Subject Index N-Acetyl aspartate, magnetic resonance spectroscopy studies in 104 α 2 -Adrenergic receptor, therapeutic targeting 13 Adrenocorticotropic hormone (ACTH) Agomelatine, mechanism of action 4, 5 levels 25 functional overview 22 regulation of release 22 stimulation test 26, 27 γ-aminobutyric acid (GABA) magnetic resonance spectroscopy studies in 103, 104 therapeutic targeting of receptors 5, 6, 90 treatment-resistant study prospects 96 98 Aminoglutethimide, antidepressant activity 28 Amitriptyline, serotonin 5-HT 2C receptor effects 165 Amoxapine antidepressant activity 11, 12 serotonin 5-HT 2C receptor effects 165 Amphetamine, depressant effects 12 Anhedonia, animal models of 129, 130 Animal models, clinical relevance 134, 135 comorbid conditions 131 endophenotype-style approaches anhedonia 129, 130 cognitive function 130 rationale 128, 129 sleep disturbances 131 forced swimming test 124, 127, 128, 146 genetic predisposition inbred strains 133 knockout and knockdown 133, 134, 146 rationale for models 132, 133 mouse strains antidepressant studies 146 148 genetic modifications 133, 134, 146 inbred strains 144, 145 monoamine synthesis deficiency norepinephrine 148, 149 serotonin 149 151 selective breeding 145 olfactory bulbectomy studies 127 overview 124 128 prospects for study 135 rat strains Flinders sensitive line 140, 141 selective breeding 142 Wistar-Kyoto rat antidepressant studies 143, 144 phenotype 141, 142 social stress-based models 132 tail suspension test 126, 127, 146 Anterior cingulate cortex (ACC) activity in ketamine response prediction 95 cingulotomy 117 Antidepressant therapy duration 256 Antidepressants dosing 255 Antipsychotics antidepressant activity 260, 261 management 245, 246 Apoptosis, omega-3 fatty acid protection 82, 83 Arginine vasopressin (AVP) levels 24, 25 functional overview 22 269
glucocorticoid feedback 22, 23 receptors 21 regulation of release 21 Aripiprazole, management 245, 245 Artemin, antidepressant effects on expression 213 Asenapine, antidepressant activity 261 Atomoxetine, immunosuppression 65 Bipolar disorder circadian disturbances, see Circadian rhythm omega-3 fatty acid trials 77, 78 Brain-derived neurotrophic factor (BDNF) antidepressants activity of factor 205, 206, 230, 231 expression response 202 202 mechanism of action 13, 14, 201, 202, 206, 207 receptor activation 204, 205 pathophysiology 201, 202 functional overview 201 levels in ketamine response prediction 95, 96 omega-3 fatty acid upregulation 83 prospects for study 214 stress response 202 Bupropion HBr formulation 259 mechanism of action 5 Cariprazine, antidepressant activity 261 Celecoxib, antidepressant activity 64, 66 Chromatin remodeling, see DNA methylation; Histone modification Ciliary neurotrophic factor (CNTF), role 213 Circadian rhythm animal models of sleep disturbances 131 bipolar disorder findings hormone rhythms cortisol 38 growth hormone 38 melatonin 38, 39 prolactin 38 sleep and daily rhythms 37 clock genes bipolar disorder studies clinical studies 40 preclinical studies 42 44 overview 39 41 dysfunction in psychiatric disorders 33, 34 major findings hormone rhythms cortisol 35, 36 melatonin 36 prolactin 36, 37 thyroid hormone 36 sleep disturbances 35 temperature dysregulation 35 therapeutic manipulation antidepressant mechanisms 46 bright light therapy 44, 45 kinase inhibitors 45 prospects 46, 47 sleep deprivation 44 Citalopram, serotonin 5-HT 2C receptor effects 164 166 Classification, antidepressants 9 Clomipramine, serotonin 5-HT 2C receptor effects 166, 167 Clozapine, antidepressant activity 11, 12 Cocaine, depressant effects 12 Cognitive behavioral therapy, imaging studies 118 Combination antidepressant therapy first-line treatment 259 polypharmacy rules 257 principles 256, 257 management 246 Computed tomography (CT), brain morphometry in 105 108 Corticotropin-releasing hormone (CRH) levels 23, 24 glucocorticoid feedback 22, 23 neurotransmitter regulation of release 21, 27 receptors 21 Cortisol circadian disturbances bipolar disorder 38 major 35, 36 levels 25 receptors 22 synthesis inhibitors for management 28 Cyclooxygenase (COX) inhibitor antidepressant activity 64, 66 isozymes 67 270 Subject Index
