Hormones, Gender and the Aging Brain: The Endocrine Basis of Geriatric Psychiatry

Cover......Page 1
Half-title......Page 3
Title......Page 5
Copyright......Page 6
Dedication......Page 7
Contents......Page 9
Contributors......Page 11
Preface......Page 15
Acknowledgments......Page 19
Part I Overview......Page 21
Introduction......Page 23
Endocrine disorders as a cause of mental illness......Page 24
Hormones and aging......Page 25
Estrogen and cognitive dysfunction......Page 27
Testosterone and behavior......Page 28
Depression and the hypothalamic–pituitary–adrenal axis......Page 29
Conclusions......Page 30
REFERENCES......Page 31
Endocrine steroid synthesis......Page 35
Neurosteroids......Page 38
General principles......Page 39
CNS Localization and subtypes......Page 41
Classical effects involve changes in neurotransmission......Page 43
Novel effects of steroids......Page 44
Interactions with other steroids......Page 45
Summary and conclusions......Page 46
REFERENCES......Page 47
Part II Hormones and mental health in the elderly......Page 55
The physiology of the HPA axis......Page 57
Animal studies......Page 59
Human studies......Page 61
The HPA axis in human disease states associated with aging......Page 63
Conclusions and future directions......Page 64
REFERENCES......Page 65
Introduction......Page 73
Physiology of the thyroid axis......Page 74
Regulation......Page 75
Effects of HPT-axis hormones on the brain: TRH and metabolites......Page 76
The HPT axis in the elderly......Page 77
Hypothyroidism......Page 78
Hyperthyroidism......Page 79
Geriatric depression......Page 80
Therapeutic effects of HPT axis-related hormones in affective disorders......Page 83
Relationship between treatment modalities for affective disorders and the thyroid axis......Page 84
Cognitive effects of HPT axis in aging......Page 86
Summary and conclusions......Page 87
REFERENCES......Page 88
Epidemiology of depressive disorders in aging......Page 104
The estrogen deficiency hypothesis of depression......Page 105
Epidemiologic evidence that estrogen use is protective against depression......Page 106
Estrogen therapy for mood disorders......Page 107
Recent clinical trials of estrogen replacement to improve mood......Page 109
Selective estrogen receptor modulators......Page 112
Tamoxifen......Page 113
Serotonin......Page 114
Estrogen and 5–HT2 receptors......Page 115
Estrogen and the serotonin transporter......Page 116
Estrogen and serotonergic antidepressant response......Page 117
Imaging data......Page 118
Estrogen and norepinephrine......Page 119
Progestin......Page 120
The role of the HPA and HPG axes in mood......Page 121
Estrogen metabolism......Page 122
Effects of estrogen on peripheral target tissues......Page 123
Estrogen replacement therapy regimens......Page 124
Compliance with ERT......Page 125
REFERENCES......Page 126
Overview......Page 134
Methodologic problems......Page 135
Testosterone secretion......Page 136
Testosterone levels through life......Page 138
Prenatal organizing effects......Page 139
Postpubertal behavioral effects......Page 140
Dominance and submission......Page 141
Aggression......Page 142
Cognition......Page 143
Testosterone in aging men......Page 144
Testosterone and male depressive illness......Page 145
Depression in hypogonadal men......Page 146
The HPG axis in depressed men......Page 147
Exogenous testosterone administration......Page 150
Androgen administration to non-depressed eugonadal men......Page 151
Androgen administration to depressed men......Page 153
Treatment with exogenous testosterone......Page 155
ACKNOWLEDGMENT......Page 156
REFERENCES......Page 157
DHEA(S) as a neurosteroid......Page 164
DHEA(S) levels decrease as a function of aging, chronic stress and illness......Page 165
DHEA(S) improves learning and memory in animals......Page 166
Antidepressant and anti-anxiety effects in animals......Page 167
Mood......Page 168
Response to antidepressant and antianxiety medication......Page 169
General functional abilities and sense of well-being......Page 170
Cognitive function......Page 171
Well-being and general functioning......Page 174
Mood......Page 175
Memory......Page 176
Summary......Page 178
REFERENCES......Page 179
