Decreased plasma neuropeptides in first-episode schizophrenia, bipolar disorder, major depressive disorder: associations with clinical symptoms and cognitive function

Background There is an urgent need to identify differentiating and disease-monitoring biomarkers of schizophrenia, bipolar disorders (BD), and major depressive disorders (MDD) to improve treatment and management. Methods We recruited 54 first-episode schizophrenia (FES) patients, 52 BD patients, 35 MDD patients, and 54 healthy controls from inpatient and outpatient clinics. α-Melanocyte Stimulating Hormone (α-MSH), β-endorphin, neurotensin, orexin-A, oxytocin, and substance P were investigated using quantitative multiplex assay method. Psychotic symptoms were measured using the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS), manic symptoms using the Young Mania Rating Scale (YMRS), and depressive symptoms using 17 item-Hamilton Depression Rating Scale (HAMD). We additionally measured cognitive function by using a battery of tests given to all participants. Results α-MSH, neurotensin, orexin-A, oxytocin, and substance P were decreased in the three patient groups compared with controls. Neurotensin outperformed all biomarkers in differentiating patient groups from controls. There were no significant differences for 6 neuropeptides in their ability to differentiate between the three patient groups. Higher neurotensin was associated with better executive function across the entire sample. Lower oxytocin and higher substance p were associated with more psychotic symptoms in FES and BD groups. β-endorphin was associated with early morning wakening symptom in all three patient groups. Conclusion Our research shows decreased circulating neuropeptides have the potential to differentiate severe mental illnesses from controls. These neuropeptides are promising treatment targets for improving clinical symptoms and cognitive function in FES, BD, and MDD.

[1]  H. Kunugi,et al.  Plasma neuropeptide levels in patients with schizophrenia, bipolar disorder, or major depressive disorder and healthy controls: A multiplex immunoassay study , 2022, Neuropsychopharmacology reports.

[2]  Shoji Nakamura Integrated pathophysiology of schizophrenia, major depression, and bipolar disorder as monoamine axon disorder. , 2022, Frontiers in bioscience.

[3]  D. Baldwin,et al.  Treatment of Symptom Clusters in Schizophrenia, Bipolar Disorder and Major Depressive Disorder With the Dopamine D3/D2 Preferring Partial Agonist Cariprazine , 2021, Frontiers in Psychiatry.

[4]  H. Lane,et al.  Oxytocin in Schizophrenia: Pathophysiology and Implications for Future Treatment , 2021, International journal of molecular sciences.

[5]  K. Blennow,et al.  The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease , 2021, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[6]  Xudong Huang,et al.  Roles of β-Endorphin in Stress, Behavior, Neuroinflammation, and Brain Energy Metabolism , 2020, International journal of molecular sciences.

[7]  J. Wiltfang,et al.  The Role of Proopiomelanocortin and α-Melanocyte-Stimulating Hormone in the Metabolic Syndrome in Psychiatric Disorders: A Narrative Mini-Review , 2019, Front. Psychiatry.

[8]  Xiao-hong Ma,et al.  Plasma neuropeptides as circulating biomarkers of multifactorial schizophrenia. , 2019, Comprehensive psychiatry.

[9]  M. Ota,et al.  Reduced plasma orexin-A levels in patients with bipolar disorder , 2019, Neuropsychiatric disease and treatment.

[10]  Fei Wang,et al.  The Relationship Between Cognitive Dysfunction and Symptom Dimensions Across Schizophrenia, Bipolar Disorder, and Major Depressive Disorder , 2019, Front. Psychiatry.

[11]  Tianzi Jiang,et al.  Common and Specific Functional Activity Features in Schizophrenia, Major Depressive Disorder, and Bipolar Disorder , 2019, Front. Psychiatry.

[12]  M. Romans Altered , 2019 .

[13]  Robert A. Cribbie,et al.  Assessment of neuropsychological performance in Mexico City youth using the Cambridge Neuropsychological Test Automated Battery (CANTAB) , 2018, Journal of clinical and experimental neuropsychology.

[14]  T. Hökfelt,et al.  Neuropeptide and Small Transmitter Coexistence: Fundamental Studies and Relevance to Mental Illness , 2018, Front. Neural Circuits.

[15]  T. Hökfelt,et al.  Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide , 2016, Proceedings of the National Academy of Sciences.

[16]  R. Mizrahi,et al.  Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review , 2016, Molecular Psychiatry.

[17]  R. Ophoff,et al.  Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis. , 2016, Schizophrenia bulletin.

[18]  C. Chiou,et al.  Global economic burden of schizophrenia: a systematic review , 2016, Neuropsychiatric disease and treatment.

[19]  R. Yolken,et al.  Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset , 2015, Translational Psychiatry.

[20]  B. Druss,et al.  Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. , 2015, JAMA psychiatry.

[21]  L. Lecea,et al.  The Hypocretin/Orexin System: An Increasingly Important Role in Neuropsychiatry , 2015, Medicinal research reviews.

[22]  Jing-ping Zhao,et al.  Association of Neurotensin Receptor 1 Gene Polymorphisms with Processing Speed in Healthy Chinese-Han Subjects , 2014, Journal of Molecular Neuroscience.

[23]  Jing-ping Zhao,et al.  Association of Neurotensin Receptor 1 Gene Polymorphisms with Processing Speed in Healthy Chinese-Han Subjects , 2014, Journal of Molecular Neuroscience.

[24]  Mary E. Ziegler,et al.  G protein-linked signaling pathways in bipolar and major depressive disorders , 2013, Front. Genet..

