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Depression in Neurological disorders

Dr pavan kumar kadiyala

 Depression is a relatively common psychiatric

comorbidity of most neurological disorders, with  prevalence rates ranging between 20 and 50% among patients with stroke, multiple sclerosis, epilepsy, Parkinson’s disease and dementia.  Depression is an independent predictor of poor quality of life in these patients and  has a negative impact on the response to treatment, course and recovery of neurological deficits.

 Comorbid depressive disorders in neurologic

patients can be indistinguishable to the primary mood disorders.  The great overlap of medical and psychiatric symptoms in depression and neurologic disorders may lead to both false-positive and false-negative diagnoses of depression.  Patient with comorbid condition have lower response rate and /or a longer time to response, greater reports of side effect early in treatment and greater likely hood of dropping out.

Neurobiology .


 With respect to cortical function. .Clinical phenomenology  depression since long have been suggested as dysfunction of basic CNS processes. depression involves multiple disturbances of information processing.

Emotional Processing and the Brain  Four brain regions in the regulation of normal     emotions: The PFC. and The amygdala . The anterior cingulate. The hippocampus.

nucleus accumbens. prefrontal cortex (PFC). neurocognitive  dysfunction involving the changes (poor concentration and abstraction)  Anhedonia and hippocampus. hypothalamus. and PFC. . and other limbic structures  neural circuits involved in the decreased consummatory behavior (appetite and libido) anticipation and consummation of rewards. which involve the thalamus.

hair pulling. subcortical connecting the thalamus. stereotypical behaviors striatum of furrowed brow. psychomotor  dysfunction of circuits disturbances (retardation. hypersomnolence. pacing and frequent postural basal ganglia. and shifts. biting at the lips or nail beds. and compulsive scratching  circadian rhythms  dysregulation of thalamic (insomnia. nuclei and the brainstem diurnal mood variation) .

and the thalamus  Structural brain changes:  reduced hippocampal and caudate volumes suggesting more focal defects in relevant neurobehavioral systems  Functional changes:  hypoperfusion in frontal (left).Neuroimaging  most consistent abnormality . the basal ganglia. temporal and parietal areas  Reduced blood flow and metabolism in .increased frequency of abnormal hyperintensities in subcortical regions. such as periventricular regions.

reduced monoamine function ie. NE. 5HT. hypercortisolemia  Decreased brain-derived neurotrophic growth factor  Thyroid dysfunction in 5-10%  Blunted GH and prolactin response to serotonin agonists . DA  Endocrine factors:  Stress . Neurotransmitters:  Monoamine theory .Increased HPA activity.

head injury  Infectious: HIV. Huntingtons. Brucellosis  Endocrine and Metabolic: hypothyroidism. epilepsy. Cushings. tumor. EBV. dementia. porphyria. parathyroid disease.Medical causes of depression  Neurological: CVA. PD. Addisons. MS. CCF . Vit B12 and folate deficiency  Cardiac disease: MI.

opioids . cocaine. OCP. salbutamol  Drugs and toxins: alcohol. l- dopa. benzodiazepines. antihypertensives.RA  Cancers  Medications: analgesics. cannabis. Connective tissue disorders: SLE. steroids. cytotoxins. cimetidine.

depression. particularly head and neck pain. than the general public (O’Reardon 2007).  Patients with depression are more vulnerable to general pain and traumatic pain sequelae.4% of the general population.  Headache. and other neuropsychological comorbidities.Depression and headache  Major depression is present in nearly 18% of migraineurs compared to 7. are fundamentally neurophysiological disorders. .

including anatomical relationships. both depression and headache share certain neurophysiological commonalities. . and vice versa.  So failure to effectively treat depression may prevent the successful control of headache  Some medications used to treat headache patients may paradoxically worsen or contribute significantly to depression. possibly in the prefrontal cortex.

valproic acid. beta     blockers. such as phenelzine. Recent reports suggest that transcranial magnetic stimulation (TMS) may provide treatment for . may have an important role. There may be a secondary improvement. For severe intractable cases. preventive agents topiramate. by reducing the headache itself. however. lithium and MAO inhibitors. in mood. depression may be a side effect of these medications.

efficacy of fluoxetine and venlafaxine for migraine . These may be key factors in both the sleep and headache phenomena and perhaps depression as well. nortriptyline. doxepin. weight gain and anticholinergic effects. Amitriptyline. TCAs were recognized as useful for both chronic pain (including headache) and depression. Targeted mechanisms involve the suprachiasmic      nucleus of the hypothalamus and the neurohormone melatonin. an anti-inflammatory neuromodulating substance.

