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Query: UMLS:C0011570 (depression)
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Psychiatric manifestations are frequently associated with pernicious anemia including depression, mania, psychosis, dementia. We report a case of a patient with vitamin B12 deficiency, who has presented severe depression with delusion and Capgras' syndrome, delusion with lability of mood and hypomania successively, during a period of two Months. Case report - Mme V., a 64-Year-old woman, was admitted to the hospital because of confusion. She had no history of psychiatric problems. She had history of diabetes, hypertension and femoral prosthesis. The red blood count revealed a normocytosis with anemia (hemoglobin=11,4 g/dl). At admission she was uncooperative, disoriented in time and presented memory and attention impairment and sleep disorders. She seemed sad and older than her real age. Facial expression and spontaneous movements were reduced, her speech and movements were very slow. She had depressed mood, guilt complex, incurability and devaluation impressions. She had a Capgras' syndrome and delusion of persecution. Her neurologic examination, cerebral scanner and EEG were postponed because of uncooperation. Further investigations confirmed anemia (hemoglobin=11,4 g/dl) and revealed vitamin B12 deficiency (52 pmol/l) and normal folate level. Antibodies to parietal cells were positive in the serum and antibodies to intrinsic factor were negative. An iron deficiency was associated (serum iron=7 micromol/l; serum ferritin concentration=24 mg/l; serum transferrin concentration=3,16 g/l). This association explained normocytocis anemia. Thyroid function, hepatic and renal tests, glycemia, TP, TCA, VS, VDRL-TPHA were normal. Vitamin B12 replacement therapy was started with hydroxycobalamin 1 000 ng/day im for 10 days and iron replacement therapy. Her mental state improved dramatically within a few days. After one week of treatment the only remaining symptoms were lability of mood, delusion of persecution, Capgras' syndrome but disappeared totally 9 days after the beginning of the treatment. A neurologic examination was possible because of cooperation. All the tendon reflexes of inferior members were absent. The plantars were in flexion and there was a left inferior member hypoesthesia. The cerebral scan and EEG were normal. Fundic biopsy, realized by fibroscopy, revealed fundic atrophia and intestinal metaplasia compatible with Biermers' disease. The iron deficiency exploration concluded diet deficiency. Mme V. appeared euphoric, her speech was very rapid with play on words and overactivity. This hypomania state totally disappeared 3 days after. Six Months after her hospitalisation, she presented an hypothyroidism (TSH=3,780; T3=1,35; T4=1,08). A thyroid hormones replacement was started and she continued to receive Monthly B12 replacement. Discussion - This case report illustrates psychiatric manifestations of Biermers' disease. The clinical arguments in favour are: white woman, more than 60 Years old, no history of psychiatric problems, atypical symptoms (confusional state with psychiatric symptoms), fluctuation of symptoms (severe depression with confusional state, delusion of persecution and Capgras' syndrome; delusion with lability of mood and hypomania), dramatic improvement after 9 days of vitamin B12 replacement therapy. The biological arguments are: anemia, vitamin B12 deficiency, normal folate level, atrophia and fundic metaplasia, positive antibodies to parietal cells in the serum, association between Biermers' disease and autoimmune disease (Haschimoto thyroidite). Psychiatric manifestations can occur in the presence of low serum B12 levels but in the absence of the other well recognized neurological and haematological abnormalities of pernicious anemia. Mental or psychological changes may precede haematological signs by Months or Years. They can be the initial symptoms or the only ones. Verbank et al. described the case of a patient with vitamin B12 deficiency in whom hypomania, paranoia and depression had been successively presented during a period of 5 Years before anemia have been developed. The case of Mme V. is similar in the succession of severe depression with delusion of persecution and Capgras' syndrome, delusion with lability of mood and hypomania, during a period of two Months. This report seems to be the first one of a sequence of several psychiatric states with pernicious anemia during a period of two Months with normocytosis anemia. To illustrate this illness we reviewed the literature regarding psychopathology associated with B12 deficiency. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. The neuropsychiatric severity by vitamin B12 deficiency and the therapeutic efficacy depends on the duration of signs and symptoms. Conclusion - We recommend consideration of B12 deficiency and serum B12 determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. B12 levels should be evaluated with treatment resistant depressive disorders, dementia, psychosis or risk factors for malnutrition such as alcoholism or advancing age associated with neurological symptoms, anemia, malabsorption, gastrointestinal surgery, parasite infestation or strict vegetarian diet. In first intention, B12 deficiency should be researched by serum B12 determination (normal 200-950 pg/ml). Studies of methylmalonic acid and homocysteine showed that they are very sensitive functional indicators of cobalamin status especially when other evidence of cobalamin (B12) deficiency was equivocal. Measurement of methylmalonic acid (normal 73-271 nmol/l) and homocysteine (normal 5,4-13,9 micromol/l) should not replace the measurement of serum cobalamin.
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PMID:[Psychiatric manifestations of vitamin B12 deficiency: a case report]. 1502 91

