psychopathology, an increasing appreciation of the role of neurobiology in individual differences in personality and their pathology in personality disorders has emerged. Individual differences in the regulation and organization of cognitive processes, affective reactivity, impulse/action patterns, and anxiety may in the extreme provide susceptibilities to personality disorders such as borderline and schizotypal personality disorder. A low threshold for impulsive aggression, as observed in borderline and antisocial personality disorders, may be related to excessive amygdala reactivity, reduced prefrontal inhibition, and diminished serotonergic facilitation of prefrontal controls. Affective instability may be mediated by excessive limbic reactivity in gabaminergic/glutamatergic/cholinergic circuits, resulting in an increased sensitivity or reactivity to environmental emotional stimuli as in borderline personality disorder and other cluster B personality disorders. Disturbances in cognitive organization and information processing may contribute to the detachment, desynchrony with the environment, and cognitive/perceptional distortions of cluster A or schizophrenia spectrum personality disorders. A low threshold for anxiety may contribute to the avoidant, dependent, and compulsive behaviors observed in cluster C personality disorders. These alterations in critical regulatory domains will influence how representations of self and others are internalized. Aspects of neurobiological functioning themselves become cognized through the medium of figurative language into an ongoing narrative of the self, one that can be transformed through the analytic process, allowing for the modulation of genetic/biological thresholds.
MeSH term(s)	Brain/physiopathology ; Brain Mapping ; Humans ; Nerve Net/physiopathology ; Neurotransmitter Agents/physiology ; Personality Disorders/physiopathology ; Personality Disorders/psychology ; Personality Disorders/therapy ; Psychoanalytic Theory ; Psychoanalytic Therapy ; Temperament/physiology
Chemical Substances	Neurotransmitter Agents
Language	English
Publishing date	2009-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	219420-x
ISSN	1941-2460 ; 0003-0651
ISSN (online)	1941-2460
ISSN	0003-0651
DOI	10.1177/0003065109333502
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Article ; Online: Frontotemporal thalamic connectivity in schizophrenia and schizotypal personality disorder.

Szeszko, Philip R / Gohel, Suril / Vaccaro, Daniel H / Chu, King-Wai / Tang, Cheuk Y / Goldstein, Kim E / New, Antonia S / Siever, Larry J / McClure, Margaret / Perez-Rodriguez, M Mercedes / Haznedar, M Mehmet / Byne, William / Hazlett, Erin A

Psychiatry research. Neuroimaging

2022 Volume 322, Page(s) 111463

Abstract: Schizotypal personality disorder (SPD) resembles schizophrenia, but with attenuated brain abnormalities and the absence of psychosis. The thalamus is integral for processing and transmitting information across cortical regions and widely implicated in ... ...

Abstract	Schizotypal personality disorder (SPD) resembles schizophrenia, but with attenuated brain abnormalities and the absence of psychosis. The thalamus is integral for processing and transmitting information across cortical regions and widely implicated in the neurobiology of schizophrenia. Comparing thalamic connectivity in SPD and schizophrenia could reveal an intermediate schizophrenia-spectrum phenotype to elucidate neurobiological risk and protective factors in psychosis. We used rsfMRI to investigate functional connectivity between the mediodorsal nucleus (MDN) and pulvinar, and their connectivity with frontal and temporal cortical regions, respectively in 43 healthy controls (HCs), and individuals in the schizophrenia-spectrum including 45 psychotropic drug-free individuals with SPD, and 20 individuals with schizophrenia-related disorders [(schizophrenia (n = 10), schizoaffective disorder (n = 8), schizophreniform disorder (n = 1) and psychosis NOS (n = 1)]. Individuals with SPD had greater functional connectivity between the MDN and pulvinar compared to individuals with schizophrenia. Thalamo-frontal (i.e., between the MDN and rostral middle frontal cortex) connectivity was comparable in SPD and HCs; in SPD greater connectivity was associated with less symptom severity. Individuals with schizophrenia had less thalamo-frontal connectivity and thalamo-temporal (i.e., pulvinar to the transverse temporal cortex) connectivity compared with HCs. Thalamo-frontal functional connectivity may be comparable in SPD and HCs, but abnormal in schizophrenia, and that this may be protective against psychosis in SPD.
MeSH term(s)	Humans ; Magnetic Resonance Imaging ; Schizophrenia/diagnostic imaging ; Schizotypal Personality Disorder/diagnostic imaging ; Temporal Lobe ; Thalamus/diagnostic imaging
Language	English
Publishing date	2022-02-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	445361-x
ISSN	1872-7506 ; 1872-7123 ; 0925-4927 ; 0165-1781
ISSN (online)	1872-7506 ; 1872-7123
ISSN	0925-4927 ; 0165-1781
DOI	10.1016/j.pscychresns.2022.111463
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Article ; Online: The interpersonal dimension of borderline personality disorder: toward a neuropeptide model.