and carer stress. disability (measured by ADL).DEPRESSION IN PARKINSON’S DISEASE  Diagnosis and management of depression in Parkinson’s disease (PD) is important for two main reasons:  firstly. This effect is independent from the effect of motor disability. depression is common in PD and  secondly depression causes significant morbidity in terms of quality of life. .

with a peak early in the illness (possibly related to increased life events) and another gradual increase as the illness reaches its latter stages Depressive illness also appears to be more common in those people with more rapidly . Epidemiology  prevalence of depression in PD is probably      between 20–45% male=female prevalence of depression relative to the course of PD is biphasic.

psychiatric symptoms (particularly depression and anxiety) may precede motor symptoms of PD by a number of years (as often they do in Huntington’s disease). correlates well with PET studies suggesting that the  onset of the disease process may predate motor symptoms by the same time period . Studies .  The average time between onset of depressive symptoms and motor symptoms was around 6 years.

bradyphrenia.  The patient often appears hunched with a lack of an obvious affective response and spontaneity (the patient with PD may well have an intact affective response but may not be able effectively to translate this into motor phenomena). and reduced libido. loss of interest and concentration. .  Symptoms that are common to both depression and idiopathic Parkinson’s disease include motor slowing.Diagnosis of depression in Parkinson’s disease  difficult because of the clinical overlap between the two syndromes. weight loss.  The “body language” of depression looks similar to that of PD at first glance. sleep and appetite disturbance.

themselves. . pervasive low mood with diurnal variation (for at least two weeks) early morning wakening pessimistic thoughts about the world. and the future (out of context with their level of disability or their previous attribution style) suicidal ideation. Symptoms that may help in the diagnosis of     depression in people with PD include.

Beck depression inventory is not a useful rating scale in PD. The Montgomery and Asberg depression rating scale (MADRS) and the Hamilton depression scale (HAM-D) have performed better. .motor symptoms of PD may be temporarily alleviated by a but that does not change the overall prognosis of the illness. There is transient dysphoria during surgery for PD following pallidotomy and DBS(esp stimulation around subthalamic N). TCAs and SSRIs as Rx ECT. Low mood can also occur as a consequence of     medications used to treat Parkinson’s disease or other conditions (such as hypertension).

Rates of depression are higher in nursing home settings and younger people with MS were more likely to be depressed than their older counterparts with similar levels of physical disability. prevalence . “depressogenic” MS lesion . Like Parkinson’s disease.DEPRESSION IN MULTIPLE SCLEROSIS  Depressed mood also contributes significantly to     reductions in quality of life for people with MS.right temporal lesions.25%. vegetative or somatic symptoms do not tend to be good diagnostic discriminators for depression in MS. .

 “disinterest in sex” was uniquely related to depression in MS (rather than fatigue or physical disability).  Pervasive mood change• Diurnal variation in mood• Beck’s “cognitive triad”• Mood congruent psychotic symptoms• Suicidal ideation• A change in function not related to physical disability  All the anti-spasticity drugs associated with low mood (including baclofen. and tizanidine) and following the abrupt discontinuation of baclofen and other antispasticity drugs . dantrolene.

social isolation. . and substance abuse  controversy over whether interferon treatment is a risk factor for depression in MS.Suicidal behaviour in MS  15% of the deaths were recorded as suicide. young age of onset.  being male. previous history of depression.

 Mild to moderate forms of depression . .CBT.Treatment  SSRIs (sertraline and fluoxetine).MS symptoms worsened in around 20% cases.  ECT.

DEPRESSION AND STROKE  Pathophysiology  sudden. employment. younger. multiple loss events (loss of physical      function. Peak incidence of depression is between six months and two years post-stroke and point prevalence for depression varies between 10– 34% according to studies. more often white and less likely to be alive . change in social or marital status) lose the neurological capacity to process these loss events Affect areas of the brain directly involved in control of mood.

especially in the first few months after stroke. clear relation between proximity of the lesion to the left frontal pole and depression.  a brain infarct affecting the pallidum was a strong predictive factor for post-stroke depression .

The patient may appear to be extremely retarded but may function at a high level within a structured environment. and disturbance in vegetative functions make difficult. Pathological emotionalism is relatively common after stroke. A deterioration in function over a few days or weeks following a period of improvement is one clinical clue for the development of depression.Diagnosis  Communication difficulties. affecting up to 20% of patients in 1st 6 months post-stroke but tending to improve over next year. impairments of facial and     emotional expression. such as bromocriptine treat abulia. Dopamine agonists. . treated with antidepressant medication and levodopa Extreme abulia can sometimes be mistaken for depression and can be related to either frontal (especially left frontal) and diencephalic lesions.

