B i o l o g y
o f b i p o l a r d i s o r d e rThis
is a comprehensive review of biological abnormalities observed in bipolar/unipolarmood
disorders. We do not ignore that conflicting results may be found in the
literature, butattempted, nevertheless, to
summarize the currents trends.Bipolar
DepressionUnipolar
DepressionCHALLENGE
TESTSDexamethasoneCortisol nonsuppression1Cortisol nonsuppressionHypotheses: decreased sensitivity
of pituitary glucocorticoid receptors to dexamethasone
and/or hyperresponsivity of the adrenal gland to ACTH stimulation and/or hypothalamic CRH hyperactivity.Protirelin (TRH)Blunted TSH response2,3Blunted TSH responseHypothesis: downregulation of
pituitary TRH receptors secondary to a prolonged increase in endogenous TRH stimulationDopamine (DA)Blunted PRL response to Normal PRL, GH, cortisol, and ACTHapomorphine3response to apomorphineHypothesis: hyposensitivity of
postsynaptic pituitary D2 receptorsNorepinephrine (NE)Blunted GH response Blunted GH response to clonidineto clonidine4Hypothesis: hyposensitivity of
postsynaptic 2 adrenoreceptorsSerotonin (5-HT)The following have been found inconsistently
and nonspecifically in bipolar/unipolardepression:
(i) blunted PRL and/or cortisol response to d,l- or d-fenfluramine, mCPP,clomipramine, 5-HT1A agonists;
(ii) blunted PRL and GH response to L-tryptophanHypothesis: decreased presynaptic
5-HT activity and/or decreased sensitivity of postsynaptic 5-HT1A receptorsMONOAMINESNorepinephrine (NE)Low levels of urinary, plasma, Increased urinary NE, NMN,and CSF MHPG5and MHPG levelsIncreased plasma NE and CSF MHPG levelsHypothesis: decreased Hypothesis: increased presynaptic NE activitypresynaptic NE activitySerotonin (5-HT)The following have been
found inconsistently and nonspecifically forbipolar/unipolar
depression: low urinary, plasma, and CSF 5-HIAA levels (dec-creased presynaptic 5-HT activity)
Dopamine (DA)Decreased CSF HVA levels in retarded
patients (deccreased presynaptic DA activity)
Alert