Thyroid dysfunction is extremely common in women and has unique consequences related to menstrual cyclicity and reproduction. Even minimal hypothyroidism can increase rates of miscarriage and fetal death and may also have adverse effects on later cognitive development of the offspring. Hyperthyroidism during pregnancy may also have adverse consequences. Accordingly, thyrotropin (TSH) determination is warranted for all women planning pregnancy or those already pregnant. Replacement doses should be carefully monitored throughout pregnancy because the increased renal iodine loss and estrogen-induced rise in thyroxine-binding globulin (TBG) often result in a higher dose requirement. Although thyroid abnormalities are part of the standard differential diagnosis of menstrual disorders, recent studies indicate that these are relatively infrequent causes. Nonetheless, TSH is still required as part of the laboratory evaluation of women with abnormal cycles. The incidence of postpartum thyroiditis is high--6%-8% in various studies. A TSH should be performed in all postpartum patients who are depressed, who complain of unusual fatigue or anxiety or have any of the classical symptoms of hyperthyroidism or hypothyroidism. Practitioners providing health care for women should be alert to thyroid disorders as possible etiological factors in nonspecific symptoms such as fatigue and depression. However, most women with these symptoms are euthyroid; replacement therapy for them is not indicated. The long-standing dogma of thyroidology that replacement with levothyroxine alone is satisfactory for all hypothyroid patients has recently been questioned but results of trials are inconclusive. Nonetheless, satisfactory regimens can be found for the vast majority of patients.
Thyroid 2004
PMID:Thyroid dysfunction and women's reproductive health. 1567

Although hypothyroidism is purportedly an important cause of depression, prior studies have involved small samples of young people and produced conflicting results. We examined the yield of thyroid-stimulating hormone (TSH) testing in a large group of elderly patients with major depression or dysthymic disorder. The study sample comprised 883 outpatients aged 60 years or older from 18 primary care sites enrolled in the intervention arm of a clinical trial of depression management. Thyroid function was assessed by a single TSH value. Depressive diagnoses were confirmed with the Structured Clinical Interview for DSM-IV (SCID) and depression severity was assessed with the HSCL-20, a modified depression scale of the Hopkins Symptom Checklist. TSH results were available for 725 (82.1%) participants. Although 32 (4.4%) of those tested had TSH>5 mIU/L, the vast majority (27/32) had marginally elevated results (5.1-9.4 mIU/L). Only five patients (0.7%) had TSH levels >10 mIU/L. Patients with elevated TSH did not differ from those with TSH < or = 5 mIU/L in the severity or symptom pattern of depression as measured by the baseline HSCL-20 score (P=.37) or SCID score (P=.44). These findings should caution physicians against acceptance of borderline TSH values as the primary cause of a patient's clinical depression.
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PMID:Low yield of thyroid-stimulating hormone testing in elderly patients with depression. 1523 26

Conflicting results have recently been published about the benefits of combined T(4) and T(3) in treating hypothyroid patients. However, these studies may have been underpowered to detect differences in psychological well-being specifically related to T(4) replacement. We conducted a large, double-blind, randomized controlled trial of partial substitution of 50 microg T(4) by 10 microg T(3) vs. the original dose of T(4) in 697 hypothyroid patients. Thyroid function showed a rise in TSH (132%), a fall in free T(4) (35%, P < 0.001), and unchanged basal free T(3) levels (P = 0.92). At 3 months, there was a large (39%) placebo effect improvement in psychiatric caseness defined by the General Health Questionnaire (GHQ) 12 score in the control group compared with baseline, and this was sustained at 12 months. Differences vs. the intervention (T(3)) group were more modest with improvements in GHQ caseness (odds ratio, 0.61; 95% confidence interval, 0.42, 0.90; P = 0.01) and Hospital Anxiety and Depression questionnaire-anxiety scores at 3 months (P < 0.03) but not GHQ Likert scores, Hospital Anxiety and Depression questionnaire-depression, thyroid symptoms, or visual analog scales of mood and the initial differences were lost at 12 months. These results may be consistent with a subgroup of patients showing transient improvement after partial substitution with T(3) but do not provide conclusive evidence of specific benefit from partial substitution of T(4) by T(3) in patients on T(4) replacement. They also emphasize the large and sustained placebo effect that can follow changes in thyroid hormone administration.
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PMID:Partial substitution of thyroxine (T4) with tri-iodothyronine in patients on T4 replacement therapy: results of a large community-based randomized controlled trial. 1558 51