 In the community. HADS and GHQ-12 are recommended .Rating scales for depression poststroke  On acute hospital wards. the “signs of depression” scale  In rehabilitation settings. the best validated scales were the hospital anxiety and depression scale (HADS) and the general health questionnaire-12 (GHQ-12).

sertraline) and other antidepressants (reboxetine) are superior to placebo  TMS . psychotherapy better than medications in preventing of depression post-stroke  Treatment trials have indicated that SSRI treatments (citalopram.

Depression and Dementia  depression can be an early sign of dementia .

activation of hysterical mechanisms.Some depressive patients show cognitive abnormalities. . These can be due to personal predisposition. changes in level of arousal and as a part of the general of psychomotor retardation. cerebral metabolic abnormalities.

The ageing process affecting the brain such as the neuronal loss may combine with the neurochemical changes in depression and lead to cognitive failure. this syndrome should be considered to be organic in origin and should be labeled as dementia of depression rather than pseudodementia . Therefore. It is these chemical and physiological alternations which are responsible for both depression and the cognitive changes.

 Dothiepin is an effective antidepressant with anxiolytic action and has lesser anticholinergic side-effects. but antidepressants should be administered daily for several weeks or months .  Hypnotics and tranquilizers can be used on an SOS basis.

 Interictal depressions are common in patients with late onset epilepsy. during status epilepticus.  The longer the duration of epilepsy the more sever the depression Depression is more closely related to temporal lobe epilepsy than to other types of epilepsy  Laterality of lesion responsible for depression reported is controversial as both dominant hemispheric as well as non-dominant hemispheric lesions have been involved. .Epilepsy and Depression  depression is a frequent complication of epilepsy. in children. Fears and depression are the commonest ictal experiences. petit mal status and partial seizure status. and in complex partial seizures.  can be related ictally or post ictally  Ictal depression occurs with temporal lobe seizures.

The suicidal rate is higher among epileptics than in the general population. serotonin. The implicated biochemical abnormalities are. pituitary axis and disturbances in folic acid metabolism . Temporal lobe epileptics carry the greatest risk. There may be family history of depression in more than 50% of cases. The onset and subsidence of depression tends to be     sudden and the mood disorder fluctuates markedly. disorders of noradrenaline. anxiety and hostility. dopamine. and gamma-aminobutyric acid metabolism and malfunctioning of the hypothalamic. Paranoid features frequently accompany the depression as well as depresonalisation.

The folic acid metabolism is least affected by carbamazepine and sodium valproate. RBCs and CSF have been demonstrated in epileptics with mental symptoms including depression. The level of psychopathology correlates positively with phenobarbitone and negatively with carbamazepine Low foliate levels in serum. Folic acid supplements do not influence the onset of prognosis of the depressive state. . However S-adenosylmethionine which is involved in folate metabolism seems to have antidepressant properties. Patients receiving carbamazepine are the least      depressed while patients receiving phenobarbitone are the most depressed.

 Patients receiving anticonvulsants demonstrate lower antidepressant level than patients who are not receiving anticonvulsants.Treatment  need a higher dose of antidepressants  All non-MAOI and some MAOI antidepressants lower the sedation threshold and can potentially aggravate clinical seizures  Therapeutic doses of antidepressants can do this in predisposed individuals who have a family history of epilepsy.  Electroconvulsive therapy is not contraindicated in epilepsy and can be life-saving in suicidal epileptics . existing brain damage or previous history of ECT.

 The frontal location is characterized by irritability.Cerebral Tumors and Depression  Frontal and temporal locations of tumour are associated with the greatest frequency of both depression and personality disturbances. and apathy. depression or euphoria. Irritability is a frequent presenting symptom  Parietal lobe tumours are less likely to produce mental changes .

 Chances of death by suicide is considerably increased after head injury.Headtrauma and Depression  Depression is the most common emotional reaction to head injury  "reactive" depression.  Significantly. after the injury has been observed in 40% of patients who committed suicide.symptoms may last for many months after the injury. a change in the character of the person. . accounting for 14% of all deaths.

Later on the mood becomes apathetic. self neglect and euphoria replace the depression.Huntington's Chorea and Depression  Psychiatric changes may be present for some time before the onset of involuntary movements or intellectual impairment  The depression can be severe in the early stages when the patient still retains insight. .  The depression responds to antidepressant drugs and electroconvulsive therapy.

 Antidepressants and E.T. schizophrenia like. These may respond to a reduction in dose of the steroids.  Immunosuppresive drugs like cylcophosphamide and azathioprine can be tried instead of steroids.C.Systemic Lupus Erythematosus and Depression  The functional psychoses in SLE can be depressive. .  Steroids which are the mainstay of treatment in SLE can precipitate or aggravate the mental symptoms. can be used for treating the depression. manic. or rarely.

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