Possible biological mechanisms of estrogen’s effect on cognition......Page 188
Estrogen and cognition in non-demented women......Page 189
Estrogen therapy and dementia risk......Page 192
Estrogen for treatment of Alzheimer’s disease......Page 193
Testosterone......Page 194
Conclusions......Page 196
REFERENCES......Page 197
Introduction......Page 203
Cholinergic neurons and cognition......Page 204
Estrogen and basal forebrain cholinergic neurons......Page 205
Estrogen replacement and acetylcholine release......Page 209
Estrogen replacement and learning and memory......Page 210
Effects on growth factors and growth factor receptors......Page 214
Changes in cholinergic parameters associated with long-term loss of ovarian function......Page 220
Other effects of estrogen......Page 223
Effects on other neurotransmitter systems......Page 224
Effects on hippocampal connectivity......Page 226
Effects on ß-amyloid processing......Page 227
Neuroprotective effects......Page 228
Summary and conclusions......Page 229
REFERENCES......Page 231
Age of onset of schizophrenia......Page 243
Symptom presentation......Page 244
Course of illness......Page 245
Cognitive performance......Page 246
Neuroradiological abnormalities......Page 247
Report of ongoing studies assessing gender differences in clinical and neuropsychological variables of schizophrenia......Page 248
Materials and methods......Page 249
Statistical methods......Page 250
Discussion and summary......Page 251
REFERENCES......Page 255
Anxiety disorder overview......Page 261
Generalized anxiety disorder (GAD)......Page 263
Panic disorder......Page 264
Simple phobia......Page 266
Social phobia......Page 267
OCD......Page 269
PTSD......Page 270
Estrogen......Page 272
Progesterone......Page 274
Female reproductive cycles impact on course of anxiety......Page 276
REFERENCES......Page 277
Introduction......Page 287
Sex differences in the response to noxious stimuli in the laboratory......Page 288
Sex differences in health care utilization and chronic pain conditions......Page 291
Sex differences in responses to analgesic drugs......Page 292
Hormonal factors in human pain sensitivity......Page 293
Sex differences and hormonal factors in pain sensitivity in animal subjects......Page 294
Animal sex differences and hormonal factors in the analgesic responses to environmental stress and pharmaceuticals......Page 296
Magnitudinal differences in analgesia between the sexes......Page 297
Qualitative differences in analgesia between the sexes......Page 298
Conclusions......Page 300
REFERENCES......Page 301
Part III Effects of hormones and behavior on immune function......Page 307
Estrogen and immune function......Page 309
Estrogen-related differences in physiological reactivity to brief stressors......Page 312
Estrogen-related differences in immune reactivity to stress: possible pathways......Page 314
REFERENCES......Page 316
Introduction......Page 322
Sex differences in the neuroendocrine stress response: the role of glucocorticoids and their receptors.......Page 323
Mechanism of glucocorticoid regulation of immune function......Page 324
Mechanism of sex steroid regulation of immune function......Page 326
Cellular events induced by sex steroids......Page 327
Direct effects of sex steroids on immune function......Page 328
Aging......Page 329
Areas for further study......Page 331
REFERENCES......Page 332
Part IV Hormones and gender differences in psychotropic drug metabolism......Page 339
Introduction......Page 341
Gastric effects......Page 342
Phase one and phase two metabolism......Page 343
Effects of exogenous estrogen......Page 345
Menstrual cycle effects......Page 346
Summary......Page 347
ACKNOWLEDGMENT......Page 348
REFERENCES......Page 349
Introduction......Page 354
Influence of aging on benzodiazepine pharmacokinetics and pharmacodynamics......Page 356
Influence of oral contraceptives on benzodiazepine pharmacokinetics and pharmacodynamics......Page 357
Neurosteroids......Page 359
Postmenopausal women and GABA-active drugs......Page 361
Influence of endogenous progesterone on GABA-active drugs......Page 363
Influence of aging on allopregnanolone concentrations......Page 365
Conclusions......Page 366
REFERENCES......Page 367
Index......Page 371