For more than 40 years thyroid hormones and mood disorders have been associated. Some psychiatric symptoms are produced by thyroid illnesses and there is a frequent association of thyroid dysfunction with mood disorders. Therefore, routine thyroid function assessment in patients with mood disorders and the treatment of sub-clinical thyroid dysfunctions is recommended. The usefulness of adding thyroid hormones to antidepressive treatment in euthyroid patients to obtain a potentiation effect has been probed repeatedly. The most common strategy is potentiation with T3, but high doses of T4 have been also used in patients with resistant depression. Thyroid hormones exert their action in the central nervous system through a variety of mechanisms: modulation of gene expression of several groups of proteins, some of them with known physiopathological implications in mood disorders and the influence over serotonin and noradrenergic neurotransmission, known to be one of the modes of action of antidepressants. Finally, it is also important to stress the complex relationship between psychiatric drugs, deiodinases and thyroid hormones, that can potentially help to understand the mechanisms of action of these drugs.
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PMID:[Mood disorders, psychopharmacology and thyroid hormones]. 1569 6

Thyroid dysfunction is a well-known contributor to psychiatric morbidity. To investigate the mechanism(s) by which thyroid hormone availability affects cerebral activity, a group of thyroidectomized individuals were studied at two points in time: when markedly hypothyroid in preparation for a thyroid cancer metastatic survey and when clinically and/or biochemically euthyroid. The analysis consisted of single photon emission computed tomography (SPECT) using a lipophilic radiopharmaceutical, technetium-99m (Tc-99m) ethyl cysteinate dimer (ECD), and measurement of mood, anxiety, and psychomotor function, at both points in time. Both increases and decreases in regional cerebral radiotracer activity were found in the hypothyroid condition relative to the euthyroid condition, and the neuropsychological assessment demonstrated significantly greater depression, anxiety, and psychomotor slowing during the hypothyroid state. Increased radiotracer activity was seen in frontal and temporal regions, posterior cingulate gyrus, thalamus, and putamen. Decreased activity was seen in the occipital cortex, and the pre- and postcentral gyri. This distribution pattern is partially consistent with findings in persons with depression and anxiety unrelated to thyroid disease, supporting the link between the symptoms observed in our subjects and their marked hypothyroidism. Finally, these results support the need to consider the effect of the thyroid state on cellular mechanisms of uptake and retention of cerebral blood flow radiopharmaceuticals when studying 'noneuthyroid' individuals.
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PMID:Cerebral accumulation of Tc-99m ethyl cysteinate dimer (ECD) in severe, transient hypothyroidism. 1607 89

Currently, the prevailing diagnostic systems of mental disorders, including Depressions and anxieties are based on descriptive phenomenological approach and not on etiology and pathophysiology. However, cumulative knowledge suggests that the field is moving towards establishment of subtypes or phenotypes of depressions based on different pathophysiologies, which may result in differential treatment responses. What is currently defined as 'Major Depressive Disorder (MDD)' may be the end-result of multiple heterogeneous biological and psychosocial processes. Therefore, MDD is actually a first step towards a differential diagnosis that eventually may lead to pathophysiology-based entities. Several hormonal systems may play a major role in the pathophysiology of several subtypes of depressions and anxieties. They include but are not limited to dysregulation of the hypothalamic-pituitary-adrenal (HPA) system, HP-Gonadal (HPG) and Thyroid (HPT) systems as well as their interactions with immune and other biological and psychosocial processes. Elucidation of the multiple underlying mechanisms of depressions and anxieties should lead to targeted treatment modalities and improvement of treatment responses.
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PMID:Major depression is not a diagnosis, it is a departure point to differential diagnosis -- clinical and hormonal considerations (a commentary and elaboration on Antonejevic's paper). 1595 Mar 91

