Depression in Neurological disorders

Dr pavan kumar kadiyala

Introduction
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, Parkinsons 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

Clinical phenomenology
depression since long have been suggested as

dysfunction of basic CNS processes.

With respect to cortical function, depression

involves multiple disturbances of information processing.

Emotional Processing and the Brain

Four brain regions in the regulation of normal

emotions: The PFC, The anterior cingulate, The hippocampus, and The amygdala

 neurocognitive

dysfunction involving the

changes (poor concentration and abstraction)

Anhedonia and

hippocampus, prefrontal cortex (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, hypothalamus, nucleus accumbens, and PFC.

 psychomotor

dysfunction of

circuits disturbances (retardation, subcortical connecting the thalamus, pacing and frequent postural basal ganglia, and shifts, stereotypical behaviors striatum of furrowed brow, hair pulling, biting at the lips or nail beds, and compulsive scratching

circadian rhythms dysregulation of thalamic (insomnia, hypersomnolence, nuclei and the brainstem diurnal mood variation)

Neuroimaging
most consistent abnormality - increased

frequency of abnormal hyperintensities in subcortical regions, such as periventricular regions, the basal ganglia, 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), temporal and parietal areas Reduced blood flow and metabolism in

 Neurotransmitters: Monoamine theory - reduced monoamine function

ie, 5HT, NE, DA

Endocrine factors:

Stress - Increased HPA activity, hypercortisolemia

Decreased brain-derived neurotrophic growth factor Thyroid dysfunction in 5-10% Blunted GH and prolactin response to serotonin

agonists

Medical causes of depression

Neurological: CVA, epilepsy, PD, dementia, MS,

tumor, Huntingtons, head injury

Infectious: HIV, EBV, Brucellosis Endocrine and Metabolic: hypothyroidism,

Cushings, Addisons, parathyroid disease, porphyria, Vit B12 and folate deficiency
Cardiac disease: MI, CCF

 Connective tissue disorders: SLE,RA Cancers Medications: analgesics, antihypertensives, l-

dopa, steroids, OCP, cytotoxins, cimetidine, salbutamol

Drugs and toxins: alcohol, benzodiazepines,

cannabis, cocaine, opioids

Depression and headache

Major depression is present in nearly 18% of

migraineurs compared to 7.4% of the general population. Headache, depression, and other neuropsychological comorbidities, are fundamentally neurophysiological disorders. Patients with depression are more vulnerable to general pain and traumatic pain sequelae, particularly head and neck pain, than the general public (OReardon 2007).

 both depression and headache share certain

neurophysiological commonalities, including anatomical relationships, possibly in the prefrontal cortex. 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, and vice versa.

 preventive agents topiramate, valproic acid, beta

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

 Targeted mechanisms involve the suprachiasmic

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

DEPRESSION IN PARKINSONS DISEASE

Diagnosis and management of depression in

Parkinsons disease (PD) is important for two main reasons: firstly, depression is common in PD and secondly depression causes significant morbidity in terms of quality of life, disability (measured by ADL), and carer stress. This effect is independent from the effect of motor disability.

 Epidemiology

prevalence of depression in PD is probably

between 2045% male=female prevalence of depression relative to the course of PD is biphasic, 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

 Studies - psychiatric symptoms (particularly

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

Diagnosis of depression in Parkinsons disease

difficult because of the clinical overlap between the

two syndromes. Symptoms that are common to both depression and idiopathic Parkinsons disease include motor slowing, bradyphrenia, sleep and appetite disturbance, weight loss, loss of interest and concentration, and reduced libido. The body language of depression looks similar to that of PD at first glance. 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).

 Symptoms that may help in the diagnosis of

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

 Low mood can also occur as a consequence of

medications used to treat Parkinsons disease or other conditions (such as hypertension). There is transient dysphoria during surgery for PD following pallidotomy and DBS(esp stimulation around subthalamic N). 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. TCAs and SSRIs as Rx ECT- motor symptoms of PD may be temporarily alleviated by a but that does not change the overall prognosis of the illness.

DEPRESSION IN MULTIPLE SCLEROSIS

Depressed mood also contributes significantly to

reductions in quality of life for people with MS. depressogenic MS lesion - right temporal lesions. prevalence - 25%. 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. Like Parkinsons disease, 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 Becks 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, dantrolene, and tizanidine) and following the abrupt discontinuation of baclofen and other antispasticity drugs

Suicidal behaviour in MS
15% of the deaths were recorded as suicide.

being male, young age of onset, previous history

of depression, social isolation, and substance abuse controversy over whether interferon treatment is a risk factor for depression in MS.

Treatment
SSRIs (sertraline and fluoxetine).

Mild to moderate forms of depression - CBT.

ECT- MS symptoms worsened in around 20%

cases.

DEPRESSION AND STROKE

Pathophysiology sudden, multiple loss events (loss of physical

function, employment, 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. 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. younger, more often white and less likely to be alive

 clear relation between proximity of the lesion to

the left frontal pole and depression, especially in the first few months after stroke. a brain infarct affecting the pallidum was a strong predictive factor for post-stroke depression

Diagnosis
Communication difficulties, impairments of facial and

emotional expression, and disturbance in vegetative functions make difficult. A deterioration in function over a few days or weeks following a period of improvement is one clinical clue for the development of depression. Pathological emotionalism is relatively common after stroke, affecting up to 20% of patients in 1st 6 months post-stroke but tending to improve over next year. 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. The patient may appear to be extremely retarded but may function at a high level within a structured environment. Dopamine agonists, such as bromocriptine treat abulia.

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). In the community, HADS and GHQ-12 are recommended

 psychotherapy better than medications in

preventing of depression post-stroke Treatment trials have indicated that SSRI treatments (citalopram, sertraline) and other antidepressants (reboxetine) are superior to placebo TMS

Depression and Dementia

depression can be an early sign of dementia

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

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

 Dothiepin is an effective antidepressant with

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

Epilepsy and Depression

depression is a frequent complication of epilepsy. can be related ictally or post ictally Ictal depression occurs with temporal lobe seizures,

during status epilepticus, petit mal status and partial seizure status. Fears and depression are the commonest ictal experiences. Interictal depressions are common in patients with late onset epilepsy, in children, and in complex partial seizures. 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.

 The onset and subsidence of depression tends to be

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

 Patients receiving carbamazepine are the least

depressed while patients receiving phenobarbitone are the most depressed. The level of psychopathology correlates positively with phenobarbitone and negatively with carbamazepine Low foliate levels in serum, RBCs and CSF have been demonstrated in epileptics with mental symptoms including depression. 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. The folic acid metabolism is least affected by carbamazepine and sodium valproate.

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, existing brain damage or previous history of ECT. Patients receiving anticonvulsants demonstrate lower antidepressant level than patients who are not receiving anticonvulsants. Electroconvulsive therapy is not contraindicated in epilepsy and can be life-saving in suicidal epileptics

Cerebral Tumors and Depression

Frontal and temporal locations of tumour are

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

Headtrauma and Depression

Depression is the most common emotional

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

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. Later on the mood becomes apathetic, self neglect and euphoria replace the depression. The depression responds to antidepressant drugs and electroconvulsive therapy.

Systemic Lupus Erythematosus and Depression

The functional psychoses in SLE can be

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

Thank u