[25]  B. Gaszner,et al.  Role of neuropeptides in anxiety, stress, and depression: From animals to humans , 2013, Neuropeptides.

[26]  J. Frazier,et al.  The role of oxytocin in psychiatric disorders: a review of biological and therapeutic research findings. , 2013, Harvard review of psychiatry.

[27]  M. Olive,et al.  Neuropeptide systems and schizophrenia. , 2013, CNS & neurological disorders drug targets.

[28]  K. Tomizawa,et al.  Oxytocin: a therapeutic target for mental disorders , 2012, The Journal of Physiological Sciences.

[29]  K. Arima,et al.  Negative correlation between cerebrospinal fluid oxytocin levels and negative symptoms of male patients with schizophrenia , 2012, Schizophrenia Research.

[30]  A. Kasarskis,et al.  Altered sleep and affect in the neurotensin receptor 1 knockout mouse. , 2012, Sleep.

[31]  F. Holsboer,et al.  Neuropeptide receptor ligands as drugs for psychiatric diseases: the end of the beginning? , 2012, Nature Reviews Drug Discovery.

[32]  D. Penn,et al.  Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia , 2011, Schizophrenia Research.

[33]  R. Moyzis,et al.  Neurotensin Receptor 1 Gene (NTSR1) Polymorphism Is Associated with Working Memory , 2011, PloS one.

[34]  Vera Ignjatovic,et al.  Age-Related Differences in Plasma Proteins: How Plasma Proteins Change from Neonates to Adults , 2011, PloS one.

[35]  Jaung-Geng Lin,et al.  Endogenous Opiates in the Nucleus Tractus Solitarius Mediate Electroacupuncture-Induced Sleep Activities in Rats , 2011, Evidence-based complementary and alternative medicine : eCAM.

[36]  P. Singru,et al.  Involvement of α-MSH in the social isolation induced anxiety- and depression-like behaviors in rat , 2010, Neuropharmacology.

[37]  E. Eşel,et al.  Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment , 2009, Psychiatry Research.

[38]  R. Lanius,et al.  The role of β-endorphin in the pathophysiology of major depression , 2009, Neuropeptides.

[39]  Peter B. Jones,et al.  Combining dimensional and categorical representation of psychosis: the way forward for DSM-V and ICD-11? , 2009, Psychological Medicine.

[40]  R. Morrison,et al.  Study design, precision, and validity in observational studies. , 2009, Journal of palliative medicine.

[41]  D. Wied,et al.  Neuropeptides involved in the pathophysiology of schizophrenia and major depression , 2009, Neurotoxicity Research.

[42]  E. Bracci,et al.  Substance P depolarizes striatal projection neurons and facilitates their glutamatergic inputs , 2008, The Journal of physiology.

[43]  Lung-Chang Lin,et al.  Neuropeptide Y Gene Polymorphism and Plasma Neuropeptide Y Level in Febrile Seizure Patients in Taiwan , 2007, The Kaohsiung journal of medical sciences.

[44]  R. Baldessarini,et al.  Effects of treatment latency on response to maintenance treatment in manic-depressive disorders. , 2007, Bipolar disorders.

[45]  C. Nemeroff,et al.  Involvement of neuropeptide systems in schizophrenia: human studies. , 2007, International review of neurobiology.

[46]  A. Deutch,et al.  Neurotensin Activates GABAergic Interneurons in the Prefrontal Cortex , 2005, The Journal of Neuroscience.

[47]  X. Langlois,et al.  Gene expression profiles highlight adaptive brain mechanisms in corticotropin releasing factor overexpressing mice. , 2004, Brain research. Molecular brain research.

[48]  J. Panksepp,et al.  Future of Neuropeptides in Biological Psychiatry and Emotional Psychopharmacology: Goals and Strategies , 2004 .

[49]  Bondy Brigitta Pathophysiology of depression and mechanisms of treatment , 2002, Dialogues in clinical neuroscience.

[50]  A Carlsson,et al.  Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence. , 2001, Annual review of pharmacology and toxicology.

[51]  F. Quehenberger,et al.  Prolactin and beta‐endorphin serum elevations after ECT in manic patients , 2000, Acta psychiatrica Scandinavica.

[52]  P. Rabbitt,et al.  A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: Implications for theories of executive functioning and cognitive aging , 1998, Journal of the International Neuropsychological Society.

[53]  C. Nemeroff,et al.  CSF neurotensin concentrations and antipsychotic treatment in schizophrenia and schizoaffective disorder. , 1997, The American journal of psychiatry.

[54]  C. Hammen,et al.  Relapse and impairment in bipolar disorder. , 1995, The American journal of psychiatry.

[55]  R. Suddath,et al.  Cerebrospinal fluid oxytocin concentration in schizophrenic patients does not differ from control subjects and is not changed by neuroleptic medication , 1994, Schizophrenia Research.

[56]  C. Nemeroff,et al.  Neuropeptides, Dopamine, and Schizophrenia a , 1988, Annals of the New York Academy of Sciences.

[57]  W. Gattaz,et al.  Vasopressin-oxytocin in cerebrospinal fluid of schizophrenic patients and normal controls , 1985, Psychoneuroendocrinology.

[58]  T. Crow,et al.  Peptides, the limbic lobe and schizophrenia , 1983, Brain Research.

[59]  C. Nemeroff,et al.  Subnormal CSF levels of neurotensin in a subgroup of schizophrenic patients: normalization after neuroleptic treatment. , 1982 .

[60]  D. Wechsler Manual for the Wechsler Adult Intelligence Scale. , 1955 .