Conflicting results have recently been published about the benefits of combined thyroxine (T4) and triiodothyronine (T3) in treating hypothyroid patients. However these studies may have been underpowered to detect differences in psychological well-being specifically related to thyroxine replacement. We conducted a large, double-blind, randomized controlled trial of partial substitution of 50 microg of T4 by 10 microg of T3 (T3) vs placebo (T4 alone - 50 microg of T4 replaced) in 697 hypothyroid patients. Thyroid function showed a rise in the TSH (132%), a fall in Free T4 (35%, P <0.001) and unchanged basal Free T3 levels (P=0.92). At 3 months there was a large (39%) <<placebo effect>> improvement in <<psychiatric caseness>> defined by the General Health Questionnaire 12 score (GHQ 12) in the control group compared with baseline and this was sustained at 12 months. Differences vs the intervention (T3) group were more modest with improvements in GHQ caseness (OR - 0.61; 95% CI: 0.42, 0.90; P=0.01) and HADS anxiety scores at 3 months (P <0.03) but not GHQ Likert scores, HADS depression, thyroid symptoms or visual analog scales of mood and the initial differences were lost at 12 months. These results may be consistent with a subgroup of patients showing transient improvement following partial substitution with T3 but do not provide conclusive evidence of specific benefit from partial substitution of T4 by T3 in patients on thyroxine replacement. They also emphasize the large and sustained <<placebo effect>> that can follow changes in thyroid hormone administration.
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PMID:[Critical appraisal: combined T3 and T4 replacement therapy is not better than replacement with T4 alone]. 1631 7

Hypothalamic pituitary thyroid (HPT) axis abnormalities and alterations in major depression are reported in the literature. The aim of our study was to evaluate the effect of mirtazapine on thyroid hormones after 6 months of therapy in a sample of adult outpatients with Major Depression (MD). 17 adult outpatients (7 men, 10 women) with MD according to DSM-IV criteria, were included in the study. All participants had to have met criteria for a major depressive episode with a score of at least 15 on the Hamilton Depression Rating Scale (HAM-D). Fasting venous blood samples were obtained for determination of serum Thyroid Stimulating Hormone (TSH), Free T3 (FT3) and Free T4 (FT4) concentrations both at baseline and after 6 months of therapy. HAM-D scores decreased significantly from the first day of treatment to the end of the treatment period (P<0.001) and twelve patients (70.6%) were classified as responders. A significant increase in FT3 concentrations was found between baseline and the end of the treatment period (P=0.015), whereas FT4 concentrations decreased (P=0.046). No significant changes were found in TSH levels. Higher FT4 concentrations at baseline predicted higher HAM-D scorers both at baseline and at the end of the treatment period. Furthermore, higher FT3 concentrations at endpoint were found to be predictors of lower HAM-D scores. Long-term treatment with mirtazapine increases FT3 levels and decreases FT4 maybe involving the deiodination process of T4 into T3.
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PMID:Effect of mirtazapine on thyroid hormones in adult patients with major depression. 1638 23

We determined the frequency of thyroid autoantibodies in fibromyalgia (FM) patients and the relationship between FM symptoms and these antibodies. Euthyroid 128 FM patients, 64 rheumatoid arthritis (RA) patients, and 64 healthy control subjects were included in the study. The sociodemographic features and the clinical features of FM patients were determined. By using a visual analog scale, patients were questioned about the severity of FM-related symptoms. All patients were administered with Duke-Anxiety Depression (Duke-AD) scale, the physical function items of the fibromyalgia impact questionnaire scale. Thyroid autoimmunity was defined as the presence of detectable antithyroglobulin (TgAb) and/or antithyroid peroxidase (TPOAb) antibodies by the immunometric methods. Patients with a connective tissue disorder, hypo- or hyperthyroidism, and patients who had psychiatric treatment within the last 6 months were not included into the study. The frequencies of thyroid autoimmunity in FM (34.4%) and RA (29.7%) patients were significantly higher than controls (18.8%) (p<0.05). Twenty-six (20.3%) FM patients had positive TgAb and 31 (24.2%) had positive TPOAb. When patients with thyroid autoimmunity were compared to others, it was seen that the mean age, the percentage of postmenopausal patients, the frequency of dryness of the mouth, and the percentage of patients with a previous psychiatric treatment were higher in this group (p<0.05). FM patients had thyroid autoimmunity similar to the frequency in RA and higher than controls. Age and postmenopausal status seemed to be associated with thyroid autoimmunity in FM patients. The presence of thyroid autoimmunity had no relationship with the depression scores of FM patients.
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PMID:The frequency of thyroid antibodies in fibromyalgia patients and their relationship with symptoms. 1654 Dec 3


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