Post stroke depression underdiagnosed, undertreated, underestimated?

Definition Better to speak of neuropsychiatric disorders with cerebrovascular disease Includes depression, anxiety, apathy, cognitive impairment, mania, psychosis, pathological affective display, catastrophic reactions, anosognosia

DSM 5 criteria Vascular depression (associated with microangiopathy) PSD Due to stroke with “depressive features, major depression-like episode or mixed mood features” Depressed features or loss of interest or pleasure with four other symptoms of depression, lasting more than 2 weeks

Differing from geriatric depression without vascular genesis Greater cognitive impairment Greater physical impairment Poor response to treatment (?) Less family and personal history More cardiovascular risk factors (associated with severity of depression?)

Incidence and prevalence Stroke risk between 10-20 in 10000 (55-64 yo) abd 200 in 10000 (>85 y olds) Around 31% of stroke patients at any time within 5 y after stroke Previous analysis up to 52% cumulative risk Caution> meta analysis, not distinguishing between major depression and other forms, other formal weaknesses

Personal experiences?

Risk factors Genetic factors: 5-HTTLPR and STin2VTNR polymorphisms DNA methylation status

Coincidence ?

Other factors: Gender? Age? Cardiovascular risk factors surprisingly not Depression in men underdiagnosed Diabetes Personal and possibly family history

Stroke characateristic and lesion Mechanism apparently irrelevant Localisation (left frontal, proximity to frontal pole) – better evidence shortly after stroke Size of stroke, physical disability Cognitive impairment more important than physical

Pathomechanisms

Candidates Disruption of prefrontal-subcortical circuits Increased activation of the default mode network, decreased activation of task related networks, dorsolateral prefrontal cortex Transcortical magnet stimulation only effective if directed at this area

Reverse causality

Other biological factors: alterations in Ascending monoamine systems Hypothalamic-pituitary-adrenal axis Alterations in neuroplasticity Excess in proinflammatory cytokines, cortisol Altered glutamate levels in the cingulate cortex Hypothesis for the efficacy of SSRI increased neuroplasticity, hippocampal neurogenesis (?) BDNF, interleukin levels (serum) predictive

Detection Patient Health Questionaire?

Geriatric depression scale (short)

Consequences Depression severity predictive of impairment of ADLs Increased mortality (even with mild PSD). One study reports odd-ratio of 1.41 at 5 Years

Therapy Significant effect of SSRI and Tricyclics No evidence for treatment of non-depressed patients

Complications SSRI increased risk of haemorrhagic complications Increased risk of falls Increased risk for stroke, myocardial infarction and all-cause mortality Relapse all depression if premature cessation of therapy 80%

Prevention Psychotherapy better evidence than in treatment Number of social ties inversely related to severity Marital status, living situation not correlated Lack of social support at admission increased risk Citalopram vs problem solving therapy vs placebo 8.5% vs 11.9% vs 22.4% (n=58)

Future research