Stanley, Barbara / Siever, Larry J

The American journal of psychiatry

2009 Volume 167, Issue 1, Page(s) 24–39

Abstract: Borderline personality disorder is characterized by affective instability, impulsivity, identity diffusion, and interpersonal dysfunction. Perceived rejection and loss often serve as triggers to impulsive, suicidal, and self-injurious behavior, affective ...

Abstract	Borderline personality disorder is characterized by affective instability, impulsivity, identity diffusion, and interpersonal dysfunction. Perceived rejection and loss often serve as triggers to impulsive, suicidal, and self-injurious behavior, affective reactivity, and angry outbursts, suggesting that the attachment and affiliative system may be implicated in the disorder. Neuropeptides, including the opioids, oxytocin, and vasopressin, serve a crucial role in the regulation of affiliative behaviors and thus may be altered in borderline personality disorder. While clinical data are limited, the authors propose alternative neuropeptide models of borderline personality disorder and review relevant preclinical research supporting the role of altered neuropeptide function in this disorder in the hope of stimulating more basic research and the development of new treatment approaches.
MeSH term(s)	Borderline Personality Disorder/diagnosis ; Borderline Personality Disorder/physiopathology ; Borderline Personality Disorder/psychology ; Humans ; Interpersonal Relations ; Models, Neurological ; Models, Psychological ; Neuropeptides/physiology ; Opioid Peptides/physiology ; Vasopressins/physiology
Chemical Substances	Neuropeptides ; Opioid Peptides ; Vasopressins (11000-17-2)
Language	English
Publishing date	2009-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	280045-7
ISSN	1535-7228 ; 0002-953X
ISSN (online)	1535-7228
ISSN	0002-953X
DOI	10.1176/appi.ajp.2009.09050744
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Article ; Online: Correlates of suicidal behaviors and genetic risk among United States veterans with schizophrenia or bipolar I disorder.

Bigdeli, Tim B / Barr, Peter B / Rajeevan, Nallakkandi / Graham, David P / Li, Yuli / Meyers, Jacquelyn L / Gorman, Bryan R / Peterson, Roseann E / Sayward, Frederick / Radhakrishnan, Krishnan / Natarajan, Sundar / Nielsen, David A / Wilkinson, Anna V / Malhotra, Anil K / Zhao, Hongyu / Brophy, Mary / Shi, Yunling / O'Leary, Timothy J / Gleason, Theresa /

Przygodzki, Ronald / Pyarajan, Saiju / Muralidhar, Sumitra / Gaziano, J Michael / Huang, Grant D / Concato, John / Siever, Larry J / DeLisi, Lynn E / Kimbrel, Nathan A / Beckham, Jean C / Swann, Alan C / Kosten, Thomas R / Fanous, Ayman H / Aslan, Mihaela / Harvey, Philip D

Molecular psychiatry

2024

Abstract: Persons diagnosed with schizophrenia (SCZ) or bipolar I disorder (BPI) are at high risk for self-injurious behavior, suicidal ideation, and suicidal behaviors (SB). Characterizing associations between diagnosed health problems, prior pharmacological ... ...

Abstract	Persons diagnosed with schizophrenia (SCZ) or bipolar I disorder (BPI) are at high risk for self-injurious behavior, suicidal ideation, and suicidal behaviors (SB). Characterizing associations between diagnosed health problems, prior pharmacological treatments, and polygenic scores (PGS) has potential to inform risk stratification. We examined self-reported SB and ideation using the Columbia Suicide Severity Rating Scale (C-SSRS) among 3,942 SCZ and 5,414 BPI patients receiving care within the Veterans Health Administration (VHA). These cross-sectional data were integrated with electronic health records (EHRs), and compared across lifetime diagnoses, treatment histories, follow-up screenings, and mortality data. PGS were constructed using available genomic data for related traits. Genome-wide association studies were performed to identify and prioritize specific loci. Only 20% of the veterans who reported SB had a corroborating ICD-9/10 EHR code. Among those without prior SB, more than 20% reported new-onset SB at follow-up. SB were associated with a range of additional clinical diagnoses, and with treatment with specific classes of psychotropic medications (e.g., antidepressants, antipsychotics, etc.). PGS for externalizing behaviors, smoking initiation, suicide attempt, and major depressive disorder were associated with SB. The GWAS for SB yielded no significant loci. Among individuals with a diagnosed mental illness, self-reported SB were strongly associated with clinical variables across several EHR domains. Analyses point to sequelae of substance-related and psychiatric comorbidities as strong correlates of prior and subsequent SB. Nonetheless, past SB was frequently not documented in health records, underscoring the value of regular screening with direct, in-person assessments, especially among high-risk individuals.
Language	English
Publishing date	2024-03-15
Publishing country	England
Document type	Journal Article
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-024-02472-1
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