Deep brain stimulation (DBS), therapyresistant management 249 Desipramine immunosuppression 65 serotonin 5-HT 2C receptor effects 166, 169 Desvenlafaxine 260 Dexamethasone suppression test 26 Dextroamphetamine, therapy-resistant management 246 Disability, association 1 DNA methylation affective disorders 186 190 DNA methyltransferases 187, 188 epigenetics overview 183 186 prospects for study 196 Docosahexaenoic acid, see Omega-3 fatty acids Dopamine positron emission tomography studies in 102, 103, 111 triple reuptake inhibitors 261 uptake inhibition 3 5 Dopamine receptor alleles in 111 therapeutic targeting 7, 8 Dopamine transporter, therapeutic targeting 7, 8 Dopamine-β-hydroxylase (DBH), knockout mouse 148, 149 Eicosapentaenoic acid, see Omega-3 fatty acids Electroconvulsive therapy (ECT) magnetic resonance spectroscopy studies 116 management 247, 248 Electroencephalography (EEG) antidepressant studies 114 studies 109 Epigenetics, see DNA methylation; Histone modification Escitalopram binding kinetics 3 efficacy 11 Etanercept, antidepressant activity 66 Excitotoxicity, and neurodegeneration 61 Fatty acids, see Omega-3 fatty acids; Omega-6 fatty acids Fibroblast growth factor (FGF) antidepressant response 209 dysregulation 209 Flinders sensitive line, rat 140, 141 Fluoxetine, serotonin 5-HT 2C receptor effects 164 167, 169, 170 Fluvoxamine, serotonin 5-HT 2C receptor effects 165, 166 Forced swimming test, see Animal models, Glial-derived neurotrophic factor (GDNF) antidepressant effects on expression 213 levels 212, 213 Glucocorticoid receptor antagonist trials 263 antidepressant response 28 gene methylation 189, 190 resistance and cytokines 56 Growth hormone, circadian disturbances in bipolar disorder 38 High-resolution research tomography (HRRT), studies 103 Hippocampus dysfunction in 225 neurogenesis antidepressant response 228 230, 235 pathophysiology 235, 236 inhibitor effects on antidepressant efficacy 231 233 mechanisms of antidepressant action 233 235 neurotrophin studies 230, 231 overview 225, 226 stress and effects 226 228 Histone modification affective disorder studies acetylation 191 194 methylation 194 196 epigenetics overview 183 186 prospects for study 196 Imipramine, serotonin 5-HT 2C receptor effects 165 167 Indoleamine 2,3-dioxygenase (IDO) cytokine regulation 56, 57, 62 therapeutic targeting 66 Inflammation studies 57 59 mood effects 58, 59 therapeutic targeting in 65 67 Subject Index 271
Inflammation, omega-3 fatty acid antiinflammatory activity 81, 82 Infliximab, antidepressant activity 66 Insulin-like growth factor 1 (IGF-1) antidepressant activity 209 antidepressant effects on expression 209 sources 209 Interferon therapy brain effects 55 dopamine response 55 mood effects 56 Ketamine, antidepressant activity overview 12, 263 repeated-dose studies 93 response prediction in treatment-resistant major age 94 alcohol abuse family history 94, 95 anterior cingulate cortex activity 95 brain-derived neurotrophic factor 95, 96 single-dose studies 91 93 Ketoconazole, antidepressant activity 28 Leukemia inhibitory factor (LIF), role 213 Lithium antidepressant augmentation 12, 115 management 247 Loxapine, antidepressant activity 11, 12 LUAA21004 selective serotonin reuptake inhibitor 262 LUAA24530 triple reuptake inhibitor 261 Lurasidone, antidepressant activity 261 Magnetic resonance imaging (MRI) brain morphometry in 105 108 functional studies in 108, 109, 118 Magnetic resonance spectroscopy (MRS) N-acetyl aspartate studies in 104 γ-aminobutyric acid studies in 103, 104 antidepressant studies 115 electroconvulsive therapy studies 116 Magnetoencephalography (MEG), studies 109 Major depressive disorder (MDD) circadian disturbances, see Circadian rhythm incidence trends 1 multisystem manifestations 9, 10, 15 omega-3 fatty acid trials 75 77 Melatonin circadian disturbances bipolar disorder 38, 39 major 36 receptor therapeutic targeting 4, 5 Menopause-associated, omega-3 fatty acid trials 79, 80 N-Methyl-D-aspartate (NMDA) therapeutic targeting of receptors 90, 263, 264 treatment-resistant study prospects 96 98 Methylphenidate, management 246 L-5-Methyltetrahydrofolate, antidepressant activity 262 Metyrapone, antidepressant activity 28 Mianserin mechanism of action 13 serotonin 5-HT 2C receptor effects 164, 165, 167, 170 MIF-1, antidepressant activity 263 Mineralocorticoid receptor, antidepressant response 28 Mirtazapine, mechanism of action 13 Monoamine oxidase, therapeutic targeting 8 Mouse models, see Animal models, Nefazodone, mechanism of action 5, 6 Nerve growth factor (NGF) antidepressant effects on expression 207, 208 effects on expression 207 Neurotrophin 3 (NT-3) antidepressant activity 208 receptors 208 stress effects 208 Neurotrophin 4/5 (NT-4/5), expression in bipolar disorder 209 Neurturin, antidepressant effects on expression 213 Nialamide, serotonin 5-HT 2C receptor effects 166, 167 Norepinephrine synthesis knockout in mice 148, 149 triple reuptake inhibitors 261 uptake inhibition 2 4 272 Subject Index
Nuclear factor-κb (NF-κB), brain effects 55 Olanzapine, management 245 Olfactory bulbectomy, animal studies 127 Omega-3 fatty acids brain and immune function 73, 74 cardiovascular protection 80, 81 changes 75 clinical trials bipolar disorder 77, 78 major 75 77 menopause-associated 79, 80 Parkinson,s disease-associated 80 perinatal 76, 79 mechanisms of action anti-inflammatory activity 81, 82 antioxidant activity 82, 83 apoptosis protection 82, 83 brain-derived neurotrophic factor upregulation 83 prospects for study 84 eicosapentaenoic acid health benefits 72 Omega-6 fatty acids brain and immune function 73, 74 changes 75 Parkinson,s disease-associated, omega-3 fatty acid trials 80 Paroxetine, serotonin 5-HT 2C receptor effects 166, 167, 169, 170 Perinatal, omega-3 fatty acid trials 76, 79 Persephin, antidepressant effects on expression 213 Personality disorder, recognition 258 Phenelzine, serotonin 5-HT 2C receptor effects 166 Pindolol antidepressant augmentation 12 management 247 Polyunsaturated fatty acids, see Omega-3 fatty acids; Omega-6 fatty acids Positron emission tomography (PET) antidepressant studies 115 dopamine studies in 102, 103, 111 Pramipexole, management 246 Prolactin, circadian disturbances bipolar disorder 38 major 36, 37 Quetiapine antidepressant activity 261 management 245 Rat models, see Animal models, Riluzole, antidepressant activity 66 Ritanserin, serotonin 5-HT 2C receptor effects 167 RNA editing, antidepressant effects on serotonin 5-HT 2C receptor 172, 173 Serotonin antidepressant effects on neurotransmission 6, 7 corticotropin-releasing hormone release stimulation 27 synthesis knockout in mice 149 151 triple reuptake inhibitors 261 Serotonin receptor alleles in 111, 112 classification 3 5-HT 2C anxiety and defense behavior modulation 157 159 role 155 157 desensitization by antidepressants brain distribution 171, 172 functional studies 166 168 in vitro studies 162, 163 model studies 169 171 receptors in vivo 163 166 RNA editing 172, 173 prospects for study 173, 174 stress response 159 162 stress and 59, 60 therapeutic targeting 3 6, 262 Serotonin transporter cytokine effects 55 therapeutic targeting 2, 3 Sertraline, serotonin 5-HT 2C receptor effects 166, 168, 170 Sleep deprivation therapy imaging studies 117, 118 overview 44 Subject Index 273
Sleep disturbances, see Circadian rhythm STAR,D trial 11, 89 Stress animal models, see Animal models, studies cytokines 57 59 neurodegeneration 61 63 serotonin response 59, 60 developmental programming 27, 28 hippocampal neurogenesis response 226 228 neurotrophic factor response 202, 207, 208 serotonin 5-HT 2C receptor anxiety and defense behavior modulation 157 159 stress response 159 162 Substance P, receptor antagonists 263 Switching, antidepressants 256 Tail suspension test, see Animal models, Therapy-resistant (TRD) definition 243, 244 glutamate neurotransmitter study prospects 96 98 ketamine response predictors in treatmentresistant major age 94 alcohol abuse family history 94, 95 anterior cingulate cortex activity 95 brain-derived neurotrophic factor 95, 96 management antidepressant combinations 246 atypical antipsychotics 245, 246 deep brain stimulation 249 electroconvulsive therapy 247, 248 miscellaneous drugs 246, 247 prospects for study 249 transcranial magnetic stimulation 248 vagus nerve stimulation 248, 249 prevalence 244 risk factors 245 Thymus, antidepressant effects 64, 65 Thyroid hormone circadian disturbances in major 36 management 247 Transcranial magnetic stimulation (TMS) imaging studies 116 management 248 Transforming growth factor-β (TGF-β), antidepressant effects on expression 212 Traxoprodil, antidepressant activity 12, 13 Trazodone, mechanism of action 5, 6 TREK-1, therapeutic targeting limitations 5 Tricyclic antidepressants (TCAs), efficacy compared with modern drugs 11 TrkB, activation by antidepressants 204, 205 Trozodone, formulations 259, 260 Tryptophan, cytokine regulation of synthesis 62 Tryptophan hydroxylase (TPH) knockout mouse 150, 151 mouse strain variations 149, 150 Tumor necrosis factor-α (TNF-α), antidepressant activity of inhibitors 66 Vagus nerve stimulation (VNS) imaging studies 116, 117 management 248, 249 Vascular endothelial growth factor (VEGF) antidepressant activity 211, 230, 231 antidepressant effects on expression 211 receptors 211 Vasopressin, see Arginine vasopressin Wistar-Kyoto rat antidepressant studies 143, 144 phenotype 141, 142 274 Subject Index